Montelukast

R03D - Other systemic drugs for obstructive airway diseases ATC R03DC03 Small molecule approved 1998 Oral Natural product Black-box warning

JFDA label: Singulair Tablets

⚠ Black-Box Warning

Mechanism of Action

Selective leukotriene receptor antagonist that inhibits the cysteinyl leukotriene receptor. Cysteinyl leukotrienes and leukotriene receptor occupation have been correlated with the pathophysiology of asthma, including airway edema, smooth muscle contraction, and altered cellular activity associated with the inflammatory process, which contribute to the signs and symptoms of asthma. Cysteinyl leukotrienes are also released from the nasal mucosa following allergen exposure leading to symptoms associated with allergic rhinitis (Jarvis, 2000).

Indications

Off-label

Chronic urticaria
Urticaria (nonsteroidal anti-inflammatory drug–induced)

Contraindications

Source: Lexicomp

Hypersensitivity to montelukast or any component of the formulation Absolute

Adverse Reactions

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

Nervous system disorders (3)

Common dizziness · fatigue · Headache

Hepatobiliary disorders (2)

Common increased serum ALT · Increased serum AST

Renal and urinary disorders (1)

Common Pyuria

Gastrointestinal disorders (7)

Common Abdominal pain · diarrhea · dyspepsia · gastroenteritis · nausea · tooth infection · toothache

Skin and subcutaneous tissue disorders (6)

Common Atopic dermatitis · dermatitis · eczema · skin infection · skin rash · urticaria

Musculoskeletal and connective tissue disorders (1)

Common Weakness

Eye disorders (2)

Common Conjunctivitis · myopia

Ear and labyrinth disorders (3)

Common Otalgia · otitis · otitis media

Infections and infestations (3)

Common Influenza · varicella · viral infection

General disorders and administration site conditions (2)

Common Fever · trauma

Respiratory, thoracic and mediastinal disorders (12)

Common acute bronchitis · Cough · epistaxis · laryngitis · nasal congestion · pharyngitis · pneumonia · rhinitis · rhinorrhea · sinus headache · sinusitis · upper respiratory tract infection

Dosing

Source: Lexicomp

Note: Patients with both asthma and allergic rhinitis should take only one dose in the evening. Allergic rhinitis (perennial or seasonal): Oral: 10 mg once daily Asthma: Oral: 10 mg once daily (in the evening) Bronchoconstriction, exercise-induced (prevention): Oral: 10 mg at least 2 hours prior to exercise. Note: Additional doses should not be administered within 24 hours. Daily administration to prevent exercise-induced bronchoconstriction has not been evaluated. Patients receiving montelukast for another indication should not take an additional dose to prevent exercise-induced bronchoconstriction. Chronic urticaria (off-label use): Oral: 10 mg once daily (DiLorenzo 2004; Nettis 2004) Urticaria (nonsteroidal anti-inflammatory drug–induced) (off-label use): Oral: 10 mg once daily (Pacor 2001)

(For additional information see "Montelukast: Pediatric drug information") Note: Patients with both asthma and allergic rhinitis should take only one dose in the evening. Asthma: Oral: Children ≥1 to 4 mg (oral granules) once daily (in the evening) Children ≥2 to 4 mg (chewable tablet or oral granules) once daily (in the evening) Children ≥6 years and Adolescents 5 mg (chewable tablet) once daily (in the evening) Adolescents ≥15 years: 10 mg once daily (in the evening) Bronchoconstriction, exercise-induced (prevention): Note: Additional doses should not be administered within 24 hours. Daily administration to prevent exercise-induced bronchoconstriction has not been evaluated. Patients receiving montelukast for another indication should not take an additional dose to prevent exercise-induced bronchoconstriction. Oral: Children ≥6 years and Adolescents 5 mg (chewable tablet) at least 2 hours prior to exercise Adolescents ≥15 years: 10 mg once daily at least 2 hours prior to exercise Perennial allergic rhinitis: Oral: Children 6 months to 4 mg (oral granules) once daily Children ≥2 to 4 mg (chewable tablet or oral granules) once daily Children ≥6 years and Adolescents 5 mg (chewable tablet) once daily Adolescents ≥15 years: 10 mg once daily Seasonal allergic rhinitis: Oral: Children ≥2 to 4 mg (chewable tablet or oral granules) once daily Children ≥6 years and Adolescents 5 mg (chewable tablet) once daily Adolescents ≥15 years: 10 mg once daily Urticaria (nonsteroidal anti-inflammatory drug-induced) (off-label use): Oral: Adolescents ≥15 years: 10 mg once daily (Pacor 2001)

Refer to adult dosing.

No dosage adjustment necessary.

Mild-to-moderate impairment: No dosage adjustment necessary. Severe impairment: No dosage adjustment provided in manufacturer’s labeling; has not been studied.

Warnings & Precautions

Source: Lexicomp

Eosinophilia and vasculitis

In rare cases, patients may present with systemic eosinophilia, sometimes presenting with clinical features of vasculitis consistent with eosinophilic granulomatosis with polyangiitis (formerly known as Churg-Strauss), a condition which is often treated with systemic corticosteroid therapy. Healthcare providers should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal association between montelukast and these underlying conditions has not been established.

Neuropsychiatric events

Postmarketing reports of behavioral changes (eg, abnormal dreams, agitation, aggression, anxiety, attention deficit, depression, disorientation, hallucinations, hostility, insomnia, irritability, memory disturbances, restlessness, sleep disturbance, suicide ideation/behavior, and tremor) have been noted in pediatric, adolescent, and adult patients. In a retrospective analysis performed by Merck, serious behavior-related events were rare (Philip, 2009a); assess patients for behavioral changes. Patients should be instructed to notify the prescriber if behavioral changes occur. Disease related concerns:

Acute asthma/bronchospasm

Not FDA approved for use in the reversal of bronchospasm in acute asthma attacks, including status asthmaticus. Some studies, however, support its use as adjunctive therapy (Cylly, 2003; Ferreira, 2001; Harmancik, 2006). Appropriate rescue medication should be available. Montelukast treatment should continue during acute asthma exacerbation.

Aspirin-sensitive asthmatics

Montelukast will not interrupt bronchoconstrictor response to aspirin or other NSAIDs. Patients with known aspirin sensitivity should continue to avoid these agents. Concurrent drug therapy issues:

Corticosteroids

When inhaled or systemic corticosteroid reduction is considered in patients initiating or receiving montelukast, appropriate clinical monitoring and a gradual dose reduction of the steroid are recommended.

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Dosage form specific issues:

Chewable tablet

Contains phenylalanine.

Pregnancy & Lactation

Pregnancy

FDA category B

Safe

Leukotriene receptor antagonist; can be continued in pregnancy if needed for asthma control

Lactation

RID 0.68%

Montelukast is present in breast milk (Datta 2017). The relative infant dose (RID) of montelukast is 0.68% when calculated using an average breast milk concentration compared to a weight-adjusted maternal dose of 10 mg/day (Datta 2017). In general, breastfeeding is considered acceptable when the RID is The RID of montelukast was calculated using an average milk concentration of 5.3 ng/mL (average range: 2.87 to 9.12 ng/mL), providing an estimated daily infant dose via breast milk of 0.798 mc

Monitoring

Clinical pearl	Mood or behavior changes, including suicidal thinking/behavior

Chemistry & Properties

Formula	C35H36ClNO3S
Molecular weight	586.2 g/mol
IUPAC name	2-[1-[[(1R)-1-[3-[(E)-2-(7-chloroquinolin-2-yl)ethenyl]phenyl]-3-[2-(2-hydroxypropan-2-yl)phenyl]propyl]sulfanylmethyl]cyclopropyl]acetic acid
CAS	158966-92-8
PubChem CID	5281040
InChIKey	`UCHDWCPVSPXUMX-TZIWLTJVSA-N`
logP	8.95 (XLogP 7.7)
Polar surface area	70.42 Å²
H-bond acceptors / donors	4 / 2
Drug-likeness (QED)	0.17
Lipinski violations	2

SMILES

CC(C)(O)c1ccccc1CC[C@@H](SCC1(CC(=O)O)CC1)c1cccc(/C=C/c2ccc3ccc(Cl)cc3n2)c1

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	35.0%
Half-life	1.446 h
Volume of distribution	0.376 L/kg
Protein binding	99.2%
BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP1A2	Inhibitor	—
CYP1A2	Substrate	—
CYP2B6	Inhibitor	—
CYP2B6	Substrate	—
CYP2C19	Substrate	—
CYP2C8	Inhibitor	—
CYP2C8	Substrate	IC₅₀ 0.27213418516308907 µM
CYP2C9	Substrate	—
CYP3A4	Substrate	—
CYP3A5	Substrate	—

Receptor binding (top 2)

Target	Action	Affinity
CysLT1 receptor (CYSLTR1)	Antagonist	pIC50 8.6
CysLT1 receptor (CYSLTR1)	Antagonist	pKi 8.6

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MDR1 (Inhibitor)MRP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)OATP2B1 (Inhibitor)P-gp (Inhibitor)OATP2B1 (Substrate)P-gp (Substrate)

Drug–drug interactions (86, DDInter)

Interacting drug	Severity	Management
Abametapir (topical)	moderate
Abiraterone	moderate
Alpelisib	moderate
Aminoglutethimide	moderate
Amiodarone	moderate
Amobarbital	moderate
Apalutamide	moderate
Bexarotene	moderate
Bosentan	moderate
Butabarbital	moderate
Butalbital	moderate
Carbamazepine	moderate
Cenobamate	moderate
Dabrafenib	moderate
Deferasirox	moderate
Delavirdine	moderate
Dexamethasone	moderate
Duvelisib	moderate
Echinacea	moderate
Efavirenz	moderate
Elagolix	moderate
Enzalutamide	moderate
Etravirine	moderate
Felbamate	moderate
Fenofibrate	moderate
Fluconazole	moderate
Fluvoxamine	moderate
Fosphenytoin	moderate
Fostamatinib	moderate
Gemfibrozil	moderate
Griseofulvin	moderate
Imatinib	moderate
Isoniazid	moderate
Ivacaftor	moderate
Ivosidenib	moderate
Lapatinib	moderate
Larotrectinib	moderate
Lefamulin	moderate
Leflunomide	moderate
Letermovir	moderate

Showing 40 of 86.

Registered Products (49)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Azma-Ban	Tablet 10 mg	7 tab pack varies	AL-RAM PHARMA.INDUS.CO.LTD/JORDAN	3.620
Lukast	Tablet 4 mg	10 tab pack varies	Pharma International Company/ Jordan	4.460
Lukast	Tablet 5 mg	10 tab pack varies	Pharma International Company/ Jordan	5.090
Lukast	Tablet 10 mg	10 tab pack varies	Pharma International Company/ Jordan	5.090
Montas 4mg Chew Tab	Chewable Tablet as Sodium 4 mg	28 tab	Noor Drug Store	6.350
Azma-Ban	Tablet 10 mg	14 tab pack varies	AL-RAM PHARMA.INDUS.CO.LTD/JORDAN	7.110
Montas-5mg Chewable Tab	Chewable Tablet as Sodium 5 mg	28 tab	Noor Drug Store	7.620
Moncas	Tablet 4 mg	28 tab	Orient Montreal Drug Store	7.880
Montas	Tablet as Sodium 10 mg	28 tab	Noor Drug Store	8.130
M-KAST 10	Tablet 10.38 mg	30 tab	AL Rahma Drug Store	8.160
M-KAST 5	Tablet 5.19 mg	30 tab	AL Rahma Drug Store	8.160
Moncas	Tablet 5 mg	28 tab	Orient Montreal Drug Store	8.430
Moncas	Film-Coated Tablet 10 mg	28 Film	Orient Montreal Drug Store	8.430
monkasta	Tablet 10 mg	28 tab	Abu Sheikha Drug Store	8.820
Airfast Pediatrics 4mg Granules	Granules 4 mg	28 sachet	Sukhtian Group	8.940
Airfast 4 mg Chewable tablets	Chewable Tablet 4.16 mg	30 tab	Sukhtian Group	9.930
Montal	Tablet 4 mg	30 tab pack varies	Al-Taqqadom Pharmaceutical Industries	9.930
Sincast	Tablet 4 mg	28 tab	THE JORDANIAN PHARMACEUTICAL MANUFACTURING COMPANY/JORDAN	10.310
Sincast	Tablet 5 mg	30 tab	THE JORDANIAN PHARMACEUTICAL MANUFACTURING COMPANY/JORDAN	11.050
Montal	Tablet 5 mg	30 tab pack varies	Al-Taqqadom Pharmaceutical Industries	11.060
Montal	Tablet 10 mg	30 tab pack varies	Al-Taqqadom Pharmaceutical Industries	11.060
Airfast 5 mg Chewable tablets	Chewable Tablet 5.2 mg	30 tab	Sukhtian Group	11.290
Airfast	Tablet 10 mg	30 tab	Sukhtian Group	11.300
Sincast 10	Tablet 10 mg	30 tab	THE JORDANIAN PHARMACEUTICAL MANUFACTURING COMPANY/JORDAN	11.300
Singulair Chewable Tablets	Chewable Tablet 4 mg	28 tab	Adatco Drug Store	11.850
Asmatec	Tablet 4 mg	30 tab	Hikma Pharmaceuticals Co.Ltd/Jordan	12.770
Lukast	Tablet 4 mg	30 tab pack varies	Pharma International Company/ Jordan	12.770
Montolair kids	Tablet 4.2 mg	30 tab	SAVVY PHARMA/JORDAN	12.770
Motrinex 4mg Chewable Tab	Chewable Tablet 4 mg	30 tab pack varies	Dar Al Dawa Development and Investment Co Ltd/Jordan	12.770
Singulair Paediatric Granules	Granules 4 mg	28 sachet	Adatco Drug Store	12.770
Unicast Chewable Tablet	Chewable Tablet 4 mg	30 tab	UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN	12.770
Singulair Paediatric	Tablet 5 mg	28 tab	Adatco Drug Store	13.050
Singulair Tablets	Tablet 10 mg	28 tab	Adatco Drug Store	13.050
Motrinex 10 mg F.C Tab	Film-Coated Tablet 10 mg	30 tab pack varies	Dar Al Dawa Development and Investment Co Ltd/Jordan	13.390
Motrinex Chewable Tablet	Chewable Tablet 5 mg	30 tab pack varies	Dar Al Dawa Development and Investment Co Ltd/Jordan	13.390
Montolair Kids	Tablet 5.2 mg	30 tab	SAVVY PHARMA/JORDAN	13.440
Azma-Ban	Tablet 10 mg	28 tab pack varies	AL-RAM PHARMA.INDUS.CO.LTD/JORDAN	13.550
Montolair 10mg F.C Tab	Film-Coated Tablet 10 mg	30 tab	SAVVY PHARMA/JORDAN	13.580
Unicast 10 Tablet	Tablet 10 mg	30 tab	UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN	14.500
Unicast 5 Chewable Tab	Chewable Tablet 5 mg	30 tab	UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN	14.500
Asmatec	Tablet 5 mg	30 tab	Hikma Pharmaceuticals Co.Ltd/Jordan	14.520
Lukast	Tablet 10 mg	30 tab pack varies	Pharma International Company/ Jordan	14.520
Lukast	Tablet 5 mg	30 tab pack varies	Pharma International Company/ Jordan	14.520
Motrinex 4mg Chewable Tab	Chewable Tablet 4 mg	500 tab pack varies	Dar Al Dawa Development and Investment Co Ltd/Jordan	185.170
Motrinex 10 mg F.C Tab	Film-Coated Tablet 10 mg	500 tab pack varies	Dar Al Dawa Development and Investment Co Ltd/Jordan	194.150
Motrinex Chewable Tablet	Chewable Tablet 5 mg	500 tab pack varies	Dar Al Dawa Development and Investment Co Ltd/Jordan	246.240
Montal	Tablet 4 mg	1000 tab pack varies	Al-Taqqadom Pharmaceutical Industries	281.350
Montal	Tablet 5 mg	1000 tab pack varies	Al-Taqqadom Pharmaceutical Industries	313.370
Montal	Tablet 10 mg	1000 tab pack varies	Al-Taqqadom Pharmaceutical Industries	313.370