Azelastine; fluticasone is a combination of an antihistamine (H1-blocker) and a corticosteroid administered by nasal inhalation for treating the symptoms of seasonal allergic rhinitis in adult and pediatric patients 6 years of age and older. Clinical trials compared azelastine; fluticasone combination therapy to monotherapy with azelastine nasal spray, monotherapy with fluticasone nasal spray, or placebo. Combination treatment demonstrated a statistically significant greater decrease in the reflective nasal symptom score compared with the single agents alone or placebo. Rhinitis guidelines suggest that clinicians consider the combination of an intranasal corticosteroid/antihistamine combination for those patients with moderate/severe seasonal or perennial allergic rhinitis that is resistant to pharmacologic monotherapy, and the combination may be considered for initial treatment of moderate/severe nasal symptoms of seasonal allergic rhinitis in patients more than 12 years of age.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Inhalation Administration
Intranasal Inhalation Administration
-Shake the bottle gently prior to each use.
-Before using for the first time the unit must be primed. Pointed away from the body and away from others, pump the spray 6 times or until fine mist appears. If the unit has not been used for 14 days, re-prime with 1 spray or until a fine mist appears.
-Instruct patient on the proper use of nasal spray.
-After administration, wipe the tip of the spray bottle with a clean tissue. Replace the cap.
Fluticasone has a relatively low risk of hypothalamic-pituitary-adrenal (HPA) suppression when used intranasally at recommended doses. Pharmacologic doses of fluticasone administered for prolonged periods can, however, result in adrenocortical insufficiency. After chronic or prolonged use, the dose of azelastine; fluticasone should be reduced slowly. Adrenal suppression and increased intracranial pressure have been reported with the use and/or withdrawal of intranasal steroids in pediatric patients. Patients who experience HPA suppression will require increased doses of corticosteroid therapy during periods of excessive stress. To minimize the effects of inhaled corticosteroids, each patient should be titrated to the lowest effective dose.
Monitor the growth of pediatric patients receiving intranasal corticosteroids, including azelastine; fluticasone nasal spray. Growth inhibition has been observed in some children after therapy with high-dose fluticasone inhalations. 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. The long-term effects of this reduction in growth velocity associated with intranasal corticosteroids, including the impact on final adult height, are unknown. The potential for "catch-up" growth following discontinuation of treatment with intranasal corticosteroids has not been adequately studied. Consider the potential growth effects of prolonged treatment versus the clinical benefits obtained and the risks/benefits of treatment alternatives.
Infection is possible in patients receiving intranasal corticosteroid therapy. In a 12-month safety trial comparing azelastine; fluticasone nasal spray with fluticasone propionate nasal spray in adolescents and adults, the most frequently reported adverse reactions (>= 2%) with azelastine; fluticasone nasal spray were fever, cough, nasal congestion, and rhinitis, upper respiratory tract infection, and pharyngitis. In pediatric patients 6-11 years of age, oropharyngeal pain, cough, fever, otitis media, otitis externa, and upper respiratory tract infection were among the most frequently reported reactions (>= 2%). Secondary bacterial, viral (>= 2%), and fungal infections have been observed during treatment with inhaled fluticasone. Local immunosuppression associated with intranasal fluticasone use may be manifested as an overgrowth of fungus in the nose and throat; in clinical trials with fluticasone propionate administered intranasally, the development of candidiasis of the nose and pharynx has occurred. In addition, adverse events affecting the respiratory tract have been experienced by recipients of fluticasone therapy. The most commonly reported respiratory adverse events with fluticasone nasal spray included cough (3.6-3.8%), rhinitis (1-13%), pharyngitis (6-7.8%), and bronchitis (1-3%). Respiratory adverse effects also occurred with azelastine nasal spray and included rhinitis (>= 2%) and pharyngitis (>= 2%). The following adverse reactions have been observed in < 2% of patients receiving azelastine nasal spray in clinical trials but more frequently than placebo: nasal congestion, nasopharyngitis, post nasal drip, sinusitis, bronchitis, pharyngolaryngeal pain, dry throat, paranasal sinus hypersecretion, and toothache (dental pain). Patients using azelastine; fluticasone nasal spray for several months or longer should be examined periodically for candida infection or other signs of adverse effects on the nasal mucosa.
Somnolence (drowsiness) has been reported in < 1% of 853 patients >= 12 years of age taking azelastine; fluticasone nasal spray. In adolescent and adult clinical trials comparing azelastine; fluticasone nasal spray to monotherapy with azelastine nasal spray or fluticasone nasal spray, or placebo, headache (2%) and pain were reported in a similar number of patients as those taking azelastine nasal spray. In pediatric patients 6-11 years of age, headache (>= 2%) was one of the most frequently reported adverse reactions; very rarely, drowsiness was reported. Adverse reactions associated with azelastine nasal spray formulations that occurred in >= 2% of patients and more frequently than placebo include headache, somnolence (drowsiness) (2-11.5%), myalgia, fatigue, dizziness, and weight gain. In clinical trials, rheumatoid arthritis has been observed in < 2% of patients receiving azelastine nasal spray, but more frequently than placebo. Nervousness, tolerance, confusion, involuntary muscle contractions, aches and pains, paresthesias, and urinary retention have been reported during the post-marketing of the combination product or one of its components.
Nasal and inhaled corticosteroid therapy, like fluticasone, has been associated with the development of cataracts, increased intraocular pressure or ocular hypertension, and glaucoma in adults. Patients should inform his/her health care provider if a change in vision is noted while using azelastine; fluticasone nasal spray. In a 12-month controlled study, 405 adolescent and adult patients receiving azelastine; fluticasone nasal spray and 207 patients receiving fluticasone propionate nasal spray for perennial allergic or vasomotor rhinitis (VMR) were evaluated for the development of glaucoma and cataracts. In the azelastine; fluticasone nasal spray group, one patient had increased intraocular pressure at month 6. In addition, three patients had evidence of posterior subcapsular cataract at month 6 and one at the end of treatment. In the fluticasone propionate group, three patients had evidence of posterior subcapsular cataract at the end of treatment. Blurred vision, cataracts, conjunctivitis, ocular irritation, eye swelling or ocular inflammation, glaucoma or increased intraocular pressure or ocular hypertension, visual impairment, and xerophthalmia (ocular dryness or dry eyes) have been reported during post-marketing use of the combination product or one of its components. Patients with a change in vision or a history of increased intraocular pressure, glaucoma, or cataracts should be closely monitored during corticosteroid therapy.
Hypersensitivity reactions can rarely occur in patients receiving azelastine; fluticasone nasal spray. Urticaria (>= 2%) was one of the most frequently reported reactions in pediatric patients 6-11 years of age during clinical trials. Anaphylaxis/anaphylactoid reactions which in rare instances were severe have been reported during post-marketing use of azelastine; fluticasone or one of its individual components. Angioedema, facial edema, tongue edema, dyspnea, bronchospasm, wheezing, erythema, face swelling, pruritus, rash (unspecified), and urticaria have also been reported. Nocturnal dyspnea has been observed in < 2% of patients receiving azelastine nasal spray in clinical trials, but more frequently than placebo. Asthma exacerbation (3.3-7.2%) was reported in patients receiving fluticasone nasal spray.
Cardiovascular effects may occur in patients receiving azelastine; fluticasone nasal spray. Atrial fibrillation, sinus tachycardia, palpitations, chest pain (unspecified), and hypertension have been reported with post-marketing use of azelastine; fluticasone or one of its individual components.
Although not specifically reported in patients receiving azelastine; fluticasone nasal spray, nasal ulceration, nasal septal perforation, and impaired wound healing have been reported in patients receiving intranasal corticosteroids. Nasal septum perforation is a rare, but severe complication of intranasal steroids. Epistaxis (>= 2%) has been reported in patients receiving azelastine; fluticasone nasal spray; in adolescent and adult trials, 2% of the cases were mild and < 1% were moderate. In pediatric patients 6-11 years of age, 9% of patients had mild and 1% had moderate epistaxis. No patients in either group had reports of severe epistaxis. In clinical trials comparing azelastine; fluticasone nasal spray to monotherapy with azelastine nasal spray or fluticasone nasal spray, or placebo, dysgeusia (4%) was reported in a similar number of patients as those taking azelastine nasal spray. Adverse events that have been experienced by recipients of fluticasone nasal spray include: bloody nasal secretions (1-3%), dysphonia (2-19%), epistaxis (6-6.9%), hoarseness (2-9%), nasal burning/nasal irritation (2.4-3.2%), nasal excoriation or ulcer (1%), pharyngolaryngeal pain (> 3%), rhinorrhea (1-3%), ageusia or loss of taste, xerostomia, anosmia or loss of smell, nasal discomfort, nasal dryness, nasal septum perforation, nasal soreness, and rhinalgia. Application site irritation, dysphonia, hoarseness, nasal septal perforation, nasal discomfort, nasal dryness, nasal irritation, nasal sores, nasal ulcer, sore throat, throat irritation and dryness, voice changes, parosmia, and disturbance (dysosmia) or loss of sense of smell (anosmia) and/or taste have been reported during post-marketing use of azelastine; fluticasone or one of its individual components. Adverse reactions associated with azelastine nasal spray formulations that occurred in >= 2% of patients and more frequently than placebo include: bitter taste (dysgeusia) (8-10%), nasal irritation, xerostomia, paroxysmal sneezing, and epistaxis. The severity of these events was generally mild. Skin laceration and nasal dryness were observed in < 2% of patients receiving azelastine nasal spray in clinical trials but more frequently than placebo.
Prolonged and high doses of inhaled corticosteroids, such as fluticasone (especially when used in combination with frequent courses of systemic corticosteroids), may be associated with reduced bone mineral density. Further, decreases in bone mineral density have been reported in patients receiving long-term therapy with inhaled corticosteroids. This may in turn result in the development of osteopenia or osteoporosis. Due to a low systemic absorption after appropriate use, adverse effects on bone are not expected with nasal azelastine; fluticasone therapy.
In rare cases, patients taking products that contain inhaled fluticasone propionate, such as azelastine; fluticasone nasal spray, 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 fluticasone therapy. Patients 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 fluticasone has not yet been established, however, consistent with findings in clinical trails, systemic eosinophilic conditions have been reported in rare cases in patients on inhaled fluticasone propionate in post-marketing reports.
In a 12-month adolescent and adult safety trial comparing azelastine; fluticasone nasal spray with fluticasone propionate nasal spray, diarrhea (>= 2%) was one of the most frequently reported gastrointestinal adverse reactions with azelastine; fluticasone nasal spray. In pediatric patients 6-11 years of age, nausea, vomiting, diarrhea, and upper abdominal pain were among the most frequently reported adverse reactions (>= 2%). Diarrhea (1-3%) and abdominal pain (1-3%) have been reported in patients receiving fluticasone nasal spray. In clinical trials with azelastine nasal spray, diarrhea (< 2%) and nausea (>= 2%) sometimes associated with vomiting, were reported in patients more frequently than placebo.
Azelastine; fluticasone nasal spray may cause sedation, and patients should be advised to avoid driving or operating machinery until they know how this product will affect them. In addition, patients should be informed that alcohol consumption may intensify the sedative effects of the drug.
As with any long-term topical treatment of the nasal cavity, patients using azelastine; fluticasone intranasally over several months or longer should be examined periodically for possible changes in the nasal mucosa. Further, because of the inhibitory effect of corticosteroids on wound healing, patients who have experienced recent nasal septal perforation or ulcer, nasal surgery, or nasal trauma should not use a nasal corticosteroid until healing has occurred.
Care should be taken to avoid ocular exposure and use around the eyes as cases of visual impairment and ocular hypertension have been reported with topical corticosteroids. Ophthalmic administration of topical corticosteroids should be avoided. Glaucoma and/or cataracts have occurred during use of nasal and inhaled corticosteroids. In a 12-month controlled study, 405 patients receiving azelastine; fluticasone nasal spray and 207 patients receiving fluticasone propionate nasal spray for perennial allergic or vasomotor rhinitis (VMR) were evaluated for the development of glaucoma and cataracts. In the azelastine; fluticasone nasal spray group, one patient had increased intraocular pressure at month 6. In addition, three patients had evidence of posterior subcapsular cataract at month 6 and one at the end of treatment. In the fluticasone propionate group, three patients had evidence of posterior subcapsular cataract at the end of treatment. Patients with a change in vision or a history of increased intraocular pressure, glaucoma, or cataracts should be closely monitored during corticosteroid therapy.
Although patients receiving systemic corticosteroid therapy are more susceptible to secondary infection than patients not receiving corticosteroids, administration via the nasal inhalation route minimizes this risk. The incidence or course of acute bacterial or viral infection is probably minimally affected by inhaled corticosteroids in immunocompetent individuals; however, close monitoring of patients with immunosuppression is recommended if treatment with an inhaled corticosteroid is necessary. Chickenpox (varicella) and measles, for example, can have a more serious or even fatal course in susceptible pediatric or adult patients using corticosteroids. In children or adults who have not had these diseases or been properly immunized, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affect the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (See the respective package inserts for complete VZIG and IG prescribing information.) If chickenpox develops, treatment with antiviral agents may be considered. Corticosteroids should be used with caution, if at all, in patients with an active or quiescent tuberculosis infection of the respiratory tract; untreated local or systemic fungal infection or bacterial infections; systemic viral infection or parasitic infections; or ocular herpes simplex because of the potential for worsening of these infections.
Hypothalamic-pituitary-adrenal (HPA) suppression can occur when intranasal steroids are used at higher than recommended dosages or when recommended dosages are used in susceptible individuals. If HPA suppression occurs, the dosage of azelastine; fluticasone nasal spray should be discontinued slowly, in accordance with accepted procedures for discontinuing oral corticosteroid therapy. Coadministration of intranasal corticosteroids with other inhaled corticosteroids could increase the risk of HPA suppression. Substitution of a topical corticosteroid for systemic corticosteroid can produce withdrawal symptoms (e.g., joint and/or muscular pain, lassitude, and depression) and signs of adrenal insufficiency. Monitor for these signs and symptoms in patients who are switched from a long-term systemic corticosteroid therapy to topical corticosteroids. Patients who require long-term systemic corticosteroid therapy may experience a severe exacerbation of their symptoms from decreasing systemic corticosteroid treatment too rapidly.
Azelastine; fluticasone is not approved for use in neonates, infants, and children less than 6 years of age. Growth inhibition has been observed in some pediatric patients (all ages) following therapy with high-dose fluticasone propionate inhalations. The effect of fluticasone on final adult height is not known. Children and adolescents receiving azelastine; fluticasone nasal spray should be routinely monitored for possible adverse effects on growth patterns. The potential for growth effects should be weighed against the clinical benefit obtained and the availability of other treatment alternatives. Pediatric patients may be more susceptible to developing systemic toxicity; adrenal suppression and increased intracranial pressure have been reported with the use and/or discontinuation of intranasal steroids in pediatric patients.
Limited data from postmarketing experience over decades of use with azelastine and fluticasone in pregnant women have not identified any drug associated risks of miscarriage, birth defects, or other adverse maternal or fetal outcomes. Azelastine; fluticasone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Azelastine and fluticasone have been shown to be teratogenic and developmentally toxic in animal studies of mice, rats and/or rabbits. In general, corticosteroids do cross the placenta, and animal studies have shown some teratogenic effects with subdermal or systemic exposure. Hypoadrenalism may occur in infants following maternal exposure to corticosteroids during pregnancy. Because there is a natural increase in corticosteroid production during pregnancy, most women require lower doses of corticosteroids and many will not need corticosteroid treatment during pregnancy.
Azelastine; fluticasone may be used during breast-feeding. While data on the presence of azelastine; fluticasone combination products in human milk, the effects on the breast-feeding infant, or the effects on milk production following use of the medication are limited, fluticasone propionate concentrations in plasma after intranasal therapeutic doses are low and therefore human breast milk concentrations are likely to be correspondingly low during breast-feeding. Other corticosteroids have been detected in human milk, and an infant of a lactating woman treated with azelastine; fluticasone should be monitored for possible signs of breast-milk rejection related to the bitter taste of azelastine.
Use caution in using azelastine; fluticasone in anyone reporting hypersensitivity to the medications or any other components of the product. Although true corticosteroid hypersensitivity is rare, patients who have demonstrated a prior hypersensitivity reaction to fluticasone should not receive any form of fluticasone. 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.
Detrimental effects on bone metabolism, such as osteoporosis are expected to be much lower with inhaled, rather than systemically administered corticosteroids. Some patients receiving inhaled steroids may be at increased risk of bone loss compared to healthy individuals. The effect of azelastine; fluticasone nasal spray on osteoporosis is not known; therefore, it should be used cautiously in patients with osteoporosis despite the low systemic bioavailability.
For the management of symptoms of seasonal allergies, including seasonal allergic rhinitis:
Nasal dosage (nasal spray suspension; e.g., Dymista):
Adults: 1 spray per nostril twice daily. Each actuation contains 137 mcg of azelastine and 50 mcg of fluticasone.
Children and Adolescents 6 years and older: 1 spray per nostril twice daily. Each actuation contains 137 mcg of azelastine and 50 mcg of fluticasone.
Maximum Dosage Limits:
-Adults
2 sprays/day per nostril.
-Geriatric
2 sprays/day per nostril.
-Adolescents
2 sprays/day per nostril.
-Children
>= 6 years: 2 sprays/day per nostril.
< 6 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
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: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression. (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; Caffeine; Dihydrocodeine: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Acetaminophen; Caffeine; Pyrilamine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
Acetaminophen; Chlorpheniramine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression. (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; Dextromethorphan; Pseudoephedrine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression. (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; Codeine: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking azelastine. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Acetaminophen; Dextromethorphan; Doxylamine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
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; Diphenhydramine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
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; Hydrocodone: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking azelastine. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
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; Oxycodone: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Acetaminophen; Pamabrom; Pyrilamine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
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.
Acrivastine; Pseudoephedrine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
Adagrasib: (Major) Coadministration of inhaled fluticasone propionate and adagrasib is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A substrate; adagrasib is a strong CYP3A inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
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.
Alfentanil: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
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.
Alprazolam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and benzodiazepines. Concurrent use may result in additive CNS depression.
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.
Amitriptyline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and tricyclic antidepressants. Concurrent use may result in additive CNS depression.
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.
Amobarbital: (Moderate) An enhanced CNS depressant effect may occur when azelastine, an antihistamine, is combined with CNS depressants including the barbiturates.
Amoxapine: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including amoxapine.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Coadministration of inhaled fluticasone propionate and clarithromycin is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; clarithromycin is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Amphotericin B lipid complex (ABLC): (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Amphotericin B liposomal (LAmB): (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
Amphotericin B: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
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.
Anxiolytics; Sedatives; and Hypnotics: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with CNS depressants including anxiolytics, sedatives, and hypnotics.
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) An enhanced CNS depressant effect may occur when azelastine, an antihistamine, is combined with CNS depressants including the barbiturates. (Moderate) Coadministration may result in decreased exposure to fluticasone. Butalbital is a CYP3A4 inducer; fluticasone is a CYP3A4 substrate. Monitor for decreased response to fluticasone 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 excessive sedation and somnolence during coadministration of azelastine and skeletal muscle relaxants. Concurrent use may result in additive CNS depression. (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: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking azelastine. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and skeletal muscle relaxants. Concurrent use may result in additive CNS depression. (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: (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.
Aspirin, ASA; Oxycodone: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (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: (Major) Coadministration of inhaled fluticasone propionate and atazanavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Atazanavir; Cobicistat: (Major) Coadministration of inhaled fluticasone propionate and atazanavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate. (Major) Coadministration of inhaled fluticasone propionate and cobicistat is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
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.
Atropine; Difenoxin: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including opiate agonists. A dose reduction of one or both drugs may be warranted.
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.
Baclofen: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and skeletal muscle relaxants. Concurrent use may result in additive CNS depression.
Barbiturates: (Moderate) An enhanced CNS depressant effect may occur when azelastine, an antihistamine, is combined with CNS depressants including the barbiturates.
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.
Belladonna; Opium: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
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.
Benzhydrocodone; Acetaminophen: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Benzodiazepines: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and benzodiazepines. Concurrent use may result in additive CNS depression.
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.
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.
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: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
Brompheniramine; Dextromethorphan; Phenylephrine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression. (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: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression. (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; Pseudoephedrine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
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.
Buspirone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and buspirone. Concurrent use may result in additive CNS depression.
Butalbital; Acetaminophen: (Moderate) An enhanced CNS depressant effect may occur when azelastine, an antihistamine, is combined with CNS depressants including the barbiturates. (Moderate) Coadministration may result in decreased exposure to fluticasone. Butalbital is a CYP3A4 inducer; fluticasone is a CYP3A4 substrate. Monitor for decreased response to fluticasone during concurrent use.
Butalbital; Acetaminophen; Caffeine: (Moderate) An enhanced CNS depressant effect may occur when azelastine, an antihistamine, is combined with CNS depressants including the barbiturates. (Moderate) Coadministration may result in decreased exposure to fluticasone. Butalbital is a CYP3A4 inducer; fluticasone is a CYP3A4 substrate. Monitor for decreased response to fluticasone during concurrent use.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking azelastine. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) An enhanced CNS depressant effect may occur when azelastine, an antihistamine, is combined with CNS depressants including the barbiturates. (Moderate) Coadministration may result in decreased exposure to fluticasone. Butalbital is a CYP3A4 inducer; fluticasone is a CYP3A4 substrate. Monitor for decreased response to fluticasone during concurrent use.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking azelastine. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) An enhanced CNS depressant effect may occur when azelastine, an antihistamine, is combined with CNS depressants including the barbiturates. (Moderate) Coadministration may result in decreased exposure to fluticasone. Butalbital is a CYP3A4 inducer; fluticasone is a CYP3A4 substrate. Monitor for decreased response to fluticasone 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.
Butorphanol: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including butorphanol.
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.
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.
Cannabidiol: (Major) Avoid concomitant use of cannabidiol with azelastine nasal solution. Concomitant use may cause somnolence, reductions in mental alertness, or additional CNS impairment. Educate patients about the signs and symptoms of CNS depression.
Capsaicin; Metaxalone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and skeletal muscle relaxants. Concurrent use may result in additive CNS depression.
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.
Carbamazepine: (Moderate) Hepatic microsomal enzyme inducers, including carbamazepine, can increase the metabolism of fluticasone. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with fluticasone.
Carbidopa; Levodopa; Entacapone: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including COMT inhibitors. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Carbinoxamine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
Carisoprodol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and skeletal muscle relaxants. Concurrent use may result in additive CNS depression.
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.
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: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and azelastine. Concurrent use may result in additive CNS depression.
Ceritinib: (Major) Coadministration of inhaled fluticasone propionate and ceritinib is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Chlophedianol; Dexbrompheniramine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
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.
Chloramphenicol: (Major) Coadministration of inhaled fluticasone propionate and chloramphenicol is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Chlorcyclizine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
Chlordiazepoxide: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and benzodiazepines. Concurrent use may result in additive CNS depression.
Chlordiazepoxide; Amitriptyline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and benzodiazepines. Concurrent use may result in additive CNS depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and tricyclic antidepressants. Concurrent use may result in additive CNS depression.
Chlordiazepoxide; Clidinium: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and benzodiazepines. Concurrent use may result in additive CNS depression.
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: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
Chlorpheniramine; Codeine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression. (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking azelastine. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Chlorpheniramine; Dextromethorphan: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression. (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; Dextromethorphan; Pseudoephedrine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
Chlorpheniramine; Hydrocodone: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression. (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking azelastine. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression. (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Chlorpheniramine; Phenylephrine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression. (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; Pseudoephedrine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
Chlorpromazine: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including phenothiazines.
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.
Chlorzoxazone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and skeletal muscle relaxants. Concurrent use may result in additive CNS depression.
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: (Minor) The mean Cmax and AUC of azelastine may be increased when coadministered with cimetidine. Theoretically, systemic exposure of nasally administered azelastine may be increased by coadministration with cimetidine, although an interaction has not been documented.
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: (Major) Coadministration of inhaled fluticasone propionate and clarithromycin is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; clarithromycin is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Clemastine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
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.
Clomipramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and tricyclic antidepressants. Concurrent use may result in additive CNS depression.
Clonazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and benzodiazepines. Concurrent use may result in additive CNS depression.
Clorazepate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and benzodiazepines. Concurrent use may result in additive CNS depression.
Cobicistat: (Major) Coadministration of inhaled fluticasone propionate and cobicistat is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Codeine: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking azelastine. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Codeine; Guaifenesin: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking azelastine. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Codeine; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking azelastine. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking azelastine. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and promethazine. Concurrent use may result in additive CNS depression. (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.
Codeine; Promethazine: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking azelastine. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and promethazine. Concurrent use may result in additive CNS depression.
COMT inhibitors: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including COMT inhibitors. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
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.
Cyclobenzaprine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and skeletal muscle relaxants. Concurrent use may result in additive CNS depression.
Cyproheptadine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
Dantrolene: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and skeletal muscle relaxants. Concurrent use may result in additive CNS depression.
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: (Major) Coadministration of inhaled fluticasone propionate and darunavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; darunavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Darunavir; Cobicistat: (Major) Coadministration of inhaled fluticasone propionate and cobicistat is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate. (Major) Coadministration of inhaled fluticasone propionate and darunavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; darunavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Coadministration of inhaled fluticasone propionate and cobicistat is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate. (Major) Coadministration of inhaled fluticasone propionate and darunavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; darunavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
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.
Delavirdine: (Major) Coadministration of inhaled fluticasone propionate and delavirdine is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; delavirdine is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
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.
Desipramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and tricyclic antidepressants. Concurrent use may result in additive CNS depression.
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.
Deutetrabenazine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as azelastine, may have additive effects and worsen drowsiness or sedation.
Dexbrompheniramine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
Dexbrompheniramine; Pseudoephedrine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
Dexchlorpheniramine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
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: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression. (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.
Diazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and benzodiazepines. Concurrent use may result in additive CNS depression.
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.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
Diflunisal: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Dimenhydrinate: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
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: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
Diphenhydramine; Ibuprofen: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression. (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Diphenhydramine; Naproxen: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression. (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Diphenhydramine; Phenylephrine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression. (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.
Diphenoxylate; Atropine: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including opiate agonists. A dose reduction of one or both drugs may be warranted.
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.
Doxepin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and tricyclic antidepressants. Concurrent use may result in additive CNS depression.
Doxylamine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
Doxylamine; Pyridoxine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
Droperidol: (Major) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including droperidol. Following administration of droperidol, lower doses of the other CNS depressant should be used. (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.
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: (Moderate) Administering fluticasone with elbasvir; grazoprevir may result in elevated fluticasone plasma concentrations. Fluticasone is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Coadministration of inhaled fluticasone propionate and cobicistat is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of inhaled fluticasone propionate and cobicistat is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
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.
Entacapone: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including COMT inhibitors. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
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.
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: (Minor) Coadministration of orally administered azelastine (4 mg twice daily) with erythromycin (500 mg three times daily for 7 days) resulted in a slightly lower Cmax and a slightly higher AUC for azelastine compared to azelastine alone. The clinical relevance is unknown.
Esketamine: (Major) Closely monitor patients receiving esketamine and azelastine for sedation and other CNS depressant effects. Instruct patients who receive a dose of esketamine not to drive or engage in other activities requiring alertness until the next day after a restful sleep.
Estazolam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and benzodiazepines. Concurrent use may result in additive CNS depression.
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.
Eszopiclone: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with CNS depressants including anxiolytics, sedatives, and hypnotics.
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.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
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.
Etomidate: (Minor) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including general anesthetics.
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.
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.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and azelastine. Concurrent use may result in additive CNS depression.
Fenoprofen: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Fentanyl: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
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.
Fluphenazine: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including phenothiazines.
Flurazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and benzodiazepines. Concurrent use may result in additive CNS depression.
Flurbiprofen: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
Fosamprenavir: (Major) Coadministration of inhaled fluticasone propionate and fosamprenavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; fosamprenavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
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.
Fosphenytoin: (Moderate) Monitor for decreased corticosteroid efficacy if fluticasone is used with fosphenytoin; a dosage increase may be necessary. Concurrent use may decrease the exposure of fluticasone.
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.
Gabapentin: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and azelastine. Concomitant use of gabapentin with azelastine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
General anesthetics: (Minor) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including general anesthetics.
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) Instruct patients using inhaled fluticasone propionate products to avoid grapefruit juice. Patients using fluticasone furoate products should be aware of the potential for increased adverse effects if they regularly consume grapefruit juice. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; grapefruit juice is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
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.
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.
Homatropine; Hydrocodone: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking azelastine. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
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: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking azelastine. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Hydrocodone; Ibuprofen: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking azelastine. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Hydromorphone: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
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.
Hydroxyzine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
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.
Ibuprofen; Oxycodone: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (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) Coadministration of inhaled fluticasone propionate and idelalisib is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Imipramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and tricyclic antidepressants. Concurrent use may result in additive CNS depression.
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: (Major) Coadministration of inhaled fluticasone propionate and indinavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; indinavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
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.
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.
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.
Isoflurane: (Minor) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including general anesthetics.
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: (Major) Coadministration of inhaled fluticasone propionate and itraconazole is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; itraconazole is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Ketamine: (Minor) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including general anesthetics.
Ketoconazole: (Major) Coadministration of inhaled fluticasone propionate and ketoconazole is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; ketoconazole is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with ketoconazole increased plasma fluticasone exposure by 1.9-fold with a 45% decrease in plasma cortisol AUC, but had no effect on urinary excretion of cortisol. Ketoconazole increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate. (Minor) Theoretically, systemic exposure of nasally administered azelastine may be increased by coadministration with ketoconazole, although an interaction has not been documented.
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; Amoxicillin; Clarithromycin: (Major) Coadministration of inhaled fluticasone propionate and clarithromycin is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; clarithromycin is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and azelastine. Dosage adjustments of lemborexant and azelastine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Letermovir: (Moderate) A clinically relevant increase in the plasma concentration of fluticasone may occur if given with letermovir. In patients who are also receiving treatment with cyclosporine, the magnitude of this interaction may be amplified. Concurrent use of all 3 drugs together is not recommended because increased systemic corticosteroid adverse events may develop. Fluticasone is a CYP3A4 substrate. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates is similar to a strong CYP3A4 inhibitor. In a drug interaction study, use of fluticasone with another strong CYP3A4 inhibitor resulted in a 1.9-fold increase in plasma fluticasone exposure and a 45% decrease in plasma cortisol exposure, but had no effect on urinary excretion of cortisol.
Levoketoconazole: (Major) Coadministration of inhaled fluticasone propionate and ketoconazole is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; ketoconazole is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with ketoconazole increased plasma fluticasone exposure by 1.9-fold with a 45% decrease in plasma cortisol AUC, but had no effect on urinary excretion of cortisol. Ketoconazole increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate. (Minor) Theoretically, systemic exposure of nasally administered azelastine may be increased by coadministration with ketoconazole, although an interaction has not been documented.
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.
Levorphanol: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Reduce the initial dose of levorphanol by approximately 50% or more. Educate patients about the risks and symptoms of excessive CNS depression.
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.
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.
Lofexidine: (Moderate) Monitor for additive sedation during coadministration of lofexidine and azelastine. Lofexidine can potentiate the effects of CNS depressants. Patients should be advised to avoid driving or performing any other tasks requiring mental alertness until the effects of the combination are known.
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: (Major) Coadministration of inhaled fluticasone propionate and lonafarnib is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; lonafarnib is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
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) Coadministration of inhaled fluticasone propionate and ritonavir is not recommended; use caution with inhaled fluticasone furoate. During post-marketing use, there have been reports of clinically significant drug interactions in patients receiving inhaled fluticasone propionate with ritonavir, resulting in systemic corticosteroid effects including Cushing's syndrome and adrenal suppression. Fluticasone is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with ritonavir increased plasma fluticasone propionate exposure resulting in an 86% decrease in serum cortisol AUC. Another strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Lorazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and benzodiazepines. Concurrent use may result in additive CNS depression.
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.
Lumateperone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lumateperone and sedating azelastine. Concurrent use may result in additive CNS depression.
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 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.
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.
Maprotiline: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including maptrotiline.
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.
Meclizine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
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.
Meperidine: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Meprobamate: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with CNS depressants including anxiolytics, sedatives, and hypnotics.
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.
Metaxalone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and skeletal muscle relaxants. Concurrent use may result in additive CNS depression.
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.
Methadone: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
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.
Methocarbamol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and methocarbamol. Concurrent use may result in additive CNS depression.
Methohexital: (Moderate) An enhanced CNS depressant effect may occur when azelastine, an antihistamine, is combined with CNS depressants including the barbiturates.
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: (Major) 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 topical 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.
Midazolam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and benzodiazepines. Concurrent use may result in additive CNS depression.
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.
Mirtazapine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and mirtazapine. Concurrent use may result in additive CNS depression.
Mitotane: (Moderate) Use caution if mitotane and fluticasone are used concomitantly, and monitor for decreased efficacy of fluticasone and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and fluticasone is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of fluticasone.
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.
Morphine: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. For extended-release morphine tablets, start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of excessive CNS depression.
Morphine; Naltrexone: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. For extended-release morphine tablets, start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of excessive CNS depression.
Nabumetone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Nalbuphine: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including nalbuphine.
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.
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: (Major) Coadministration of inhaled fluticasone propionate and nefazodone is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; nefazodone is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate. (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including nefazodone.
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: (Major) Coadministration of inhaled fluticasone propionate and nelfinavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; nelfinavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
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.
Nirmatrelvir; Ritonavir: (Major) Coadministration of inhaled fluticasone propionate and ritonavir is not recommended; use caution with inhaled fluticasone furoate. During post-marketing use, there have been reports of clinically significant drug interactions in patients receiving inhaled fluticasone propionate with ritonavir, resulting in systemic corticosteroid effects including Cushing's syndrome and adrenal suppression. Fluticasone is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with ritonavir increased plasma fluticasone propionate exposure resulting in an 86% decrease in serum cortisol AUC. Another strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
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.
Nortriptyline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and tricyclic antidepressants. Concurrent use may result in additive CNS depression.
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.
Oliceridine: (Major) Concomitant use of oliceridine with azelastine may cause excessive sedation and somnolence. Limit the use of oliceridine with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
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.
Opicapone: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including COMT inhibitors. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Orphenadrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and skeletal muscle relaxants. Concurrent use may result in additive CNS depression.
Oxaprozin: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding.
Oxazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and benzodiazepines. Concurrent use may result in additive CNS depression.
Oxycodone: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Oxymetholone: (Moderate) Concomitant use of oxymetholone with corticosteroids or corticotropin, ACTH may cause increased edema. Manage edema with diuretic and/or digitalis therapy.
Oxymorphone: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Reduce the initial oxymorphone dosage by 1/3 to 1/2. Educate patients about the risks and symptoms of excessive CNS depression.
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.
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.
Pentazocine; Naloxone: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including pentazocine.
Pentobarbital: (Moderate) An enhanced CNS depressant effect may occur when azelastine, an antihistamine, is combined with CNS depressants including the barbiturates.
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.
Perphenazine: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including phenothiazines.
Perphenazine; Amitriptyline: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including phenothiazines. (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and tricyclic antidepressants. Concurrent use may result in additive CNS depression.
Phenobarbital: (Moderate) An enhanced CNS depressant effect may occur when azelastine, an antihistamine, is combined with CNS depressants including the barbiturates. (Moderate) Coadministration may result in decreased exposure to fluticasone. Phenobarbital is a CYP3A4 inducer; fluticasone is a CYP3A4 substrate. Monitor for decreased response to fluticasone during concurrent use.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) An enhanced CNS depressant effect may occur when azelastine, an antihistamine, is combined with CNS depressants including the barbiturates. (Moderate) Coadministration may result in decreased exposure to fluticasone. Phenobarbital is a CYP3A4 inducer; fluticasone is a CYP3A4 substrate. Monitor for decreased response to fluticasone during concurrent use.
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.
Phenytoin: (Moderate) Monitor for decreased corticosteroid efficacy if fluticasone is used with phenytoin; a dosage increase may be necessary. Concurrent use may decrease the exposure of fluticasone.
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.
Pitolisant: (Major) Avoid coadministration of pitolisant with azelastine as the effect of pitolisant may be decreased. Pitolisant increases histamine concentrations in the brain; therefore, H1-receptor antagonists like azelastine, may reduce pitolisant efficacy.
Posaconazole: (Major) Coadministration of inhaled fluticasone propionate and posaconazole is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; posaconazole is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
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.
Pramipexole: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including pramipexole.
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.
Pregabalin: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and azelastine. Concomitant use of pregabalin with azelastine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
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) An enhanced CNS depressant effect may occur when azelastine, an antihistamine, is combined with CNS depressants including the barbiturates. (Moderate) Coadministration may result in decreased exposure to fluticasone. Primidone is a CYP3A4 inducer; fluticasone is a CYP3A4 substrate. Monitor for decreased response to fluticasone during concurrent use.
Prochlorperazine: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including phenothiazines.
Promethazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and promethazine. Concurrent use may result in additive CNS depression.
Promethazine; Dextromethorphan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and promethazine. Concurrent use may result in additive CNS depression.
Promethazine; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and promethazine. Concurrent use may result in additive CNS depression. (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.
Propofol: (Minor) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including general anesthetics.
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.
Protriptyline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and tricyclic antidepressants. Concurrent use may result in additive CNS depression.
Pseudoephedrine; Triprolidine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
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.
Quazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and benzodiazepines. Concurrent use may result in additive CNS depression.
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.
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.
Remifentanil: (Minor) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Remimazolam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and benzodiazepines. Concurrent use may result in additive CNS depression.
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.
Ribociclib: (Major) Coadministration of inhaled fluticasone propionate and ribociclib is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; ribociclib is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Ribociclib; Letrozole: (Major) Coadministration of inhaled fluticasone propionate and ribociclib is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; ribociclib is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Ritonavir: (Major) Coadministration of inhaled fluticasone propionate and ritonavir is not recommended; use caution with inhaled fluticasone furoate. During post-marketing use, there have been reports of clinically significant drug interactions in patients receiving inhaled fluticasone propionate with ritonavir, resulting in systemic corticosteroid effects including Cushing's syndrome and adrenal suppression. Fluticasone is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with ritonavir increased plasma fluticasone propionate exposure resulting in an 86% decrease in serum cortisol AUC. Another strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
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.
Ropinirole: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including ropinirole.
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.
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) Coadministration of inhaled fluticasone propionate and saquinavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; saquinavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
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.
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.
Secobarbital: (Moderate) An enhanced CNS depressant effect may occur when azelastine, an antihistamine, is combined with CNS depressants including the barbiturates.
Sedating H1-blockers: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
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.
Selegiline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and azelastine. Concurrent use may result in additive CNS depression.
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.
Sevoflurane: (Minor) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including general anesthetics.
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.
Skeletal Muscle Relaxants: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and skeletal muscle relaxants. Concurrent use may result in additive CNS depression.
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 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.
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: (Major) Avoid concomitant use of stiripentol with azelastine nasal solution. Concomitant use may cause somnolence, reductions in mental alertness, or additional CNS impairment. Educate patients about the signs and symptoms of CNS depression.
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.
Sufentanil: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
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.
Tapentadol: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
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.
Temazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and benzodiazepines. Concurrent use may result in additive CNS depression.
Testosterone: (Moderate) Monitor for fluid retention during concurrent corticosteroid and testosterone use. Concurrent use may result in increased fluid retention.
Thalidomide: (Major) Avoid the concomitant use of thalidomide with opiate agonists; antihistamines; antipsychotics; anxiolytics, sedatives, and hypnotics; and other central nervous system depressants due to the potential for additive sedative effects.
Theophylline, Aminophylline: (Minor) Coadministration of oral azelastine 4 mg twice daily and theophylline 300 mg or 400 mg twice daily did not result in a significant pharmacokinetic interaction.
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.
Thioridazine: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including phenothiazines.
Thiothixene: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including thiothixene.
Tipranavir: (Major) Coadministration of inhaled fluticasone propionate and tipranavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; tipranavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
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.
Tizanidine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and tizanidine. Concurrent use may result in additive CNS depression.
Tolcapone: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including COMT inhibitors. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
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.
Tramadol: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Tramadol; Acetaminophen: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Trazodone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and trazodone. Concurrent use may result in additive CNS depression.
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.
Triazolam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and benzodiazepines. Concurrent use may result in additive CNS depression.
Tricyclic antidepressants: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and tricyclic antidepressants. Concurrent use may result in additive CNS depression.
Trifluoperazine: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including phenothiazines.
Trimipramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and tricyclic antidepressants. Concurrent use may result in additive CNS depression.
Triprolidine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
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: (Major) Coadministration of inhaled fluticasone propionate and tucatinib is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; tucatinib is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
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.
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.
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; Amoxicillin; Clarithromycin: (Major) Coadministration of inhaled fluticasone propionate and clarithromycin is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; clarithromycin is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Voriconazole: (Moderate) Monitor for potential adrenal dysfunction with concomitant use of voriconazole and fluticasone. 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 administration of another strong CYP3A4 inhibitor increased plasma fluticasone propionate exposure resulting in a 45% to 86% decrease in serum cortisol AUC and increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol. Voriconazole is a strong CYP3A4 inhibitor, and fluticasone 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.
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.
Zafirlukast: (Minor) Zafirlukast inhibits the CYP3A4 isoenzymes and should be used cautiously in patients stabilized on drugs metabolized by CYP3A4, such as corticosteroids.
Zaleplon: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with CNS depressants including anxiolytics, sedatives, and hypnotics.
Zolpidem: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with CNS depressants including anxiolytics, sedatives, and hypnotics.
Zuranolone: (Major) Avoid the use of multiple sedating agents due to the risk for additive CNS depression. If use is necessary, consider a downward dosage adjustment of either or both medications, especially in patients with additional risk factors for sedation-related harm.
Mechanism of Action:-Azelastine: Azelastine and its metabolite, desmethylazelastine, are H1-receptor antagonists. Azelastine also inhibits histamine release from mast cells. As an inhibitor of mast cell histamine release, azelastine is 5000-times more potent than sodium cromoglycate, astemizole, or theophylline. Azelastine and desmethylazelastine compete with free histamine for binding at H1-receptor sites, thereby inhibiting the physiologic effects of histamine. Based on in vitro studies, azelastine inhibits other mediators of allergic reactions (e.g., leukotrienes and PAF). Decreased chemotaxis and activation of eosinophils have also been demonstrated with azelastine. Azelastine may also interfere with histamine- and leukotriene-induced bronchospasm. The drug has negligible anticholinergic activity.
-Fluticasone: In the treatment of allergies, intranasal fluticasone reduces allergic responses of several cell types (e.g., mast cells and eosinophils) involved in the allergic response by the same cellular mechanism as the topical corticosteroids. Clinically, symptoms such as rhinorrhea and postnasal drip, nasal congestion, sneezing, and pharyngeal itching are reduced. In vitro studies indicate that the binding affinity of fluticasone furoate for the human glucocorticoid receptor is 1.7 and 29.9 times that of fluticasone propionate and dexamethasone, respectively. The clinical significance of these findings is currently unknown.
Azelastine; fluticasone is administered by intranasal administration.
-Azelastine: The steady-state volume of distribution of azelastine is 14.5 L/kg (based on IV and oral administration). The plasma protein binding of azelastine and its principal active metabolite, desmethylazelastine, are approximately 88% and 97%, respectively. Azelastine is metabolized via the cytochrome P450 enzyme system; the specific P450 isoenzymes responsible for the biotransformation of azelastine have not been identified. The total clearance of azelastine is approximately 0.50 L/kg/hr. The elimination half-life of azelastine is approximately 25 hours following administration of azelastine; fluticasone nasal spray. Approximately 75% of an oral dose of radiolabeled azelastine was excreted in the feces with < 10% excreted as unchanged azelastine.
-Fluticasone: Following intravenous administration, the initial disposition phase for fluticasone propionate was rapid and consistent with its high lipid solubility and tissue binding. The average volume of distribution is 4.2 L/kg. Fluticasone propionate is highly bound (91%) to human plasma proteins with no obvious concentration relationship. Fluticasone propionate is weakly and reversibly bound to erythrocytes and freely equilibrates between erythrocytes and plasma. Following intravenous dosing, fluticasone propionate had a terminal elimination half-life of approximately 7.8 hours. A minimal amount of the radiolabeled oral dose (< 5%) was excreted in the urine as metabolites, with the remainder excreted in the feces as parent drug and metabolites.
-Route-Specific Pharmacokinetics
Other Route(s)
Intranasal Route
Following intranasal administration of two sprays per nostril of azelastine; fluticasone nasal spray, the Cmax was 194.5 +/- 74.4 pg/mL for azelastine and 10.3 +/- 3.9 pg/mL for fluticasone propionate. The AUC was 4217 +/- 2618 hour x pg/mL for azelastine and 97.7 +/- 43.1 hour x pg/mL for fluticasone. The median Tmax from a single dose was a half-hour for azelastine and 1 hour for fluticasone. Systemic bioavailability of azelastine from Dymista nasal spray was comparable with monotherapy azelastine hydrochloride nasal spray (i.e., approximately 40%). Systemic bioavailability of fluticasone from Dymista nasal spray was 44-61% higher than monotherapy fluticasone propionate (bioavailability for monotherapy fluticasone nasal spray was <2%). Due to the low intranasal bioavailability, pharmacokinetic data for fluticasone propionate were obtained via other routes of administration. Studies using oral dosing of radiolabeled fluticasone propionate showed negligible oral bioavailability and high extraction from plasma; the majority of the circulating radioactivity was due to an inactive metabolite.
-Special Populations
Hepatic Impairment
Azelastine pharmacokinetics are not affected by hepatic disease following oral administration.
Renal Impairment
Renal insufficiency (CrCl < 50 mL/min) is associated with increased azelastine Cmax and AUC by 70-75% following oral administration.
Pediatrics
Azelastine pharmacokinetics are not affected by age following oral administration.
Geriatric
Azelastine pharmacokinetics are not affected by age following oral administration.
Gender Differences
Azelastine pharmacokinetics are not affected by gender following oral administration.