Azelastine is a phthalazinone second-generation antihistamine (H1-blocker) and an inhibitor of mast cell histamine release. An opthalmic solution is used for itching of the eye related to allergic conjunctivitis. Azelastine is used intranasally in adult and pediatric patients for the management of symptoms associated with allergic or vasomotor rhinitis. Azelastine nasal spray (Astepro) became FDA approved for non-prescription (OTC) sale in June 2021, for use in patients 6 years and older for seasonal and perennial allergy symptoms. Guidelines strongly recommend intranasal antihistamines, such as azelastine, as an initial treatment option for seasonal allergic rhinitis and as a first-line monotherapy option for patients with nonallergic rhinitis. They also recommend intranasal antihistamines as a first-line option for patients with intermittent allergic rhinitis. Intranasal antihistamines have a more rapid onset of action than intranasal corticosteroids and oral antihistamines do, are more effective than oral antihistamines in the control of nasal congestion, and provide a favorable safety profile.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Inhalation Administration
Intranasal Inhalation Administration
-Before using for the first time the nasal spray unit must be primed. Pointed away from the body, pump the activator 4 to 6 times until fine mist appears. If the unit has not been used for 3 days, re-prime twice 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.
-To avoid the spread of infection, do not use the sprayer for more than one person.
Ophthalmic Administration
-For topical ophthalmic use only. Do not give by injection or orally.
-Wash hands before and after use. Tilt the head back slightly and pull the lower eyelid down with the index finger. Squeeze the prescribed number of drops into the conjunctival sac and gently close eyes for 1 to 2 minutes. Do not blink.
-Avoid contamination. Do not touch the tip of the dropper to the eye, fingertips, or other surface.
-Patients should wait at least 10 minutes after instilling the ophthalmic solution before inserting contact lenses.
-To avoid the spread of infection, do not share drops between patients.
Respiratory or nasal adverse effects have been reported with both the ophthalmic drops and nasal spray formulations of azelastine. Effects reported with both formulations include dyspnea (1-10% with the ophthalmic drops; < 2% with the nasal spray, nocturnal dyspnea also reported with the nasal spray at < 2%), pharyngitis (1-10%; 3.8%), rhinitis (1-10%; 2-17%), and asthma (1-10%; 4.5%). Influenza like symptoms were reported with use of the ophthalmic drops (1-10%). Nasal irritation has been reported with the nasal spray formulation as a burning sensation (4.1%) and discomfort (1-4%). Epistaxis (>= 2%), nasal congestion (< 2%), nasal dryness (< 2%), paranasal sinus hypersecretion (< 2%), post-nasal drip (< 2%), nasal sores, nasopharyngitis, dysosmia, and anosmia have also been reported with the nasal spray. Focused nasal examinations were performed and showed that the incidence of nasal mucosal ulceration in each treatment group was approximately 1% at baseline and approximately 1.5% throughout the 12 month treatment period. Other adverse effects reported only with the nasal spray include bronchospasm (< 2%), cough (11.4%), laryngitis (< 2%), sinusitis (>= 3.2%), sneezing including paroxysmal sneezing (1-3.1%), throat irritation (reported as burning, < 2%), dry throat (< 2%), and xerostomia (2.8%). In pediatric nasal spray studies, cough, epistaxis, sneezing, rhinalgia, and upper respiratory infection were frequently reported (>= 2%).
Nervous system adverse effects have been reported with both the ophthalmic drops and nasal spray formulations of azelastine. Headache was reported with the nasal spray at rates of >= 5% and 14.8%; with the ophthalmic solution headache was reported in approximately 15% of patients. Fatigue was also reported with the use of either formulation; 1-10% with the ophthalmic solution and up to 2.3% with the nasal spray. Other adverse effects reported only with the nasal spray include anxiety (< 2%), confusion, dizziness (2%), depression (< 2%), drowsiness (somnolence, 1-11.5%), dysesthesia (7.9%), hyperkinesis (< 2%), hypoesthesia (< 2%), nervousness, parosmia, paresthesias, sleep disorder, abnormal thinking, depersonalization, tolerance, and vertigo (< 2%). Insomnia has been reported with post-marketing use.
Ophthalmic adverse effects have been reported with both the ophthalmic drops and nasal spray formulations of azelastine. The most frequently reported adverse reaction with the ophthalmic solution is ocular irritation with burning and stinging upon administration (approximately 30%). Conjunctivitis (1-10% in ophthalmic solution; 5.1% with nasal spray), ocular pain (1-10%; < 2%), temporary blurred vision (1-10%; post-market reports), eye abnormality (0; < 2%), and watery eyes (0; < 2%) were also reported. Abnormal vision and xerophthalmia were reported post-marketing with the nasal spray.
Sinus tachycardia, hypertension, and flushing were reported in < 2% of patients receiving azelastine nasal spray, but the incidence exceeded that listed for patients receiving placebo. Palpitations, chest pain (unspecified), and atrial fibrillation have been reported during post-marketing use. Cardiovascular adverse effects have not been reported with the ophthalmic formulation of azelastine.
There have been post-marketing reports of anaphylactoid reactions with the use of azelastine nasal spray and, thus, could occur with the ophthalmic solution. Dermatologic adverse effects have been reported with both the ophthalmic drops and nasal spray formulations. Pruritus was reported in 1-10% with ophthalmic solution and post-marketing with the nasal spray. Eczema, hair and follicle infection, furunculosis, and skin laceration were reported in < 2% of patients who used the nasal spray in clinical trials. Contact dermatitis has also been reported. Rash (unspecified) and facial edema were reported with post-marketing use of the nasal spray.
Dysgeusia, described as a bitter taste, has been reported with both the ophthalmic solution (approximately 10%) and the nasal spray (>= 2%) formulations of azelastine. There have been post-marketing reports of a sweet taste, the disturbance of taste, and the loss of taste with the nasal spray. Other gastrointestinal adverse effects have been reported with the nasal spray formulation during clinical trials. Nausea was reported in 2.8% and weight gain in 2% of patients. Vomiting and oropharyngeal pain were among the most common adverse effects reported in children 6 months to 5 years with Astepro nasal spray (>= 2%), but were reported in < 2% of all patients receiving Astelin nasal spray. Abdominal pain, appetite stimulation, constipation, gastroenteritis, glossitis, stomatitis (ulcerative and aphthous), elevated hepatic enzymes (specifically SGPT), diarrhea, and toothache were reported in < 2% of patients.
Urogenital adverse events were reported with the use of azelastine nasal spray, but not with the ophthalmic solution. Albuminuria, amenorrhea, breast pain, hematuria, and increased urinary frequency were reported in < 2% of patients; urinary retention was reported with post-marketing use.
In clinical trials, myalgia (1.5%), temporomandibular dislocation (< 2%), and rheumatoid arthritis (< 2%) were reported in patients using the azelastine nasal spray. Involuntary muscle contractions were reported with post-marketing use. Musculoskeletal adverse reactions were not reported with the ophthalmic solution.
Infection, including upper respiratory, viral, and herpes simplex infection, was reported in 2-3% of patients using azelastine nasal spray in clinical trials. Fever, malaise, pain in the extremities, and back pain were also reported. In pediatric nasal spray trials, fever, upper respiratory infection, and otitis media were frequently reported (>= 2%).
There is insufficient data to determine dose-response differences for the nasal or ophthalmic dosage forms of azelastine in elderly versus younger adult patients. No pharmacokinetic differences are observed in elderly patients following oral administration (investigational).
Azelastine 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.
Patients should not wear contact lenses if their eyes are red. Azelastine ophthalmic solution should not be used to treat contact lens-related irritation. The preservative in ophthalmic preparation, benzalkonium chloride, may be absorbed by soft contact lenses. Patients who wear soft contact lenses should be instructed to wait at least 10 minutes after instilling azelastine ophthalmic solution before inserting their contact lenses.
Azelastine nasal spray may be used if you are breast-feeding. Breastfed infants of lactating women treated with azelastine nasal spray should be monitored for possible signs of milk rejection related to the bitter taste of azelastine. While data on the presence of azelastine in human milk, the effects on the breast-fed infant, or the effects on milk production following use of the drug are limited, it's important to consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition when using this medication. There is likely limited exposure to azelastine from nasal or ophthalmic dosage forms, however, oral non-sedating antihistamines, such as loratadine, are generally preferred if an agent is needed for allergy symptoms. The British Society for Allergy and Clinical Immunology recommends loratadine at the lowest dose as a preferred antihistamine in breast-feeding women.
Limited data from postmarketing experience over decades of use with azelastine in pregnant women have not identified any drug associated risks of miscarriage, birth defects, or other adverse maternal or fetal outcomes. Azelastine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. In animal reproduction studies, there was no evidence of fetal harm at oral doses approximately 4 times and higher than the clinical daily dose. Oral administration of azelastine to pregnant mice, rats, and rabbits, during the period of organogenesis, produced developmental toxicity that included structural abnormalities, decreased embryo-fetal survival, and decreased fetal body weights at doses 180 times and higher than the maximum recommended human daily intranasal dose (MRHDID). However, the relevance of these findings in animals to pregnant women was considered questionable based upon the high animal to human dose multiple. Pregnant patients should see their health care professional for a proper diagnosis and for treatment recommendations. The American College of Obstetricians and Gynecologists (ACOG) and the American College of Allergy, Asthma, and Immunology consider loratadine an acceptable alternative in pregnancy, preferably after the first trimester, when first generation antihistamines are not tolerated.
For the management of symptoms of seasonal allergies or perennial allergies, including allergic rhinitis:
-for seasonal allergic rhinitis:
Nasal dosage (Astelin nasal spray or generic equivalents):
Adults: 1 to 2 sprays (137 mcg/spray using 0.1% spray) per nostril twice daily.
Children and Adolescents 12 years and older: 1 to 2 sprays (137 mcg/spray using 0.1% spray) per nostril twice daily.
Children 5 to 11 years: 1 spray (137 mcg/spray using 0.1% spray) per nostril twice daily.
Nasal dosage (Astepro nasal spray or generic equivalents only):
Adults: 1 to 2 sprays per nostril twice daily using the 0.1% (137 mcg/spray) or the 0.15% (205.5 mcg/spray) nasal spray. The 0.15% nasal spray may also be given as 2 sprays per nostril once daily.
Children and Adolescents 12 to 17 years: 1 to 2 sprays per nostril twice daily using the 0.1% (137 mcg/spray) or the 0.15% (205.5 mcg/spray) nasal spray. The 0.15% nasal spray may also be given as 2 sprays per nostril once daily.
Children 6 to 11 years: 1 spray per nostril twice daily using the 0.1% (137 mcg/spray) or the 0.15% (205.5 mcg/spray) nasal spray.
Children 2 to 5 years: 1 spray per nostril twice daily using the 0.1% (137 mcg/spray) nasal spray. Prescription use only in this age group; do not use the 0.15% (205.5 mcg/spray) nasal spray.
-for perennial allergic rhinitis:
Nasal dosage (Astepro nasal spray or generic equivalents only):
Adults: Prescription dosing: 2 sprays per nostril twice daily using the 0.15% nasal spray (205.5 mcg/spray). Nonprescription (OTC) dosing: 1 to 2 sprays per nostril twice daily using the 0.15% (205.5 mcg/spray) nasal spray. It may also be given as 2 sprays per nostril once daily.
Children and Adolescents 12 to 17 years: Prescription dosing: 2 sprays per nostril twice daily using the 0.15% nasal spray (205.5 mcg/spray). Nonprescription (OTC) dosing: 1 to 2 sprays per nostril twice daily using the 0.15% (205.5 mcg/spray) nasal spray. It may also be given as 2 sprays per nostril once daily.
Children 6 to 11 years: 1 spray per nostril twice daily using the 0.1% (137 mcg/spray) or the 0.15% (205.5 mcg/spray) nasal spray.
Infants and Children 6 months to 5 years: 1 spray per nostril twice daily using the 0.1% (137 mcg/spray) nasal spray. Prescription use only in this age group; do not use the 0.15% (205.5 mcg/spray) product.
For the treatment of symptoms of vasomotor rhinitis:
Nasal dosage (Astelin nasal spray or generic equivalents):
Adults: 2 sprays per nostril twice daily of 0.1% nasal spray (137 mcg/spray).
Children and Adolescents 12 years and older: 2 sprays per nostril twice daily of 0.1% nasal spray (137 mcg/spray).
For the treatment of ocular pruritus associated with allergic conjunctivitis:
Ophthalmic dosage (0.05% ophthalmic solution):
Adults: 1 drop in the affected eye(s) twice daily.
Children and Adolescents 3 to 17 years: 1 drop in the affected eye(s) twice daily.
Maximum Dosage Limits:
NOTE: Do not exceed recommended dosage limits for the specific product prescribed; the following are general guidelines:
-Adults
4 nasal sprays/day per nostril; 2 ophthalmic drops/day per affected eye.
-Geriatric
4 nasal sprays/day per nostril; 2 ophthalmic drops/day per affected eye.
-Adolescents
4 nasal sprays/day per nostril; 2 ophthalmic drops/day per affected eye.
-Children
12 years: 4 sprays/day per nostril (205.5 mcg/spray); 2 ophthalmic drops/day per affected eye.
6 to 11 years: 2 sprays/day per nostril (205.5 mcg/spray); 2 ophthalmic drops/day per affected eye.
3 to 5 years: 2 sprays/day per nostril (137 mcg/spray); 2 ophthalmic drops/day per affected eye.
1 to 3 years: 2 sprays/day per nostril (137 mcg/spray); the safety and efficacy of the ophthalmic drops have not been established.
-Infants
6 to 12 months: 2 sprays/day per nostril (137 mcg/spray); the safety and efficacy of the ophthalmic drops have not been established.
Less than 6 months: Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
No dosage adjustment is needed.
Patients with Renal Impairment Dosing
No dosage adjustment is needed.
*non-FDA-approved indication
Acetaminophen; Aspirin; Diphenhydramine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
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.
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.
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; Diphenhydramine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
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; 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.
Acrivastine; Pseudoephedrine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
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.
Alprazolam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and benzodiazepines. Concurrent use may result in additive CNS depression.
Amitriptyline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and tricyclic antidepressants. Concurrent use may result in additive CNS depression.
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.
Anxiolytics; Sedatives; and Hypnotics: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with CNS depressants including anxiolytics, sedatives, and hypnotics.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) An enhanced CNS depressant effect may occur when azelastine, an antihistamine, is combined with CNS depressants including the barbiturates.
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.
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.
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.
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.
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.
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.
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.
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.
Brompheniramine; Phenylephrine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
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.
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.
Butalbital; Acetaminophen; Caffeine: (Moderate) An enhanced CNS depressant effect may occur when azelastine, an antihistamine, is combined with CNS depressants including the barbiturates.
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.
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.
Butorphanol: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including butorphanol.
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.
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.
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.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and azelastine. Concurrent use may result in additive CNS depression.
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.
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.
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.
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.
Chlorpheniramine; Phenylephrine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
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.
Chlorzoxazone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and skeletal muscle relaxants. Concurrent use may result in additive CNS depression.
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.
Clemastine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
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.
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.
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.
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.
Desipramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and tricyclic antidepressants. Concurrent use may result in additive CNS depression.
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; Diphenhydramine; Phenylephrine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
Diazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and benzodiazepines. Concurrent use may result in additive CNS depression.
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.
Dimenhydrinate: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
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.
Diphenhydramine; Naproxen: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
Diphenhydramine; Phenylephrine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
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.
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.
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.
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.
Eszopiclone: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with CNS depressants including anxiolytics, sedatives, and hypnotics.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
Etomidate: (Minor) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including general anesthetics.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and azelastine. Concurrent use may result in additive CNS depression.
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.
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.
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.
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.
Guaifenesin; 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.
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.
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.
Hydrocodone; 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.
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.
Hydroxyzine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
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.
Imipramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and tricyclic antidepressants. Concurrent use may result in additive CNS depression.
Isoflurane: (Minor) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including general anesthetics.
Ketamine: (Minor) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including general anesthetics.
Ketoconazole: (Minor) Theoretically, systemic exposure of nasally administered azelastine may be increased by coadministration with ketoconazole, although an interaction has not been documented.
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.
Levoketoconazole: (Minor) Theoretically, systemic exposure of nasally administered azelastine may be increased by coadministration with ketoconazole, although an interaction has not been documented.
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.
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.
Lorazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and benzodiazepines. Concurrent use may result in additive CNS depression.
Lumateperone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lumateperone and sedating azelastine. Concurrent use may result in additive CNS depression.
Maprotiline: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including maptrotiline.
Meclizine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
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.
Metaxalone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and skeletal muscle relaxants. Concurrent use may result in additive CNS depression.
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.
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.
Midazolam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and benzodiazepines. Concurrent use may result in additive CNS depression.
Mirtazapine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and mirtazapine. Concurrent use may result in additive CNS depression.
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.
Nalbuphine: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including nalbuphine.
Nefazodone: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including nefazodone.
Nortriptyline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and tricyclic antidepressants. Concurrent use may result in additive CNS depression.
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.
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.
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.
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.
Pentazocine: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including pentazocine.
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.
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.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) An enhanced CNS depressant effect may occur when azelastine, an antihistamine, is combined with CNS depressants including the barbiturates.
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.
Pramipexole: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including pramipexole.
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.
Primidone: (Moderate) An enhanced CNS depressant effect may occur when azelastine, an antihistamine, is combined with CNS depressants including the barbiturates.
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.
Propofol: (Minor) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including general anesthetics.
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.
Quazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and benzodiazepines. Concurrent use may result in additive CNS depression.
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.
Ropinirole: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including ropinirole.
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.
Selegiline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and azelastine. Concurrent use may result in additive CNS depression.
Sevoflurane: (Minor) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including general anesthetics.
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.
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.
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.
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.
Temazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and benzodiazepines. Concurrent use may result in additive CNS depression.
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.
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.
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.
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.
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.
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.
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.
Azelastine is administered intranasally or via the topical ophthalmic route. Protein binding of azelastine is approximately 88%. Any absorbed azelastine is oxidatively metabolized to the principle active metabolite, desmethylazelastine; the specific cytochrome P450 enzymes have not been identified. Both unchanged drug and its active metabolite are excreted primarily in the feces.
-Route-Specific Pharmacokinetics
Oral Route
Based on oral administration studies, the elimination half-life of azelastine is about 22 hours. The elimination half-life of desmethylazelastine is about 54 hours after oral administration of azelastine.
Intravenous Route
Based on intravenous administration studies, the elimination half-life of azelastine is about 22 hours.
Other Route(s)
Nasal Route
The systemic bioavailability of azelastine following intranasal administration is approximately 40%. Peak plasma concentrations occur in 2 to 3 hours. After single-dose intranasal administration, plasma concentrations of the active metabolite desmethylazelastine were not measurable; however, following intranasal dosing to steady-state, plasma concentrations of desmethylazelastine ranged from 20% to 30% of azelastine concentrations.
Ophthalmic Route
Absorption following azelastine ocular administration is relatively low (less than 1 ng/mL after 56 days of treatment). Following ocular administration, the onset of action is within 3 minutes, and the duration of action is about 8 hours.
-Special Populations
Hepatic Impairment
Azelastine pharmacokinetics are not affected by hepatic disease following oral administration (investigational).
Renal Impairment
Renal insufficiency (CrCl less than 50 mL/minute) is associated with increased azelastine Cmax and AUC by 70% to 75%.
Pediatrics
Azelastine pharmacokinetics are not affected by age following oral administration (investigational).
Geriatric
Azelastine pharmacokinetics are not affected by age following oral administration (investigational).
Gender Differences
Azelastine pharmacokinetics are not affected by gender following oral administration (investigational).