Budesonide is a corticosteroid that is administered via intranasal inhalation, oral inhalation, rectally, or orally. Budesonide has potent glucocorticoid and weak mineralocorticoid activity. Budesonide formulations are used to manage symptoms associated with allergic rhinitis, selected lung diseases, inflammatory bowel disease (Crohn's disease and ulcerative colitis), eosinophilic esophagitis (EoE), or primary immunoglobulin A nephropathy (IgAN) in adults, depending on the formulation chosen. Inhaled budesonide possesses high topical anti-inflammatory activity but low systemic activity. Inhaled corticosteroids (ICS) are the preferred pharmacologic treatment in the long-term management of persistent asthma for most patients. Maintenance ICS therapy may also decrease the frequency and severity of exercise-induced bronchoconstriction (EIB); short-acting beta-2 agonists (SABAs) also help prevent EIB, but tolerance can develop with regular SABA use. According to guidelines, budesonide in combination with an inhaled long-acting beta-2 agonist (LABA) is not recommended for COPD treatment; however, it is an option for those patients with stable disease who are already receiving this therapy with no major symptoms or exacerbations. Escalation to triple therapy with a long-acting muscarinic antagonist (LAMA), a LABA, and an ICS should be considered for patients who have further COPD exacerbations or major symptoms. Patients with COPD who have concomitant asthma should be treated with an ICS. Budesonide nasal spray allows for once-daily dosing for allergic rhinitis. Rhinitis guidelines strongly recommend intranasal corticosteroids as the preferred medication when choosing monotherapy for persistent allergic rhinitis; they may also be offered as first-line therapy for nonallergic rhinitis (NAR) although intranasal antihistamines are strongly recommended as a first-line monotherapy option for NAR. Oral budesonide has been shown to be superior to placebo and equivalent to prednisolone, but with fewer adverse reactions, in treating active Crohn's disease. A budesonide oral tablet with a proprietary delivery system (MMX, a multi-matrix system) that delivers medicine to the colon, has been shown to be effective at inducing remission in patients with active, mild to moderate ulcerative colitis. Several studies also indicate the benefit of oral budesonide in treating microscopic colitis and, specifically, collagenous colitis. Clinical trials have shown patients with EoE taking oral budesonide suspension for 12 weeks were able to achieve histological remission (38% to 53.1%) and helped improve or eliminated dysphagia symptoms.
General Administration Information
For storage information, see specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
Delayed-release capsules (e.g., Entocort EC and equivalent generics):
-Administer the total daily dose in the morning, with or without food.
-Administer whole; do not chew or crush.
-For patients unable to swallow an intact capsule, open the capsules and empty the granules onto one tablespoonful (15 mL) of applesauce. Ensure the applesauce is not hot and that it is soft enough to be swallowed without chewing. Mix and consume the entire contents within 30 minutes. Do not chew or crush. Follow with 240 mL (8 ounces) of water.
-Do not administer with grapefruit juice; patient should avoid consumption of grapefruit juice for the duration of therapy.
Delayed-release capsules (e.g., Tarpeyo):
-Administer the total daily dose in the morning at least 1 hour before a meal.
-Administer whole; do not open, chew, or crush.
-Do not administer with grapefruit juice; patient should avoid consumption of grapefruit juice for the duration of therapy.
-If a dose is missed, take the prescribed dose at the next scheduled time. Do not double the next dose.
Extended-release capsules (e.g., Ortikos):
-Administer the total daily dose in the morning, with or without food.
-Administer whole; do not chew or crush.
-Do not administer with grapefruit juice; patient should avoid consumption of grapefruit juice for the duration of therapy.
Extended-release tablets (e.g., Uceris):
-Administer the total daily dose in the morning, with or without food.
-Administer whole; do not chew, break, or crush.
-Do not administer with grapefruit juice; patient should avoid consumption of grapefruit juice for the duration of therapy.
Oral Liquid Formulations
-Do not take oral budesonide suspension with food or liquid at the time of ingestion.
-Do not mix with food or liquid.
-Shake the oral budesonide suspension packet for at least 10 seconds prior to opening.
-Squeeze the packet from the bottom to the top into the mouth. Repeat 2 to 3 times to ensure the packet is empty.
-Swallow the budesonide suspension.
-Do not drink or eat for at least 30 minutes after swallowing budesonide suspension. After 30 minutes, rinse the mouth with water and spit out the contents without swallowing.
-Avoid grapefruit juice for the duration of therapy.
Extemporaneous Compounding-Oral
NOTE: There is an FDA-approved oral suspension of budesonide (2 mg/10 mL single dose packet) commercially available.-For the treatment of eosinophilic esophagitis, an oral viscous suspension of budesonide should be used.
-The patient should not consume food or drink for 30 minutes after the viscous suspension administration.
Extemporaneous compounding instructions for budesonide oral suspension:
-Oral viscous suspension prepared with Splenda:
-To compound, mix each 0.5 mg/2 mL ampule of the liquid inhalation suspension with 5 packets of sucralose (Splenda) to make a final volume of 8 to 12 mL.
-The suspension should be administered immediately after compounding as no data are available regarding stability.
-Oral viscous suspension prepared with Neocate Nutra:
-For a 1-mg dose, add two 0.5 mg/2 mL ampules of the liquid inhalation suspension to 2.5 mL of Neocate Nutra and mix into a slurry.
-For a 2-mg dose, add four 0.5 mg/2 mL ampules of the liquid inhalation suspension to 5 mL of Neocate Nutra and mix into a slurry.
-The suspension should be administered immediately after compounding as no data are available regarding stability.
Inhalation Administration
Oral Inhalation Administration
Dry powder for inhalation (Pulmicort Flexhaler):
-Instruct patient on proper administration technique. Most children younger than 4 years of age may not generate sufficient inspiratory flow to activate dry powder inhalers.
-A new inhaler should be primed before use, per the priming instructions that come with the device. While priming the inhaler, the inhaler should always be held in an upright position.
-To load the dose on a primed inhaler, keep the inhaler in an upright position and twist the brown grip fully to the right as far as it will go, then twist it back fully to the left; there will be the sound of a "click".
-When inhaling, the inhaler may be held in an upright or horizontal position. Turn head away from the inhaler and breathe out. Place the mouthpiece between the lips and inhale deeply and forcefully. Remove the inhaler from the mouth and exhale normally. Do not blow or exhale into the mouthpiece. Do not chew or bite on the mouthpiece.
-If more than 1 dose is required, repeat the steps described above.
-After the last dose, rinse the mouth with water; do not swallow the water.
-The inhaler should be kept clean and dry at all times. Do not immerse it in water. Wipe the outside of the mouthpiece 1 time each week with a dry tissue. The inhaler should not be used if it has been damaged or if the mouthpiece has become detached.
-The inhaler contains either 60 puffs or 120 puffs after prepared for the first use. The dose indicator window shows approximately how much medicine is left. The indicator is marked in intervals of 10 doses. Markings are either with numbers or dashes (alternating), counting down to "0". Your inhaler is empty when the number "0" on the red background reaches the middle of the dose indicator window; when this occurs, throw away the inhaler.
Inhalation suspension for nebulization (Pulmicort Respules):
-Administer via jet nebulizer connected to an air compressor with adequate airflow, and equipped with a mouthpiece or suitable face mask. Ultrasonic nebulizers are not suitable for administration and are not recommended.
-See manufacturer's direction on the use of nebulizer and preparation of the solution.
-Gently shake the ampule in a circular motion before opening it and placing the suspension in the nebulizer reservoir.
-A Pari-LC-Jet Plus Nebulizer (with face mask or mouthpiece) connected to a Pari Master compressor was used to deliver budesonide inhalation suspension during the clinical trials. The safety and efficacy of budesonide inhalation suspension delivered by other nebulizers and compressors have not been studied.
-The choice of using a mouthpiece versus a face mask must be made based on the skills and understanding of each patient.
-Use of the 'blow by' technique (i.e., holding the face mask or open tube near the patient's nose and mouth) is not recommended.
-The effects of mixing budesonide with other nebulizable medications have not been adequately assessed; administer budesonide inhalation suspension separately in the nebulizer.
-Storage: Store inhalation suspension upright at controlled room temperature and protect from light. When the envelope has been opened, the shelf life of the unused ampules is 2 weeks; return unused ampules to the aluminum foil envelope to protect from light. Any opened ampule should be used promptly. Do not refrigerate or freeze.
Intranasal Inhalation Administration
-Instruct patient on proper nasal inhalation priming and administration technique.
-Shake the nasal spray well before administering.
-Prior to initial use, the container must be shaken gently and the pump must be primed by actuating 8 times. If used daily, the pump does not need to be reprimed. If the spray is not used for 2 consecutive days, reprime with 1 spray or until a fine spray appears. If not used for more than 14 days, rinse the applicator and reprime with 2 sprays or until a fine spray appears.
-The patient should blow nose gently prior to use. With head upright, spray the medicine into each nostril. The patient should sniff briskly while squeezing the bottle quickly and firmly.
-After administration, wipe spray tip dry with a clean tissue and replace outer cap.
-The cap and spray tip should be cleaned regularly. Remove the cap and gently pull the spray tip away from the bottle. Wash in warm water and rinse in cold tap water; shake to remove excess water. Allow cap and spray tip to air dry completely before reassembling.
-To avoid the spread of infection, do not use the nasal spray container for more than 1 person.
Rectal Administration
Rectal Foam
-For rectal use only.
-The product is flammable. Avoid fire, flames, and smoking during and immediately following administration.
-Budesonide rectal foam should be temporarily discontinued prior to initiation of bowel preparation for colonoscopy and should not be resumed until a health care provider is consulted.
-Prior to rectal foam use, the patient should use the bathroom to empty bowels.
-The foam can be used in a standing, lying, or sitting position (e.g., while using the toilet).
-When budesonide rectal foam is applied in the evening, use immediately prior to bedtime. The patient should not try not to have a bowel movement again until the next morning.
-Before the first use, remove the safety tab from under the pump dome. The canister cannot be used if safety tab is not removed.
-The applicators are in a special tray. Applicators are for single use. Use a new applicator for each dose. Each applicator is coated with a lubricant; petrolatum or petroleum jelly can also be used if additional lubrication is needed. To remove an applicator from the tray, hold the tray firmly and pull.
-Push the applicator firmly onto the nozzle of the canister.
-To unlock the canister, twist the dome on the top of the canister until the semi-circular notch underneath the dome is in line with the nozzle.
-Warm the canister by holding it in the hands while shaking it vigorously for 10 to 15 seconds. Place the forefinger on the top of pump dome and then turn the canister upside down. The canister will only work properly when held with the pump dome pointing down.
-Insert the applicator into the rectum as far as it is comfortable. The easiest way for the patient to use budesonide rectal foam is to keep one foot on the floor and raise the other foot onto a firm surface such as a chair or stool.
-To administer a dose of budesonide rectal foam- use the forefinger to fully push down the pump dome one time and hold it for about 2 seconds in that position. Release finger pressure on the pump dome and hold the applicator in place for 10 to 15 seconds. Remove the applicator. The foam will still expand a little and may drop out of the applicator or anus.
-Remove the applicator from the canister and place the used applicator in the plastic bag provided. Throw the plastic bag away in household trash.
-To prevent loss of budesonide rectal foam from the canister between uses, turn the pump dome around so that the semi-circular notch faces the opposite direction to the nozzle.
-Wash hands with soap and water following administration.
Respiratory infection (8% to 11%), sinusitis (8%), and viral infection (6%) have been reported in adult patients during clinical trials with oral budesonide. Ear infection (unspecified), bronchitis, abscess, rhinitis, dyspnea, and pharynx disorder were reported in less than 5% of adult patients receiving oral budesonide. Respiratory tract infection (including acute sinusitis, sinusitis, nasopharyngitis, respiratory tract infection, viral respiratory infection, upper respiratory tract infection, viral upper respiratory tract infection, and rhinitis) were reported in 13% of adult and pediatric patients receiving oral budesonide suspension for eosinophilic esophagitis (EoE). Throat irritation/oropharyngeal pain (3%) and nasal congestion (less than 2%) were reported in patients receiving oral budesonide suspension for EoE. Nasal or respiratory adverse events reported during treatment with nasal budesonide include cough (2%), epistaxis (8%), pharyngitis (4%), nasal irritation (2%), sinusitis (3% or more), and bronchospasm (2%). Respiratory infection (3% to 38%), rhinitis (7% to 12%), cough (5% to 9%), nasopharyngitis (9%), nasal congestion (3%), pharyngitis (3%), allergic rhinitis (2%), viral upper respiratory tract infection (2%), otitis media (1% to 12%), ear infection (2% to 5%), epistaxis (2% to 4%) and viral infection (2% to 5%) were reported by patients receiving budesonide inhalation powder or budesonide inhalation suspension. Chest pain, dysphonia, stridor, otalgia, external ear infection, voice alteration, and cervical lymphadenopathy were also reported in 1% to less than 3% of patients. Throat irritation and bronchitis has also been reported during postmarketing use of budesonide inhalation powder and suspension. Nasal septum perforation, anosmia, pharynx disorders (throat irritation, throat pain, swollen throat, burning throat, itchy throat), and wheezing have been reported with intranasal budesonide during postmarketing experience.
Headache (10% to 21%), dizziness (7%), fatigue (2% to 5%), mood changes (2.5% to 6.5%), and insomnia (up to 6.5%) were reported during clinical trials in adult patients with oral budesonide. Agitation, amnesia, confusion, hyperkinesis, nervousness, paresthesias, sleep changes, somnolence or drowsiness, tremor, and vertigo have been reported in less than 5% of adult patients receiving oral budesonide. Headache/migraine (5%) were reported in adult and pediatric patients receiving oral budesonide suspension for eosinophilic esophagitis (EoE). Fatigue, feeling abnormal, depression, irritability, restlessness, and tremor were reported in less than 2% of adult and pediatric patients receiving oral budesonide suspension for EoE. Insomnia, sleep disorder, and depression were reported in less than 1% of adult patients using budesonide rectal foam. In pediatric patients (age 12 months to 8 years), hyperkinesia (restlessness), fatigue, and emotional lability was reported in 1% to less than 3% of patients receiving budesonide inhalation suspension. Headache (3% or more) and migraine (1% to 3%) have been reported in with budesonide inhalation powder and suspension. Psychosis, emotional lability, depression, aggressive reactions, irritability, nervousness, restlessness, anxiety, and headache have been reported in postmarketing experience with budesonide inhalation powder and suspension. Mood swings, agitation, confusion, insomnia, nervousness, dizziness, and sleep disorder have been reported in postmarketing experience with oral budesonide. Mood swings and dizziness have been reported in postmarketing experience with rectal budesonide.
Dermatitis (6% or less) was reported in adult patients receiving oral budesonide. Alopecia, eczema (atopic dermatitis), skin disorder, hyperhidrosis, and purpura were reported in less than 5% of adult patients receiving oral budesonide during clinical trials. Ecchymosis (8%) has been reported in patients receiving nasal budesonide in clinical trials. In pediatric patients, rash was reported in up to 4% of patients receiving budesonide inhalation suspension (age 12 months to 8 years). Allergic reaction, contact dermatitis, ecchymosis, eczema, pustular rash, pruritus, and purpura occurred in 1% to less than 3% of patients receiving inhaled budesonide power or suspension. Anaphylactic reactions, angioedema, bronchospasm, dermatitis, rash, ecchymosis, urticaria, and facial skin irritation have been reported with postmarketing use of budesonide inhalation powder, inhalation suspension, and intranasal budesonide. Wheezing or bronchospasm in patients with severe milk protein hypersensitivity has been reported in postmarketing experience with budesonide inhalation powder use. Anaphylactoid reactions, maculopapular rash, and allergic dermatitis have been reported with oral and rectal budesonide during postmarketing use. Discontinue budesonide if such reactions occur.
Budesonide therapy, just like any corticosteroid, has been associated with the development of cataracts, increased ocular pressure or ocular hypertension, and glaucoma. Long-term use of inhaled corticosteroids may increase the risk of these eye problems. Regular eye examinations should be done. Eye abnormality and abnormal vision/visual impairment was reported in less than 5% of adult patients receiving oral budesonide during clinical trials. In pediatric patients (age: 12 months to 8 years), conjunctivitis (less than 1% to 4%) and ocular infection (unspecified) (1% to less than 3%) were reported in patients receiving budesonide inhalation suspension. Cataracts, glaucoma, and increased intraocular pressure have been reported during postmarketing experience with budesonide inhalation powder, inhalation suspension, and intranasal budesonide.
Pharmacologic doses of corticosteroids administered for prolonged periods can result in hypothalamic-pituitary-adrenal (HPA) suppression. Adrenocortical insufficiency was reported in 1% more of adult patients taking oral budesonide. In a study looking at response to ACTH stimulation in patients receiving oral budesonide 9 mg once daily, the proportion of patient with an abnormal response was 47% at 4 weeks and 79% at 8 weeks. Adrenal suppression, including adrenal insufficiency, was reported in 2% of adult and pediatric patients receiving oral budesonide suspension for eosinophilic esophagitis (EoE). A decrease in blood cortisol (17%) and adrenal insufficiency (4%) has been reported in adult patients using budesonide rectal foam. Adrenal insufficiency and withdrawal symptoms may occur after treatment discontinuation or when transitioning from systemic corticosteroids to inhaled corticosteroids. Patients should taper slowly if discontinuing corticosteroids or when transitioning from systemic corticosteroids to inhaled budesonide suspension or dry powder inhaler. Symptoms of adrenal insufficiency include tiredness, weakness, nausea and vomiting, and low blood pressure. The severity of glucocorticoid-induced secondary adrenocortical insufficiency varies among individuals and is dependent on the dose, frequency, time of administration, and duration of therapy. Use of inhaled corticosteroids with systemic corticosteroids could increase the likelihood of HPA suppression as compared with a therapeutic dose of either alone. Symptoms of hypocorticism and hypercorticism have been reported during postmarketing experience with budesonide inhaled suspension.
Corticosteroids may cause growth inhibition in pediatric subjects. Data regarding effects on growth are conflicting; the lowest effective dose of any corticosteroid dosage form should be utilized and growth should be routinely monitored during use. Growth inhibition has been observed in the absence of laboratory evidence of hypothalamic-pituitary-adrenal (HPA) suppression, suggesting that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in children. With orally inhaled corticosteroids, the mean reduction in growth velocity is approximately 1 centimeter/year (range 0.3 to 1.8 centimeter/year) and appears to be related to the dose and duration of exposure. In a study, children 5 to 12 years of age with asthma receiving inhaled budesonide experienced a 1.1 centimeter reduction in growth compared to the placebo group by the end of 1 year. By the end of 4 years, the growth velocities of both groups were similar. In general, the benefits of regular inhaled corticosteroid use outweigh the potential risk of relatively small and non-cumulative growth suppression in children with asthma; however, growth should be monitored. Further study is needed to determine the long-term effects of growth velocity reduction in children, including the impact on final adult height. To minimize the effects of inhaled corticosteroids, titrate to the lowest effective dose. Growth suppression has been reported with postmarketing experience with budesonide inhalation suspension.
Arthralgia (2% to 6%) and arthritis (less than 5%) was reported in adult patients receiving oral budesonide. Arthralgia was reported in less than 2% of adult and pediatric patients receiving oral budesonide suspension for eosinophilic esophagitis (EoE). Arthralgia was reported in adult patients receiving budesonide via a dry powder inhaler. Fracture was reported in 1% to less than 3% of pediatric patients (age 12 months to 8 years) receiving budesonide inhalation suspension during clinical trials. Prolonged use (e.g., more than 1 year) of high doses of inhaled corticosteroids, such as budesonide, especially when used in combination with frequent courses of systemic corticosteroids, may be associated with skeletal changes and reduced bone mineral density (BMD), which may increase the risk of osteopenia and osteoporosis. The clinical significance of small changes in BMD with regard to long-term outcomes, such as fracture, is unknown. Avascular necrosis of the femoral head and osteoporosis were reported with postmarketing experience with budesonide inhalation suspension.
Signs and symptoms of hypercorticism (Cushing's syndrome) have been reported in adult patients receiving oral budesonide and included: flushing (less than 5%), acne vulgaris (1% to 15%), bruising easily (5% to 15%), moon face or Cushingoid features (1% to 11%), swollen ankles (2% to 7%), hirsutism (0% to 5%), buffalo hump (1%), skin striae (2% or less), fluid retention (1% to 2%), and face edema (8% or less). Hirsutism and dermatitis acneiform were reported in less than 2% of adult and pediatric patients receiving oral budesonide suspension for eosinophilic esophagitis (EoE). Acne (less than 1%) and hyperglycemia (less than 1%) has been reported in adult patients receiving budesonide rectal foam. Benign increased intracranial pressure has been reported during postmarketing experience with budesonide.
Nausea (5% to 11%), diarrhea (10%), dyspepsia (6% to 7%), abdominal pain (6%), upper abdominal pain (3% to 4%), abdominal distension (2%), flatulence (2% to 6%), constipation (2% or less), vomiting (6%), and weight gain (7% or less) were reported in adult patients receiving oral budesonide during clinical trials. Anus disorder, enteritis, epigastric pain, gastrointestinal fistula, glossitis, hemorrhoids, GI obstruction, tongue edema, tooth disorder, and appetite stimulation were reported in less than 5% of patients. Gastroenteritis (3%) and erosive esophagitis (2%) were reported in adult and pediatric patients receiving oral budesonide suspension for eosinophilic esophagitis (EoE). Xerostomia, dysgeusia, dyspepsia, erosive duodenitis, gastrointestinal motility disorder, esophageal food impaction, and palatal swelling were all reported in less than 2% of patients receiving oral budesonide suspension for EoE. Nausea (2%) was reported in adult patients using budesonide rectal foam. Nausea (2%), viral gastroenteritis (2%), dry mouth (1% to less than 3%), and taste perversion/dysgeusia (1% to less than 3%) were reported in adult and pediatric patients receiving budesonide inhalation powder (age 6 years and older). Gastroenteritis (5%), vomiting (2% to 4%), diarrhea (2% to 4%), abdominal pain (2% to 3%), and anorexia (1% to less than 3%) were reported in pediatric patients receiving budesonide inhalation suspension. Rectal GI bleeding has been reported during postmarketing experience with oral budesonide tablets. Pancreatitis has also been reported during postmarketing experience for budesonide.
Peripheral edema (17%) and hypertension (12% or less) have been reported during clinical trials in adult patients receiving oral budesonide. Palpitations, sinus tachycardia, dependent edema, and chest pain (unspecified) were reported in less than 5% of adult patients receiving oral budesonide during clinical trials. Palpitations, hypertension, and syncope were reported in less than 2% of adult and pediatric patients receiving oral budesonide suspension for eosinophilic esophagitis (EoE). In pediatric patients, chest pain has been reported in 1% to less than 3% of patient receiving budesonide inhalation suspension. Syncope has been reported in 1% to less than 3% of pediatric patients using budesonide inhalation powder. An increase in blood pressure has been reported during postmarketing experience with budesonide.
In rare cases, persons receiving inhaled budesonide may present with eosinophilia and clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition often treated with systemic corticosteroids. These events have happened most commonly in association with systemic corticosteroid withdrawal in conjunction with the introduction of inhaled corticosteroid therapy. Persons presenting with eosinophilia, vasculitis with granulomas, worsening pulmonary symptoms, and/or neuropathy may have this condition, which may be severe. Similar cases have been reported with the use of other inhaled corticosteroids. A causal relationship to budesonide has not yet been established.
Muscle spasms or muscle cramps (12% or less), back pain (7%), unspecified musculoskeletal pain (5%), and myalgia (less than 5%) were reported in adult patients receiving oral budesonide during clinical trials. Muscle spasms (less than 2%) were reported in adult and pediatric patients receiving oral budesonide suspension for eosinophilic esophagitis (EoE). Neck pain, myalgia, and hypertonia were reported in 1% to 3% of patients receiving inhaled budesonide powder or budesonide inhalation suspension during clinical trials. Pain (unspecified) was reported during postmarketing experience with budesonide inhalation suspension.
Asthenia, influenza or flu-like disorder, malaise, and fever occurred in less than 5% of adult patients receiving oral budesonide during clinical trials. Fever was reported in 3% or more of patients using inhaled budesonide via a dry power inhaler. Fatigue and flu-like disorder were reported in 1% to less than 3% of pediatric patients (age 12 months to 8 years) receiving budesonide inhalation suspension during clinical trials. Fever has been reported during postmarketing experience with oral, rectal, and inhaled budesonide.
Leukocytosis (increased white blood cell count) was reported in 1% to 6% in adult patients receiving oral budesonide. Hypokalemia was reported in less than 5% of patients receiving one oral capsule formulation at incidences greater than with placebo, and greater than 1% of patients receiving other oral formulations. Anemia, hematuria, pyuria, increased erythrocyte sedimentation rate, increased alkaline phosphatase, atypical neutrophils, increased c-reactive protein, and adrenal insufficiency where reported in 1% or more of adult patients taking oral budesonide. Hyperkalemia, elevated hepatic enzymes (transaminases increased), and dyslipidemia were reported in less than 2% of adult and pediatric patients receiving oral budesonide suspension for eosinophilic esophagitis (EoE).
Gastrointestinal mucosal candidiasis (including esophageal candidiasis, oropharyngeal candidiasis, oral candidiasis) was reported in 8% of adult and pediatric patients receiving oral budesonide suspension for eosinophilic esophagitis (EoE). Fungal skin infection, paronychia, pneumonia, sepsis, and bronchitis were reported in less than 2% of patients receiving oral budesonide suspension for eosinophilic esophagitis (EoE). Urinary tract infection and thrush have occurred in less than 5% of adult patients receiving oral budesonide during clinical trials. In clinical studies with intranasal budesonide, the development of localized infections of the nose and pharynx with Candida albicans has occurred. Oral candidiasis infection was reported in 1% of adult and pediatric patients receiving budesonide inhalation powder (age 6 years and older). Rinsing the mouth after use of budesonide inhalation powder may minimize the incidence of oropharyngeal thrush. Moniliasis (3% to 4%) was reported in pediatric patients (age 12 months to 8 years) receiving budesonide inhalation suspension during clinical trials. Herpes simplex and infection (unspecified) were reported in 1% to less than 3% of pediatric patients. Monitor patients on long-term budesonide therapy for signs of infection. Discontinuation of budesonide may be required.
Dysuria, increased urinary frequency (micturition frequency), and nocturia were reported in less than 5% of adult patients receiving oral budesonide during clinical trials.
Vaginal bleeding (intermenstrual bleeding) and menstrual irregularity/menstrual disorder has been reported in less than 5% of adult patients receiving oral budesonide during clinical trials.
Use of budesonide should not contraindicate administration of live-virus vaccines. According to the Advisory Committee on Immunization Practices (ACIP), administration of live-virus vaccines is safe and effective when steroid therapy is administered topically or by inhalation.
Inhaled budesonide is contraindicated as primary therapy for patients with status asthmaticus or other types of acute bronchospasm for which intensive therapy is warranted. Patients should be advised that budesonide is not to be used as a bronchodilator and is not indicated for relief of acute bronchospasm.
Systemic corticosteroids, including budesonide, may cause immunosuppression and increase the risk of infection with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic pathogens. Corticosteroids can: 1) Reduce resistance to new infections, 2) Exacerbate existing infections, 3) Increase the risk of disseminated infections, 4) Increase the risk of reactivation or exacerbation of latent infections 5) Mask some signs of infection. Corticosteroid-associated infections can be mild but can be severe and at times fatal. The rate of infectious complications increases with increasing corticosteroid dosages. Monitor for the development of infection and consider corticosteroid withdrawal or dosage reduction as needed. If budesonide is used to treat a condition in patients with latent tuberculosis (TB) or tuberculin reactivity, reactivation of TB may occur. Closely monitor such patients for TB reactivation. During prolonged budesonide therapy, patients with latent TB or tuberculin reactivity should receive chemoprophylaxis. Viral infection, such as varicella zoster (chickenpox or shingles) and measles can have a serious or even fatal course in non-immune patients taking corticosteroids; other herpes infection (herpes simplex) may also disseminate in immunosuppressed individuals. Corticosteroids should be used with caution, if at all, in patients with ocular herpes simplex. In corticosteroid-treated patients who have not had these diseases or are nonimmune, avoid exposure of these people to these viral infections. If a corticosteroid-treated patient is exposed to varicella, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If varicella develops, consider treatment with antiviral. If a corticosteroid-treated patient is exposed to measles, prophylaxis with immunoglobulin (IG) may be indicated. Hepatitis B exacerbation/reactivation can occur in patients who are hepatitis B virus carriers treated with immunosuppressive dosages of corticosteroids, including budesonide. Reactivation can also occur infrequently in corticosteroid-treated people who appear to have resolved hepatitis B infection. Screen patients for hepatitis B infection before initiating immunosuppressive (e.g., prolonged) treatment with systemic corticosteroids. For individuals who show evidence of hepatitis B infection, consult providers with expertise in managing hepatitis B regarding monitoring and consideration for hepatitis B antiviral therapy. Systemic budesonide use is contraindicated in the presence of a systemic fungal infection. Corticosteroids, including budesonide, may exacerbate systemic fungal infections; therefore, avoid corticosteroid use in the presence of a fungal infection unless a corticosteroid is needed to control drug reactions. If a fungal infection develops during chronic corticosteroid therapy, corticosteroid withdrawal or dosage reduction is recommended. Corticosteroids, including budesonide, may activate latent amebiasis. Latent or active amebiasis should be ruled out before initiating budesonide in people who have spent time in the tropics or have unexplained diarrhea. Corticosteroids, including budesonide, should be used with great care in the presence of known or suspected Strongyloides (threadworm) helminth infection. Corticosteroid-induced immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia. In selected patients from strongyloidiasis endemic areas who need systemic corticosteroids, consider administering prophylactic treatment. Also avoid corticosteroids, including budesonide, in people with cerebral malaria. These precautions and considerations also apply to budesonide rectal foam and inhalational product use. Administration via the nasal route generally minimizes systemic infection risk. Localized fungal infection of the nose, mouth, and pharynx with Candida albicans has been reported with inhalational or nasal corticosteroid use. Instruct patients to rinse mouth after each use of nasal or inhaled budesonide to minimize risk. Patients using budesonide nasal spray for extended periods (i.e., months) should be examined periodically for evidence of infection or other adverse effects on the nasal mucosa.
Corticosteroids may cause growth inhibition in infants, children, and adolescents. Data regarding effects on growth are conflicting; the lowest effective dose of any corticosteroid dosage form should be utilized and growth should be routinely monitored during use. Controlled clinical studies have shown that inhaled corticosteroids (ICS) may cause a dose-dependent effect on growth. Growth inhibition has been observed in the absence of laboratory evidence of hypothalamic-pituitary-adrenal (HPA) suppression, suggesting that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in pediatric patients. Controlled clinical studies have shown that ICS may cause a mean reduction in growth velocity of approximately 1 centimeter (cm) per year (range: 0.3 to 1.8 cm/year) and that this reduction appears to depend on dose and duration of exposure. Pediatric patients receiving any formulation of budesonide should be monitored closely for growth inhibition.
Studies of pregnant women have not shown that inhaled budesonide increases the risk of abnormalities when administered during pregnancy. A review of Swedish registries of more than 2,000 births indicated that no increased risk for congenital malformations during early pregnancy with budesonide inhalation powder or solution. Despite adverse effects in animal studies, fetal harm appears remote. Corticosteroid treatment may not be necessary during pregnancy due to a natural increase in corticosteroid production; however, poorly controlled maternal asthma also poses risk to the mother and the fetus. Low-dose inhaled corticosteroids are considered first-line therapy for control of mild persistent asthma during pregnancy according to the National Asthma Education and Prevention Program (NAEPP) Asthma and Pregnancy Working Group; of the inhaled corticosteroids, more data are available for budesonide use in pregnancy. Data on the use of medium- to high-dose inhaled corticosteroid use during pregnancy are limited. However, dose titration may be considered for those with moderate to severe persistent asthma, preferably using budesonide. However, there are no data to indicate safety concerns with other inhaled corticosteroids, and maintaining a previously established treatment regimen may be more beneficial to the patient. Selection of any pharmacologic treatment for asthma control during pregnancy should include the specific needs of the patient, based on an individual evaluation, and consideration of the potential benefits or risks to the fetus. A position statement by the American College of Allergy, Asthma and Immunology also considers budesonide a good choice for pregnant women requiring high doses of inhaled steroids for effective asthma management. Limited published studies report on the use of oral budesonide in pregnant patients; however, the data are insufficient to inform a drug-associated risk of major birth defects and miscarriage. Oral budesonide products (e.g., Entocort EC, Ortikos, Uceris, Tarpeyo) have been teratogenic and embryocidal in animal studies. At subcutaneous budesonide doses that were 0.3 to 0.5 or 0.03 to 0.05 times the maximum recommended human dose (MRHD) in pregnant rats and rabbits, respectively, fetal loss, decreased pup weights, and skeletal anomalies occurred. There is a natural increase in endogenous corticosteroid production during pregnancy, and many women will require a lower exogenous dose or no corticosteroid treatment at all during pregnancy. Oral budesonide (e.g., Entocort EC, Ortikos, Uceris, Eohilia, Tarpeyo) products should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus. Some studies show an association of adverse pregnancy outcomes in women with Crohn's disease with increased disease activity (increased stool activity and abdominal pain) which can lead to preterm birth and low birth weight infants. Counsel the patients about the importance of controlling the disease. IgA nephropathy in pregnancy is associated with adverse maternal outcomes, including increased rates of cesarean section, pregnancy-induced hypertension, pre-eclampsia and preterm delivery, and adverse fetal/neonatal outcomes, including stillbirth and low birth weight. Hypoadrenalism may occur in an infant born to a mother receiving corticosteroids during pregnancy, and the infant should be carefully observed for signs of hypoadrenalism, such as poor feeding, irritability, weakness, and vomiting.
Oral, nasal, rectal, and inhaled forms of budesonide are compatible with breast-feeding. The amount of infant exposure from use of inhaled budesonide by the breast-feeding parent is negligible. Budesonide is excreted into breast milk in small amounts with a relative infant dose (RID) of 0.3%. In addition, budesonide has an oral bioavailability of 10.7%, further limiting total infant exposure. Based on data from a small number (n = 8) of breast-feeding women taking inhaled dry powder budesonide 200 to 400 mcg twice daily, approximately 0.3% to 1% of the dose inhaled by the mother is available via breast milk to an exclusively breast-fed infant. Budesonide plasma concentrations obtained in five of the infants in this study about 140 minutes after maternal drug administration and 90 minutes after breast-feeding were below quantifiable levels. Low-dose inhaled corticosteroids are considered first line therapy for control of mild persistent asthma during pregnancy and lactation according to the National Asthma Education and Prevention Program (NAEPP) Asthma and Pregnancy Working Group. Due to greater availability of data, budesonide is considered the preferred agent in this population. Reviewers and an expert panel consider all inhaled corticosteroids acceptable to use during breast-feeding. Single- and repeated-dose pharmacokinetic studies have shown that maximum plasma budesonide concentrations after a 9 mg oral daily dose are up to 10-times greater than the concentrations measured after inhaled doses of 400 to 800 mcg/day. Assuming that the coefficient of extrapolation between inhaled and oral doses is constant across all doses, it is possible that budesonide exposure to breast-feeding infants after maternal oral ingestion may be up to 10-times higher than exposure to infants after maternally inhaled budesonide.
When budesonide is used chronically, systemic effects such as hypercorticism and adrenal axis suppression may occur. Pediatric patients with Crohn's disease and patients with moderate to severe hepatic impairment (Child-Pugh Class B and C) could be at increased risk due to increased systemic exposure of oral budesonide. Hypothalamic-pituitary-adrenal (HPA) axis suppression can occur with any budesonide formulation, including budesonide inhalation. Corticosteroids can reduce the response of the HPA axis to stress. Observe patients during periods of stress e.g., trauma, surgery, infection) for evidence of inadequate adrenal response. Patients may require systemic corticosteroids during periods of physiologic stress. When discontinuing therapy or switching between corticosteroids, monitor for signs of adrenal axis suppression, benign increased intracranial pressure, and withdrawal of steroid therapy. Adrenocortical function monitoring may be required in these patients. Transferring a patient from systemic corticosteroids to inhaled budesonide should be done with care to avoid symptoms of HPA suppression. Avoid abrupt discontinuation in systemic corticosteroid to reduce symptoms of acute corticosteroid withdrawal. Deaths due to adrenal insufficiency have been reported in asthma patients during and after such a change. After withdrawal from systemic therapy, a number of months are required for recovery of HPA-axis function. Patients previously maintained on doses equivalent to 20 mg/day or more of prednisone may be at increased risk. Use of budesonide inhalation suspension should be used concurrently with patient's maintenance dose of systemic corticosteroid. After a week, gradually reduce the systemic corticosteroid dose (not more than 25% of the prednisone dose or its equivalent). Further reductions in the systemic corticosteroid dose maybe be made every 1 or 2 weeks. When transferring from systemic corticosteroids to a budesonide inhaler, reduce the daily prednisone dose (or equivalent steroid dose) by 2.5 mg per week. The transfer from systemic corticosteroid therapy to budesonide may also result in unmasking of allergies or other immunologic conditions, such as rhinitis, eczema, eosinophilia, conjunctivitis, or arthritis, that were previously controlled by treatment with systemic corticosteroids.
Glucocorticoids, such as budesonide, should be avoided in patients with Cushing's disease since they can produce or aggravate Cushing's syndrome. It is possible that systemic corticosteroid effects such as hypercortisolism may appear in a small number of patients receiving inhaled budesonide, particularly at higher doses. If features consistent with hypercorticism or Cushing's disease occur, the steroid should be reduced slowly, consistent with accepted procedures for management of symptoms and for tapering of systemic steroids.
Due to the inhibitory effects of glucocorticoids on wound healing, intranasal budesonide should be avoided in patients with a recent history of oral surgery or nasal surgery, nasal trauma, or nasal septal ulcers until their condition has healed. Intranasal budesonide overuse, improper use, or chronic use might lead to nasal septal perforation; patients who experience recurrent episodes of epistaxis (nosebleeds) or nasal septum discomfort while taking this medication should contact their prescriber for evaluation. If perforation occurs, the drug should be discontinued until healing is complete.
Corticosteroids, including inhaled budesonide, can decrease bone mineral density (BMD). The clinical significance of these small changes in BMD with regard to long-term outcomes is unknown. Monitor patients, especially those with risk factors, such as preexisting osteopenia, prolonged immobilization, family history of osteoporosis, tobacco smoking, malnutrition, post menopausal status, advanced age, or chronic use of other medications that may reduce bone mass.
Although oral budesonide has weak mineralocorticoid properties, hypertension due to edema and electrolyte imbalance may occur. Prolonged administration of systemic glucocorticoids also can result in edema and hypertension. In a review of 93 studies of corticosteroid use, hypertension was found to develop 4 times as often in steroid recipients compared to control groups.
Monitor patient at risk for diabetes, have diabetes mellitus, have a family history of diabetes, or have peptic ulcer disease. Budesonide may exacerbate these conditions (increase in blood sugar/hyperglycemia or GI perforation).
Budesonide undergoes extensive hepatic metabolism. Patients who have moderate to severe hepatic impairment may be at an increased risk of hypercorticism and adrenal axis suppression due to increased budesonide systemic exposure. No dosage adjustment is suggested for nasal, inhaled, or rectal budesonide. In patients with mild hepatic impairment, no dosage adjustments for oral formulations are recommended; however, avoidance or dosage adjustment is product specific in patients with moderate to severe hepatic disease receiving oral formulations. Monitor all patients on any form of budesonide for signs and symptoms of hypercorticism. Consider discontinuing budesonide if hypercorticism is observed.
Glaucoma, increased intraocular pressure, and cataracts have been reported following use of budesonide, including inhaled and intranasal budesonide. Monitor patients for any change in vision, especially in those with a history of increased intraocular pressure, visual disturbance, glaucoma, and/or cataracts.
Systemic glucocorticoids, like budesonide, should be used with caution in patients with myasthenia gravis who are being treated with anticholinesterase agents. Muscle weakness may be transiently increased during the initiation of systemic glucocorticoid therapy in patients with myasthenia gravis, necessitating respiratory support.
Budesonide treatment is contraindicated in patients with hypersensitivity to budesonide or any of the ingredients of the product chosen for use. Anaphylactic reactions have occurred with some budesonide formulations. Budesonide inhalation powder contains small amounts of lactose, which contain trace levels of milk protein. Patients with a severe milk protein hypersensitivity may experience an allergic reaction to this product. True corticosteroid hypersensitivity is rare, nevertheless patients who have demonstrated a prior hypersensitivity reaction to budesonide should not receive any form of budesonide. It is possible, though also rare, that such patients will display cross-hypersensitivity to other corticosteroids. It is advisable that patients who have a hypersensitivity reaction to any corticosteroid undergo skin testing, which, although not a conclusive predictor, may help to determine if hypersensitivity to another corticosteroid exists. Such patients should be carefully monitored during and following the administration of any corticosteroid.
There is no special precaution needed for the dosage of inhaled, rectal, or nasal budesonide in older adults. In general, oral budesonide dose selection for a geriatric adult should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy, particularly with chronic use. According to the Beers Criteria, systemic corticosteroids are considered potentially inappropriate medications (PIMs) for use in geriatric patients with delirium or at high risk for delirium; avoid when possible in these patient populations due to the possibility of new-onset delirium or exacerbation of the current condition. Oral corticosteroids may be required for chronic conditions but should be prescribed in the lowest effective dose and for the shortest possible duration.
Erosive esophagitis (2%) has been reported in patients receiving oral budesonide suspension. These patients had no erosions present at baseline esophagogastroduodenoscopy (EGD). After 12 weeks of treatment with oral budesonide suspension, 2 subjects had Los Angeles (LA) classification grade A, 1 subject had LA grade B, and 1 subject had LA grade C erosive esophagitis. All but 1 of the 4 patients developed erosive esophagitis while receiving concomitant therapy with a PPI. Advise patients and caregivers to report new or worsening signs of symptoms of erosive esophagitis to their healthcare provider. Consider endoscopic evaluation as appropriate.
Kaposi's sarcoma has been reported with systemic corticosteroid use, most often for chronic conditions. Use with budesonide orally with caution. Discontinuation of the systemic corticosteroid may result in clinical improvement of Kaposi's sarcoma.
As with other inhaled asthma medications, paradoxical bronchospasm can occur with an immediate increase in wheezing after administration of inhaled budesonide. If bronchospasm occurs after inhalation, treat immediately with an inhaled, short-acting bronchodilator, discontinue budesonide, and institute alternative therapy.
INHALED DOSAGE RANGES BY PRODUCT
The ranges presented help define low, medium, and high ICS daily dosing according to asthma treatment recommendations. The NAEPP 2020 focused updates state that ICS ranges from the NAEPP 2007 guidelines need to be updated in future NAEPP guidance.
Budesonide dry powder inhaler
Children 4 years and younger: Not available
Children 5 years:
-GINA: Not available
-NAEPP-Low Dose: 180 mcg to 400 mcg
-Medium Dose: more than 400 mcg and up to 800 mcg
-High Dose: more than 800 mcg
Children 6 to 11 years:
-GINA-Low Dose: 100 mcg to 200 mcg
-Medium Dose: more than 200 mcg and up to 400 mcg
-High Dose: more than 400 mcg
-NAEPP-Low Dose: 180 mcg to 400 mcg
-Medium Dose: more than 400 mcg and up to 800 mcg
-High Dose: more than 800 mcg
Adults, Adolescents, and Children 12 years and older:
-GINA-Low Dose: 200 mcg to 400 mcg
-Medium Dose: more than 400 mcg and up to 800 mcg
-High Dose: more than 800 mcg
-NAEPP-Low Dose: 180 mcg to 600 mcg
-Medium Dose: more than than 600 mcg and up to 1,200 mcg
-High Dose: more than 1,200 mcg
Budesonide nebulizer suspension
Infants:
-GINA: Not available
-NAEPP:
--Low Dose: 0.25 mg to 0.5 mg
-Medium Dose: more than 0.5 mg and up to 1 mg
-High Dose: more than 1 mg
Children 1 to 4 years:
-GINA-Low Dose: 0.5 mg (for ages 1 year and older)
-Medium Dose: NA
-High Dose: NA
-NAEPP-Low Dose: 0.25 mg to 0.5 mg
-Medium Dose: more than 0.5 mg and up to 1 mg
-High Dose: more than 1 mg
Children 5 years:
-GINA-Low Dose: 0.5 mg
-Medium Dose: NA
-High Dose: NA
-NAEPP-Low Dose: 0.5 mg
-Medium Dose: 1 mg
-High Dose: 2 mg
Children 6 to 11 years:
-GINA-Low Dose: 0.25 mg to 0.5 mg
-Medium Dose: more than 0.5 mg and up to 1 mg
-High Dose: more than 1 mg
-NAEPP-Low Dose: 0.5 mg
-Medium Dose: 1 mg
-High Dose: 2 mg
Adults, Adolescents, and Children 12 years and older: Not available
For asthma maintenance treatment:
Respiratory (Inhalation) dosage (inhalation powder; e.g., Pulmicort Flexhaler):
Adults: 360 mcg (2 actuations of 180 mcg/actuation) inhaled by mouth twice daily; 180 mcg (1 actuation of 180 mcg/actuation) twice daily may be appropriate for some patients. Max: 720 mcg (4 actuations of 180 mcg/actuation) twice daily. Titrate to the lowest effective dose once asthma stability is achieved.
Children and Adolescents 6 to 17 years: 180 mcg (1 actuation of 180 mcg/actuation or 2 actuations of 90 mcg/actuation) inhaled by mouth twice daily; 360 mcg (2 actuations of 180 mcg/actuation) twice daily may be appropriate for some patients. Max: 360 mcg (2 actuations of 180 mcg/actuation) twice daily. Titrate to the lowest effective dose once asthma stability is achieved.
Respiratory (Inhalation) dosage (inhalation suspension; e.g., Pulmicort Respules)*:
Adults*: 1 to 2 mg inhaled by nebulizer twice daily for initiation of therapy. Usual dose: 0.5 to 1 mg inhaled by nebulizer twice daily. Max: 4 mg/day. Titrate to the lowest effective dose once asthma stability is achieved.
Children and Adolescents 12 to 17 years*: 1 to 2 mg inhaled by nebulizer twice daily for initiation of therapy. Usual dose: 0.5 to 1 mg inhaled by nebulizer twice daily. Max: 4 mg/day. Titrate to the lowest effective dose once asthma stability is achieved.
Children 9 to 11 years*: 0.5 to 1 mg inhaled by nebulizer twice daily for initiation of therapy. Usual dose: 0.25 to 0.5 mg inhaled by nebulizer twice daily. Max: 2 mg/day. Titrate to the lowest effective dose once asthma stability is achieved.
Children 1 to 8 years: 0.25 to 1 mg inhaled by nebulizer once daily or 0.25 to 0.5 mg inhaled by nebulizer twice daily. Base starting dose on prior asthma therapy and disease severity. Max: 1 mg/day. If once-daily treatment does not provide adequate control, increase the daily dose and/or administer in divided doses twice daily. Titrate to the lowest effective dose once asthma stability is achieved. Short-term, high-dose nebulized budesonide can have an early clinical effect by day 2 of treatment.
Infants 3 to 11 months*: 0.5 to 1 mg inhaled by nebulizer twice daily for initiation of therapy. Usual dose: 0.25 to 0.5 mg inhaled by nebulizer twice daily. Max: 2 mg/day. Titrate to the lowest effective dose once asthma stability is achieved. Limited data from small safety studies used 0.25 to 1 mg/day via nebulizer once daily or in 2 divided doses.
For the treatment bronchospasm* (e.g., episodic wheezing):
-for the treatment of transient increase in bronchospasm* (e.g., episodic wheezing) as asthma reliever therapy:
Respiratory (Inhalation) dosage; (inhalation powder; e.g., Pulmicort Flexhaler):
Adults: 180 to 360 mcg (1 to 2 actuations of 180 mcg/actuation) inhaled by mouth as needed whenever a short-acting beta-agonist (SABA) is given. NAEPP only recommends as-needed inhaled corticosteroid/SABA as an option for patients with mild persistent asthma.
Children and Adolescents 12 to 17 years: 180 to 360 mcg (1 to 2 actuations of 180 mcg/actuation) inhaled by mouth as needed whenever a short-acting beta-agonist (SABA) is given. NAEPP only recommends as-needed inhaled corticosteroid/SABA as an option for patients with mild persistent asthma.
Children 6 to 11 years: 180 mcg (1 actuation of 180 mcg/actuation or 2 actuations of 90 mcg/actuation) as needed whenever a short-acting beta-agonist (SABA) is given. NAEPP does not recommend intermittent as-needed inhaled corticosteroid/SABA therapy in this age group because therapy has not been adequately studied.
Respiratory (Inhalation) dosage (inhalation suspension; e.g., Pulmicort Respules):
Children 1 to 8 years: 0.25 to 0.5 mg inhaled by nebulizer as needed whenever a short-acting beta-agonist (SABA) is given. NAEPP does not recommend intermittent as-needed inhaled corticosteroid/SABA therapy in this age group because therapy has not been adequately studied.
-for the treatment of episodic wheezing* at the start of a respiratory tract infection:
Respiratory (Inhalation) dosage (inhalation suspension; e.g., Pulmicort Respules):
Infants and Children 1 month to 4 years: 1 mg inhaled by nebulizer twice daily for 7 days in combination with as-needed short-acting beta-agonist (SABA).
For exercise-induced bronchospasm prophylaxis*:
Oral Inhalation dosage (inhalation powder; e.g., Pulmicort Flexhaler):
Adults: 180 to 360 mcg (1 to 2 oral inhalations of 180 mcg/actuation) twice daily is usual dose range. FDA-approved Max: 4 oral inhalations of 180 mcg/actuation twice daily (720 mcg twice daily). The efficacy of budesonide in the treatment of EIB has been studied in adults. Titrate to the lowest effective dose. Regular ICS (controller) use reduces the incidence of EIB.
Children and Adolescents 6 years and older: 180 to 360 mcg (1 to 2 oral inhalations of 180 mcg/actuation) twice daily is the usual dose range. Max: 2 oral inhalations of 180 mcg/actuation twice daily (360 mcg twice daily). The efficacy of budesonide for EIB has been studied in pediatric patients. Titrate to the lowest effective dose. Regular ICS (controller) use reduces the incidence of EIB.
For the treatment of chronic obstructive pulmonary disease (COPD)* (e.g., chronic bronchitis* or emphysema*):
Oral Inhalation dosage (inhalation powder; e.g., Pulmicort Flexhaler):
Adults: The optimal dose for the maintenance treatment of COPD is not established; typical doses of 180 to 360 mcg (1 to 2 actuations of 180 mcg/actuation strength) twice daily may be considered. Not for the relief of acute bronchospasm; use a short-acting beta-2 agonist (SABA). According to guidelines, inhaled corticosteroid (ICS) in combination with a long-acting beta-2 agonist (LABA) is not recommended for COPD treatment; however, it is an option for those patients with stable disease who are already receiving this therapy with no major symptoms or exacerbations. Escalation to triple therapy with a long-acting muscarinic antagonist (LAMA), a LABA, and an ICS should be considered for patients who have further exacerbations or major symptoms.
Nebulized Inhalation dosage (suspension for nebulization; e.g., Pulmicort Respules):
Adults: The optimal dose is not established; used for COPD exacerbations. 1 to 2 mg every 6 hours via nebulizer is a common dosage; some studies have used 2 mg twice daily. Reported total daily dose range for acute exacerbations of COPD: 4 to 8 mg/day. Usual Max: 2 mg/dose. Nebulized budesonide for the treatment of exacerbations may be an alternative to oral corticosteroids in some patients.
For the treatment of laryngotracheobronchitis (croup)*:
Respiratory (Inhalation) dosage (inhalation suspension):
Infants, Children, and Adolescents 3 months to 17 years: 2 mg inhaled by nebulizer as a single dose, or alternatively, 1 mg inhaled by nebulizer every 30 minutes for 2 doses. Budesonide is considered an alternative to a single dose of oral dexamethasone, particularly in those unable to take oral medication. Efficacy has been demonstrated in several studies. Most studies have shown comparable efficacy outcomes with dexamethasone for the treatment of croup; however, some studies have shown dexamethasone to be superior to budesonide. The addition of budesonide to dexamethasone therapy has not resulted in an additive benefit.
For the management of symptoms of seasonal allergies and perennial allergies, including allergic rhinitis:
Nasal dosage (non-prescription OTC use, e.g., Rhinocort Allergy 32 mcg/spray or generic equivalent):
Adults: 2 sprays (32 mcg/spray) in each nostril once daily. After clinical response has been obtained, decrease to 1 spray in each nostril once daily. If no response after 2 weeks, consult a health care provider. Prior to non-prescription OTC status, maximum dosages of 256 mcg/day were FDA-approved.
Children and Adolescents 12 to 17 years: 2 sprays (32 mcg/spray) in each nostril once daily. After clinical response has been obtained, decrease to 1 spray in each nostril once daily. If no response after 2 weeks, consult a health care provider. Prior to non-prescription OTC status, maximum dosages of 256 mcg/day were FDA-approved.
Children 6 to 11 years: Initially, 1 spray (32 mcg/spray) in each nostril once daily. If symptoms do not improve, may increase to 2 sprays in each nostril once daily. After clinical response has been obtained, decrease to 1 spray in each nostril once daily. Non-prescription use in younger children is intended to be assisted by an adult. If the child uses this product for longer than 2 months per year, or, if there is no response to treatment after 2 weeks, consult a pediatrician. Prior to non-prescription OTC status, maximum dosages of 128 mcg/day were FDA-approved.
For the treatment of mild to moderate Crohn's disease involving the ileum and/or ascending colon:
Oral dosage (delayed-release or extended-release capsules; e.g., Entocort EC, Ortikos):
Adults: 9 mg PO once daily for up to 8 weeks, then 6 mg PO once daily for up to 3 months. Taper to complete cessation if symptom control is still maintained at 3 months. Continued treatment for more than 3 months has not been shown to provide substantial benefit. A repeat 8-week course may be given for recurring episodes of active disease. A Crohn's Disease Activity Index (CDAI) less than 150 after 8 weeks of treatment for active disease is recommended before maintenance treatment is initiated. Guidelines strongly recommend that budesonide not be used to maintain remission of Crohn's disease beyond 4 months.
Children and Adolescents 8 to 17 years weighing more than 25 kg: 9 mg PO once daily for up to 8 weeks, then 6 mg PO once daily for 2 weeks. Repeat courses may be needed if active disease recurs.
For the treatment of mildly to moderately active ulcerative colitis for the induction of remission:
Oral dosage (extended-release tablets):
Adults: 9 mg PO once daily in the morning for up to 8 weeks. Guidelines recommend oral budesonide to induce remission in persons with ulcerative colitis; however, guidelines recommend against systemic corticosteroids for the maintenance of remission.
Rectal dosage (rectal foam):
NOTE: Budesonide rectal foam is indicated for mildly to moderately active distal ulcerative colitis extending up to 40 cm from the anal verge.
Adults: 2 mg rectally twice daily for 2 weeks, then 2 mg rectally once daily at bedtime for 4 weeks.
For the treatment of collagenous colitis* (a form of microscopic colitis):
Oral dosage (extended-release capsules; e.g., Entocort EC):
Adults: 9 mg PO once daily or on a tapering schedule for 8 weeks has been used in clinical trials. A Cochrane review of IBD and functional bowel disorder trials concluded that budesonide is effective and well-tolerated for inducing and maintaining clinical and histological response in patients with collagenous colitis. In a placebo-controlled, randomized trial (n = 28), 8 of 14 patients receiving 9 mg/daily were considered responders (p = 0.05), with patients reporting improved stool consistency. Histological findings included a significant decrease in the lamina propria infiltrates in the budesonide group (p is less than 0.001). Another controlled trial (n = 20) studied a tapering regimen of 9 mg PO for 4 weeks, 6 mg for 2 weeks, and 3 mg for 2 weeks. All 10 patients in the budesonide group experienced a clinical response, and treated patients reported reduced stool weight and frequency; histological inflammation was also significantly improved.
For the treatment of primary immunoglobulin A (IgA) nephropathy in persons at risk of disease progression to reduce the loss of kidney function:
Oral dosage (delayed-release capsules; Tarpeyo):
Adults: 16 mg PO once daily in the morning for 9 months. When discontinuing therapy, reduce dose to 8 mg PO once daily for the last 2 weeks of therapy. The safety and efficacy of treatment with subsequent courses have not been established.
For the treatment of autoimmune hepatitis* in combination with azathioprine:
Oral dosage:
Adults: 3 mg PO 3 times daily, initially. When biochemical remission is achieved, taper dose gradually over 6 months to 3 mg PO once daily or the lowest dose to maintain remission. Guidelines recommend budesonide in combination with azathioprine as first-line therapy in adults who present with autoimmune hepatitis (AIH) who do not have cirrhosis, acute severe AIH, or acute liver failure. May attempt steroid withdrawal while continuing azathioprine.
Children and Adolescents: 3 mg PO 3 times daily, initially. When biochemical remission is achieved, taper dose gradually over 6 months to 3 mg PO once daily or the lowest dose to maintain remission. Guidelines recommend budesonide in combination with azathioprine as first-line therapy in children who present with autoimmune hepatitis (AIH) who do not have cirrhosis, acute severe AIH, or acute liver failure. May attempt steroid withdrawal while continuing azathioprine.
For the treatment of graft-versus-host disease (GVHD)*:
Oral dosage:
Adults: 3 mg PO 3 times daily.
Children and Adolescents 6 to 17 years: 3 mg PO 3 times daily.
For the treatment of eosinophilic esophagitis:
Oral dosage (oral suspension):
Adults: 2 mg PO twice daily for 12 weeks.
Children and Adolescents 11 to 17 years: 2 mg PO twice daily for 12 weeks.
Oral dosage (inhalation suspension; e.g., Pulmicort Respules)*:
Adults: 1 mg PO (swallowed) twice daily for 8 weeks, then reduce dose to the lowest dose that maintains remission. Oral administration of viscous budesonide slurry achieves higher histological remission rates compared vs. oral administration by spraying and swallowing due to longer contact time with the oral mucosa.
Children and Adolescents: 0.5 mg PO (swallowed) twice daily for 8 weeks, then reduce dose to the lowest dose that maintains remission. Oral administration of viscous budesonide slurry achieves higher histological remission rates compared vs. oral administration by spraying and swallowing due to longer contact time with the oral mucosa.
Maximum Dosage Limits:
-Adults
256 mcg/day intranasally; 1,440 mcg/day via dry powder inhaler (DPI) is the FDA-approved maximum dosage; doses of the nebulizer suspension as high as 8 mg/day have been used off-label. 9 mg/day PO for extended release or delayed release capsules (i.e., Ortikos, Entocort EC); 9 mg/day PO for delayed release tablets (i.e., Uceris); 16 mg/day PO for delayed release capsules (i.e., Tarpeyo); 4mg/day PO for oral suspension (i.e., Eohilia); 4 mg/day rectally.
-Geriatric
256 mcg/day intranasally; 1,440 mcg/day via dry powder inhaler (DPI) is the FDA-approved maximum dosage; doses of the nebulizer suspension as high as 8 mg/day have been used off-label. 9 mg/day PO for extended release or delayed release capsules (i.e., Ortikos, Entocort EC); 9 mg/day PO for delayed release tablets (i.e., Uceris); 16 mg/day PO for delayed release capsules (i.e., Tarpeyo); 4mg/day PO for oral suspension (i.e., Eohilia); 4 mg/day rectally.
-Adolescents
256 mcg/day intranasally; 720 mcg/day via dry powder inhaler (DPI) is the FDA-approved maximum dosage; nebulizer suspension doses as high as 4 mg/day have been used off-label. 9 mg/day PO for extended release or delayed release capsules (i.e., Ortikos, Entocort EC); 4 mg/day PO for oral suspension (i.e., Eohilia). Safety and efficacy of delayed release tablets (i.e., Uceris), delayed release capsules (i.e., Tarpeyo), and rectal formulations have not been established.
-Children
12 years: 256 mcg/day intranasally; 720 mcg/day via dry powder inhaler (DPI) is the FDA-approved maximum dosage; nebulizer suspension doses as high as 4 mg/day have been used off-label. 9 mg/day PO for extended release or delayed release capsules (i.e., Ortikos, Entocort EC); 4 mg/day PO for oral suspension (i.e., Eohilia). Safety and efficacy of delayed release tablets (i.e., Uceris), delayed release capsules (i.e., Tarpeyo), and rectal formulations have not been established.
11 years: 128 mcg/day intranasally; 720 mcg/day via dry powder inhaler (DPI) is the FDA-approved maximum dosage; nebulizer suspension doses as high as 2 mg/day have been used off-label. 9 mg/day PO for extended release or delayed release capsules (i.e., Ortikos, Entocort EC); 4 mg/day PO for oral suspension (i.e., Eohilia). Safety and efficacy of delayed release tablets (i.e., Uceris), delayed release capsules (i.e., Tarpeyo), and rectal formulations have not been established.
9 to 10 years: 128 mcg/day intranasally; 720 mcg/day via dry powder inhaler (DPI) is the FDA-approved maximum dosage; nebulizer suspension doses as high as 2 mg/day have been used off-label. 9 mg/day PO for extended release or delayed release capsules (i.e., Ortikos, Entocort EC). Safety and efficacy of delayed release tablets (i.e., Uceris), delayed release capsules (i.e., Tarpeyo), oral suspension (i.e., Eohilia), and rectal formulations have not been established.
8 years: 128 mcg/day intranasally; 720 mcg/day via dry powder inhaler (DPI) is the FDA-approved maximum dosage; 1 mg/day of the nebulizer suspension is the FDA-approved maximum dosage; however, doses as high as 2 mg/day have been used off-label. 9 mg/day PO for extended release or delayed release capsules (i.e., Ortikos, Entocort EC). Safety and efficacy of delayed release tablets (i.e., Uceris), delayed release capsules (i.e., Tarpeyo), oral suspension (i.e., Eohilia), and rectal formulations have not been established.
6 to 7 years: 128 mcg/day intranasally; 720 mcg/day via dry powder inhaler (DPI) is the FDA-approved maximum dosage; 1 mg/day of the nebulizer suspension is the FDA-approved maximum dosage; however, doses as high as 2 mg/day have been used off-label. Safety and efficacy of extended release or delayed release capsules (i.e., Ortikos, Entocort EC), delayed release tablets (i.e., Uceris), delayed release capsules (i.e., Tarpeyo), oral suspension (i.e., Eohilia), and rectal formulations have not been established.
1 to 5 years: 1 mg/day of the nebulizer suspension is the FDA-approved maximum dosage; however, doses as high as 2 mg/day have been used off-label. Safety and efficacy of other formulations have not been established.
-Infants
Safety and efficacy have not been established; however, doses up to 2 mg/day of the nebulizer suspension have been used off-label.
Patients with Hepatic Impairment Dosing
Nasal or Inhaled products: No dosage adjustment suggested.
Rectal foam: No dosage adjustment needed. Monitor the patient for signs and symptoms of hypercorticism. Consider drug discontinuation in cases of hypercorticism.
Oral delayed-release capsules (e.g., Entocort EC)
Mild hepatic impairment (Child-Pugh Class A): No dosage adjustment is needed.
Moderate hepatic impairment (Child-Pugh Class B): Consider a reduced dose of 3 mg once daily. Monitor the patient for signs/symptoms of hypercorticism. Consider drug discontinuation in cases of hypercorticism.
Severe hepatic impairment (Child-Pugh Class C): Avoid use.
Oral delayed-release capsules or Oral budesonide suspension (e.g., Tarpeyo, Eohilia)
Mild hepatic impairment (Child-Pugh Class A): No dosage adjustment is needed.
Moderate hepatic impairment (Child-Pugh Class B): Monitor the patient for signs and symptoms of hypercorticism. Consider drug discontinuation in cases of hypercorticism.
Severe hepatic impairment (Child-Pugh Class C): Avoid use.
Oral extended-release capsules (i.e., Ortikos)
Mild hepatic impairment (Child-Pugh Class A): No dosage adjustment is needed.
Moderate or severe hepatic impairment (Child-Pugh Class B or C): Avoid use.
Oral delayed-release tablet (i.e., Uceris)
Mild hepatic impairment (Child-Pugh Class A): No dosage adjustment is needed.
Moderate or severe hepatic impairment (Child-Pugh Class B or C): Monitor the patient for signs and symptoms of hypercorticism. Consider drug discontinuation in cases of hypercorticism.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Abatacept: (Moderate) Concomitant use of immunosuppressives, as well as long-term corticosteroids, may potentially increase the risk of serious infection in abatacept treated patients. Advise patients taking abatacept to seek immediate medical advice if they develop signs and symptoms suggestive of infection.
Acarbose: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.
Acetaminophen; Aspirin: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.
Acetaminophen; Aspirin; diphenhydrAMINE: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
Acetaminophen; Dextromethorphan; guaiFENesin; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
Acetaminophen; guaiFENesin; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
Acetaminophen; Ibuprofen: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Acetaminophen; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
acetaZOLAMIDE: (Moderate) Corticosteroids may increase the risk of hypokalemia if used concurrently with acetazolamide. Hypokalemia may be especially severe with prolonged use of corticotropin, ACTH. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy.
Adagrasib: (Moderate) Avoid coadministration of oral budesonide and adagrasib due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; adagrasib is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold.
Aldesleukin, IL-2: (Major) Avoid coadministration of corticosteroids with aldesleukin. Corticosteroids can be immunosuppressive. Aldesleukin is an interleukin-2 lymphocyte growth factor which induces lymphokine-activated killer (LAK) cells, natural killer (NK) cells, and interferon gamma production. Concomitant use may reduce the efficacy of aldesleukin.
Alemtuzumab: (Moderate) Concomitant use of alemtuzumab with immunosuppressant doses of corticosteroids may increase the risk of immunosuppression. Monitor patients carefully for signs and symptoms of infection.
Aliskiren; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Alogliptin: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Alogliptin; metFORMIN: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Alogliptin; Pioglitazone: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor blood glucose during concomitant corticosteroid and thiazolidinedione use; a thiazolidinedione dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Alpha-glucosidase Inhibitors: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Aluminum Hydroxide: (Moderate) Enteric-coated budesonide granules dissolve at a pH more than 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide.
Aluminum Hydroxide; Magnesium Carbonate: (Moderate) Enteric-coated budesonide granules dissolve at a pH more than 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide.
Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Enteric-coated budesonide granules dissolve at a pH more than 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Enteric-coated budesonide granules dissolve at a pH more than 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide.
Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) Enteric-coated budesonide granules dissolve at a pH more than 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide.
Amifampridine: (Moderate) Carefully consider the need for concomitant treatment with systemic corticosteroids and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Systemic corticosteroids may increase the risk of seizures in some patients.
aMILoride: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
aMILoride; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
Aminolevulinic Acid: (Minor) Corticosteroids administered prior to or concomitantly with photosensitizing agents used in photodynamic therapy may decrease the efficacy of the treatment.
Aminosalicylate sodium, Aminosalicylic acid: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.
amLODIPine; Celecoxib: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
amLODIPine; Valsartan; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Avoid coadministration of oral budesonide and clarithromycin due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; clarithromycin is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum.
Amphotericin B lipid complex (ABLC): (Moderate) Monitor serum electrolytes and cardiac function during concomitant use. Corticosteroids have potassium-wasting effects and may potentiate hypokalemia during amphotericin B therapy and increase the risk for cardiac dysfunction. There have been cases reported in which concomitant use of amphotericin B and systemic corticosteroids was followed by cardiac enlargement and congestive heart failure.
Amphotericin B liposomal (LAmB): (Moderate) Monitor serum electrolytes and cardiac function during concomitant use. Corticosteroids have potassium-wasting effects and may potentiate hypokalemia during amphotericin B therapy and increase the risk for cardiac dysfunction. There have been cases reported in which concomitant use of amphotericin B and systemic corticosteroids was followed by cardiac enlargement and congestive heart failure.
Amphotericin B: (Moderate) Monitor serum electrolytes and cardiac function during concomitant use. Corticosteroids have potassium-wasting effects and may potentiate hypokalemia during amphotericin B therapy and increase the risk for cardiac dysfunction. There have been cases reported in which concomitant use of amphotericin B and systemic corticosteroids was followed by cardiac enlargement and congestive heart failure.
Antacids: (Moderate) Enteric-coated budesonide granules dissolve at a pH more than 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide.
Anthrax Vaccine: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Antithymocyte Globulin: (Moderate) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Aprepitant, Fosaprepitant: (Minor) Use caution if budesonide and aprepitant are used concurrently and monitor for an increase in budesonide-related adverse effects for several days after administration of a multi-day aprepitant regimen; however, due to low systemic exposure, clinically significant drug interactions are unlikely with budesonide for oral or intranasal inhalation. After administration, fosaprepitant is rapidly converted to aprepitant and shares the same drug interactions. Budesonide is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer; substitution of fosaprepitant 115 mg IV on day 1 of the 3-day regimen may lessen the inhibitory effects of CYP3A4. The AUC of a single dose of another CYP3A4 substrate, midazolam, increased by 2.3-fold and 3.3-fold on days 1 and 5, respectively, when coadministered with a 5-day oral aprepitant regimen. After a 3-day oral aprepitant regimen, the AUC of midazolam increased by 25% on day 4, and decreased by 19% and 4% on days 8 and 15, respectively, when given on days 1, 4, 8, and 15. As a single 40-mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.2-fold; the midazolam AUC increased by 1.5-fold after a single 125-mg dose of oral aprepitant. After single doses of IV fosaprepitant, the midazolam AUC increased by 1.8-fold (150 mg) and 1.6-fold (100 mg); less than a 2-fold increase in the midazolam AUC is not considered clinically important. Due to low systemic exposure, clinically significant drug interactions are unlikely with budesonide for oral or intranasal inhalation.
Arsenic Trioxide: (Moderate) Caution is advisable during concurrent use of arsenic trioxide and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with arsenic trioxide.
Articaine; EPINEPHrine: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Asparaginase Erwinia chrysanthemi: (Moderate) Concomitant use of L-asparaginase with corticosteroids can result in additive hyperglycemia. L-Asparaginase transiently inhibits insulin production contributing to hyperglycemia seen during concurrent corticosteroid therapy. Insulin therapy may be required in some cases. Administration of L-asparaginase after rather than before corticosteroids reportedly has produced fewer hypersensitivity reactions.
Aspirin, ASA: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Coadministration may result in decreased exposure to budesonide. Butalbital is a CYP3A4 inducer; budesonide is a CYP3A4 substrate. Monitor for decreased response to budesonide during concurrent use. (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.
Aspirin, ASA; Caffeine: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Major) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.
Aspirin, ASA; Dipyridamole: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.
Aspirin, ASA; Omeprazole: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance. (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum.
Aspirin, ASA; oxyCODONE: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.
Atazanavir: (Moderate) Coadministration of budesonide with atazanavir may cause elevated budesonide serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 substrate; atazanavir is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
Atazanavir; Cobicistat: (Moderate) Avoid coadministration of oral budesonide and cobistat due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Elevated budesonide serum concentrations may result in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 and P-glycoprotein (P-gp) substrate; cobicistat is a strong inhibitor of CYP3A4 and P-gp. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use. (Moderate) Coadministration of budesonide with atazanavir may cause elevated budesonide serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 substrate; atazanavir is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
Atenolol; Chlorthalidone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Atracurium: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years.
Avacopan: (Moderate) Avoid coadministration of oral budesonide with avacopan due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A substrate and avacopan is a moderate CYP3A inhibitor.
azaTHIOprine: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Azilsartan; Chlorthalidone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Bacillus Calmette-Guerin Vaccine, BCG: (Contraindicated) Avoid the administration of live virus vaccines with high-dose corticosteroid therapy and for at least 1 month following treatment. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated live virus vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 1 month after discontinuation. Patients with altered immunocompetence may be at increased risk for severe adverse reactions due to uninhibited growth of the attenuated live virus. Additionally, vaccine efficacy may be diminished in patients receiving any supraphysiologic dose of corticosteroid.
Basiliximab: (Minor) Because systemically administered corticosteroids have immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives.
Benazepril; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.
Berotralstat: (Moderate) Avoid coadministration of systemic budesonide with berotralstat due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A4 substrate and berotralstat is a moderate CYP3A4 inhibitor.
Bexagliflozin: (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Bexarotene: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents, such as bexarotene.
Bismuth Subsalicylate: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.
Bismuth Subsalicylate; metroNIDAZOLE; Tetracycline: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.
Bisoprolol; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Bortezomib: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
Brompheniramine; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
Bumetanide: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
BUPivacaine; EPINEPHrine: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
BUPivacaine; Meloxicam: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
buPROPion: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk.
buPROPion; Naltrexone: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk.
Butalbital; Acetaminophen: (Moderate) Coadministration may result in decreased exposure to budesonide. Butalbital is a CYP3A4 inducer; budesonide is a CYP3A4 substrate. Monitor for decreased response to budesonide during concurrent use.
Butalbital; Acetaminophen; Caffeine: (Moderate) Coadministration may result in decreased exposure to budesonide. Butalbital is a CYP3A4 inducer; budesonide is a CYP3A4 substrate. Monitor for decreased response to budesonide during concurrent use.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Coadministration may result in decreased exposure to budesonide. Butalbital is a CYP3A4 inducer; budesonide is a CYP3A4 substrate. Monitor for decreased response to budesonide during concurrent use.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Coadministration may result in decreased exposure to budesonide. Butalbital is a CYP3A4 inducer; budesonide is a CYP3A4 substrate. Monitor for decreased response to budesonide during concurrent use. (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.
Cabozantinib: (Minor) Monitor for an increase in budesonide-related adverse reactions if coadministration with cabozantinib is necessary. Budesonide is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Caffeine; Sodium Benzoate: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia.
Calcium Carbonate: (Moderate) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. In addition, calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Moderate) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. In addition, calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function. (Moderate) Monitor for loss of oral, enteric-coated budesonide efficacy during concomitant famotidine use. Since the dissolution of oral, enteric-coated budesonide is pH dependent, the release properties and uptake of the drug may be altered when used after H2-blockers.
Calcium Carbonate; Magnesium Hydroxide: (Moderate) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. In addition, calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function.
Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Moderate) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. In addition, calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function.
Calcium Carbonate; Simethicone: (Moderate) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. In addition, calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function.
Calcium; Vitamin D: (Moderate) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. In addition, calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function.
Canagliflozin: (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Canagliflozin; metFORMIN: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Candesartan; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Captopril; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Carmustine, BCNU: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Carvedilol: (Minor) Increased concentrations of budesonide may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and budesonide is a P-gp substrate.
Celecoxib: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Celecoxib; Tramadol: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Ceritinib: (Major) Avoid coadministration of oral budesonide and ceritinib due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold.
Chikungunya Vaccine, Live: (Contraindicated) Avoid the administration of live virus vaccines with high-dose corticosteroid therapy and for at least 1 month following treatment. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated live virus vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 1 month after discontinuation. Patients with altered immunocompetence may be at increased risk for severe adverse reactions due to uninhibited growth of the attenuated live virus. Additionally, vaccine efficacy may be diminished in patients receiving any supraphysiologic dose of corticosteroid.
Chlorambucil: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Chlorothiazide: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Chlorpheniramine; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
Chlorthalidone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine. High-dose corticosteroid therapy may impair immune function and is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days.
Choline Salicylate; Magnesium Salicylate: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.
Cimetidine: (Moderate) Monitor for loss of oral, enteric-coated budesonide efficacy and budesonide-related adverse events during concomitant cimetidine use. Since the dissolution of oral, enteric-coated budesonide is pH dependent, the release properties and uptake of the drug may be altered when used after H2-blockers. In an open, non-randomized, cross-over study, coadministration of cimetidine resulted in a 52% and 31% increase in the budesonide peak plasma concentration and AUC, respectively, after administration of cimetidine 1 g/day (200 mg with meals and 400 mg at night) for 2 separate 3-day periods where oral, delayed-release budesonide 4 mg was administered either alone or on the last day of a cimetidine treatment period.
Ciprofloxacin: (Moderate) Avoid coadministration of oral budesonide with ciprofloxacin due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A substrate and ciprofloxacin is a moderate CYP3A inhibitor. Also, quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon.
Cisatracurium: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years.
Cladribine: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Clarithromycin: (Moderate) Avoid coadministration of oral budesonide and clarithromycin due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; clarithromycin is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold.
Clofarabine: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Cobicistat: (Moderate) Avoid coadministration of oral budesonide and cobistat due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Elevated budesonide serum concentrations may result in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 and P-glycoprotein (P-gp) substrate; cobicistat is a strong inhibitor of CYP3A4 and P-gp. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
Codeine; Phenylephrine; Promethazine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
Conivaptan: (Moderate) Avoid coadministration of systemic budesonide with conivaptan due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A substrate and conivaptan is a moderate CYP3A inhibitor.
Conjugated Estrogens: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.
Conjugated Estrogens; Bazedoxifene: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.
Conjugated Estrogens; medroxyPROGESTERone: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.
Crizotinib: (Moderate) Avoid coadministration of systemic budesonide with crizotinib due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A4 substrate and crizotinib is a moderate CYP3A inhibitor.
cycloSPORINE: (Moderate) Avoid coadministration of oral budesonide and cyclosporine if possible due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure of budesonide may also increase. Budesonide is a CYP3A4 substrate; cyclosporine is a CYP3A4 inhibitor. In the presence of another CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold.
Dabrafenib: (Major) The concomitant use of dabrafenib and budesonide may lead to decreased budesonide concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of budesonide efficacy. Dabrafenib is a moderate CYP3A4 inducer and budesonide is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Danazol: (Moderate) Avoid coadministration of oral budesonide and danazol due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; danazol is a moderate CYP3A4 inhibitor. In the presence of a strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold.
Dapagliflozin: (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Dapagliflozin; metFORMIN: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Dapagliflozin; sAXagliptin: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Darunavir: (Moderate) Coadministration of budesonide with darunavir may cause elevated budesonide serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 substrate; darunavir is an inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
Darunavir; Cobicistat: (Moderate) Avoid coadministration of oral budesonide and cobistat due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Elevated budesonide serum concentrations may result in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 and P-glycoprotein (P-gp) substrate; cobicistat is a strong inhibitor of CYP3A4 and P-gp. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use. (Moderate) Coadministration of budesonide with darunavir may cause elevated budesonide serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 substrate; darunavir is an inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Avoid coadministration of oral budesonide and cobistat due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Elevated budesonide serum concentrations may result in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 and P-glycoprotein (P-gp) substrate; cobicistat is a strong inhibitor of CYP3A4 and P-gp. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use. (Moderate) Coadministration of budesonide with darunavir may cause elevated budesonide serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 substrate; darunavir is an inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
Deferasirox: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including corticosteroids.
Delafloxacin: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon.
Delavirdine: (Moderate) Avoid coadministration of oral budesonide and delavirdine due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; delavirdine is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to the dengue virus vaccine. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 1 month after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Denosumab: (Moderate) The safety and efficacy of denosumab use in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with denosumab may be at a greater risk of developing an infection.
Desmopressin: (Major) Desmopressin is contraindicated with concomitant inhaled or systemic corticosteroid use due to an increased risk of hyponatremia. Desmopressin can be started or resumed 3 days or 5 half-lives after the corticosteroid is discontinued, whichever is longer.
Desogestrel; Ethinyl Estradiol: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.
Dexbrompheniramine; Dextromethorphan; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
Dexlansoprazole: (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum.
Dextromethorphan; buPROPion: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk.
Dextromethorphan; diphenhydrAMINE; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
Dextromethorphan; guaiFENesin; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
Diclofenac: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Diclofenac; miSOPROStol: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Dienogest; Estradiol valerate: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.
Diflunisal: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
dilTIAZem: (Minor) Diltiazem may increase plasma concentrations of oral budesonide due to inhibition of the CYP3A4 isoenzymet, and can enhance the cortisol suppression associated with budesonide administered via inhalation.
Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
diphenhydrAMINE; Ibuprofen: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
diphenhydrAMINE; Naproxen: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
diphenhydrAMINE; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
Diphtheria Toxoid, Tetanus Toxoid, Acellular Pertussis Vaccine, DTaP; Haemophilus influenzae type b Conjugate Vaccine; Hepatitis B Vaccine, Recombinant; Inactivated Poliovirus Vaccine, IPV: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Diphtheria Toxoid, Tetanus Toxoid, Acellular Pertussis Vaccine, DTaP; Haemophilus influenzae type b Conjugate Vaccine; Inactivated Poliovirus Vaccine, IPV: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Diphtheria Toxoid, Tetanus Toxoid, Acellular Pertussis Vaccine, DTaP; Hepatitis B Vaccine, Recombinant; Inactivated Poliovirus Vaccine, IPV : (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Diphtheria Toxoid, Tetanus Toxoid, Acellular Pertussis Vaccine, DTaP; Inactivated Poliovirus Vaccine, IPV: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Diphtheria Toxoid; Tetanus Toxoid Adsorbed, DT, Td: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Diphtheria/Tetanus Toxoids; Pertussis Vaccine: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Dofetilide: (Major) Corticosteroids can cause increases in blood pressure, sodium and water retention, and hypokalemia, predisposing patients to interactions with certain other medications. Corticosteroid-induced hypokalemia could also enhance the proarrhythmic effects of dofetilide.
Dronedarone: (Moderate) Dronedarone is metabolized by and is an inhibitor of CYP3A; drondarone also inhibits P-gp. Budesonide is a substrate for CYP3A4 and P-gp. The concomitant administration of dronedarone with CYP3A4 and P-gp substrates may result in increased exposure of the substrate and should, therefore, be undertaken with caution.
droPERidol: (Moderate) Caution is advised when using droperidol in combination with corticosteroids which may lead to electrolyte abnormalities, especially hypokalemia or hypomagnesemia, as such abnormalities may increase the risk for QT prolongation or cardiac arrhythmias.
Drospirenone; Estetrol: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.
Drospirenone; Estradiol: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.
Drospirenone; Ethinyl Estradiol: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.
Dulaglutide: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Duvelisib: (Major) Avoid coadministration of systemic budesonide with duvelisib due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor.
Echinacea: (Moderate) Echinacea possesses immunostimulatory activity and may theoretically reduce the response to immunosuppressant drugs like corticosteroids. For some patients who are using corticosteroids for serious illness, such as cancer or organ transplant, this potential interaction may result in the preferable avoidance of Echinacea. Although documentation is lacking, coadministration of echinacea with immunosuppressants is not recommended by some resources.
Econazole: (Minor) In vitro studies indicate that corticosteroids inhibit the antifungal activity of econazole against C. albicans in a concentration-dependent manner. When the concentration of the corticosteroid was equal to or greater than that of econazole on a weight basis, the antifungal activity of econazole was substantially inhibited. When the corticosteroid concentration was one-tenth that of econazole, no inhibition of antifungal activity was observed.
Elagolix; Estradiol; Norethindrone acetate: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.
Elbasvir; Grazoprevir: (Minor) Administering budesonide with grazoprevir may result in elevated budesonide plasma concentrations. Budesonide is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
Elexacaftor; tezacaftor; ivacaftor: (Moderate) Use caution when administering ivacaftor and budesonide concurrently. Ivacaftor is an inhibitor of CYP3A and P-glycoprotein (Pgp). Co-administration of ivacaftor with CYP3A and Pgp substrates, such as budesonide, can increase budesonide exposure leading to increased or prolonged therapeutic effects and adverse events.
Eliglustat: (Moderate) Coadministration of oral budesonide and eliglustat may result in increased plasma concentrations of budesonide. Monitor patients closely for corticosteroid-related adverse effects; if appropriate, consider reducing the budesonide dosage and titrating to clinical effect. Budesonide is a substrate of the intestinal drug efflux pump, P-glycoprotein (P-gp); eliglustat is a P-gp inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Avoid coadministration of oral budesonide and cobistat due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Elevated budesonide serum concentrations may result in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 and P-glycoprotein (P-gp) substrate; cobicistat is a strong inhibitor of CYP3A4 and P-gp. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Avoid coadministration of oral budesonide and cobistat due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Elevated budesonide serum concentrations may result in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 and P-glycoprotein (P-gp) substrate; cobicistat is a strong inhibitor of CYP3A4 and P-gp. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
Empagliflozin: (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Empagliflozin; Linagliptin: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Empagliflozin; Linagliptin; metFORMIN: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Empagliflozin; metFORMIN: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Enalapril; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
ePHEDrine: (Moderate) Ephedrine may enhance the metabolic clearance of corticosteroids. Decreased blood concentrations and lessened physiologic activity may necessitate an increase in corticosteroid dosage.
ePHEDrine; guaiFENesin: (Moderate) Ephedrine may enhance the metabolic clearance of corticosteroids. Decreased blood concentrations and lessened physiologic activity may necessitate an increase in corticosteroid dosage.
EPINEPHrine: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Eprosartan; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Erlotinib: (Moderate) Monitor for symptoms of gastrointestinal (GI) perforation (e.g., severe abdominal pain, fever, nausea, and vomiting) if coadministration of erlotinib with budesonide is necessary. Permanently discontinue erlotinib in patients who develop GI perforation. The pooled incidence of GI perforation clinical trials of erlotinib ranged from 0.1% to 0.4%, including fatal cases; patients receiving concomitant budesonide may be at increased risk.
Ertugliflozin: (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Ertugliflozin; metFORMIN: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Ertugliflozin; SITagliptin: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Erythromycin: (Moderate) Avoid coadministration of oral budesonide with erythromycin due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor.
Esomeprazole: (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum.
Esterified Estrogens: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.
Esterified Estrogens; methylTESTOSTERone: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.
Estradiol: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.
Estradiol; Levonorgestrel: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.
Estradiol; Norethindrone: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.
Estradiol; Norgestimate: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.
Estradiol; Progesterone: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.
Estramustine: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Estrogens: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.
Estropipate: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.
Ethacrynic Acid: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
Ethinyl Estradiol; Norelgestromin: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.
Ethinyl Estradiol; Norethindrone Acetate: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.
Ethinyl Estradiol; Norgestrel: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.
Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.
Etodolac: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Etonogestrel; Ethinyl Estradiol: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.
Etravirine: (Moderate) Etravirine is a CYP3A4 inducer and a P-glycoprotein (PGP) inhibitor and budesonide is a CYP3A4 substrate and a substrate/inhibitor of PGP. Caution is warranted if these drugs are coadministered.
Exenatide: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Famotidine: (Moderate) Monitor for loss of oral, enteric-coated budesonide efficacy during concomitant famotidine use. Since the dissolution of oral, enteric-coated budesonide is pH dependent, the release properties and uptake of the drug may be altered when used after H2-blockers.
Fedratinib: (Moderate) Avoid coadministration of systemic budesonide with fedratinib due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A4 substrate and fedratinib is a moderate CYP3A4 inhibitor.
Fenoprofen: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Fluconazole: (Moderate) Avoid coadministration of oral budesonide with fluconazole due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A substrate and fluconazole is a moderate CYP3A inhibitor.
Fludarabine: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Flurbiprofen: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
fluvoxaMINE: (Moderate) Avoid coadministration of oral budesonide and fluvoxamine if possible due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; fluvoxamine is a moderate CYP3A4 inhibitor. In the presence of a strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold.
Fosamprenavir: (Major) Avoid coadministration of oral budesonide with fosamprenavir due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
Fosinopril; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Furosemide: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
Gallium Ga 68 Dotatate: (Moderate) Repeated administration of high corticosteroid doses prior to gallium Ga 68 dotatate may result in false negative imaging. High-dose corticosteroid therapy is generally defined as at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. Corticosteroids can down-regulate somatostatin subtype 2 receptors: thereby, interfering with binding of gallium Ga 68 dotatate to malignant cells that overexpress these receptors.
Gemifloxacin: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon.
Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and budesonide as coadministration may increase serum concentrations of budesonide and increase the risk of adverse effects. Glecaprevir is a P-glycoprotein (P-gp) inhibitor; budesonide is a P-gp substrate. (Moderate) Caution is advised with the coadministration of pibrentasvir and budesonide as coadministration may increase serum concentrations of budesonide and increase the risk of adverse effects. Pibrentasvir is a P-glycoprotein (P-gp) inhibitor; budesonide is a P-gp substrate.
Glimepiride: (Moderate) Monitor blood glucose during concomitant corticosteroid and sulfonylurea use; a sulfonylurea dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
glipiZIDE: (Moderate) Monitor blood glucose during concomitant corticosteroid and sulfonylurea use; a sulfonylurea dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
glipiZIDE; metFORMIN: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor blood glucose during concomitant corticosteroid and sulfonylurea use; a sulfonylurea dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
glyBURIDE: (Moderate) Monitor blood glucose during concomitant corticosteroid and sulfonylurea use; a sulfonylurea dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
glyBURIDE; metFORMIN: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor blood glucose during concomitant corticosteroid and sulfonylurea use; a sulfonylurea dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Glycerol Phenylbutyrate: (Moderate) Corticosteroids may induce elevated blood ammonia concentrations. Corticosteroids should be used with caution in patients receiving glycerol phenylbutyrate. Monitor ammonia concentrations closely.
Grapefruit juice: (Major) Grapefruit juice, an inhibitor of gut mucosal CYP3A4, roughly doubles the bioavailability of oral budesonide. Patients should not eat grapefruit or drink grapefruit juice during the entire treatment period with oral budesonide.
Griseofulvin: (Moderate) Theoretically, induction of the cytochrome P450 3A4 isoenzyme by griseofulvin may result in a lowering of budesonide plasma concentrations, reducing the clinical effect.
guaiFENesin; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
Haemophilus influenzae type b Conjugate Vaccine: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Haloperidol: (Moderate) Caution is advisable during concurrent use of haloperidol and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with haloperidol.
Hemin: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Corticosteroids increase the activity of this enzyme should not be used with hemin.
Hepatitis A Vaccine, Inactivated: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Hepatitis A Vaccine, Inactivated; Hepatitis B Vaccine, Recombinant: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Hepatitis B Vaccine, Recombinant: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Human Papillomavirus 9-Valent Vaccine: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
hydroCHLOROthiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
hydroCHLOROthiazide, HCTZ; Moexipril: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
HYDROcodone; Ibuprofen: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Hydroxyurea: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.
Ibritumomab Tiuxetan: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Ibuprofen: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Ibuprofen; Famotidine: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. (Moderate) Monitor for loss of oral, enteric-coated budesonide efficacy during concomitant famotidine use. Since the dissolution of oral, enteric-coated budesonide is pH dependent, the release properties and uptake of the drug may be altered when used after H2-blockers.
Ibuprofen; oxyCODONE: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Ibuprofen; Pseudoephedrine: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with budesonide, a CYP3A substrate, as budesonide toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Incretin Mimetics: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Indapamide: (Moderate) Additive hypokalemia may occur when indapamide is coadministered with other drugs with a significant risk of hypokalemia such as systemic corticosteroids. Coadminister with caution and careful monitoring.
Indinavir: (Minor) Use caution when budesonide is coadministered with drugs that inhibit CYP3A enzymes, such as indinavir, and consider dose reduction. Toxicity may occur, particularly excessive HPA-axis suppression.
Indomethacin: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Inebilizumab: (Moderate) Concomitant usage of inebilizumab with immunosuppressant drugs, including systemic corticosteroids, may increase the risk of infection. Consider the risk of additive immune system effects when coadministering therapies that cause immunosuppression with inebilizumab.
Influenza Virus Vaccine: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Insulin Aspart: (Moderate) Monitor blood glucose during concomitant corticosteroid and insulin use; an insulin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Insulin Aspart; Insulin Aspart Protamine: (Moderate) Monitor blood glucose during concomitant corticosteroid and insulin use; an insulin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Insulin Degludec: (Moderate) Monitor blood glucose during concomitant corticosteroid and insulin use; an insulin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Insulin Degludec; Liraglutide: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor blood glucose during concomitant corticosteroid and insulin use; an insulin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Insulin Detemir: (Moderate) Monitor blood glucose during concomitant corticosteroid and insulin use; an insulin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Insulin Glargine: (Moderate) Monitor blood glucose during concomitant corticosteroid and insulin use; an insulin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Insulin Glargine; Lixisenatide: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor blood glucose during concomitant corticosteroid and insulin use; an insulin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Insulin Glulisine: (Moderate) Monitor blood glucose during concomitant corticosteroid and insulin use; an insulin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Insulin Lispro: (Moderate) Monitor blood glucose during concomitant corticosteroid and insulin use; an insulin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Insulin Lispro; Insulin Lispro Protamine: (Moderate) Monitor blood glucose during concomitant corticosteroid and insulin use; an insulin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Insulin, Inhaled: (Moderate) Monitor blood glucose during concomitant corticosteroid and insulin use; an insulin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Insulins: (Moderate) Monitor blood glucose during concomitant corticosteroid and insulin use; an insulin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Interferon Alfa-2b: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Intranasal Influenza Vaccine: (Contraindicated) Avoid the administration of live virus vaccines with high-dose corticosteroid therapy and for at least 1 month following treatment. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated live virus vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 1 month after discontinuation. Patients with altered immunocompetence may be at increased risk for severe adverse reactions due to uninhibited growth of the attenuated live virus. Additionally, vaccine efficacy may be diminished in patients receiving any supraphysiologic dose of corticosteroid. (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Irbesartan; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with budesonide may result in increased serum concentrations of budesonide. Budesonide is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring are advised if these drugs are used together.
Isophane Insulin (NPH): (Moderate) Monitor blood glucose during concomitant corticosteroid and insulin use; an insulin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Isoproterenol: (Moderate) The risk of cardiac toxicity with isoproterenol in asthma patients appears to be increased with the coadministration of corticosteroids. Intravenous infusions of isoproterenol in refractory asthmatic children at rates of 0.05 to 2.7 mcg/kg/min have caused clinical deterioration, myocardial infarction (necrosis), congestive heart failure and death.
ISOtretinoin: (Minor) Both isotretinoin and corticosteroids can cause osteoporosis during chronic use. Patients receiving systemic corticosteroids should receive isotretinoin therapy with caution.
Itraconazole: (Moderate) Avoid coadministration of oral budesonide and itraconazole due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; itraconazole is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold.
Ivacaftor: (Moderate) Use caution when administering ivacaftor and budesonide concurrently. Ivacaftor is an inhibitor of CYP3A and P-glycoprotein (Pgp). Co-administration of ivacaftor with CYP3A and Pgp substrates, such as budesonide, can increase budesonide exposure leading to increased or prolonged therapeutic effects and adverse events.
Ivosidenib: (Moderate) Monitor for loss of efficacy of budesonide during coadministration of ivosidenib; a budesonide dose adjustment may be necessary. Budesonide is a sensitive substrate of CYP3A4; ivosidenib induces CYP3A4 and may lead to decreased budesonide concentrations.
Japanese Encephalitis Virus Vaccine: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Ketoconazole: (Moderate) Monitor for corticosteroid-related adverse effects during chronic concomitant use of inhaled or nasal budesonide and ketoconazole. Avoid concomitant use of oral budesonide and ketoconazole. Budesonide is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor. Ketoconazole has been observed to increase the overall exposure of oral budesonide by 8-fold. The total absolute bioavailability of inhaled and nasal budesonide products ranges from 6% to 39% of the labeled dose.
Ketoprofen: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Ketorolac: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Lansoprazole: (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum.
Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Avoid coadministration of oral budesonide and clarithromycin due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; clarithromycin is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum.
Ledipasvir; Sofosbuvir: (Minor) Caution and close monitoring of budesonide-associated adverse reactions is advised with concomitant administration of ledipasvir. Budesonide is a substrate of the drug transporter P-glycoprotein (P-gp); ledipasvir is a P-gp inhibitor. Taking these drugs together may increase budesonide plasma concentrations.
Lefamulin: (Moderate) Avoid coadministration of systemic budesonide with oral lefamulin due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A4 substrate and oral lefamulin is a moderate CYP3A4 inhibitor; an interaction is not expected with intravenous lefamulin.
Lenacapavir: (Moderate) Avoid coadministration of oral budesonide with lenacapavir due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A substrate and lenacapavir is a moderate CYP3A inhibitor.
Letermovir: (Moderate) A clinically relevant increase in the plasma concentration of budesonide may occur when given concurrently with letermovir; monitor for adverse events. Avoid coadministration of oral budesonide and letermovir in patients who are also receiving treatment with cyclosporine, because the magnitude of this interaction may be amplified. Budesonide is a sensitive CYP3A4 substrate. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. Concurrent use of a strong inhibitor increased the AUC of oral budesonide by 8-fold.
levoFLOXacin: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon.
Levoketoconazole: (Moderate) Monitor for corticosteroid-related adverse effects during chronic concomitant use of inhaled or nasal budesonide and ketoconazole. Avoid concomitant use of oral budesonide and ketoconazole. Budesonide is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor. Ketoconazole has been observed to increase the overall exposure of oral budesonide by 8-fold. The total absolute bioavailability of inhaled and nasal budesonide products ranges from 6% to 39% of the labeled dose.
Levonorgestrel; Ethinyl Estradiol: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.
Lidocaine; EPINEPHrine: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Linagliptin: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Linagliptin; metFORMIN: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Liraglutide: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Lisinopril; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Live Vaccines: (Contraindicated) Avoid the administration of live virus vaccines with high-dose corticosteroid therapy and for at least 1 month following treatment. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated live virus vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 1 month after discontinuation. Patients with altered immunocompetence may be at increased risk for severe adverse reactions due to uninhibited growth of the attenuated live virus. Additionally, vaccine efficacy may be diminished in patients receiving any supraphysiologic dose of corticosteroid.
Lixisenatide: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Lomustine, CCNU: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Lonafarnib: (Moderate) Avoid coadministration of oral budesonide and lonafarnib due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; lonafarnib is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold.
Lonapegsomatropin: (Moderate) Corticosteroids can retard bone growth and therefore, can inhibit the growth-promoting effects of somatropin. If corticosteroid therapy is required, the corticosteroid dose should be carefully adjusted.
Loop diuretics: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
Lopinavir; Ritonavir: (Major) Avoid coadministration of oral budesonide and ritonavir due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. (Moderate) Decreased lopinavir plasma concentrations have been observed when systemic budesonide and lopinavir are coadministered, increasing the risk for HIV treatment failure. Consider use of an alternative corticosteroid. If concurrent use is required, caution and careful monitoring of HIV treatment status is recommended.
Losartan; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Lumacaftor; Ivacaftor: (Moderate) Concomitant use of budesonide and lumacaftor; ivacaftor may alter the therapeutic effects of budesonide; caution and close monitoring are advised if these drugs are used together. Budesonide is a primary substrate of CYP3A4 and a substrate of the P-glycoprotein (P-gp) efflux transporter. Lumacaftor is a strong CYP3A inducer; in vitro data also suggest lumacaftor; ivacaftor may induce and/or inhibit P-gp. Although induction of budesonide through the CYP3A pathway may lead to decreased drug efficacy, the net effect of lumacaftor; ivacaftor on P-gp transport is not clear. Monitor the patient for decreased corticosteroid efficacy or increased or prolonged therapeutic effects and adverse events. (Moderate) Use caution when administering ivacaftor and budesonide concurrently. Ivacaftor is an inhibitor of CYP3A and P-glycoprotein (Pgp). Co-administration of ivacaftor with CYP3A and Pgp substrates, such as budesonide, can increase budesonide exposure leading to increased or prolonged therapeutic effects and adverse events.
Lumacaftor; Ivacaftor: (Moderate) Concomitant use of budesonide and lumacaftor; ivacaftor may alter the therapeutic effects of budesonide; caution and close monitoring are advised if these drugs are used together. Budesonide is a primary substrate of CYP3A4 and a substrate of the P-glycoprotein (P-gp) efflux transporter. Lumacaftor is a strong CYP3A inducer; in vitro data also suggest lumacaftor; ivacaftor may induce and/or inhibit P-gp. Although induction of budesonide through the CYP3A pathway may lead to decreased drug efficacy, the net effect of lumacaftor; ivacaftor on P-gp transport is not clear. Monitor the patient for decreased corticosteroid efficacy or increased or prolonged therapeutic effects and adverse events.
Lutetium Lu 177 dotatate: (Major) Avoid repeated administration of high doses of glucocorticoids during treatment with lutetium Lu 177 dotatate due to the risk of decreased efficacy of lutetium Lu 177 dotatate. Lutetium Lu 177 dotatate binds to somatostatin receptors, with the highest affinity for subtype 2 somatostatin receptors (SSTR2); glucocorticoids can induce down-regulation of SSTR2.
Macimorelin: (Major) Avoid use of macimorelin with drugs that directly affect pituitary growth hormone secretion, such as corticosteroids. Healthcare providers are advised to discontinue corticosteroid therapy and observe a sufficient washout period before administering macimorelin. Use of these medications together may impact the accuracy of the macimorelin growth hormone test.
Magnesium Hydroxide: (Moderate) Enteric-coated budesonide granules dissolve at a pH more than 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide.
Magnesium Salicylate: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.
Magnesium Salts: (Moderate) Enteric-coated budesonide granules dissolve at a pH more than 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide.
Mannitol: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia. Also, corticotropin may cause calcium loss and sodium and fluid retention. Mannitol itself can cause hypernatremia. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Contraindicated) Avoid the administration of live virus vaccines with high-dose corticosteroid therapy and for at least 1 month following treatment. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated live virus vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 1 month after discontinuation. Patients with altered immunocompetence may be at increased risk for severe adverse reactions due to uninhibited growth of the attenuated live virus. Additionally, vaccine efficacy may be diminished in patients receiving any supraphysiologic dose of corticosteroid.
Measles/Mumps/Rubella Vaccines, MMR: (Contraindicated) Avoid the administration of live virus vaccines with high-dose corticosteroid therapy and for at least 1 month following treatment. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated live virus vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 1 month after discontinuation. Patients with altered immunocompetence may be at increased risk for severe adverse reactions due to uninhibited growth of the attenuated live virus. Additionally, vaccine efficacy may be diminished in patients receiving any supraphysiologic dose of corticosteroid.
Mecasermin, Recombinant, rh-IGF-1: (Moderate) Additional monitoring may be required when coadministering systemic or inhaled corticosteroids and mecasermin, recombinant, rh-IGF-1. In animal studies, corticosteroids impair the growth-stimulating effects of growth hormone (GH) through interference with the physiological stimulation of epiphyseal chondrocyte proliferation exerted by GH and IGF-1. Dexamethasone administration on long bone tissue in vitro resulted in a decrease of local synthesis of IGF-1. Similar counteractive effects are expected in humans. If systemic or inhaled glucocorticoid therapy is required, the steroid dose should be carefully adjusted and growth rate monitored.
Meclofenamate Sodium: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Mefenamic Acid: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Meglitinides: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Meloxicam: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Meningococcal Group B Vaccine (3 strain): (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Meningococcal Group B Vaccine (4 strain): (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Meningococcal Groups A, B, C, W, and Y Vaccine (5 valent): (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Meningococcal Groups A, C, W, and Y Vaccine (4 valent): (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Mercaptopurine, 6-MP: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
metFORMIN: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
metFORMIN; Repaglinide: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
metFORMIN; sAXagliptin: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
metFORMIN; SITagliptin: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
methazolAMIDE: (Moderate) Corticosteroids may increase the risk of hypokalemia if used concurrently with methazolamide. Hypokalemia may be especially severe with prolonged use of corticotropin, ACTH. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy. The chronic use of corticosteroids may augment calcium excretion with methazolamide leading to increased risk for hypocalcemia and/or osteoporosis.
Methenamine; Sodium Salicylate: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.
Methoxsalen: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
metOLazone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Metoprolol; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
metyraPONE: (Contraindicated) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test. Although systemic absorption of nasal corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results.
Micafungin: (Moderate) Leukopenia, neutropenia, anemia, and thrombocytopenia have been associated with micafungin. Patients who are taking immunosuppressives such as the corticosteroids with micafungin concomitantly may have additive risks for infection or other side effects. In a pharmacokinetic trial, micafungin had no effect on the pharmacokinetics of prednisolone. Acute intravascular hemolysis and hemoglobinuria was seen in a healthy volunteer during infusion of micafungin (200 mg) and oral prednisolone (20 mg). This reaction was transient, and the subject did not develop significant anemia.
miFEPRIStone: (Major) Mifepristone for termination of pregnancy is contraindicated in patients on long-term corticosteroid therapy and mifepristone for Cushing's disease or other chronic conditions is contraindicated in patients who require concomitant treatment with systemic corticosteroids for life-saving purposes, such as serious medical conditions or illnesses (e.g., immunosuppression after organ transplantation). For other situations where corticosteroids are used for treating non-life threatening conditions, mifepristone may lead to reduced corticosteroid efficacy and exacerbation or deterioration of such conditions. This is because mifepristone exhibits antiglucocorticoid activity that may antagonize corticosteroid therapy and the stabilization of the underlying corticosteroid-treated illness. Mifepristone may also cause adrenal insufficiency, so patients receiving corticosteroids for non life-threatening illness require close monitoring. Because serum cortisol levels remain elevated and may even increase during treatment with mifepristone, serum cortisol levels do not provide an accurate assessment of hypoadrenalism. Patients should be closely monitored for signs and symptoms of adrenal insufficiency, If adrenal insufficiency occurs, stop mifepristone treatment and administer systemic glucocorticoids without delay; high doses may be needed to treat these events. Factors considered in deciding on the duration of glucocorticoid treatment should include the long half-life of mifepristone (85 hours).
Miglitol: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Mitotane: (Moderate) Use caution if mitotane and budesonide are used concomitantly, and monitor for decreased efficacy of budesonide and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and budesonide is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of budesonide. Theoretically, inhibition of CYP3A may also be clinically significant for inhaled forms of budesonide, including budesonide nasal spray.
mitoXANTRONE: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Modafinil: (Moderate) Theoretically, induction of the cytochrome P450 3A4 isoenzyme by modafinil may result in a lowering of budesonide plasma concentrations, reducing the clinical effect.
Moxifloxacin: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon.
Nabumetone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Nafcillin: (Moderate) Theoretically, induction of the cytochrome P450 3A4 isoenzyme, such as nafcillin, may result in a lowering of budesonide plasma concentrations, reducing the clinical effect.
Naproxen: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Naproxen; Esomeprazole: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum.
Naproxen; Pseudoephedrine: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Natalizumab: (Major) Ordinarily, patients receiving chronic immunosuppressant therapy should not be treated with natalizumab. Treatment recommendations for combined corticosteroid therapy are dependent on the underlying indication for natalizumab therapy. Corticosteroids should be tapered in those patients with Crohn's disease who are on chronic corticosteroids when they start natalizumab therapy, as soon as a therapeutic benefit has occurred. If the patient cannot discontinue systemic corticosteroids within 6 months, discontinue natalizumab. The concomitant use of natalizumab and corticosteroids may further increase the risk of serious infections, including progressive multifocal leukoencephalopathy, over the risk observed with use of natalizumab alone. In multiple sclerosis (MS) clinical trials, an increase in infections was seen in patients concurrently receiving short courses of corticosteroids. However, the increase in infections in natalizumab-treated patients who received steroids was similar to the increase in placebo-treated patients who received steroids. Short courses of steroid use during natalizumab, such as when they are needed for MS relapse treatment, appear to be acceptable for use concurrently.
Nateglinide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Nefazodone: (Moderate) Avoid coadministration of oral budesonide and nefazodone due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; nefazodone is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold.
Nelarabine: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Nelfinavir: (Moderate) Avoid coadministration of oral budesonide and nelfinavir due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; nelfinavir is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold.
Neostigmine: (Moderate) Concomitant use of anticholinesterase agents, such as neostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, anticholinesterase agents should be withdrawn at least 24 hours before initiating systemic corticosteroid therapy.
Neostigmine; Glycopyrrolate: (Moderate) Concomitant use of anticholinesterase agents, such as neostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, anticholinesterase agents should be withdrawn at least 24 hours before initiating systemic corticosteroid therapy.
Neuromuscular blockers: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years.
NiCARdipine: (Minor) Nicardipine may increase plasma concentrations of budesonide due to inhibition of the CYP3A4 isoenzyme. Use caution when budesonide is coadministered with drugs that inhibit CYP3A enzymes and consider dose reduction.
Nirmatrelvir; Ritonavir: (Major) Avoid coadministration of oral budesonide and ritonavir due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold.
Nirogacestat: (Moderate) Avoid coadministration of oral budesonide with nirogacestat due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A substrate and nirogacestat is a moderate CYP3A inhibitor.
Nizatidine: (Moderate) Monitor for loss of oral, enteric-coated budesonide efficacy during concomitant nizatidine use. Since the dissolution of oral, enteric-coated budesonide is pH dependent, the release properties and uptake of the drug may be altered when used after H2-blockers.
Non-Live Vaccines: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Nonsteroidal antiinflammatory drugs: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.
Norethindrone; Ethinyl Estradiol: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.
Norgestimate; Ethinyl Estradiol: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.
Ofatumumab: (Moderate) Concomitant use of ofatumumab with corticosteroids may increase the risk of immunosuppression. Monitor patients carefully for signs and symptoms of infection. Ofatumumab has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis, including immunosuppressant doses of corticosteroids.
Ofloxacin: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon.
Olmesartan; amLODIPine; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Olmesartan; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Omeprazole: (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum.
Omeprazole; Amoxicillin; Rifabutin: (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum.
Omeprazole; Sodium Bicarbonate: (Major) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum.
Oritavancin: (Minor) Budesonide is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of oral budesonide may be reduced if these drugs are administered concurrently.
Oxaprozin: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Oxymetholone: (Moderate) Concomitant use of oxymetholone with corticosteroids or corticotropin, ACTH may cause increased edema. Manage edema with diuretic and/or digitalis therapy.
Palbociclib: (Moderate) Monitor for an increase in budesonide-related adverse reactions if coadministration with palbociclib is necessary, including excessive HPA-axis suppression; this may also be clinically significant for inhaled forms of budesonide. Palbociclib is a weak time-dependent inhibitor of CYP3A while budesonide is a CYP3A4 substrate.
Pancuronium: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years.
Pantoprazole: (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum.
PAZOPanib: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and budesonide, a CYP3A4 substrate, may cause an increase in systemic concentrations of budesonide. Use caution when administering these drugs concomitantly.
Pegaspargase: (Moderate) Monitor for an increase in glucocorticoid-related adverse reactions such as hyperglycemia and osteonecrosis during concomitant use of pegaspargase and glucocorticoids.
penicillAMINE: (Major) Agents such as immunosuppressives have adverse reactions similar to those of penicillamine. Concomitant use of penicillamine with these agents is contraindicated because of the increased risk of developing severe hematologic and renal toxicity.
Pentostatin: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
PHENobarbital: (Moderate) Coadministration may result in decreased exposure to budesonide. Phenobarbital is a CYP3A4 inducer; budesonide is a CYP3A4 substrate. Monitor for decreased response to budesonide during concurrent use. Dose adjustments may be necessary.
PHENobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Coadministration may result in decreased exposure to budesonide. Phenobarbital is a CYP3A4 inducer; budesonide is a CYP3A4 substrate. Monitor for decreased response to budesonide during concurrent use. Dose adjustments may be necessary.
Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
Photosensitizing agents (topical): (Minor) Corticosteroids administered prior to or concomitantly with photosensitizing agents used in photodynamic therapy may decrease the efficacy of the treatment.
PHYSostigmine: (Moderate) Concomitant use of anticholinesterase agents, such as physostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase inhibitors at least 24 hours before initiating corticosteroid therapy.
Pimozide: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as high-dose, systemic corticosteroid therapy. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia. Topical corticosteroids are less likely to interact.
Pioglitazone: (Moderate) Monitor blood glucose during concomitant corticosteroid and thiazolidinedione use; a thiazolidinedione dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Pioglitazone; Glimepiride: (Moderate) Monitor blood glucose during concomitant corticosteroid and sulfonylurea use; a sulfonylurea dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor blood glucose during concomitant corticosteroid and thiazolidinedione use; a thiazolidinedione dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Pioglitazone; metFORMIN: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor blood glucose during concomitant corticosteroid and thiazolidinedione use; a thiazolidinedione dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Piroxicam: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Pneumococcal Vaccine, Polyvalent: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Ponesimod: (Moderate) Monitor for signs and symptoms of infection. Additive immune suppression may result from concomitant use of ponesimod and high-dose corticosteroid therapy which may extend the duration or severity of immune suppression. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days.
Posaconazole: (Moderate) Avoid coadministration of oral budesonide and posaconazole due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of budesonide. Further, both budesonide and posaconazole are substrates of the drug efflux protein, P-glycoprotein (P-gp), which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and budesonide, ultimately resulting in an increased risk of adverse events.
Potassium-sparing diuretics: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
Pramlintide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): (Moderate) Corticosteroids blunt the adrenal secretion of endogenous DHEA and DHEAS, resulting in reduced DHEA and DHEAS serum concentrations.
Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Moderate) Corticosteroids blunt the adrenal secretion of endogenous DHEA and DHEAS, resulting in reduced DHEA and DHEAS serum concentrations.
Prilocaine; EPINEPHrine: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Primidone: (Moderate) Coadministration may result in decreased exposure to budesonide. Primidone is a CYP3A4 inducer; budesonide is a CYP3A4 substrate. Monitor for decreased response to budesonide during concurrent use.
Promethazine; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
Propranolol: (Moderate) Monitor blood sugar during concomitant corticosteroid and propranolol use due to risk for hypoglycemia. Concurrent use may increase risk of hypoglycemia because of loss of the counter-regulatory cortisol response.
Proton pump inhibitors: (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum.
Purine analogs: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
pyRIDostigmine: (Moderate) Concomitant use of anticholinesterase agents, such as pyridostigmine, and corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, anticholinesterase agents should be withdrawn at least 24 hours before initiating corticosteroid therapy.
Quinapril; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
RABEprazole: (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum.
Rabies Vaccine: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Regular Insulin: (Moderate) Monitor blood glucose during concomitant corticosteroid and insulin use; an insulin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Regular Insulin; Isophane Insulin (NPH): (Moderate) Monitor blood glucose during concomitant corticosteroid and insulin use; an insulin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Relugolix; Estradiol; Norethindrone acetate: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.
Repaglinide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Respiratory Syncytial Virus Vaccine: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Ribociclib: (Moderate) Avoid coadministration of oral budesonide and ribociclib due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; ribociclib is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold.
Ribociclib; Letrozole: (Moderate) Avoid coadministration of oral budesonide and ribociclib due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; ribociclib is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold.
Ritlecitinib: (Moderate) Avoid coadministration of oral budesonide with ritlecitinib due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A substrate and ritlecitinib is a moderate CYP3A inhibitor.
Ritonavir: (Major) Avoid coadministration of oral budesonide and ritonavir due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold.
riTUXimab: (Moderate) Rituximab and corticosteroids are commonly used together; however, monitor the patient for immunosuppression and signs and symptoms of infection during combined chronic therapy.
riTUXimab; Hyaluronidase: (Moderate) Rituximab and corticosteroids are commonly used together; however, monitor the patient for immunosuppression and signs and symptoms of infection during combined chronic therapy.
Rocuronium: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years.
Rosiglitazone: (Moderate) Monitor blood glucose during concomitant corticosteroid and thiazolidinedione use; a thiazolidinedione dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Rotavirus Vaccine: (Contraindicated) Avoid the administration of live virus vaccines with high-dose corticosteroid therapy and for at least 1 month following treatment. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated live virus vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 1 month after discontinuation. Patients with altered immunocompetence may be at increased risk for severe adverse reactions due to uninhibited growth of the attenuated live virus. Additionally, vaccine efficacy may be diminished in patients receiving any supraphysiologic dose of corticosteroid.
Salicylates: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.
Salsalate: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.
Saquinavir: (Major) Avoid coadministration of saquinavir and orally administered budesonide and use inhaled formulations with caution. Saquinavir may inhibit CYP3A4 metabolism of budesonide, resulting in increased plasma budesonide concentrations and reduced serum cortisol concentrations. Theoretically, inhibition of CYP3A4 may be clinically significant for inhaled forms of budesonide, including budesonide nasal spray. There have been reports of clinically significant drug interactions in patients receiving ritonavir with other corticosteroids, resulting in systemic corticosteroid effects including Cushing syndrome and adrenal suppression. Similar results are expected with saquinavir. Consider using an alternative treatment to budesonide, such as a corticosteroid not metabolized by CYP3A4 (i.e., beclomethasone or prednisolone). If corticosteroid therapy is to be discontinued, consider tapering the dose over a period of time to decrease the potential for withdrawal.
Sargramostim, GM-CSF: (Major) Avoid the concomitant use of sargramostim and systemic corticosteroid agents due to the risk of additive myeloproliferative effects. If coadministration of these drugs is required, frequently monitor patients for clinical and laboratory signs of excess myeloproliferative effects (e.g., leukocytosis). Sargramostim is a recombinant human granulocyte-macrophage colony-stimulating factor that works by promoting proliferation and differentiation of hematopoietic progenitor cells.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving corticosteroids in greater than physiologic doses may have a diminished response to the SARS-CoV-2 virus vaccine. Counsel patients receiving corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving corticosteroids in greater than physiologic doses may have a diminished response to the SARS-CoV-2 virus vaccine. Counsel patients receiving corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving corticosteroids in greater than physiologic doses may have a diminished response to the SARS-CoV-2 virus vaccine. Counsel patients receiving corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving corticosteroids in greater than physiologic doses may have a diminished response to the SARS-CoV-2 virus vaccine. Counsel patients receiving corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
sAXagliptin: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Segesterone Acetate; Ethinyl Estradiol: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.
Semaglutide: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
SGLT2 Inhibitors: (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
SITagliptin: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Contraindicated) Avoid the administration of live virus vaccines with high-dose corticosteroid therapy and for at least 1 month following treatment. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated live virus vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 1 month after discontinuation. Patients with altered immunocompetence may be at increased risk for severe adverse reactions due to uninhibited growth of the attenuated live virus. Additionally, vaccine efficacy may be diminished in patients receiving any supraphysiologic dose of corticosteroid.
Smallpox Vaccine, Vaccinia Vaccine: (Contraindicated) Avoid the administration of live virus vaccines with high-dose corticosteroid therapy and for at least 1 month following treatment. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated live virus vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 1 month after discontinuation. Patients with altered immunocompetence may be at increased risk for severe adverse reactions due to uninhibited growth of the attenuated live virus. Additionally, vaccine efficacy may be diminished in patients receiving any supraphysiologic dose of corticosteroid.
Sodium Benzoate; Sodium Phenylacetate: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia.
Sodium Bicarbonate: (Major) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide.
Sodium Phenylbutyrate: (Moderate) The concurrent use of corticosteroids with sodium phenylbutyrate may increase plasma ammonia levels (hyperammonemia) by causing the breakdown of body protein. Patients with urea cycle disorders being treated with sodium phenylbutyrate usually should not receive regular treatment with corticosteroids.
Sodium Phenylbutyrate; Taurursodiol: (Moderate) The concurrent use of corticosteroids with sodium phenylbutyrate may increase plasma ammonia levels (hyperammonemia) by causing the breakdown of body protein. Patients with urea cycle disorders being treated with sodium phenylbutyrate usually should not receive regular treatment with corticosteroids.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Plasma concentrations of budesonide, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with voxilaprevir, a P-gp inhibitor. Monitor patients for increased side effects if these drugs are administered concurrently.
Somapacitan: (Moderate) Patients treated with glucocorticoid replacement for hypoadrenalism may require an increase in their maintenance or stress steroid doses following initiation of somapacitan. Monitor for signs/symptoms of reduced serum cortisol concentrations. Growth hormone (GH) inhibits 11betaHSD-1. Consequently, patients with untreated GH deficiency have relative increases in 11betaHSD-1 and serum cortisol. The initiation of somapacitan may result in inhibition of 11betaHSD-1 and reduced serum cortisol concentrations.
Somatrogon: (Moderate) Monitor for a decrease in serum cortisol concentrations and corticosteroid efficacy during concurrent use of corticosteroids and somatrogon. Patients treated with glucocorticoid replacement for hypoadrenalism may require an increase in their maintenance or stress steroid doses following initiation of somatrogon. Additionally, supraphysiologic glucocorticoid treatment may attenuate the growth promoting effects of somatrogon. Carefully adjust glucocorticoid replacement dosing to avoid hypoadrenalism and an inhibitory effect on growth.
Somatropin, rh-GH: (Moderate) Corticosteroids can retard bone growth and therefore, can inhibit the growth-promoting effects of somatropin. If corticosteroid therapy is required, the corticosteroid dose should be carefully adjusted.
Sotagliflozin: (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Spironolactone: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
Spironolactone; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
Stiripentol: (Moderate) Consider a dose adjustment of budesonide when coadministered with stiripentol. Coadministration may alter plasma concentrations of budesonide resulting in an increased risk of adverse reactions and/or decreased efficacy. Budesonide is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Succinylcholine: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years.
Sulfonylureas: (Moderate) Monitor blood glucose during concomitant corticosteroid and sulfonylurea use; a sulfonylurea dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Sulindac: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
SUMAtriptan; Naproxen: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Telmisartan; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Temsirolimus: (Moderate) Monitor for an increase in budesonide-related adverse reactions if coadministration with temsirolimus is necessary. Budesonide is a P-glycoprotein (P-gp) substrate and temsirolimus is a P-gp inhibitor. Concomitant use is likely to lead to increased concentrations of budesonide.
Testosterone: (Moderate) Monitor for fluid retention during concurrent corticosteroid and testosterone use. Concurrent use may result in increased fluid retention.
Tezacaftor; Ivacaftor: (Moderate) Use caution when administering ivacaftor and budesonide concurrently. Ivacaftor is an inhibitor of CYP3A and P-glycoprotein (Pgp). Co-administration of ivacaftor with CYP3A and Pgp substrates, such as budesonide, can increase budesonide exposure leading to increased or prolonged therapeutic effects and adverse events.
Thiazide diuretics: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Thiazolidinediones: (Moderate) Monitor blood glucose during concomitant corticosteroid and thiazolidinedione use; a thiazolidinedione dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Thioguanine, 6-TG: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Tick-Borne Encephalitis Vaccine: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Tirzepatide: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Tolmetin: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Torsemide: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
Trandolapril; Verapamil: (Moderate) Avoid coadministration of systemic budesonide with verapamil due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A substrate and verapamil is a moderate CYP3A inhibitor.
Tretinoin, ATRA: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
Triamterene: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
Triamterene; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Tucatinib: (Moderate) Avoid coadministration of oral budesonide and tucatinib due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; tucatinib is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold.
Typhoid Vaccine: (Contraindicated) Avoid the administration of live virus vaccines with high-dose corticosteroid therapy and for at least 1 month following treatment. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated live virus vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 1 month after discontinuation. Patients with altered immunocompetence may be at increased risk for severe adverse reactions due to uninhibited growth of the attenuated live virus. Additionally, vaccine efficacy may be diminished in patients receiving any supraphysiologic dose of corticosteroid.
Valsartan; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.
Varicella-Zoster Virus Vaccine, Live: (Contraindicated) Avoid the administration of live virus vaccines with high-dose corticosteroid therapy and for at least 1 month following treatment. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated live virus vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 1 month after discontinuation. Patients with altered immunocompetence may be at increased risk for severe adverse reactions due to uninhibited growth of the attenuated live virus. Additionally, vaccine efficacy may be diminished in patients receiving any supraphysiologic dose of corticosteroid.
Vecuronium: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years.
Vemurafenib: (Moderate) Concomitant use of vemurafenib and budesonide may result in altered concentrations of budesonide and increased concentrations vemurafenib. Vemurafenib is a substrate/inducer of CYP3A4 and a substrate/inhibitor of P-glycoprotein (PGP). Budesonide is a substrate of CYP3A4 and a substrate/inhibitor of PGP. Use caution and monitor patients for toxicity and efficacy.
Verapamil: (Moderate) Avoid coadministration of systemic budesonide with verapamil due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A substrate and verapamil is a moderate CYP3A inhibitor.
Vigabatrin: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Vonoprazan: (Moderate) Monitor for altered response to budesonide in patients receiving vonoprazan with enteric-coated or extended-release formulations of oral budesonide. Enteric-coated budesonide granules (Entocort EC) dissolve at a pH greater than 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and drugs that increase gastric pH levels, such as vonoprazan, can cause these products to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum.
Vonoprazan; Amoxicillin: (Moderate) Monitor for altered response to budesonide in patients receiving vonoprazan with enteric-coated or extended-release formulations of oral budesonide. Enteric-coated budesonide granules (Entocort EC) dissolve at a pH greater than 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and drugs that increase gastric pH levels, such as vonoprazan, can cause these products to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum.
Vonoprazan; Amoxicillin; Clarithromycin: (Moderate) Avoid coadministration of oral budesonide and clarithromycin due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; clarithromycin is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. (Moderate) Monitor for altered response to budesonide in patients receiving vonoprazan with enteric-coated or extended-release formulations of oral budesonide. Enteric-coated budesonide granules (Entocort EC) dissolve at a pH greater than 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and drugs that increase gastric pH levels, such as vonoprazan, can cause these products to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum.
Voriconazole: (Moderate) Monitor for potential adrenal dysfunction with concomitant use of voriconazole and budesonide. In patients taking corticosteroids, voriconazole-associated CYP3A4 inhibition of their metabolism may lead to corticosteroid excess and adrenal suppression. Corticosteroid exposure is likely to be increased. Concomitant oral administration of another strong CYP3A4 inhibitor increased oral budesonide systemic exposure by 8-fold. Voriconazole is a strong CYP3A4 inhibitor, and budesonide is a CYP3A4 substrate.
Vorinostat: (Moderate) Use vorinostat and corticosteroids together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Corticosteroids may cause electrolyte imbalances; hypomagnesemia, hypokalemia, or hypocalcemia and may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Voxelotor: (Moderate) Avoid coadministration of systemic budesonide with voxelotor due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A substrate and voxelotor is a moderate CYP3A inhibitor.
Warfarin: (Moderate) Monitor the INR if warfarin is administered with corticosteroids. The effect of corticosteroids on warfarin is variable. There are reports of enhanced as well as diminished effects of anticoagulants when given concurrently with corticosteroids; however, limited published data exist, and the mechanism of the interaction is not well described. High-dose corticosteroids appear to pose a greater risk for increased anticoagulant effect. In addition, corticosteroids have been associated with a risk of peptic ulcer and gastrointestinal bleeding.
Yellow Fever Vaccine, Live: (Contraindicated) Avoid the administration of live virus vaccines with high-dose corticosteroid therapy and for at least 1 month following treatment. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated live virus vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 1 month after discontinuation. Patients with altered immunocompetence may be at increased risk for severe adverse reactions due to uninhibited growth of the attenuated live virus. Additionally, vaccine efficacy may be diminished in patients receiving any supraphysiologic dose of corticosteroid.
Zafirlukast: (Minor) Zafirlukast inhibits the CYP3A4 isoenzymes and should be used cautiously in patients stabilized on drugs metabolized by CYP3A4, such as corticosteroids.
Zonisamide: (Minor) Zonisamide is a weak inhibitor of P-glycoprotein (P-gp), and budesonide is a substrate of P-gp. There is theoretical potential for zonisamide to affect the pharmacokinetics of drugs that are P-gp substrates. Use caution when starting or stopping zonisamide or changing the zonisamide dosage in patients also receiving drugs which are P-gp substrates.
Glucocorticoids are naturally occurring hormones that prevent or suppress inflammation and immune responses when administered at pharmacological doses. In general, glucocorticoids inhibit the activity of a variety of cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators involved in allergic and nonallergic/irritant-mediated inflammation (e.g., histamine, eicosanoids, leukotrienes, and cytokines). At the molecular level, unbound glucocorticoids readily cross cell membranes and bind with high affinity to specific cytoplasmic receptors. Subsequent to binding, transcription and, ultimately, protein synthesis are affected. The result can include inhibition of leukocyte infiltration at the site of inflammation, interference in the function of mediators of inflammatory response, and suppression of humoral immune responses. The anti-inflammatory actions of corticosteroids are thought to involve phospholipase A2 inhibitory proteins, collectively called lipocortins. Lipocortins, in turn, control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of the precursor molecule arachidonic acid. Some of the net effects include reduction in edema or scar tissue as well as a general suppression in immune response. The numerous adverse effects related to corticosteroid use usually depend on the dose administered and the duration of therapy.
Oral inhaled corticosteroids are believed to reduce the immediate and late-phase allergic responses associated with allergies and chronic bronchial asthma. Proposed mechanisms of action include decreased IgE synthesis, increased number of beta-adrenergic receptors on leukocytes, and decreased arachidonic acid metabolism (which decreases the amount of prostaglandins and leukotrienes released). During an immediate allergic reaction, allergens bridge the IgE antibodies on the surface of mast cells, triggering these cells to release chemotactic substances. Mast cell influx and activation, therefore, is partially responsible for the inflammation and hyperirritability of the oral mucosa. This inflammation can be retarded by administration of adrenocorticoids. Intranasal budesonide provides relief of such symptoms as watery rhinorrhea, nasal congestion, postnasal drip, sneezing, and pharyngeal itching.
Oral budesonide is a controlled-release formulation that delivers drug locally to disease sites in the terminal ileum and ascending colon. The potential for reduced toxicity results from extensive first pass metabolism of budesonide that lowers systemic bioavailability and subsequently, the frequency of corticosteroid adverse reactions.
Oral budesonide, when used to treat primary immunoglobulin A nephropathy (IgAN), can modulate the numbers and activity of mucosal B-cells present in the ileum, including the Peyer's patches, through its anti-inflammatory and immunosuppressive effects at the glucocorticoid receptor. These B-cells express glucocorticoid receptors and are responsible for the production of galactose-deficient IgA1 antibodies (Gd-Ag1) causing IgA nephropathy. It has not been established to what extent oral budesonide's efficacy is mediated via local effects in the ileum versus systemic effects.
The precise mechanism of corticosteroid action on inflammation in eosinophilic esophagitis (EoE) is not known. Corticosteroids have a wide range of inhibitory activities against multiple cell types and mediators involved in allergic inflammation.
Budesonide is administered orally, by nasal inhalation, by oral inhalation, and by nebulization. The volume of distribution is approximately 2 to 4 L/kg. The mean volume of distribution of oral budesonide suspension is 1,886 L. The drug is roughly 85% to 90% bound to plasma proteins. Protein binding is constant over the concentration range (1 to 230 nmol/L or 0.43 to 99 ng/mL). Budesonide shows little or no binding to corticosteroid binding globulin and the drug rapidly equilibrates with red blood cells in a concentration independent manner with a blood/plasma ratio of about 0.8. Limited data show distribution into breast milk of 0.39 and 0.78 nmol/L after dry powder oral inhalational administration of 400 mcg/day or 800 mcg/day, respectively. In vitro data show that metabolism occurs rapidly and primarily via CYP3A4. Oral budesonide has a high plasma clearance, 0.9 to 1.8 L/minute approaching the estimated liver blood flow, suggesting the budesonide is a high hepatic clearance medication. Budesonide undergoes approximately 80% to 90% first-pass metabolism to two inactive metabolites: 16-alpha-hydroxyprednisolone (24%) and 6-beta-hydroxybudesonide (5%). Budesonide is excreted in urine and feces in the form of metabolites. The plasma elimination half-life, after administration of intravenous doses or oral budesonide suspension, ranges between 2 and 3.6 hours. The half-life of oral budesonide delayed release capsules is 5 to 6.8 hours.
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, P-glycoprotein (P-gp)
In vitro data show that metabolism of budesonide occurs primarily by CYP3A4. Inhibitors of CYP3A4 may increase budesonide exposure and, conversely, CYP3A4 inducers may reduce budesonide plasma levels. Budesonide is also a substrate and inhibitor of P-glycoprotein transport.
-Route-Specific Pharmacokinetics
Oral Route
-Delayed-release capsules (Entocort EC): Oral budesonide capsules are an enteric-coated formulation that resists dissolution in acidic gastric contents but dissolves in the duodenum at a pH greater than 5.5. Budesonide is then released from a matrix into the GI lumen in a time-dependent fashion. Tmax varies in individual patients between 30 and 600 minutes, oral absorption averages 65%, and oral administration results in a bioavailability ranging from 9% to 21% both in diseased patients and in healthy subjects, demonstrating a high first-pass elimination of the drug. A high-fat meal has been shown to delay peak concentrations by 2.3 hours with no changes in AUC. The Cmax and AUC were similar when administration (in the fasted state) of a 9 mg intact capsule was compared to opening the capsule and sprinkling the granules on applesauce. Following oral administration of 9 mg PO once daily in patients with active Crohn's disease, the Cmax and AUC were 1.7 +/- 0.9 ng/L and 15.1 +/- 8.5 ng x hour/mL, respectively. Following repeated administration of 3 to 15 mg, budesonide pharmacokinetics were dose-proportional, and no accumulation was observed. In Crohn's disease, the onset of therapeutic effect with oral budesonide typically occurs by week 2 of treatment with peak remission rates at 8 weeks.
-Delayed-release capsules (Tarpeyo): Following single oral administration of budesonide delayed-release capsules 16 mg to healthy subjects, the average geometric mean Cmax (CV%) was 4.4 ng/mL (58.3), and AUC0 to 24 was 24.1 hour x ng/mL (49.7). Medianlag (min, max) was 3.1 hours (0, 6) while median Tmax (min, max) was 5.1 hours (4.5, 10). There was no clinically relevant food effect observed on the overall systemic exposure of budesonide when either a moderate or high fat meal was consumed 1 hour after administration of budesonide delayed-release capsules. Budesonide had a high plasma clearance, 0.9 to 1.8 L/minute in healthy adults, which is close to the estimated liver blood flow, and, accordingly, suggests that budesonide is a high hepatic clearance drug. Following single oral administration of budesonide delayed-release capsules 16 mg to healthy subjects, the elimination half-life for ranged from 5 to 6.8 hours.
-Extended-release capsules (Ortikus): Following oral administration, Tmax varied in individual patients between 2.5 to 8 hours. Mean oral bioavailability in patients and healthy subjects was 9% to 21%, which demonstrates a high first-pass elimination of budesonide. No accumulation occurred following and the pharmacokinetics were dose-proportional with repeated administration of 3 mg to 15 mg of budesonide. Oral administration of extended-release budesonide 9 mg once daily for 5 days resulted in a Cmax and AUC of 5.3 +/- 1.8 nmol/L and 37 +/- 14.6 nmol x hour/L, respectively, in healthy subjects compared to 4 +/- 2.1 nmol/L and 35 +/- 19.8 nmol x hour/L, respectively, in Crohn's disease patients. Concomitant administration of a high fat meal and extended-release budesonide delayed Tmax by 1 hour and increased overall exposure by 25%.
-Extended-release tablets (Uceris): Pharmacokinetic parameters vary per individual with an average Cmax, Tmax, and AUC of roughly 1.35 ng/mL, 13.3 hours, and 16.43 ng x hour/mL, respectively after oral administration. No accumulation was observed following seven days of 9 mg PO once daily dosing. A high-fat meal decreases budesonide Cmax, but does not affect AUC; an absorption lag time of 2.4 hours is observed under fed conditions. Once absorbed, distribution of budesonide is extensive, and protein binding is 85% to 90%.
-Oral budesonide suspension (Eohilia): After repeated twice daily administration of oral budesonide suspension in adult patients with eosinophilic esophagitis (EoE) the Cmax, Tmax, and AUC were 915 pg/mL, 2 hours (range 0.5 to 4 hours), and 5,071 pg x hour/mL. The systemic exposure of budesonide increased proportionally as the dose was increased (dose range 0.5 to 2 mg). The oral bioavailability of oral budesonide suspension is 14% under fasting state. A high fat, high calorie meal (800 to 1,000 calories, 50% fat) increased the AUC of budesonide by 26%, decreased the Cmax by 13%, and delayed the time to peak concentration by 1 hour. The increase in systemic exposure is not expected to be clinically meaningful.
Inhalation Route
-Powder for Oral Inhalation Administration (Pulmicort Flexhaler): The absolute bioavailability of orally inhaled budesonide powder is 39%. Peak steady state plasma concentrations are achieved at approximately 10 minutes post-dose and averaged 0.6 and 1.6 nmol/L at doses of 180 mcg once daily and 360 mcg twice daily, respectively.
-Nebulized Administration (Pulmicort Respules): In asthmatic children 4 to 6 years of age, the total absolute bioavailability of budesonide suspension via jet nebulizer was approximately 6% of the labeled dose. Peak steady state plasma concentrations occur at approximately 20 minutes post-dose in children.
Other Route(s)
Intranasal Route
Intranasal Administration (Rhinocort Aqua): Compared to budesonide administered intravenously, approximately 34% of an intranasal dose reaches the systemic circulation via the nasal mucosa. After nasal administration of a single dose (128 mcg), the mean peak plasma concentration of approximately 0.3 nmol/L occurs about 0.5 hours post-dose.
Rectal Route
In a population pharmacokinetic analysis in patients with distal ulcerative colitis, the estimated exposure (AUC) following administration of budesonide rectal foam (Uceris) 2 mg rectally twice daily was 4.31 ng x hour/mL with a CV of 64% in the target patient population.
-Special Populations
Hepatic Impairment
Reduced liver function may affect the elimination of corticosteroids. Systemic exposure of orally administered budesonide increases up to 3.5-fold in patients with moderate liver impairment or with hepatic cirrhosis compared to healthy controls while patients with mild hepatic impairment had an approximately 1.4 fold-higher AUC. The Cmax values demonstrated similar increases. Patients with mild liver disease appear to be minimally affected.
Renal Impairment
Patients with severe renal disease have not been evaluated. Intact budesonide is not excreted renally. Although budesonide metabolites are renally excreted (60%), their activity is negligible. An enhanced risk of adverse effects in renally compromised patients is not expected.
Pediatrics
Some differences have been noted between budesonide pharmacokinetics in pediatric and adult patients; these differences vary by dosage formulation. The plasma half-life may be slightly shorter in pediatric patients aged 10 to 14 years (1.5 hours) versus adult patients (2 hours) after receiving intravenous budesonide.
-Nasal Administration: After nasal administration, plasma concentrations of budesonide in children are approximately twice those in adults; however, time to Cmax and plasma half-life are similar between the populations.
-Nebulizer Administration: Systemic exposure, as measured by AUC and Cmax, is similar for young children and adults after inhalation of the same dose of budesonide suspension via nebulizer.
-Oral Inhalation Administration: Absolute bioavailability of oral inhaled budesonide appears to be similar in children as compared to adults.
-Oral Administration: In patients aged 9 to 14 years (n = 8) receiving oral budesonide delayed-release capsules (Entocort EC) 9 mg once daily for 7 days, the Tmax and Cmax were 5 hours and 2.58 +/- 1.51 ng/mL, respectively. The mean AUC was 17.78 +/- 5.25 ng x hour/mL which was 17% higher than in adult patients with Crohn's disease in the same study. The mean absolute oral availability was 9.2% (3% to 17%; n = 4).
-Oral budesonide suspension: In patients age 11 to 17 years receiving oral budesonide suspension 2mg twice daily, the Tmax, Cmax, and AUC were 1 hour (range 0.5 to 2 hours), 946 pg/mL, and 3,849 pg x hour/mL. Based on population pharmacokinetic analysis, the steady state exposure following oral budesonide suspension 2mg twice daily is comparable between pediatric patients (age 11 to 17 years) and adults.
Geriatric
The pharmacokinetic parameters of budesonide in geriatric patients have not been assessed. No differences in safety or efficacy due to age have been identified.
Gender Differences
No differences in pharmacokinetics of budesonide due to gender have been identified.
Ethnic Differences
No differences in pharmacokinetics of budesonide due to race have been identified.