Zafirlukast (brand name Accolate) was the first cysteinyl leukotriene receptor antagonist approved in the United States.
[1] Like other leukotriene receptor antagonists, zafirlukast is thought to be useful for the long-term treatment of asthma, but it is generally less effective than inhaled glucocorticoids as monotherapy (which are the standard of care) or long-acting beta-2 agonists in combination therapy.
[1] As a general rule, leukotriene receptor antagonists like zafirlukast are more effective in children that are younger and whose asthma is less atopic.
[3] Atopy refers to a predisposition towards developing allergic conditions, including asthma, hay fever, and eczema.
[4] The hepatic clearance of zafirlukast is impaired in adults 65 years of age and older, resulting in a 2–3 fold increase in the maximum plasma concentration and the total area under the curve.
This is due, in part, to the wide safety margin of zafirlukast in animal studies investigating teratogenicity.
Cirrhosis of the liver can increase the maximum plasma concentration and the total area under the curve (a measure of drug exposure) by 50–60%.
GI complaints can be lessened by taking zafirlukast with food, though this can dramatically impair the amount of drug that gets absorbed into the body (see the section on drug-food interactions below).
[6] Other common side effects include flu-like symptoms, sleep disturbances (abnormal dreams, insomnia), hallucinations, and daytime drowsiness.
[8] Zafirlukast-induced hepatotoxicity is characterized by a spectrum of liver damage symptoms, including fatigue, nausea, and right upper quadrant pain followed by dark urine, jaundice and pruritus.
[8] Liver enzyme elevations are common, and the pattern usually reflects hepatocellular damage, resembling acute viral hepatitis.
[8] According to the "Dear Health Care Provider" letter from AstraZeneca, zafirlukast-induced hepatotoxicity has occurred predominantly in females.
[9] Several cases of eosinophilic granulomatosis with polyangiitis have been reported with the use of zafirlukast, montelukast, pranlukast, and other asthma medications.
[10] While the exact etiology of the development of eosinophilic granulomatosis with polyangiitis symptoms in proximity to initiating zafirlukast is unknown, it is thought that withdrawal of chronic corticosteroids "unmasks" the previously undetected disease.
[2] By inhibiting the action of these specific leukotrienes, zafirlukast is thought to exert an anti-inflammatory effect against leukotriene-mediated inflammatory conditions.
[2] Zafirlukast is rapidly absorbed into the bloodstream following oral administration, reaching peak plasma levels within 3 hours of taking the dose.
[1] Albumin is the most abundant protein found in human plasma and is capable of carrying and transporting drugs (like zafirlukast) throughout the body.
The mean terminal half-life ranges 8–16 hours, following linear kinetics up to doses of 80 mg.[1] Genetic polymorphisms in the LTC4 synthase promoter may predict response to zafirlukast.
The single-nucleotide polymorphism (SNP) A444C (the wild-type DNA base adenine, at the 444th position on the gene, is mutated; cytosine is there instead), which is associated with a severe asthma phenotype, has been shown to decrease the clinical response to zafirlukast (both when the genetic alteration was heterozygous or homozygous).