Products
Zafirlukast was commercially available in the form of film-coated tablets (Accolate, off label). It was approved in many countries in 1998. It was discontinued from distribution in 2019. Montelukast is a suitable substitute.
Structure and properties
Zafirlukast (C31H33N3O6S, Mr = 575.7 g/mol) exists as a fine, white to pale yellow, amorphous powder that is practically insoluble in water. It is an indole derivative and a carbamate.
Effects
Zafirlukast (ATC R03DC01) has anti-inflammatory and antiallergic properties. The effects are due to selective and competitive antagonism of the leukotrienes LTC4, LTD4, and LTE4 at leukotriene receptors. Leukotrienes are potent inflammatory mediators that cause bronchoconstriction, induce bronchial hypersensitivity, stimulate mucus production, and promote migration of inflammatory cells into the airways. They play an important role in the development of asthma.
Indications
Prevention and long-term treatment of mild to moderate bronchial asthma. Zafirlukast is not indicated for the treatment of acute asthma attack.
Dosage
According to the SmPC. The drug is usually taken twice daily on an empty stomach, 1 hour before or 2 hours after meals.
Contraindications
- Hypersensitivity
- Liver dysfunction
- Liver cirrhosis
- Concurrent use of oral anticoagulants
Full details of precautions and interactions can be found in the drug label.
Interactions
Zafirlukast is metabolized by CYP2C9 and is an inhibitor of CYP2C9 and CYP3A4. Concurrent use of warfarin increases warfarin concentrations to a relevant extent (see Contraindications). Other interactions have been observed with acetylsalicylic acid, erythromycin, and theophylline, among others.
Adverse effects
The most common possible adverse effects include infection, headache, indigestion, rash, pruritus, muscle and joint pain, edema, malaise, hyperbilirubinemia, hypersensitivity reactions, and insomnia. Rarely, severe side effects such as liver inflammation are possible.