Montelukast

Montelukast Sodium (17380-f)

Montelukast Sodium (BANM, USAN, rINM).

MK-476.SodiumI-[({(R)-m-[(E)-2-(7-cholro-2-quinoly)-viny]-α-[o-(I-hydroxy-I-methylethyl) phenethyl]-benzyl} thio) methyl] cyclopropaneacetate,

C₃₅H₃₅CINNaO₃S = 608.2.

CAS — 158966-92-8 (montelukast); 151767-02-1 (montelukast sodium),

Montelukast Sodium 10.37mg is equivalent to montelukast 10mg.

Adverse Effects and Precautions

Suspected adverse effects reported to the UK Committee on Safety of Medicine following the launch of montelukast included oedema, agitation and restlessness, allergy including anaphylaxis, angioedema, and urtic

Aria, chest pain, tremor, dry mouth, vertigo and arthralgia

Further suspected adverse effects included nightmares, sedation, palpitations and increased sweating.

Churg-Strauss syndrome. Churg-Strauss syndrome has been reported in association with montelukast. For discussion of the unresolved role of leukotriene antagonists in this disorder and precaution to be observed.

Hepatic and renal impairment. Although there is some evidence of effects on the liver patients receiving montelukast, and although it is largely eliminated by hepatic metabolism, montelukast (unlike zafirlukast) is not considered by its UK manufacturer to be contra-indicated in hepatic impairment, and not dose adjusted is considered necessary in mild to moderate hepatic impairment.

No dosage adjustment is anticipated to be necessary in patients with renal impairment.

Interactions

The manufacturer recommends clinical monitoring when potent hepatic enzyme inducers such as phenytoin, Phenobarbital, or rifampicin are given with montelukast.

Phenobarbital. Peak serum concentration after a single dose of montelukast 10mg were reduced by 20% in 14 healthy subjects who took Phenobarbital 100mg daily for 14 days, and area under the serum concentration-time curve was reduced by 38%. However, it was not though that montelukast doses would need adjustment if given with Phenobarbital.

Pharmacokinetics

Peak plasma concentration of montelukast are achieved in 2 to 4 hours after oral administration. The mean oral bioavailability is 64%. Montelukast is more than 99% bound to plasma protein. It is extensively metabolized in the liver by cytochrome P450 isoenzymes CYP3A4, CYP2A6, and CYP2C9, and is excreted principally in the faeces via the bile. Metabolism was reduced and the elimination half-life prolonged in patients with mild to moderate hepatic impairment.

Uses and Administration

Montelukast is a selective leukotriene receptor antagonist with actions and uses similar to those of zafirluoinst although it is reported to have a longer duration of action. It is used as the sodium salt in the management of chronic asthma, in doses equivalent to 10mg of montelukast once daily at bedtime; children aged 6 to 14 years may be given the equivalent of 5mg at bedtime and children aged 2 to 5 years may be given 4mg. It should not be used to treat an acute asthma attack.

Asthma. Montauks produced modest improvement compared with place in both adults and children. It was not as effective as low-dose inhaled beclometasone in 1 study, but did permit reduction in the dose of concomitant inhaled corticosteroid in another. Miontelukast has been reviewed, and further general references for leukotiene antagonists can be found under Zafirlukast.