Azelastine

R01A - Decongestants and other nasal preparations for topical use ATC R01AC03 Small molecule approved 1996 Topical Natural product

JFDA label: Zalastin Metered Dose Nasal Spray

Mechanism of Action

12.1 Mechanism of Action Azelastine hydrochloride, a phthalazinone derivative, exhibits histamine H 1 -receptor antagonist activity in isolated tissues, animal models, and humans. Azelastine hydrochloride nasal solution is administered as a racemic mixture with no difference in pharmacologic activity noted between the enantiomers in in vitro studies. The major metabolite, desmethylazelastine, also possesses H 1- receptor antagonist activity.

Indications

Approved

Eye Manifestations — eye allergy
Hypersensitivity — allergic disease
Nasal Obstruction — Nasal congestion

Off-label

Rhinitis, Allergic, Perennial
Rhinitis, Allergic, Seasonal

Contraindications

Source: openFDA

None. None. ( 4 ) Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (3)

Rare Atrial fibrillation · Palpitations · Tachycardia

Vascular disorders (1)

Rare Hypertension

Nervous system disorders (4)

Very Common Headache · Somnolence

Common Dizziness

Rare Paraesthesia

Renal and urinary disorders (1)

Rare Urinary retention

Immune system disorders (1)

Rare Anaphylactic shock

Gastrointestinal disorders (4)

Common Dry mouth · Nausea

Rare Abdominal pain · Gastrointestinal pain

Skin and subcutaneous tissue disorders (3)

Rare Dermatitis · Pruritus · Rash

Musculoskeletal and connective tissue disorders (1)

Rare Muscle contractions involuntary

Psychiatric disorders (1)

Rare Confusional state

Eye disorders (2)

Rare Vision blurred · Xerophthalmia

Infections and infestations (4)

Common Pharyngitis · Rhinitis · Sinusitis · Upper respiratory tract infection

Investigations (2)

Common Weight increased

Rare Feeling abnormal

General disorders and administration site conditions (13)

Very Common Dysgeusia

Common Asthenia · Dysaesthesia · Fatigue · Sneezing

Rare Anaphylactoid reaction · Anosmia · Application site irritation · Chest pain · Face oedema · Nervousness · Parosmia · Tension

Respiratory, thoracic and mediastinal disorders (4)

Common Epistaxis · Nasal discomfort

Rare Dyspnoea · Throat irritation

Dosing

Source: openFDA

For intranasal use only ( 2.3 ) Seasonal allergic rhinitis: Pediatric patients 5 to 11 years of age: 1 spray per nostril twice daily ( 2.1 ) Adults and adolescents 12 years of age and older: 1 or 2 sprays per nostril twice daily ( 2.1 ) Vasomotor rhinitis: 2 sprays per nostril twice daily in adults and adolescents 12 years of age and older ( 2.2 ) Prime azelastine hydrochloride nasal solution before initial use and when it has not been used for 3 or more days ( 2.3 ) 2.1 Seasonal Allergic Rhinitis The recommended dosage of azelastine hydrochloride nasal solution in adults and adolescent patients 12 years and older with seasonal allergic rhinitis is one or two sprays per nostril twice daily. The recommended dosage of azelastine hydrochloride nasal solution in pediatric patients 5 years to 11 years of age is one spray per nostril twice daily. 2.2 Vasomotor Rhinitis The recommended dosage of azelastine hydrochloride nasal solution in adults and adolescent patients 12 years and older with vasomotor rhinitis is two sprays per nostril twice daily. 2.3 Important Administration Instructions Administer azelastine hydrochloride nasal solution by the intranasal route only. Priming: Prime azelastine hydrochloride nasal solution before initial use by releasing 4 sprays or until a fine mist appears. When azelastine hydrochloride nasal solution has not been used for 3 or more days, reprime with 2 sprays or until a fine mist appears. Avoid spraying azelastine hydrochloride nasal solution into the eyes.

Warnings & Precautions

Source: openFDA

Warnings & Precautions

Somnolence: Avoid engaging in hazardous occupations requiring complete mental alertness such as driving or operating machinery when taking azelastine hydrochloride nasal solution. ( 5.1 ) Alcohol and other central nervous system (CNS) depressants: Avoid concurrent use with azelastine hydrochloride nasal solution because further decreased alertness and impairment of CNS performance may occur. ( 5.1 )

Somnolence in Activities Requiring Mental Alertness In clinical trials

Somnolence in Activities Requiring Mental Alertness In clinical trials, the occurrence of somnolence has been reported in some patients taking azelastine hydrochloride nasal solution [ see Adverse Reactions ( 6.1 ) ]. Patients should be cautioned against engaging in hazardous occupations requiring complete mental alertness and motor coordination such as operating machinery or driving a motor vehicle after administration of azelastine hydrochloride nasal solution. Concurrent use of azelastine hydrochloride nasal solution with alcohol or other central nervous system depressants should be avoided because additional reductions in alertness and additional impairment of central nervous system performance may occur [ see Drug Interactions ( 7.1 ) ].

Pregnancy & Lactation

Pregnancy

Lactation

Caution Hale L3

Small occasional doses of azelastine nasal spray would not be expected to cause any adverse

Chemistry & Properties

Formula	C22H24ClN3O
Molecular weight	381.91 g/mol
IUPAC name	4-[(4-chlorophenyl)methyl]-2-(1-methylazepan-4-yl)phthalazin-1-one
CAS	58581-89-8
PubChem CID	2267
InChIKey	`MBUVEWMHONZEQD-UHFFFAOYSA-N`
logP	4.3 (XLogP 4.4)
Polar surface area	38.13 Å²
H-bond acceptors / donors	4 / 0
Drug-likeness (QED)	0.68
Lipinski violations	0

SMILES

CN1CCCC(n2nc(Cc3ccc(Cl)cc3)c3ccccc3c2=O)CC1

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	10.0%
Half-life	0.644 h
Volume of distribution	13.616 L/kg
Protein binding	93.4%
BBB penetrant	Yes

Enzyme interactions

Enzyme	Role	Detail
CYP1A2	Substrate	—
CYP2B6	Inhibitor	—
CYP2C19	Substrate	—
CYP2C8	Inhibitor	—
CYP2D6	Inhibitor	IC₅₀ 1.0 µM
CYP2D6	Substrate	—
CYP3A4	Inhibitor	—
CYP3A4	Substrate	—

Receptor binding (top 1)

Target	Action	Affinity
H1 receptor (HRH1)	Antagonist	pKi 8.9

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MDR1 (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Registered Products (5)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Allergodil Eye drops	Ophthalmic Solution 0.5 mg/1 ml	6 ml	Sabbagh Drug Store	5.340
Zalastin Metered Dose Nasal Spray	Spray 0.1 %	10 ml	Amman Pharmaceutical Indusries	5.400
Allergodil Nasal Spray	Spray 1 mg/ml	10 ml	Sabbagh Drug Store	5.520
Flomista Nasal Spray	Spray 0.0365 %, 0.1 %	At least 120 Metered Sprays	Amman Pharmaceutical Industries Co	12.650
Dymista Nasal Spray	Spray 50 mcg, 137 mcg	120 SPR /1 BOT	Sabbagh Drug Store	14.060