Azelastine Hydrochloride

Class: Antiallergic Agents
VA Class: OP900
Molecular Formula: C₂₂H₂₄ClN₃O•ClH
CAS Number: 79307-93-0
Brands: Astelin, Optivar

Introduction

Relatively selective histamine H₁-receptor antagonist;^{1 2} a phthalazinone derivative.^{1 2 11 13 21 24 25 27}

Uses for Azelastine Hydrochloride

Seasonal Allergic Rhinitis

Symptomatic treatment of seasonal allergic rhinitis (e.g., hay fever).^{1 11} Intranasal azelastine is at least as effective as oral antihistamines (e.g., cetirizine) or intranasal corticosteroids.^{16 17 18 19 20 21 22 23 24 27 28} May provide improvement of ocular manifestations, possibly secondary to systemic absorption of the drug.^{16 19 21 22 24 27}

Nonallergic Rhinitis

Symptomatic treatment of nonallergic (vasomotor) rhinitis.^a

Allergic Conjunctivitis

Symptomatic relief of ocular itching associated with allergic conjunctivitis.^{2 30 31}

Azelastine Hydrochloride Dosage and Administration

Administration

Administer nasal solution intranasally twice daily, using a spray pump.^{1 11}

Apply ophthalmic solution topically to the eye twice daily. ² Ophthalmic solution is not for injection or oral use.²

Intranasal Administration

Before initial use, prime the pump until a fine mist appears, using up to 4 actuations of the pump.^{1 11 14} Administration of solution in a stream of liquid rather than as a mist may fail to provide maximum benefit and may cause discomfort.¹⁴

If inhaler has not been used for ≥3 days, reprime pump with 2 actuations or until a fine mist appears.¹⁴ Reprime pump when the spray pump is inserted into the second bottle.¹⁴

To actuate the pump, hold the bottle in one hand, with 2 fingers on the shoulders of the pump unit and the thumb on the bottom of the bottle.¹⁴ Press the bottom firmly and rapidly upward with the thumb to produce a fine mist.¹⁴

Prior to administration, gently blow the nose to clear nasal passages.¹⁴ Insert nasal spray tip ¼ to ½ inch into a nostril, tilt head slightly forward while holding the bottle vertically upright, and aim spray tip toward the back of the nose.¹⁴ Rapidly and firmly press and actuate pump into the nostril while holding the other nostril closed, gently sniffing at the same time;¹⁴ do not tilt head back after dosing.¹⁴

Repeat procedure for the other nostril.¹⁴ Provide a second spray into each nostril, beginning with the first nostril.¹⁴ Alternate nostrils between each actuation of nasal spray.¹⁴

Use caution to avoid spraying nasal spray into the eyes.^{1 11 14}

Ophthalmic Administration

Remove soft contact lenses prior to administration of each dose (since benzalkonium chloride may be absorbed by the lenses); may reinsert lenses 10 minutes after administration if eyes are not red.²

Avoid contamination of the solution container.²

Dosage

Available as azelastine hydrochloride; dosage expressed in terms of the salt.^{1 2 14}

When properly primed, the nasal spray pump delivers approximately 100 metered doses per bottle.^{1 16}

Pediatric Patients

Seasonal Allergic Rhinitis

Intranasal

Children ≥12 years of age: 2 sprays (274 mcg) in each nostril twice daily.^{1 11 16}

Children 5–11 years of age: 1 spray (137 mcg) in each nostril twice daily.¹

Nonallergic Rhinitis

Intranasal

Children ≥12 years of age: 2 sprays (274 mcg) in each nostril twice daily.^a

Allergic Conjunctivitis

Ophthalmic

Children ≥3 years of age: 1 drop of a 0.05% solution in the affected eye(s) twice daily.²

Adults

Seasonal Allergic Rhinitis

Intranasal

2 sprays (274 mcg) in each nostril twice daily.^{1 11 16}

Nonallergic Rhinitis

Intranasal

2 sprays (274 mcg) in each nostril twice daily.^a

Allergic Conjunctivitis

Ophthalmic

1 drop of a 0.05% solution in the affected eye(s) twice daily.²

Special Populations

Geriatric Patients

Cautious dosing of nasal solution recommended.^a

Cautions for Azelastine Hydrochloride

Contraindications

• 
  

  Known hypersensitivity to azelastine or any ingredient in the formulation.^{a b}

  
  

Warnings/Precautions

General Precautions

CNS Effects

Somnolence reported in patients receiving azelastine nasal solution.^{1 16 19 22 24 26 28} Performance of activities requiring mental alertness and physical coordination may be impaired.^a

Concurrent use of nasal solution with other CNS depressants may potentiate CNS depression.^a (See Specific Drugs under Interactions.)

Specific Populations

Pregnancy

Category C.^{a b}

Lactation

Not known whether azelastine is distributed into milk.^{a b} Use with caution in nursing women.^{a b}

Pediatric Use

Safety and efficacy of nasal solution for treatment of seasonal allergic rhinitis not established in children <5 years of age;¹ safety and efficacy for treatment of nonallergic rhinitis not established in children <12 years of age.^a

Safety and efficacy of ophthalmic solution not established in children <3 years of age.²

Geriatric Use

Response to nasal solution does not appear to differ from that in younger adults.^a

No substantial differences in safety and efficacy of ophthalmic solution relative to younger adults.^b

Common Adverse Effects

Nasal solution: Transient nasal burning or stinging,¹⁴ bitter taste, somnolence, headache, pharyngitis, paroxysmal sneezing.^{1 16 19 22 24 26 28}

Ophthalmic solution: Transient ocular burning/stinging, bitter taste, headache.^{2 30 31}

Interactions for Azelastine Hydrochloride

Metabolized by CYP isoenzymes.^a

Specific Drugs

Drug	Interaction	Comments
CNS depressants	Potential additive CNS depression with astelazine nasal solutiona	Avoid concomitant usea
Cimetidine	Possible increased serum azelastine concentrationsa
Erythromycin	No pharmacokinetic interaction or effect on QTc observeda 16
Ketoconazole	No pharmacokinetic interaction or effect on QTc observeda 16
Ranitidine	No pharmacokinetic interaction observeda
Theophylline	No pharmacokinetic interaction observeda

Azelastine Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Following intranasal administration, systemic bioavailability is 40%.^{1 11 16} Peak plasma concentrations occur 2–3 hours after intranasal administration.^a

Absorption following ophthalmic administration is low.^b

Onset

Following intranasal administration, symptomatic relief is evident within 1 hour; substantial relief usually is apparent within 3 hours; peak effect occurs between 4–6 hours.^{1 11 13}

Following ophthalmic administration, onset of action is rapid (3 minutes).²

Duration

Following intranasal administration, effect persists throughout the 12-hour dosage interval.^{1 11 13}

Ophthalmic effect persists for about 8 hours.²

Distribution

Plasma Protein Binding

Azelastine: Approximately 88%.^a

N-desmethylazelastine: 97%.^a

Elimination

Metabolism

Metabolized primarily to N-desmethylazelastine (an active metabolite) by CYP isoenzymes.^a

Elimination Route

Approximately 75% of an oral dose is excreted in feces, with <10% as unchanged drug.^a

Half-life

Azelastine: 22 hours (following oral and IV administration).^a

N-desmethylazelastine: 54 hours.^a

Special Populations

In patients with hepatic impairment, pharmacokinetics not altered.^a

Stability

Storage

Nasal

Solution

20–25°C.^a Protect from freezing.^a

Discard both bottles 3 months after initial insertion of the spray pump into the first of the 2 bottles in the dispensing package.¹⁴

Ophthalmic

Solution

20–25°C.^b Store upright.^b

ActionsActions

• 
  

  Inhibits the release of histamine^a and other mediators (e.g., leukotrienes, platelet activating factor [PAF]) involved in allergic reactions.^{2 29}

  
  


• 
  

  May inhibit the accumulation of eosinophils at the site of allergic inflammation and prevent eosinophil degranulation.^{1 29}

  
  

Advice to Patients

• 
  

  Proper techniques for assembly and priming of nasal spray pump and for administration of the nasal solution.¹ Importance of not administering the entire dose (i.e., 4 sprays) into a single nostril.^{2 14} Give patients a copy of the manufacturer’s patient instructions.^{1 11 14}

  
  


• 
  

  Importance of learning and adhering to proper administration techniques to avoid contamination of the ophthalmic solution container.²

  
  


• 
  

  Importance of removing soft contact lenses prior to administration of each ophthalmic dose.² May reinsert contact lenses 10 minutes after administration if eyes are not red; do not wear contact lenses if eye(s) are red.² Not indicated for contact lens-related irritation.²

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.^a

  
  


• 
  

  Potential for intranasal azelastine to impair mental alertness or physical coordination; use caution when driving or operating machinery until effects on individual are known.^a Avoid concomitant use of alcohol-containing beverages or products.¹

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^a

  
  


• 
  

  Importance of informing patients of other important precautionary information.^a (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Azelastine Hydrochloride

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Ophthalmic	Solution	0.05%	Optivar (with benzalkonium chloride)	MedPointe
Nasal	Solution	0.1% (137 mcg/metered spray)	Astelin Nasal Spray (with benzalkonium chloride)	MedPointe

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Azelastine HCl 0.05% Solution (APOTEX): 6/$95.99 or 18/$259.98

Optivar 0.05% Solution (MEDA PHARMACEUTICALS): 6/$115.99 or 18/$335.95

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions May 2004. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Wallace Laboratories. Astelin (azelastine hydrochloride) nasal spray prescribing information. Cranbury, NJ; 2000 Apr.

2. Muro Pharmaceuticals. Optivar (azelastine hydrochloride) ophthalmic solution prescribing information. Tewksbury, MA; 2000 May.

3. Borge PA. Problems in allergic rhinitis. Arzneimittelforschung. 1982; 32:11199-201.

4. Anon. Treatment of seasonal and perennial allergic rhinitis. BMJ. 1981; 283:808-10. [PubMed 6117350]

5. Food and Drug Administration. Over-the-counter drugs: establishment of a monograph for OTC cold, cough, allergy, bronchodilator and antihistaminic products.

6. Douglas WW. Histamine and 5-hydroxytryptamine (serotonin) and their antagonists. In: Gilman AG, Goodman LS, Rall TW et al eds. Goodman and Gilman’s the pharmacologic basis of therapeutics. 7th ed. New York: Macmillan Publishing Company. 1985:605-638.

7. Food and Drug Administration. Cold, cough, allergy, bronchodilator, and antiasthmatic drug products for over-the-counter human use; final monograph for OTC antihistamine drug products. Final rule. [21 FR Parts 201, 310, 341, 369] Fed Regist. 1992; 57:58356-8.

8. Meltzer EO. To use or not to use antihistamines in patients with asthma. Ann Allergy. 1990; 64:183-6. [IDIS 297019] [PubMed 1967918]

9. Pierson WE, Virant FS. Antihistamines in asthma. Ann Allergy. 1989; 63:601-3. [IDIS 301484] [PubMed 2574551]

10. Simons FER, Simons KJ. The pharmacology and use of H₁-receptor-antagonist drugs. N Engl J Med. 1994; 330:1663-70. [IDIS 330632] [PubMed 7909915]

11. Wallace Laboratories. Product information form for American hospital formulary service: Astelin (azelastine hydrochloride) nasal spray. Cranbury, NJ; 1996 Oct 30.

12. Rimmer SJ, Church MK. The pharmacology and mechanisms of action of histamine H₁-antagonists. Clin Exp Allergy. 1990; 20(Suppl 2):3- 17. [IDIS 364000] [PubMed 1699644]

13. Meltzer EO, Weiler JM, Dockhorn RJ et al. Azelastine nasal spray in the management of seasonal allergic rhinitis. Ann Allergy. 1994; 72:354-9. [IDIS 328847] [PubMed 7908778]

14. Wallace Laboratories. Astelin (azelastine hydrochloride) nasal spray patient information. Cranbury, NJ. 1996 Nov.

15. Weiler JM, Donnelly A, Campbell BH et al. Multicenter double-blind, multiple dose, parallel groups efficacy and safety trial of azelastine, chlorpheniramine, and placebo in the treatment of spring allergic rhinitis. J Allergy Clin Immunol. 1988; 82:801-11. [IDIS 316632] [PubMed 3057041]

16. Anon. Azelastine spray for allergic rhinitis. Med Lett Drugs Ther. 1997; 39:45-7. [PubMed 9150688]

17. Pelucchi A, Chiapparino A, Mastropasqua B et al. Effect of intranasal azelastine and beclomethasone dipropionate on nasal symptoms, nasal cytology, and bronchial responsiveness to methacholine in allergic rhinitis in response to grass pollens. J Allergy Clin Immunol. 1995; 95:515-23. [IDIS 342616] [PubMed 7852667]

18. Spaeth J, Schultze V, Klimek L et al. Azelastine reduces histamine- induced swelling of nasal mucosa. ORL J Otorhin Relat Spec. 1996; 58:157-63.

19. LaForce C, Dockhorn RJ, Prenner BM et al. Safety and efficacy of azelastine nasal spray (Astelin NS) for seasonal allergic rhinitis: a 4-week comparative multicenter trial. Ann Allergy Asthma Immunol. 1996; 76:181- 8. [IDIS 364165] [PubMed 8595539]

20. Gastpar H, Nolte D, Aurich R et al. Comparative efficacy of azelastine nasal spray and terfenadine in seasonal and perennial rhinitis. Allergy. 1994; 49:152-8. [PubMed 7911010]

21. Charpin D, Godard P, Garay RP et al. A multicenter clinical study of the efficacy and tolerability of azelastine nasal spray in the treatment of seasonal allergic rhinitis: a comparison with oral cetirizine. Eur Arch Otorhinolaryngol. 1995; 252:455-8. [IDIS 360828] [PubMed 8719584]

22. Ratner PH, Findlay SR, Hampel F et al. A double-blind, controlled trial to assess the safety and efficacy of azelastine nasal spray in seasonal allergic rhinitis. J Allergy Clin Immunol. 1994; 94:818-25. [IDIS 338352] [PubMed 7963150]

23. Weiler JM, Meltzer EO, Benson PM et al. A dose-ranging study of the efficacy and safety of azelastine nasal spray in the treatment of seasonal allergic rhinitis with an acute model. J Allergy Clin Immunol. 1994; 94:972-80. [IDIS 340407] [PubMed 7798545]

24. Passali D, Piragine F. A comparison of azelastine nasal spray and cetirizine tablets in the treatment of allergic rhinitis. J Int Med Res. 1994; 22:17-23. [IDIS 359227] [PubMed 8187941]

25. Ciprandi G, Ricca V, Passalacqua G et al. Seasonal rhinitis and azelastine: long- or short-term treatment? J Allergy Clin Immunol. 1997; 99:301-7.

26. Azelastine-Asthma Study Group. An evaluation of the efficacy and safety of azelastine in patients with chronic asthma. J Allergy Clin Immunol. 1996; 97:1218-24. [PubMed 8648016]

27. Conde Hernandez DJ, Palma Aqilar JL, Delgado Romero J. Comparison of azelastine nasal spray and oral ebastine in treating seasonal allergic rhinitis. Curr Res Med Opin. 1995; 13:299-304.

28. Davies RJ, Bagnall AC, McCabe RN et al. Antihistamines: topical vs oral administration. Clin Exp Allergy. 1996; 26(Suppl 3):11-7. [PubMed 8735853]

29. McNeely W, Wiseman LR. Intranasal azelastine: a review of its efficacy in the management of allergic rhinitis. Drugs. 1998; 56:91-114. [PubMed 9664202]

30. Giede-Tuch C, Westhoff Z, Zarth A. Azelastine eye-drops in seasonal allergic conjunctivitis or rhinoconjunctivitis: a double-blind, randomized, placebo-controlled study. Allergy. 1998; 53:857-62. [PubMed 9788686]

31. Sabbah A, Marzetto M. Azelastine eye drops in the treatment of seasonal allergic conjunctivitis or rhinoconjunctivitis in young children. Curr Med Res Opin. 1998; 14:161-70. [PubMed 9787982]

32. Ciprandi G, Buscaglia S, Cerqueti PM et al. Drug treatment of allergic conjunctivitis: a review of the evidence. Drugs. 1992; 43:154-76. [IDIS 360840] [PubMed 1372215]

33. Morrow GL, Abbott RL. Conjunctivitis. Am Fam Physician. 1998; 57:735-46. [IDIS 418448] [PubMed 9490996]

34. Titi MJ. A critical look at ocular allergy drugs. Am Fam Physician. 1996; 53:2637-42. [IDIS 367250] [PubMed 8644576]

35. Galindez OA, Kaufman HE. Coping with the itchy-burnies: the management of allergic conjunctivitis. Ophthalmology. 1996; 103:1335-6. [IDIS 373485] [PubMed 8841290]

36. Friedlaender MH. Current concepts in ocular allergy. Ann Allergy. 1991; 67:5-10,13. [IDIS 312766] [PubMed 1859041]

37. Trocme SD. Medical therapy for ocular allergy. Mayo Clin Proc. 1992; 67:557-65. [IDIS 296611] [PubMed 1359206]

a. MedPointe. Astelin (azelastine hydrochloride nasal spray) prescribing information. Somerset, NJ; 2000 Aug.

b. MedPointe. Optivar (azelastine hydrochloride ophthalmic solution) 0.05% prescribing information. Tewksbury, MA; 2003 Apr.

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