Singulair

Leukotriene Receptor Antagonists (LTRAs)

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.

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.

Churg-Strauss syndrome / Delayed / Incidence not known
vasculitis / Delayed / Incidence not known
erythema multiforme / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
pancreatitis / Delayed / Incidence not known
erythema nodosum / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
angioedema / Rapid / Incidence not known
suicidal ideation / Delayed / Incidence not known
seizures / Delayed / Incidence not known

pyuria / Delayed / 1.0-1.0
atopic dermatitis / Delayed / 2.0
myopia / Delayed / 2.0
wheezing / Rapid / 2.0
gastritis / Delayed / 2.0
conjunctivitis / Delayed / 2.0
elevated hepatic enzymes / Delayed / 1.0
eosinophilia / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
edema / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
palpitations / Early / Incidence not known
bleeding / Early / Incidence not known
impulse control symptoms / Delayed / Incidence not known
hallucinations / Early / Incidence not known
dysphemia / Delayed / Incidence not known
depression / Delayed / Incidence not known
memory impairment / Delayed / Incidence not known
hostility / Early / Incidence not known
confusion / Early / Incidence not known
urinary incontinence / Early / Incidence not known

dizziness / Early / 1.9-1.9
fatigue / Early / 1.8-1.8
asthenia / Delayed / 1.8-1.8
nasal congestion / Early / 1.6-1.6
nausea / Early / 2.0
dyspepsia / Early / 2.0
rash / Early / 1.6
vomiting / Early / 2.0
sinusitis / Delayed / 1.0
fever / Early / 1.5
laryngitis / Delayed / 2.0
pharyngitis / Delayed / 2.0
abdominal pain / Early / 2.0
headache / Early / 1.0
cough / Delayed / 1.0
urticaria / Rapid / 2.0
infection / Delayed / 1.9
diarrhea / Early / 2.0
rhinitis / Early / 2.0
rhinorrhea / Early / 2.0
epistaxis / Delayed / 1.0
influenza / Delayed / 2.0
myalgia / Early / Incidence not known
weight loss / Delayed / Incidence not known
pruritus / Rapid / Incidence not known
arthralgia / Delayed / Incidence not known
hypoesthesia / Delayed / Incidence not known
muscle cramps / Delayed / Incidence not known
drowsiness / Early / Incidence not known
paresthesias / Delayed / Incidence not known
ecchymosis / Delayed / Incidence not known
irritability / Delayed / Incidence not known
somnambulism / Early / Incidence not known
restlessness / Early / Incidence not known
anxiety / Delayed / Incidence not known
nightmares / Early / Incidence not known
abnormal dreams / Early / Incidence not known
agitation / Early / Incidence not known
insomnia / Early / Incidence not known
tremor / Early / Incidence not known

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] 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]

Singulair

Rx

Oral leukotriene receptor antagonist (LRTA) class anti-inflammatory agent
Used for mild persistent asthma (age 1 year and older); seasonal allergic rhinitis (2 years and older), perennial allergic rhinitis (6 months and older); and exercise-induced bronchoconstriction (EIB) prophylaxis (6 years and older)
Boxed warning for serious neuropsychiatric effects; only use in allergic rhinitis patients intolerant to or not responding to other treatments

10 mg PO once daily in the evening.

10 mg PO once daily in the evening.

5 mg PO once daily in the evening.

4 mg PO once daily in the evening.

4 mg PO once daily in the evening.

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.

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.

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.

10 mg PO once daily. 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.

10 mg PO once daily. 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.

5 mg PO once daily. 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.

4 mg PO once daily. 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.

4 mg oral granules PO once daily (do not administer tablets). 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.

10 mg PO once daily. 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.

10 mg PO once daily. 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.

5 mg PO once daily. 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.

4 mg PO once daily. 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.

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.

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. 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.

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. 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. 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.

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. 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).

5 mg PO once daily at bedtime.

4 mg PO once daily at bedtime.

†Indicates off-label use

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.

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

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.
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.
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.
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.
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%.
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%.
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.
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.
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.
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.
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.
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%.
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%.
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.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with montelukast is necessary as concurrent use may decrease the exposure of warfarin leading to reduced efficacy. The R-enantiomer of warfarin is a CYP1A2 substrate and montelukast is CYP1A2 inducer. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.

Montelukast Sodium/Singulair Oral Gran: 4mg
Montelukast Sodium/Singulair Oral Tab Chew: 4mg, 5mg
Montelukast Sodium/Singulair Oral Tab: 10mg

10 mg/day PO.

10 mg/day PO.

15 years and older: 10 mg/day PO.
13 to 14 years: 5 mg/day PO.

6 to 12 years: 5 mg/day PO.
1 to 5 years: 4 mg/day PO.

6 months and older: 4 mg/day PO for perennial allergic rhinitis only.
Less than 6 months: Safety and efficacy have not been established.

Montelukast is a potent and selective antagonist of leukotriene D4 (LTD4) at the cysteinyl leukotriene receptor, CysLT1, found in the human airway. 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. 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. 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. 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.

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]

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.

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]