ACCOLATE 20MG TABLET

Indications

• Prophylaxis of asthma
• Chronic treatment of asthma

Dosage

Children: Refer to the BNF for Children for specific paediatric dosing recommendations.

Adults: Refer to the BNF for specific adult dosing recommendations.

Mechanism of action

Zafirlukast acts as a selective and competitive antagonist of the leukotriene D4 (LTD4) and E4 (LTE4) receptors. By inhibiting the binding of these leukotrienes, zafirlukast prevents the bronchoconstriction and inflammatory responses they mediate, thus alleviating symptoms of asthma and improving lung function.

Pharmacodynamics

Zafirlukast has been shown to significantly antagonize the contractile effects of leukotrienes LTC4, LTD4, and LTE4 in airway smooth muscle, both in vitro and in vivo. Its effectiveness is particularly notable in asthmatic patients, who are more sensitive to the bronchoconstrictor effects of inhaled LTD4 compared to non-asthmatics. Zafirlukast also reduces cutaneous vascular permeability and eosinophil influx into the lungs induced by LTD4, highlighting its role in modulating inflammatory processes in asthma.

Pharmacokinetics

Zafirlukast is well-absorbed following oral administration, with peak plasma concentrations typically occurring within 3 hours. It is extensively metabolized in the liver, primarily by cytochrome P450 enzymes, and has a half-life of approximately 8 to 10 hours. The drug is eliminated through both renal and fecal pathways. The pharmacokinetics may be influenced by factors such as age, liver function, and concomitant medications that affect hepatic metabolism.

Contra-indications

• Hypersensitivity to zafirlukast or any of its components
• Moderate to severe hepatic impairment

Adverse effects

• Headache
• Gastrointestinal disturbances (e.g., nausea, diarrhea)
• Elevated liver enzymes
• Rash
• Dizziness
• Respiratory infections

Interactions

• May interact with warfarin, increasing the risk of bleeding
• Concurrent use with theophylline may lead to altered levels of either drug
• May affect the metabolism of CYP2C9 substrates

Precautions

• Monitor liver function tests before and during treatment
• Use caution in patients with a history of hepatic disease
• Not indicated for the treatment of acute asthma attacks

Pregnancy

Zafirlukast should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Limited data is available on its safety in pregnancy.

Breast-feeding

Zafirlukast is excreted in breast milk. Caution should be exercised when administering to nursing women.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Tablets: 10 mg, 20 mg

Mechanism of action

Zafirlukast is a selective and competitive receptor antagonist of leukotriene D4 and E4 (LTD₄ and LTE4), components of slow-reacting substance of anaphylaxis (SRSA). Cysteinyl leukotriene production and receptor occupation have been correlated with the pathophysiology of asthma, including airway edema, smooth muscle constriction, and altered cellular activity associated with the inflammatory process, which contribute to the signs and symptoms of asthma.

Pharmacodynamics

Zafirlukast is a synthetic, selective peptide leukotriene receptor antagonist (LTRA) indicated for the prophylaxis and chronic treatment of asthma. Patients with asthma were found in one study to be 25-100 times more sensitive to the bronchoconstricting activity of inhaled LTD₄ than nonasthmatic subjects. <i>In vitro</i> studies demonstrated that zafirlukast antagonized the contractile activity of three leukotrienes (LTC₄, LTD₄ and LTE₄) in conducting airway smooth muscle from laboratory animals and humans. Zafirlukast prevented intradermal LTD₄-induced increases in cutaneous vascular permeability and inhibited inhaled LTD₄-induced influx of eosinophils into animal lungs.