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Mar.01.2021

Montelukast

Indications/Dosage

Labeled

  • allergic rhinitis
  • asthma maintenance
  • exercise-induced bronchospasm prophylaxis
  • perennial allergies
  • seasonal allergies

Off-Label

  • aspirin-induced asthma
  • atopic dermatitis
  • chronic idiopathic urticaria
  • sleep apnea
  • urticaria
† Off-label indication

For asthma maintenance treatment

Oral dosage (oral tablets)

Adults

10 mg PO once daily in the evening. LIMITATION OF USE: Montelukast is not indicated for treatment of an acute asthma attack.[29630]

Adolescents 15 to 17 years

10 mg PO once daily in the evening. LIMITATION OF USE: Montelukast is not indicated for treatment of an acute asthma attack.[29630]

Oral dosage (chewable tablets)

Adolescents and Children 6 to 14 years

5 mg PO once daily in the evening. LIMITATION OF USE: Montelukast is not indicated for treatment of an acute asthma attack.[29630]

Children 2 to 5 years

4 mg PO once daily in the evening. LIMITATION OF USE: Montelukast is not indicated for treatment of an acute asthma attack.[29630]

Oral dosage (oral granules)

Children 1 to 5 years

4 mg PO once daily in the evening. LIMITATION OF USE: Montelukast is not indicated for treatment of an acute asthma attack.[29630]

For exercise-induced bronchospasm prophylaxis

Oral dosage

Adults

10 mg PO once, given at least 2 hours before exercise. Max: 10 mg/24 hours. Patients receiving daily montelukast for another indication should not take an additional dose to prevent exercise-induced bronchospasm (EIB). Rescue medications (e.g., beta-agonists) should be available.[29630]

Adolescents 15 to 17 years

10 mg PO once, given at least 2 hours before exercise. Max: 10 mg/24 hours. Patients receiving daily montelukast for another indication should not take an additional dose to prevent exercise-induced bronchospasm (EIB). Rescue medications (e.g., beta-agonists) should be available.[29630]

Children and Adolescents 6 to 14 years

5 mg PO once, given at least 2 hours before exercise. Max: 5 mg/24 hours. Patients receiving daily montelukast for another indication should not take an additional dose to prevent exercise-induced bronchospasm (EIB). Rescue medications (e.g., beta-agonists) should be available.[29630]

For the treatment of allergic rhinitis (seasonal allergies and perennial allergies)

for perennial allergic rhinitis

Oral dosage (regular tablets, 10 mg)

Adults

10 mg PO once daily.[29630] LIMITS of USE: Montelukast should not be used for mild symptoms of allergic rhinitis, but should be reserved for patients who are not treated effectively with or cannot tolerate other allergy medication.[29630] [65079]

Adolescents 15 years and older

10 mg PO once daily.[29630] LIMITS of USE: Montelukast should not be used for mild symptoms of allergic rhinitis, but should be reserved for patients who are not treated effectively with or cannot tolerate other allergy medication.[29630] [65079]

Oral dosage (chewable tablets, 4 or 5 mg or oral granules, 4 mg packet)

Children and Adolescents 6 to 14 years

5 mg PO once daily.[29630] LIMITS of USE: Montelukast should not be used for mild symptoms of allergic rhinitis, but should be reserved for patients who are not treated effectively with or cannot tolerate other allergy medication.[29630] [65079]

Children 2 to 5 years

4 mg PO once daily.[29630] LIMITS of USE: Montelukast should not be used for mild symptoms of allergic rhinitis, but should be reserved for patients who are not treated effectively with or cannot tolerate other allergy medication.[29630] [65079]

Infants and Children 6 months to 2 years

4 mg oral granules PO once daily (do not administer tablets).[29630] LIMITS of USE: Montelukast should not be used for mild symptoms of allergic rhinitis, but should be reserved for patients who are not treated effectively with or cannot tolerate other allergy medication.[29630] [65079]

for seasonal allergic rhinitis

Oral dosage (regular tablets, 10 mg)

Adults

10 mg PO once daily.[29630] LIMITS of USE: Montelukast should not be used for mild symptoms of allergic rhinitis, but should be reserved for patients who are not treated effectively with or cannot tolerate other allergy medication.[29630] [65079]

Adolescents 15 years and older

10 mg PO once daily.[29630] LIMITS of USE: Montelukast should not be used for mild symptoms of allergic rhinitis, but should be reserved for patients who are not treated effectively with or cannot tolerate other allergy medication.[29630] [65079]

Oral dosage (chewable tablets, 4 or 5 mg or oral granules, 4 mg packet)

Children and Adolescents 6 to 14 years

5 mg PO once daily.[29630] LIMITS of USE: Montelukast should not be used for mild symptoms of allergic rhinitis, but should be reserved for patients who are not treated effectively with or cannot tolerate other allergy medication.[29630] [65079]

Children 2 to 5 years

4 mg PO once daily.[29630] LIMITS of USE: Montelukast should not be used for mild symptoms of allergic rhinitis, but should be reserved for patients who are not treated effectively with or cannot tolerate other allergy medication.[29630] [65079]

For the treatment of aspirin-induced asthma†

Oral dosage

Adults

10 mg PO once daily at bedtime. Use with an established asthma treatment regimen that includes necessary medications such as bronchodilators and inhaled or systemic corticosteroids. The benefit of montelukast in aspirin-intolerant asthmatic patients was assessed in a randomized, double-blind, placebo-controlled trial. Patients were randomized to receive montelukast 10 mg (n = 40) or placebo (n = 40) once daily at bedtime over 4 weeks. Glucocorticosteroids were used in 85% to 90% of patients and theophylline in 40% to 45% of patients at baseline. A 2-week washout period occurred prior to study entry during which no long-acting antihistamines, long-acting beta agonists, or inhaled antimuscarinics were used.At study conclusion, montelukast significantly improved FEV1 and twice daily peak expiratory flow rate (PEFR) rates vs. placebo (p less than 0.001), with mean differences in FEV1 of 10.2%, 28 L/minute (morning PEFR), and 23.1 L/minute (evening PEFR). Less rescue short-acting beta agonist (SABA) was used in treated patients vs. placebo, and the montelukast group had 54% fewer asthma exacerbations. Asthma quality of life improved; patients with nocturnal asthma slept 1.3 nights more per week compared to those treated with placebo. No significant adverse reactions were observed.[55876]

For the treatment of atopic dermatitis†

Oral dosage

Adults

10 mg PO once daily. May be used concomitantly with emollients, antihistamines, or topical corticosteroids. Montelukast efficacy was evaluated in a randomized, double-blind, placebo-controlled crossover trial in 8 adults with mild to moderate atopic dermatitis (AD). Patients in 2 treatment groups were randomized to a regimen of montelukast 10 mg/day for 4 weeks, then placebo daily for 4 weeks after a 2-day washout period, or vice versa. Topical steroids, emollients, and antihistamines were used because of flaring during washout and initial blinded study periods. At study conclusion, a significant decrease in symptom severity was demonstrated by ADASI (atopic dermatitis area and severity index) scores, with scores with montelukast decreasing from approximately 8 to 6, and scores with placebo increasing from approximately 8 to 10 (p = 0.014). Improvements in scaling/dryness, lichenification, induration, erythema, erosions, and excoriation were noted. No patient completely cleared.[55871] In a single-blind study, adult patients with moderate to severe AD were randomized to treatment with montelukast 10 mg/day with placebo tablets 3 times daily or a combination of cetirizine, corticosteroids, and 10 days of clarithromycin. Placebo topical gel or topical emulsions containing urea or ammonium lactate were offered to those treated with montelukast or the combination regimen, respectively. After 6 weeks, the severity of AD, as estimated by the SCORAD (Scoring Atopic Dermatitis) tool, decreased in each treatment group, with mean scores of 25.5 for montelukast (baseline = 46.5) and 23.3 for the combination regimen (baseline = 47.3); the difference between groups was not statistically significant. Patients felt that reduction in pruritus was the most notable symptom improvement (in both treatment groups); montelukast did not improve xerosis. No adverse reactions to treatment were reported.[55872]

For the adjunctive treatment of chronic urticaria† or chronic idiopathic urticaria†

Oral dosage

Adults

10 mg PO once daily in combination with a non-sedating antihistamine is recommended for refractory urticaria; montelukast should only be added to a treatment regimen after optimal dosing of a non-sedating antihistamine fails to control the urticaria.[55878] The efficacy and safety of montelukast for the treatment of chronic idiopathic urticaria was evaluated in a randomized, single-blind, placebo-controlled crossover study in adults with refractory urticaria (n = 30). Patients were randomized to receive montelukast 10 mg or placebo once daily at bedtime, with cetirizine 10 mg given as needed. Each treatment was given for 6 weeks with a 2-week washout period between crossover. Improvement was assessed by daily urticaria activity scores (UAS) completed by the patient, taking into account wheal numbers and itching severity, graded on a 0 to 3 severity scale (none to severe). A significant decrease in urticaria scores occurred with montelukast treatment (p < 0.001), and less cetirizine was used compared to the placebo group (p < 0.001). No significant adverse reactions were noted.[55879] Another randomized, double-blind, placebo-controlled trial evaluated the efficacy of montelukast in combination with desloratadine for the treatment of chronic urticaria. Patients (n = 81) received desloratadine 5 mg with montelukast 10 mg, desloratadine 5 mg with placebo, or placebo for 6 weeks following a 1 week single-blind placebo run-in period. A 1 week placebo washout period occurred following active treatment. Study outcomes included patient-reported symptoms of pruritus, size and number of wheals, and number of urticarial episodes graded on a 0 to 3 severity scale (none to severe). Quality of life questionnaires were assessed at each clinical visit. Significant improvement in overall urticaria symptoms was reported in each active treatment group compared to placebo (p < 0.05) and with desloratadine plus montelukast compared to desloratadine alone (p < 0.05). The montelukast combination regimen significantly reduced pruritus compared to desloratadine alone during active treatment (p < 0.05). The number of urticaria episodes did not significantly differ between the active treatment groups. Improvement in quality of life scores was greater with desloratadine plus montelukast vs. desloratadine alone throughout treatment and at follow-up after washout. No adverse reactions were reported.[55880]

Children and Adolescents

The addition of a leukotriene receptor antagonist, such as montelukast, to non-sedating antihistamine therapy is recommended if symptoms persist 1 to 4 weeks after optimal antihistamine dosing.[55878] Although specific dosing guidelines are not provided, use of typical age-adjusted doses should be considered (i.e., 4 mg/day for children aged 5 years or younger, 5 mg/day for children 6 to 14 years, and 10 mg/day for adolescents aged 15 years or older).

For the treatment of mild to moderate obstructive sleep apnea†

Oral dosage

Children 6 to 10 years

5 mg PO once daily at bedtime.[55839] [55846]

Children 2 to 5 years

4 mg PO once daily at bedtime.[55839] [55846]

Therapeutic Drug Monitoring

Maximum Dosage Limits

  • Adults

    10 mg/day PO.

  • Geriatric

    10 mg/day PO.

  • Adolescents

    15 years and older: 10 mg/day PO.

    13 to 14 years: 5 mg/day PO.

  • Children

    6 to 12 years: 5 mg/day PO.

    1 to 5 years: 4 mg/day PO.

  • Infants

    6 months and older: 4 mg/day PO for perennial allergic rhinitis only.

    Less than 6 months: Safety and efficacy have not been established.

Patients with Hepatic Impairment Dosing

No dosage adjustment is recommended for mild to moderate hepatic impairment. Montelukast has not been evaluated in patients with severe hepatic impairment or hepatitis; no dosage guidelines are available for these patients.[29630]

Patients with Renal Impairment Dosing

No dosage adjustments are recommended; montelukast is not significantly eliminated via the renal route.[29630]

† Off-label indication
Revision Date: 03/01/2021, 04:10:57 PM

References

29630 - Singulair (montelukast) package insert. Whitehouse Station, NJ: Merck and Co, Inc.; 2021 Feb.55839 - Goldbart AD, Greenberg-Dotan S, Tal A. Montelukast for children with obstructive sleep apnea: a double-blind, placebo-controlled study. Pediatrics 2012;130:e575-580.55846 - Goldbart AD, Goldman JL, Veling MC. Leukotriene modifier therapy for mild sleep-disordered breathing in children. Am J Respir Crit Care Med 2005;172:364-370.55871 - Yanase DM, David-Bajar K. The leukotriene antagonist montelukast as a therapeutic agent for atopic dermatitis. J Am Acad Dermatol 2001;44:89-93.55872 - Luigi G, Firgerio E, Altomare G. A randomized trial of leukotriene receptor antagonist montelukast in moderate to severe atopic dermatitis of adults. Eur J Dermatol 2001;11:209-213.55876 - Dahlen S, Malmstrom K, Nizankowska E, et al. Improvement of aspirin-intolerant asthma by montelukast, a leukotriene antagonist. Am J Respir Crit Care Med 2002;165:9-14.55878 - Zuberbier T, Asero R, Bindslev Jensen C, et al. EAACI/GA2LEN/EDF/WAO guideline: management of urticaria. Allergy 2009;64:1427-1443.55879 - Erbagci, Z. The leukotriene receptor antagonist montelukast in the treatment of chronic idiopathic urticaria a single-blind, placebo-controlled, crossover clinical study. J Allergy Clin Immunol 2002;110:484-488.55880 - Nettis E, Colanardi MC, Paradiso T, et al. Desloratadine in combination with montelukast in the treatment of chronic urticaria: a randomized, double-blind, placebo-controlled study. Clin Exp Allergy 2004;34:1401-1407.65079 - US Food and Drug Administration (FDA). FDA requires boxed warning about serious mental health side effects for asthma and allergy drug montelukast (Singulair); advises restricting use for allergic rhinitis. Available at: http://s2027422842.t.en25.com/e/es?s=2027422842&e=308434&elqTrackId=376c7bc788024cd5a73d955f2e3dcbdc&elq=cc7c8246f96541178cb9e7a0e8a616bc&elqaid=11491&elqat=1. Accessed March 4, 2020.

How Supplied

Montelukast Sodium Chewable tablet

Montelukast Sodium 4mg Chewable Tablet (27241-0016) (Ajanta Pharma USA Inc) null

Montelukast Sodium Chewable tablet

Montelukast Sodium 4mg Chewable Tablet (68084-0638) (American Health Packaging) (off market)

Montelukast Sodium Chewable tablet

Montelukast Sodium 4mg Chewable Tablet (60505-3573) (Apotex Corp) (off market)

Montelukast Sodium Chewable tablet

Montelukast Sodium 4mg Chewable Tablet (65862-0567) (Aurobindo Pharma USA Inc.) null

Montelukast Sodium Chewable tablet

Montelukast Sodium 4mg Chewable Tablet (42291-0622) (AvKARE, Inc.) null

Montelukast Sodium Chewable tablet

Montelukast Sodium 4mg Chewable Tablet (50268-0573) (AvPAK; a Division of AvKARE Inc) null

Montelukast Sodium Chewable tablet

Montelukast Sodium 4mg Chewable Tablet (69452-0106) (Bionpharma Inc) null

Montelukast Sodium Chewable tablet

Montelukast Sodium 4mg Chewable Tablet (31722-0727) (Camber Pharmaceuticals Inc) null

Montelukast Sodium Chewable tablet

Montelukast Sodium 4mg Chewable Tablet (57237-0212) (Citron Pharma LLC) null

Montelukast Sodium Chewable tablet

Montelukast Sodium 4mg Chewable Tablet (55111-0593) (Dr. Reddy's Laboratories, Inc.) null

Montelukast Sodium Chewable tablet

Montelukast Sodium 4mg Chewable Tablet (59762-0045) (Greenstone Ltd) (off market)

Montelukast Sodium Chewable tablet

Montelukast Sodium 4mg Chewable Tablet (00143-9651) (Hikma Pharmaceuticals USA Inc.) null

Montelukast Sodium Chewable tablet

Montelukast Sodium 4mg Chewable Tablet (00054-0288) (Hikma Pharmaceuticals USA Inc.) (off market)

Montelukast Sodium Chewable tablet

Montelukast Sodium 4mg Chewable Tablet (59746-0358) (Jubilant Cadista Pharmaceuticals Inc.) (off market)

Montelukast Sodium Chewable tablet

Montelukast Sodium 4mg Chewable Tablet (62175-0204) (Kremers Urban Pharmaceuticals Inc., a subsidiary of Lannett Company. Inc.) null

Montelukast Sodium Chewable tablet

Montelukast Sodium 4mg Chewable Tablet (33342-0110) (MacLeods Pharma) null

Montelukast Sodium Chewable tablet

Montelukast Sodium 4mg Chewable Tablet (00378-5204) (Mylan Pharmaceuticals Inc.) null

Montelukast Sodium Chewable tablet

Montelukast Sodium 4mg Chewable Tablet (00603-4653) (Par Pharmaceuticals, an Endo Company) (off market)

Montelukast Sodium Chewable tablet

Montelukast Sodium 4mg Chewable Tablet (43063-0381) (PD-Rx Pharmaceuticals, Inc.) null

Montelukast Sodium Chewable tablet

Montelukast Sodium 4mg Chewable Tablet (00781-5554) (Sandoz Inc. a Novartis Company) null

Montelukast Sodium Chewable tablet

Montelukast Sodium 4mg Chewable Tablet (70436-0090) (Slate Run Pharmaceuticals, LLC) null

Montelukast Sodium Chewable tablet

Montelukast Sodium 4mg Chewable Tablet (00093-7424) (Teva Pharmaceuticals USA) (off market)

Montelukast Sodium Chewable tablet

Montelukast Sodium 4mg Chewable Tablet (13668-0079) (Torrent Pharma, Inc) null

Montelukast Sodium Chewable tablet

Montelukast Sodium 4mg Chewable Tablet (29300-0221) (Unichem Pharmaceuticals USA, Inc) null

Montelukast Sodium Chewable tablet

Singulair 4mg Chewable Tablet (00006-1711) (Merck Sharp & Dohme Corp., a Subsidiary of Merck & Co., Inc.) null

Montelukast Sodium Chewable tablet

Singulair 4mg Chewable Tablet (00006-0711) (Merck Sharp & Dohme Corp., a Subsidiary of Merck & Co., Inc.) (off market)

Montelukast Sodium Chewable tablet

Singulair 4mg Chewable Tablet (78206-0170) (Organon LLC) null

Montelukast Sodium Chewable tablet

Singulair 4mg Chewable Tablet (55289-0990) (PD-Rx Pharmaceuticals, Inc.) (off market)

Montelukast Sodium Chewable tablet

Singulair 4mg Chewable Tablet (55289-0989) (PD-Rx Pharmaceuticals, Inc.) (off market)

Montelukast Sodium Chewable tablet

Montelukast Sodium 5mg Chewable Tablet (27241-0017) (Ajanta Pharma USA Inc) null

Montelukast Sodium Chewable tablet

Montelukast Sodium 5mg Chewable Tablet (68084-0864) (American Health Packaging) (off market)

Montelukast Sodium Chewable tablet

Montelukast Sodium 5mg Chewable Tablet (68084-0619) (American Health Packaging) (off market)

Montelukast Sodium Chewable tablet

Montelukast Sodium 5mg Chewable Tablet (60505-3574) (Apotex Corp) (off market)

Montelukast Sodium Chewable tablet

Montelukast Sodium 5mg Chewable Tablet (65862-0568) (Aurobindo Pharma USA Inc.) null

Montelukast Sodium Chewable tablet

Montelukast Sodium 5mg Chewable Tablet (42291-0623) (AvKARE, Inc.) null

Montelukast Sodium Chewable tablet

Montelukast Sodium 5mg Chewable Tablet (50268-0574) (AvPAK; a Division of AvKARE Inc) null

Montelukast Sodium Chewable tablet

Montelukast Sodium 5mg Chewable Tablet (69452-0107) (Bionpharma Inc) null

Montelukast Sodium Chewable tablet

Montelukast Sodium 5mg Chewable Tablet (31722-0728) (Camber Pharmaceuticals Inc) null

Montelukast Sodium Chewable tablet

Montelukast Sodium 5mg Chewable Tablet (57237-0213) (Citron Pharma LLC) null

Montelukast Sodium Chewable tablet

Montelukast Sodium 5mg Chewable Tablet (55111-0594) (Dr. Reddy's Laboratories, Inc.) null

Montelukast Sodium Chewable tablet

Montelukast Sodium 5mg Chewable Tablet (59762-0046) (Greenstone Ltd) (off market)

Montelukast Sodium Chewable tablet

Montelukast Sodium 5mg Chewable Tablet (00054-0289) (Hikma Pharmaceuticals USA Inc.) (off market)

Montelukast Sodium Chewable tablet

Montelukast Sodium 5mg Chewable Tablet (00143-9650) (Hikma Pharmaceuticals USA Inc.) null

Montelukast Sodium Chewable tablet

Montelukast Sodium 5mg Chewable Tablet (59746-0359) (Jubilant Cadista Pharmaceuticals Inc.) (off market)

Montelukast Sodium Chewable tablet

Montelukast Sodium 5mg Chewable Tablet (62175-0205) (Kremers Urban Pharmaceuticals Inc., a subsidiary of Lannett Company. Inc.) null

Montelukast Sodium Chewable tablet

Montelukast Sodium 5mg Chewable Tablet (33342-0111) (MacLeods Pharma) null

Montelukast Sodium Chewable tablet

Montelukast Sodium 5mg Chewable Tablet (00378-5205) (Mylan Pharmaceuticals Inc.) null

Montelukast Sodium Chewable tablet

Montelukast Sodium 5mg Chewable Tablet (00603-4654) (Par Pharmaceuticals, an Endo Company) (off market)

Montelukast Sodium Chewable tablet

Montelukast Sodium 5mg Chewable Tablet (00781-5555) (Sandoz Inc. a Novartis Company) null

Montelukast Sodium Chewable tablet

Montelukast Sodium 5mg Chewable Tablet (70436-0091) (Slate Run Pharmaceuticals, LLC) null

Montelukast Sodium Chewable tablet

Montelukast Sodium 5mg Chewable Tablet (00093-7425) (Teva Pharmaceuticals USA) (off market)

Montelukast Sodium Chewable tablet

Montelukast Sodium 5mg Chewable Tablet (13668-0080) (Torrent Pharma, Inc) null

Montelukast Sodium Chewable tablet

Montelukast Sodium 5mg Chewable Tablet (29300-0222) (Unichem Pharmaceuticals USA, Inc) null

Montelukast Sodium Chewable tablet

Singulair 5mg Chewable Tablet (00006-9275) (Merck Sharp & Dohme Corp., a Subsidiary of Merck & Co., Inc.) null

Montelukast Sodium Chewable tablet

Singulair 5mg Chewable Tablet (00006-0275) (Merck Sharp & Dohme Corp., a Subsidiary of Merck & Co., Inc.) (off market)

Montelukast Sodium Chewable tablet

Singulair 5mg Chewable Tablet (78206-0173) (Organon LLC) null

Montelukast Sodium Chewable tablet

Singulair 5mg Chewable Tablet (58864-0694) (PD-Rx Pharmaceuticals, Inc.) (off market)

Montelukast Sodium Oral granules

Montelukast Sodium 4mg Granules (27241-0015) (Ajanta Pharma USA Inc) nullMontelukast Sodium 4mg Granules package photo

Montelukast Sodium Oral granules

Montelukast Sodium 4mg Granules (59651-0329) (Aurobindo Pharma Limited) null

Montelukast Sodium Oral granules

Montelukast Sodium 4mg Granules (55111-0763) (Dr. Reddy's Laboratories, Inc.) nullMontelukast Sodium 4mg Granules package photo

Montelukast Sodium Oral granules

Montelukast Sodium 4mg Granules (00378-6040) (Mylan Pharmaceuticals Inc.) null

Montelukast Sodium Oral granules

Montelukast Sodium 4mg Granules (66993-0416) (Prasco Laboratories) nullMontelukast Sodium 4mg Granules package photo

Montelukast Sodium Oral granules

Montelukast Sodium 4mg Granules (00093-7487) (Teva Pharmaceuticals USA) nullMontelukast Sodium 4mg Granules package photo

Montelukast Sodium Oral granules

Montelukast Sodium 4mg Granules (13668-0531) (Torrent Pharma, Inc) null

Montelukast Sodium Oral granules

Singulair 4mg Granules (00006-3841) (Merck Sharp & Dohme Corp., a Subsidiary of Merck & Co., Inc.) nullSingulair 4mg Granules package photo

Montelukast Sodium Oral granules

Singulair 4mg Granules (78206-0171) (Organon LLC) null

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (16729-0119) (Accord Healthcare, Inc.) null

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (52343-0037) (Acetris Health, LLC) null

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (27241-0018) (Ajanta Pharma USA Inc) null

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (68084-0875) (American Health Packaging) null

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (68084-0620) (American Health Packaging) (off market)

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (60505-3562) (Apotex Corp) (off market)

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (65862-0574) (Aurobindo Pharma USA Inc.) null

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (42291-0621) (AvKARE, Inc.) (off market)

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (42291-0621) (AvKARE, Inc.) null

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (50268-0575) (AvPAK; a Division of AvKARE Inc) null

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (69452-0105) (Bionpharma Inc) null

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (68001-0248) (BluePoint Laboratories) (off market)

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (68001-0361) (BluePoint Laboratories) null

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (31722-0726) (Camber Pharmaceuticals Inc) null

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (57237-0255) (Citron Pharma LLC) null

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (55111-0725) (Dr. Reddy's Laboratories, Inc) null

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (55111-0725) (Dr. Reddy's Laboratories, Inc.) null

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (68462-0392) (Glenmark Pharmaceuticals) (off market)

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (59762-0030) (Greenstone Ltd) (off market)

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (00054-0259) (Hikma Pharmaceuticals USA Inc.) null

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (00143-9649) (Hikma Pharmaceuticals USA Inc.) null

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (54458-0890) (International Laboratories LLC for Walmart) (off market)

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (62175-0210) (Kremers Urban Pharmaceuticals Inc., a subsidiary of Lannett Company. Inc.) null

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (62175-0210) (Kremers Urban Pharmaceuticals Inc., a subsidiary of Lannett Company. Inc.) (off market)

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (68645-0560) (Legacy Pharmaceutical Packaging, LLC) null

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (68645-0528) (Legacy Pharmaceutical Packaging, LLC) null

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (68645-0466) (Legacy Pharmaceutical Packaging, LLC) (off market)

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (68645-0484) (Legacy Pharmaceutical Packaging, LLC) (off market)

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (33342-0102) (MacLeods Pharma) null

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (00904-6310) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (00904-6529) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (00904-6808) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) nullMontelukast Sodium 10mg Tablet package photo

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (51079-0223) (Mylan Institutional LLC ) null

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (00378-5201) (Mylan Pharmaceuticals Inc.) null

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (00603-4655) (Par Pharmaceuticals, an Endo Company) (off market)

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (43063-0380) (PD-Rx Pharmaceuticals, Inc.) (off market)

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (43063-0762) (PD-Rx Pharmaceuticals, Inc.) null

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (00781-5560) (Sandoz Inc. a Novartis Company) null

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (00093-7426) (Teva Pharmaceuticals USA) (off market)

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (13668-0081) (Torrent Pharma, Inc) null

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (29300-0220) (Unichem Pharmaceuticals USA, Inc) null

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (69367-0287) (Westminster Pharmaceuticals, LLC) null

Montelukast Sodium Oral tablet

Montelukast Sodium 10mg Tablet (72865-0175) (XL Care Pharmaceuticals, Inc) null

Montelukast Sodium Oral tablet

Singulair 10mg Tablet (00006-0117) (Merck Sharp & Dohme Corp., a Subsidiary of Merck & Co., Inc.) (off market)

Montelukast Sodium Oral tablet

Singulair 10mg Tablet (00006-9117) (Merck Sharp & Dohme Corp., a Subsidiary of Merck & Co., Inc.) null

Montelukast Sodium Oral tablet

Singulair 10mg Tablet (78206-0172) (Organon LLC) null

Montelukast Sodium Oral tablet

Singulair 10mg Tablet (58864-0658) (PD-Rx Pharmaceuticals, Inc.) (off market)

Montelukast Sodium Oral tablet

Singulair 10mg Tablet (55289-0961) (PD-Rx Pharmaceuticals, Inc.) (off market)

Description/Classification

Description

Montelukast is an oral leukotriene receptor antagonists (LTRA). Unlike zafirlukast, montelukast does not inhibit CYP2C9 or CYP3A4 and has not been found to affect the hepatic clearance of drugs metabolized by these enzymes. Montelukast is primarily used for the chronic maintenance treatment of asthma, to prevent exercise-induced bronchoconstriction (EIB), and for the treatment of perennial and seasonal allergic rhinitis.[29630] In general, montelukast is well tolerated; however, serious psychiatric effects (e.g., suicidal behaviors, aggression, depression) have been prevalent in postmarketing reports.[56750] A boxed warning exists in the product label because of serious neuropsychiatric effects.[29630] Montelukast has the most substantial evidence for seasonal and perennial allergies of the LRTAs.[56376] Montelukast should not be used for mild symptoms of allergic rhinitis, but should be reserved for patients who are not treated effectively with or cannot tolerate other allergy medication.[29630][65079] Rhinitis guidelines suggest montelukast should only be used for allergic rhinitis if there has been an inadequate response or intolerance to alternative therapies due to the risk for neuropsychiatric events and the reduced efficacy of LRTAs when compared to other agents. However, in patients with allergic rhinitis and comorbid asthma, an LTRA could be an option after weighing the benefits of LTRA monotherapy for both conditions versus an inhaled corticosteroid for asthma plus the addition of an antihistamine or intranasal corticosteroid for allergic rhinitis; the modest efficacy of montelukast and the drug's potential risks must be carefully considered.[66102] For asthma maintenance therapy, LTRAs are less effective than inhaled corticosteroids (ICSs) and are not a preferred asthma treatment for persistent asthma; however, they may be of benefit in patients with mild persistent asthma who are unwilling or unable to use ICS, experience intolerable ICS side effects, or have concomitant allergic rhinitis. In adult and adolescent patients with moderate to severe persistent asthma taking ICS, LTRAs are considered an alternative add-on therapy option. In young children with asthma, LTRA therapy reduces symptoms and the need for oral corticosteroids when compared with placebo; however, the potential for montelukast side effects in children make this agent less desirable for pediatric use for asthma.[64807][66299] For the prevention of exercise-induced bronchoconstriction (EIB), montelukast may be considered a first-line choice to add as a controller agent to an inhaled short-acting beta-2 agonist (SABA) to control EIB symptoms in patients who cannot be controlled by an inhaled SABA alone.[56291] Montelukast is FDA-approved for use in adult and pediatric patients as young as 1 year of age for the maintenance treatment of asthma, as young as 2 years of age for treatment of seasonal allergic rhinitis, and in infants as young as 6 months with perennial allergic rhinitis. Montelukast is also used for preventing exercise-induced bronchoconstriction (EIB) in adult and pediatric patients 6 years and older.[56750]

Classifications

  • Respiratory System
    • Agents for Reactive and Obstructive Airway Diseases
      • Leukotriene Modifiers
        • Leukotriene Receptor Antagonists (LTRAs)
Revision Date: 01/27/2021, 11:06:23 AM

References

29630 - Singulair (montelukast) package insert. Whitehouse Station, NJ: Merck and Co, Inc.; 2021 Feb.56291 - Parsons JP, Hallstrand TS, Mastronarde JG, et al. An official American Thoracic Society clinical practice guideline exercise induced bronchoconstriction. Am J Respir Crit Care Med 2013;187:1016-1027.56376 - Rodrigo GJ, Yanez A. The role of antileukotriene therapy in seasonal allergic rhinitis: a systematic review of randomized trials. Ann Allergy Asthma Immunol. 2006;96:779-786. Review.56750 - Institute for Safe Medication Practices (ISMP). ISMP Medication Safety Alert: Adverse drug events in children less than 18 years old. Retrieved from the World Wide Web February 25, 2014. Available at: http://www.ismp.org/Newsletters/acutecare/showarticle.aspx?id=6764807 - Global Strategy for Asthma Management and Prevention. Global Initiative for Asthma (GINA) 2020. Available from: http://www.ginasthma.org. Accessed May 20th, 2020.65079 - US Food and Drug Administration (FDA). FDA requires boxed warning about serious mental health side effects for asthma and allergy drug montelukast (Singulair); advises restricting use for allergic rhinitis. Available at: http://s2027422842.t.en25.com/e/es?s=2027422842&e=308434&elqTrackId=376c7bc788024cd5a73d955f2e3dcbdc&elq=cc7c8246f96541178cb9e7a0e8a616bc&elqaid=11491&elqat=1. Accessed March 4, 2020.66102 - Dykewicz MS, Wallace DV, Amrol DJ, et al. Rhinitis 2020: a practice parameter update. J Allergy Clin Immunol. 2020;146:721-767.66299 - Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI) administered and coordinated National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC), et al. 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol. 2020;146:1217-1270.

Administration Information

General Administration Information

For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Oral Administration

  • For asthma, montelukast is administered in the evening without regard to meals; evening administration is recommended since the drug was given at bedtime during clinical trials. However, there are no studies evaluating the relative efficacy of morning versus evening dosing. For seasonal allergies, the time of daily administration may be adjusted to suit patient needs; administer at roughly the same time daily.

Oral Solid Formulations

  • Chewable tablets: Chew tablet well prior to swallowing.
  • Oral granules: The 4 mg oral granules can be administered orally directly into the mouth, or mixed with a spoonful of cold or room temperature soft foods. Based on stability studies, only applesauce, carrots, rice or ice cream should be used. Do not open the packet until ready to use. After opening the packet, the full dose (with or without mixing with food) should be administered within 15 minutes. If mixed with food, the oral granules should not be stored for future use. Discard any unused portion. The oral granules are not intended to be dissolved in liquid for administration. However, liquids may be taken after administration.

Clinical Pharmaceutics Information

From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database
    Revision Date: 02/08/2010, 11:38:54 AM

    References

    Adverse Reactions

    Mild

    • abdominal pain
    • abnormal dreams
    • agitation
    • anxiety
    • arthralgia
    • asthenia
    • cough
    • diarrhea
    • dizziness
    • drowsiness
    • dyspepsia
    • ecchymosis
    • epistaxis
    • fatigue
    • fever
    • headache
    • hypoesthesia
    • infection
    • influenza
    • insomnia
    • irritability
    • laryngitis
    • muscle cramps
    • myalgia
    • nasal congestion
    • nausea
    • nightmares
    • paresthesias
    • pharyngitis
    • pruritus
    • rash
    • restlessness
    • rhinitis
    • rhinorrhea
    • sinusitis
    • somnambulism
    • tremor
    • urticaria
    • vomiting
    • weight loss

    Moderate

    • atopic dermatitis
    • bleeding
    • confusion
    • conjunctivitis
    • depression
    • dysphemia
    • edema
    • elevated hepatic enzymes
    • eosinophilia
    • gastritis
    • hallucinations
    • hepatitis
    • hostility
    • impulse control symptoms
    • memory impairment
    • myopia
    • palpitations
    • pyuria
    • thrombocytopenia
    • urinary incontinence
    • wheezing

    Severe

    • anaphylactoid reactions
    • angioedema
    • Churg-Strauss syndrome
    • erythema multiforme
    • erythema nodosum
    • pancreatitis
    • seizures
    • Stevens-Johnson syndrome
    • suicidal ideation
    • toxic epidermal necrolysis
    • vasculitis

    During initial clinical trials, montelukast was evaluated for safety in over 2600 adolescent (>= 15 years) and adult patients and over 1000 pediatric patients <= 14 years, many of whom received the drug for at least one year. Overall, montelukast was well tolerated. The adverse reaction profile of montelukast is generally similar among pediatric and adult patients. Adverse reactions in adults and adolescents > = 15 years with asthma that were reported more frequently in montelukast-treated patients than in placebo-treated patients included asthenia or fatigue (1.8% vs. 1.2%), fever (1.5% vs. 0.9%), trauma (1% vs. 0.8%), abdominal pain (2.9% vs. 2.5%), dyspepsia (2.1% vs. 1.1%), gastritis (1.5% vs. 0.5%), dental pain (1.7% vs. 1%), dizziness (1.9% vs. 1.4%), headache (18.4% vs. 18.1%), influenza (4.2% vs. 3.9%), nasal congestion (1.6% vs. 1.3%), cough (2.7% vs. 2.4%), pyuria (1% vs. 0.9%), and rash (unspecified) (1.6% vs. 1.2%). Other adverse reactions in adults and adolescents > = 15 years with allergic rhinitis that occurred >= 1% and more frequently than placebo included cough, sinusitis, upper respiratory infection (1.9%), sinus headache, and epistaxis. Adverse reactions reported in one or more pediatric study groups (6 months—14 years) that occurred >= 2% and more frequently than placebo include: abdominal pain, atopic dermatitis, cough, diarrhea, dyspepsia, fever, gastroenteritis, laryngitis, pharyngitis, rhinorrhea, nausea, vomiting, otitis, sinusitis, viral infection, conjunctivitis, dermatitis, rash, ear pain, eczema, pneumonia, urticaria, varicella, acute bronchitis, wheezing, tonsillitis, myopia, rhinitis (infective), skin infection, and tooth infection.[29630]

    In rare cases, patients on montelukast therapy presented with systemic eosinophilia, sometimes presenting with clinical features of vasculitis consistent with Churg-Strauss syndrome, a systemic eosinophilic vasculitis which is often treated with systemic corticosteroids. These events usually, but not always, have been associated with the reduction of oral corticosteroid therapy. Symptoms include eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy. Patients may initially complain of generalized, flu-like symptoms such as fever, myalgia, and weight loss. Pulmonary eosinophilia has been reported with post-marketing use. Although a causal relationship with leukotriene receptor antagonism has not been established, caution is advised when oral corticosteroid reduction is being considered in patients receiving montelukast.[29630]

    During premarketing clinical trials, the incidence of elevated hepatic enzymes during montelukast treatment was not significantly different from patients taking placebo. ALT increased in 2.1% of montelukast-treated patients and 2% of placebo-treated patients; AST increased in 1.6% and 1.2% of patients, respectively. Increased ALT was also reported in >= 1% of patients in a clinical trial of adults and adolescents >= 15 years with perennial allergic rhinitis. According to the manufacturer, there are reports of eosinophilic infiltration of the liver (hypersensitivity hepatitis), and, in post-marketing experience, cholestatic hepatitis, hepatocellular liver-injury, and mixed-pattern liver-injury. Most of the post-marketing events occurred in patients who had underlying potential for liver disease, such as those with a history of alcohol abuse or other forms of hepatitis.[29630]

    In post-marketing experience, the following additional adverse reactions have been reported with montelukast: hypersensitivity reactions, including anaphylaxis (anaphylactoid reactions), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), angioedema, drowsiness, pruritus, erythema nodosum, erythema multiforme, arthralgia, myalgia, muscle cramps, pancreatitis, thrombocytopenia, increased bleeding tendency, bruising (ecchymosis), edema, paresthesias, hypoesthesia, and palpitations.[29630]

    Neuropsychiatric events, including changes in mood or behavioral changes, have been reported in adult, adolescent, and pediatric patients taking montelukast. Postmarketing reports include, but are not limited to: agitation, aggressive behavior or hostility, anxiety, depression, disorientation (confusion), attention disturbance, abnormal dreams, dysphemia (stuttering), hallucinations, insomnia, irritability, memory impairment, obsessive-compulsive symptoms (impulse control symptoms), restlessness, somnambulism, suicidal ideation and behavior (including suicide), drowsiness, seizures, tic, and tremor.[29630] Nightmares may be more common in children and typically resolve after drug discontinuation.[56593] In many cases, symptoms resolved after montelukast was discontinued, however, symptoms persisted after discontinuation in some cases. Although neuropsychiatric events were not commonly observed during clinical trials, the clinical details present in some of the postmarketing reports suggest a drug-induced effect, possibly related to the leukotriene pathway. Available data are insufficient to characterize at-risk patients. Advise patients to report changes in behavior and mood; consider alternate therapy if patients develop neuropsychiatric symptoms.[29630] [52011]

    Enuresis (night-time urinary incontinence) has been reported in children during post-marketing use of montelukast.[29630]

    Revision Date: 04/17/2020, 12:29:41 PM

    References

    29630 - Singulair (montelukast) package insert. Whitehouse Station, NJ: Merck and Co, Inc.; 2021 Feb.52011 - Philip G, Hustad C, Noonan G. Reports of suicidality in clinical trials of montelukast. J Allergy Clin Immunol. 2009;124:691-696.56593 - Cereza G, Garcia Dolade N, Laporte JR. Nightmares induced by montelukast in children and adults. Eur Respir J 2012;40:1574-1575.

    Contraindications/Precautions

    Absolute contraindications are italicized.

    • acute bronchospasm
    • alcoholism
    • behavioral changes
    • breast-feeding
    • corticosteroid withdrawal
    • depression
    • geriatric
    • hepatic disease
    • hepatitis
    • infants
    • jaundice
    • neonates
    • neurologic events
    • phenylketonuria
    • pregnancy
    • psychiatric event
    • status asthmaticus
    • suicidal ideation

    The safety and efficacy of montelukast in children has been established. Additionally, in November 2005 the FDA approved revisions to the product labeling of montelukast oral formulations following the results of a 56 week study indicating that growth rates were similar among 6 to 8 year old asthmatic children receiving montelukast 5 mg per day or placebo. In addition, children receiving either montelukast or placebo had higher growth rates than those receiving inhaled beclomethasone 168 mcg twice daily.[29630]

    Montelukast is not effective for the treatment of acute asthma attacks, including status asthmaticus or acute bronchospasm. Thus, patients should be advised to have appropriate rescue medication (e.g., inhaled beta-agonist) available. In addition, according to the manufacturer, montelukast should not be used as monotherapy for the management of exercise-induced bronchospasm. However, montelukast therapy may be continued during the treatment of an acute asthmatic event. Patients should be advised not to stop taking or decrease the use of other asthma treatments when starting montelukast unless otherwise directed by their health care prescriber.

    Montelukast is contraindicated for use in those patients with hypersensitivity to any product component. Montelukast chewable tablets should be used with caution in patients with phenylketonuria. Each 4 mg and 5 mg chewable tablet contains 0.674 and 0.842 mg, respectively, of phenylalanine. Before prescribing montelukast chewable tablets to a patient with PKU, consider the combined daily amount of phenylalanine from all sources, including montelukast.[29630]

    Behavioral changes consistent with a neuro-psychiatric event have been reported in adult, adolescent, and pediatric patients taking montelukast, and some of these psychiatric and neurologic events appear to be consistent with a drug-related effect.[29630] A Boxed Warning was added to the montelukast prescribing information because of serious neuropsychiatric events and recommended that montelukast only be used to treat allergic rhinitis in patients who are not treated effectively with or cannot tolerate other allergy medicines.[29630] [65079] Postmarketing reports include psychiatric and neurologic events such as agitation, aggressive behavior or hostility, anxiousness, depression, disorientation, disturbance in attention, dream abnormalities, dysphemia (stuttering), hallucinations, insomnia, irritability, memory impairment, obsessive-compulsive symptoms, restlessness, somnambulism, suicidal ideation and behavior (including suicide), tic, and tremor. In many cases, symptoms resolved after montelukast was discontinued, however, symptoms persisted after discontinuation in some cases. Available data are insufficient to characterize at-risk patients. Advise patients and their caregivers to report changes in mood or behavior immediately. Discontinue montelukast immediately if neuropsychiatric systems occur and continue to monitor and provide supportive care until symptoms resolve. Re-evaluate the benefits and risks of restarting montelukast treatment.[29630]

    Published data from prospective and retrospective cohort studies of montelukast use during human pregnancy have not established a drug-associated risk of major birth defects. Some of these studies did have limitations including small sample size, retrospective design, and inconsistent comparator groups. In animal reproduction studies, no adverse developmental effects were observed with montelukast administration to pregnant rats and rabbits during organogenesis at oral doses approximately 100 and 110 times, respectively, the maximum recommended human daily oral dose (MRHDOD) based on AUCs.[29630] The National Asthma Education and Prevention Program, Asthma and Pregnancy Working Group list leukotriene receptor antagonists as an alternative treatment option in the recommended stepwise management of asthma in pregnancy. The Working Group states that leukotriene receptor antagonists may be considered for use during pregnancy for patients who had a favorable response prior to becoming pregnant.[45934]

    Montelukast may be used during breast-feeding when necessary. Montelukast is present in human milk. However, data available for infants exposed to montelukast either directly (for selected indications) or through breast milk do not suggest a significant risk of adverse effects. Montelukast is approved for use in infants 6 months and older and has been used in newborns in dosages that provide concentrations greater than the amounts in breastmilk. The effects of montelukast on human milk production are unknown. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for montelukast and any potential adverse effects on the breast-fed infant from montelukast or the underlying maternal condition.[29630] The National Asthma Education and Prevention Program, Asthma and Pregnancy Working Group list leukotriene receptor antagonists, such as montelukast, as an alternative treatment option in the recommended stepwise management of asthma in lactating women.[45934]

    Safety and effectiveness of montelukast have not been established in neonates and infants < 6 months of age. Montelukast is available in chewable tablets for use in children and oral granules for use in older infants and children.

    Montelukast should be used cautiously in patients with hepatic disease. Based on pharmacokinetic studies in mild-moderate stable cirrhosis, the manufacturer has recommended no specific dosage adjustments. However, use caution in patients with severe hepatic impairment, jaundice, or hepatitis. Rarely, in patients with hepatic disease (e.g., from alcoholism or hepatitis), there have been post-marketing reports of cholestatic hepatitis, hepatocellular liver injury, or mixed pattern liver injury.

    Caution is advised when oral corticosteroid withdrawal or a reduction in corticosteroid dose is being considered in patients taking montelukast. Although a causal relationship has not been established; in rare cases, reduction in oral corticosteroid dose in patients taking montelukast has resulted in Churg-Strauss syndrome, a systemic eosinophilic vasculitis. Symptoms may include eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy (see Adverse Reactions).

    The clearance of montelukast is only slightly decreased in geriatric patients. Dosage reductions in this population are not needed; clinical responses and side effects of montelukast are similar for the elderly as for younger adults.

    Revision Date: 02/26/2021, 02:57:33 PM

    References

    29630 - Singulair (montelukast) package insert. Whitehouse Station, NJ: Merck and Co, Inc.; 2021 Feb.45934 - National Heart , Lung, and Blood Institute, National Asthma Education and Prevention Program Asthma and Pregnancy Working Group. NAEPP expert panel report. Managing asthma during pregnancy: recommendations for pharmacologic treatment-2004 update. 2004;1-57. http://www.nhlbi.nih.gov/health/prof/lung/asthma/astpreg.htm65079 - US Food and Drug Administration (FDA). FDA requires boxed warning about serious mental health side effects for asthma and allergy drug montelukast (Singulair); advises restricting use for allergic rhinitis. Available at: http://s2027422842.t.en25.com/e/es?s=2027422842&e=308434&elqTrackId=376c7bc788024cd5a73d955f2e3dcbdc&elq=cc7c8246f96541178cb9e7a0e8a616bc&elqaid=11491&elqat=1. Accessed March 4, 2020.

    Mechanism of Action

    Montelukast is a potent and selective antagonist of leukotriene D4 (LTD4) at the cysteinyl leukotriene receptor, CysLT1, found in the human airway.[29630] The cysteinyl leukotrienes (LTC4, LTD4, and LTE4) are important intermediaries of allergic airway disease. They are products of arachidonic acid metabolism and are released from various cells, including mast cells and eosinophils, in response to allergens. The binding of cysteinyl leukotrienes to CysLT has been associated with asthma pathophysiology, including chemoattraction of eosinophils, stimulation of inflammatory mediators, increased endothelial membrane permeability leading to airway edema, smooth muscle contraction, and enhanced secretion of thick, viscous mucus. In addition, the cysteinyl leukotrienes prepare the immune system for future allergic response through dendritic cell maturation and migration.[29630][42834] In allergic rhinitis, the cysteinyl leukotrienes are released from nasal mucosa in response to allergen exposure during early- and late-phase reactions, producing symptoms of sneezing, nasal itching, and late-stage congestion.[29630] Montelukast improves the signs and symptoms of asthma and allergic rhinitis by inhibiting the physiologic actions of LTD4 at the CysLT1 receptor. Clinically, the drug has been shown to inhibit early- and late-phase bronchoconstriction due to antigen challenge by 75% and 57%, respectively.[29630] Montelukast does not have agonist properties at leukotriene receptors and it does not antagonize smooth muscle contractions due to LTC4, acetylcholine, histamine, prostaglandin, or serotonin.[52024]

    Revision Date: 10/17/2012, 05:00:10 PM

    References

    29630 - Singulair (montelukast) package insert. Whitehouse Station, NJ: Merck and Co, Inc.; 2021 Feb.42834 - Nayak A, Langdon RB. Montelukast in the treatment of allergic rhinitis: an evidence-based review. Drugs. 2007;67:887-90152024 - Jones TR, Labelle M, Belley M. Pharmacology of montelukast sodium (Singulair), a potent and selective leukotriene D4 receptor antagonist. Can J Physiol Pharmacol 1995;73:191-201.

    Pharmacokinetics

    Montelukast is administered orally. Montelukast is more than 99% bound to plasma proteins. The drug has a small volume of distribution; animal studies indicate minimal distribution across the blood-brain barrier. Montelukast undergoes extensive hepatic metabolism; hepatic isozymes CYP2C8, CYP2C9, and CYP3A4 are involved. At clinically relevant concentrations, CYP2C8 appears to play a significant role in the metabolism of montelukast. Plasma concentrations of metabolites of montelukast are undetectable at steady state. Montelukast and its metabolites are excreted almost exclusively via the bile; less than 0.2% of the drug is excreted in urine. Mean elimination half-life (half-life) of montelukast is 2.7 to 5.5 hours in healthy young adults. The pharmacokinetic profile of montelukast in age-appropriate doses is similar in children 2 years or older, adolescents, and adults.[29630]

     

    Affected cytochrome P450 isoenzymes: CYP2C8, CYP2C9, and CYP3A4

    In vitro studies indicate that the hepatic microsomal isoenzyme CYP2C8 plays a major role in montelukast's metabolism, with CYP2C9 and CYP3A4 also contributing to a lesser degree. However, even potent inhibitors of CYP2C8/9 and/or CYP3A4 do not result in appreciable clinical differences in montelukast pharmacokinetics despite increased exposure, and no dosage adjustments are recommended during coadministration of such inhibitors. Strong inducers also have little effect on the clinical effect of the drug, though the manufacturer recommends monitoring to ensure efficacy. While in vitro studies have shown that montelukast is a rather potent inhibitor of CYP2C8, human in vivo data against sensitive CYP2C8 substrates indicate that inhibition of CYP2C8 substrate metabolism does not occur, and thus interactions with CYP2C8 substrates is unlikely. Other hepatic CYP450 isozymes are not inhibited.[29630] [31034] [32856] [34499] A mild induction of CYP1A2 by montelukast may occur, but is likely only to be relevant for a drug like warfarin; such interactions are not established.[28549]

    Route-Specific Pharmacokinetics

    Oral Route

    Oral absorption of montelukast is rapid, with peak plasma concentrations occurring 3 to 4 hours after administration of a 10-mg film-coated tablet. For the 5-mg chewable tablet, peak concentrations are achieved 2 to 2.5 hours after administration to fasting adults. For the 4-mg chewable tablet, the mean maximal concentration is obtained 2 hours after administration in children 2 to 5 years of age in the fasted state. In the fasted state, the mean oral bioavailability is 64% for the film-coated tablet and 73% for the chewable tablet. The 4-mg oral granules dosage unit is bioequivalent to the 4-mg chewable tablet, when administered to adults in the fasting state. The comparative pharmacokinetics of two 5-mg chewable tablets versus one 10-mg regular tablet has not been evaluated. A standard meal does not affect the peak concentration or oral bioavailability of the film-coated tablet; mean bioavailability of the chewable tablet is reduced to 63% with food. However, the clinical efficacy of the chewable tablet is not affected by taking the medication with food. Therefore, all oral forms of montelukast may be administered without regard to meals.[29630]

    Special Populations

    Hepatic Impairment

    Patients with mild to moderate hepatic insufficiency and clinical evidence of cirrhosis had evidence of decreased metabolism of montelukast resulting in 41% higher mean AUC values following a single 10-mg dose. The elimination of montelukast was slightly prolonged compared with that in healthy subjects (mean half-life, 7.4 hours). No dosage adjustment is required in patients with mild or moderate hepatic impairment. The pharmacokinetics of montelukast in patients with more severe hepatic impairment or with hepatitis have not been evaluated.[29630]

    Renal Impairment

    Since montelukast and its metabolites are not excreted in the urine, the pharmacokinetics of montelukast were not evaluated in patients with renal insufficiency. No dosage adjustment is recommended in these patients.[29630]

    Pediatrics

    Adolescents 15 years or older

    The plasma concentration profile of montelukast is similar in adolescents 15 years or older and young adults after oral administration of the 10 mg film-coated tablet.[29630]

     

    Children 2 years or older and Adolescents less than 15 years

    The mean systemic exposure of the chewable tablets in children and young adolescents is similar to that of adults receiving the film-coated tablets.[29630]

     

    Children less than 2 years

    The systemic exposure to montelukast in children less than 2 years is higher than in adults; however, it is less variable compared to infants. Mean AUC (3574 ng x hour/mL) was 33% higher and mean Cmax (562 ng/mL) was 60% higher than those observed in adults (mean AUC: 2689 ng x hour/mL; mean Cmax: 353 ng/mL). Safety and tolerability of montelukast in pediatric patients 6 to 23 months of age are similar to that of pediatric patients 2 years or older.[29630]

     

    Infants 6 months or older

    The systemic exposure to montelukast and variability of montelukast plasma concentrations are higher in infants than in adults. In infants aged 6 to 11 months, the mean AUC (4296 ng x hour/mL [range: 1200 to 7153]) was 60% higher and mean Cmax (667 ng/ml [range: 201 to 1058) was 89% higher than those observed in adults (mean AUC: 2689 ng x hour/mL [range: 1521 to 4595]; mean Cmax: 353 ng/mL [range: 180 to 548]). Safety and tolerability of montelukast in pediatric patients 6 to 23 months of age are similar to that of pediatric patients 2 years or older.[29630]

    Geriatric

    Montelukast clearance is only slightly decreased in the elderly compared to younger adults.

    Gender Differences

    Gender does not affect the pharmacokinetics of montelukast.

    Revision Date: 03/01/2021, 04:17:39 PM

    References

    28549 - Coumadin (warfarin tablets) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2017 Aug.29630 - Singulair (montelukast) package insert. Whitehouse Station, NJ: Merck and Co, Inc.; 2021 Feb.31034 - Walsky RL, Gaman EA, Obach RS. Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol 2005;45:68-78.32856 - Jaakkola T, Backman JT, Neuvonen M, et al. Montelukast and zafirlukast do not affect the pharmacokinetics of the CYP2C8 substrate pioglitazone. Eur J Clin Pharmacol 2006;62:503-9.34499 - Kim KA, Park PW, Kim KR, et al. Effect of multiple doses of montelukast on the pharmacokinetics of rosiglitazone, a CYP2C8 substrate, in humans. Br J Clin Pharmacol 2007;63:339-45.

    Pregnancy/Breast-feeding

    pregnancy

    Published data from prospective and retrospective cohort studies of montelukast use during human pregnancy have not established a drug-associated risk of major birth defects. Some of these studies did have limitations including small sample size, retrospective design, and inconsistent comparator groups. In animal reproduction studies, no adverse developmental effects were observed with montelukast administration to pregnant rats and rabbits during organogenesis at oral doses approximately 100 and 110 times, respectively, the maximum recommended human daily oral dose (MRHDOD) based on AUCs.[29630] The National Asthma Education and Prevention Program, Asthma and Pregnancy Working Group list leukotriene receptor antagonists as an alternative treatment option in the recommended stepwise management of asthma in pregnancy. The Working Group states that leukotriene receptor antagonists may be considered for use during pregnancy for patients who had a favorable response prior to becoming pregnant.[45934]

    breast-feeding

    Montelukast may be used during breast-feeding when necessary. Montelukast is present in human milk. However, data available for infants exposed to montelukast either directly (for selected indications) or through breast milk do not suggest a significant risk of adverse effects. Montelukast is approved for use in infants 6 months and older and has been used in newborns in dosages that provide concentrations greater than the amounts in breastmilk. The effects of montelukast on human milk production are unknown. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for montelukast and any potential adverse effects on the breast-fed infant from montelukast or the underlying maternal condition.[29630] The National Asthma Education and Prevention Program, Asthma and Pregnancy Working Group list leukotriene receptor antagonists, such as montelukast, as an alternative treatment option in the recommended stepwise management of asthma in lactating women.[45934]

    Revision Date: 01/07/2019, 02:40:26 PM

    References

    29630 - Singulair (montelukast) package insert. Whitehouse Station, NJ: Merck and Co, Inc.; 2021 Feb.45934 - National Heart , Lung, and Blood Institute, National Asthma Education and Prevention Program Asthma and Pregnancy Working Group. NAEPP expert panel report. Managing asthma during pregnancy: recommendations for pharmacologic treatment-2004 update. 2004;1-57. http://www.nhlbi.nih.gov/health/prof/lung/asthma/astpreg.htm

    Interactions

    Level 4 (Minor)

    • Belladonna Alkaloids; Ergotamine; Phenobarbital
    • Carbamazepine
    • Enzalutamide
    • Gemfibrozil
    • Hydantoins
    • Isoniazid, INH; Pyrazinamide, PZA; Rifampin
    • Isoniazid, INH; Rifampin
    • Lumacaftor; Ivacaftor
    • Mitotane
    • Phenobarbital
    • Phenobarbital; Hyoscyamine; Atropine; Scopolamine
    • Primidone
    • Rifampin
    • Rifapentine
    • St. John's Wort, Hypericum perforatum
    • Warfarin
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Minor) Phenobarbital may reduce the systemic exposure of montelukast. However, dosage adjustment is not likely to be needed. If used together, the manufacturer recommends monitoring for proper montelukast effectiveness as a precaution. Phenobarbital is a strong CYP inducer. Montelukast is metabolized by CYP2C8 (primary), and also CYP2C9 and CYP3A4. [29630] Carbamazepine: (Minor) Carbamazepine may reduce the systemic exposure of montelukast. However, dosage adjustment is not likely to be needed. If used together, the manufacturer recommends monitoring for proper montelukast effectiveness as a precaution. Carbamazepine is a strong CYP3A inducer. Montelukast is metabolized by CYP2C8 (primary), and also CYP2C9 and CYP3A4. [29630] Enzalutamide: (Minor) Enzalutamide may reduce the systemic exposure of montelukast. However, dosage adjustment is not likely to be needed. If used together, the manufacturer recommends monitoring for proper montelukast effectiveness as a precaution. Enzalutamide is a strong CYP3A inducer. Montelukast is metabolized by CYP2C8 (primary), and also CYP2C9 and CYP3A4. [29630] [51727] Gemfibrozil: (Minor) Concentrations of montelukast may be increased with concomitant use of gemfibrozil; however, based on available clinical experience, no dosage adjustment of montelukast is required upon co-administration with gemfibrozil. At clinically relevant concentrations, CYP2C8 is the primary isozyme involved in the metabolism of montelukast; the drug is also metabolized by CYP2C9 and CYP3A4. Data from a clinical drug interaction study involving montelukast and gemfibrozil (a CYP2C8 and 2C9 inhibitor) demonstrated that gemfibrozil, at a therapeutic dose, increased the systemic exposure of montelukast by 4.4-fold. The addition of a potent CYP3A4 inhibitor did not further increase the inhibition of montelukast metabolism. [29630] Hydantoins: (Minor) Hydantoin anticonvulsants may reduce the systemic exposure of montelukast. However, dosage adjustment is not likely to be needed. If used together, the manufacturer recommends monitoring for proper montelukast effectiveness as a precaution. Hydantoin anticonvulsants are a strong CYP3A inducers. Montelukast is metabolized by CYP2C8 (primary), and also CYP2C9 and CYP3A4. [29630] Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Minor) Monitor for decreased montelukast efficacy if coadministered with rifampin. The systemic exposure of montelukast may be reduced; however, dosage adjustments are not likely to be needed. Montelukast is metabolized by CYP2C8 (primary), and also CYP2C9 and CYP3A4; rifampin is a strong CYP3A4 and moderate CYP2C9 inducer. Coadministration with another strong CYP3A4 and moderate CYP2C9 inducer decreased the exposure of montelukast by approximately 40%. [29630] [30314] Isoniazid, INH; Rifampin: (Minor) Monitor for decreased montelukast efficacy if coadministered with rifampin. The systemic exposure of montelukast may be reduced; however, dosage adjustments are not likely to be needed. Montelukast is metabolized by CYP2C8 (primary), and also CYP2C9 and CYP3A4; rifampin is a strong CYP3A4 and moderate CYP2C9 inducer. Coadministration with another strong CYP3A4 and moderate CYP2C9 inducer decreased the exposure of montelukast by approximately 40%. [29630] [30314] Lumacaftor; Ivacaftor: (Minor) Lumacaftor; ivacaftor may reduce the systemic exposure of montelukast. However, dosage adjustment is not likely to be needed. If used together, the manufacturer recommends monitoring for proper montelukast effectiveness as a precaution. Lumacaftor is a strong CYP3A inducer, and in vitro studies suggest lumacaftor; ivacaftor has the potential to induce CYP2C8 and CYP2C9. Montelukast is metabolized by CYP2C8 (primary), and also CYP2C9 and CYP3A4. [29630] [59891] Mitotane: (Minor) Mitotane may reduce the systemic exposure of montelukast. However, dosage adjustment is not likely to be needed. If used together, the manufacturer recommends monitoring for proper montelukast effectiveness as a precaution. Mitotane is a strong CYP3A inducer. Montelukast is metabolized by CYP2C8 (primary), and also CYP2C9 and CYP3A4. [29630] [41934] Phenobarbital: (Minor) Phenobarbital may reduce the systemic exposure of montelukast. However, dosage adjustment is not likely to be needed. If used together, the manufacturer recommends monitoring for proper montelukast effectiveness as a precaution. Phenobarbital is a strong CYP inducer. Montelukast is metabolized by CYP2C8 (primary), and also CYP2C9 and CYP3A4. [29630] Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Minor) Phenobarbital may reduce the systemic exposure of montelukast. However, dosage adjustment is not likely to be needed. If used together, the manufacturer recommends monitoring for proper montelukast effectiveness as a precaution. Phenobarbital is a strong CYP inducer. Montelukast is metabolized by CYP2C8 (primary), and also CYP2C9 and CYP3A4. [29630] Primidone: (Minor) Primidione, which is metabolized to phenobarbital, may reduce the systemic exposure of montelukast. However, dosage adjustment is not likely to be needed. If used together, the manufacturer recommends monitoring for proper montelukast effectiveness as a precaution. Phenobarbital is a strong CYP inducer. Montelukast is metabolized by CYP2C8 (primary), and also CYP2C9 and CYP3A4. [29630] Rifampin: (Minor) Monitor for decreased montelukast efficacy if coadministered with rifampin. The systemic exposure of montelukast may be reduced; however, dosage adjustments are not likely to be needed. Montelukast is metabolized by CYP2C8 (primary), and also CYP2C9 and CYP3A4; rifampin is a strong CYP3A4 and moderate CYP2C9 inducer. Coadministration with another strong CYP3A4 and moderate CYP2C9 inducer decreased the exposure of montelukast by approximately 40%. [29630] [30314] Rifapentine: (Minor) Monitor for decreased montelukast efficacy if coadministered with rifapentine. The systemic exposure of montelukast may be reduced; however, dosage adjustments are not likely to be needed. Montelukast is metabolized by CYP2C8 (primary), CYP2C9 and CYP3A4; rifapentine is a strong CYP3A4 and moderate CYP2C9 inducer. Coadministration with another strong CYP3A4 and moderate CYP2C9 inducer decreased the exposure of montelukast by approximately 40%. [29630] [65685] St. John's Wort, Hypericum perforatum: (Minor) St. John's Wort may reduce the systemic exposure of montelukast. However, dosage adjustment is not likely to be needed. If used together, the manufacturer recommends monitoring for proper montelukast effectiveness as a precaution. St. John's Wort is a strong CYP3A inducer. Montelukast is metabolized by CYP2C8 (primary), and also CYP2C9 and CYP3A4. [28211] [29630] Warfarin: (Minor) Montelukast is reported by the manufacturer of warfarin to be a potential inducer of CYP1A2. The manufacturer of montelukast does not report an effect on CYP1A2 or on warfarin metabolism. As a precaution, monitor for clinical effectiveness and the international normalized ratio (INR) as per standard of care in a patient taking both drugs together. [28549] [29630]
    Revision Date: 09/11/2021, 02:34:00 AM

    References

    28211 - Henderson L, Yue QY, Bergquist C, et al. St John's wort (Hypericum perforatum): drug interactions and clinical outcomes. Br J Clin Pharmacol 2002;54:349-56.28549 - Coumadin (warfarin tablets) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2017 Aug.29630 - Singulair (montelukast) package insert. Whitehouse Station, NJ: Merck and Co, Inc.; 2021 Feb.30314 - Rifadin capsules and injection (rifampin) package insert. Bridgewater, NJ: Sanofi-Aventis, LLC; 2021 Jun.41934 - Lysodren (mitotane) package insert. Princeton, NJ: Bristol-Myers Squibb Oncology; 2021 June.51727 - Xtandi (enzalutamide) capsule and tablet package insert. Northbrook, IL:Astellas Pharma US, Inc.; 2020 Oct.59891 - Orkambi (lumacaftor; ivacaftor) tablet package insert. Boston, MA: Vertex Pharmaceuticals, Inc. 2018 August65685 - Dooley KE, Bliven-Sizemore EE, Weiner M, et al. Safety and pharmacokinetics of escalating daily doses of the antituberculosis drug rifapentine in healthy volunteers. Clin Pharmacol Ther 2012; 91:5

    Monitoring Parameters

    • laboratory monitoring not necessary

    US Drug Names

    • Singulair
    ;