MINASTEM 10MG TABLET

Indications

• Seasonal allergic rhinitis
• Perennial allergic rhinitis
• Chronic urticaria
• Potential therapeutic role in asthma

Dosage

Children: Refer to BNF for Children for specific dosing guidance.

Adults: Refer to BNF for specific dosing guidance.

Mechanism of action

Astemizole competes with histamine for binding at H1-receptor sites located in the gastrointestinal tract, uterus, large blood vessels, and bronchial muscle. This reversible binding suppresses edema, flare, and pruritus associated with histaminic activity. The drug's limited ability to cross the blood-brain barrier results in minimal central nervous system depression, although it may exhibit some effects on H3-receptors.

Pharmacodynamics

As a second generation H1-receptor antagonist, astemizole does not significantly penetrate the blood-brain barrier, which helps avoid drowsiness and central nervous system depression at normal therapeutic doses. Its unique binding characteristics allow for prolonged activity, and it may irreversibly bind to H1 receptors at higher concentrations.

Pharmacokinetics

Astemizole has a notably long elimination half-life, ranging from 12 to 18 days for its metabolites. This prolonged duration of action allows for less frequent dosing, making it convenient for patients. The pharmacokinetics of astemizole are influenced by factors such as liver metabolism and potential interactions with other medications.

Contra-indications

• Hypersensitivity to astemizole or any of its ingredients
• Severe liver impairment
• Concomitant use with potent CYP3A4 inhibitors

Adverse effects

• Cardiac arrhythmias
• Prolonged QT interval
• Headache
• Dizziness
• Dry mouth
• Nausea
• Fatigue

Interactions

• CYP3A4 inhibitors (e.g., ketoconazole, erythromycin) may increase the risk of cardiac toxicity
• CYP3A4 inducers (e.g., rifampicin) may reduce the efficacy of astemizole

Precautions

• Use with caution in patients with a history of cardiac arrhythmias
• Regular monitoring of cardiac function is advised in long-term use
• Not recommended for use in pregnancy unless absolutely necessary

Pregnancy

Astemizole should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Astemizole is excreted in breast milk; therefore, caution should be exercised when administering to breastfeeding mothers.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Tablets
• Oral suspension

Mechanism of action

Astemizole competes with histamine for binding at H₁-receptor sites in the GI tract, uterus, large blood vessels, and bronchial muscle. This reversible binding of astemizole to H₁-receptors suppresses the formation of edema, flare, and pruritus resulting from histaminic activity. As the drug does not readily cross the blood-brain barrier and preferentially binds at H1 receptors in the peripehery rather than within the brain, CNS depression is minimal. Astemizole may also act on H₃-receptors, producing adverse effects. Antihistamines are effective therapy against histamine-mediated conditions, including seasonal and perennial allergic rhinitis and chronic urticaria. They may also have a therapeutic role to play in asthma. Until recently all antihistamines produced some degree of drowsiness, as well as having anticholinergic side effects. Several non-sedating antihistamines have now been developed. Evidence suggests that their freedom from central nervous system effects is due to their lack of penetration of the blood brain barrier. They also have no appreciable binding to cholinergic receptors. Two of these non-sedating antihistamines, terfenadine and astemizole, have novel binding characteristics with the histamine H1 receptor, exhibiting irreversible binding at higher concentrations. In humans astemizole has a remarkably long half-life of elimination, on the order of 12 to 18 days for metabolites. Clinical trials have demonstrated that these newer antihistamines are as effective as classical antihistamines and that they have no greater incidence of central nervous system or anticholinergic side effects than placebo. QT interval prolongation and torsade de pointes are associated with astemizole intake and have been ascribed to block the repolarizing K+ currents, specifically the rapidly activating component of the delayed rectifier iKr. ... The perforated patch clamp recording technique was used to study the effects of desmethylastemizole (20 nmol/liter) on action potentials and iKr in isolated rabbit ventricular myocytes. Desmethylastemizole produced action potential prolongation and the induction of plateau early afterdepolarizations. Under voltage clamp conditions, desmethylastemizole suppressed iKr amplitude by approximately 65%. The drug E-4031 (100 nmol/liter), which selectively blocks iKr, had a similar effect on current amplitude. Desmethylastemizole, the major astemizole metabolite, blocks the repolarizing K+ current iKr with high affinity. The clinical observation of QT prolongation and torsade de pointes found with astemizole intake may principally be caused by the proarrhythmic effects of its metabolite desmethylastemizole. Astemizole /has/ been recognized in rare cases to induce the syndrome of torsades de pointes, i.e. QT interval prolongation and life-threatening ventricular tachycardia. /It/ was found to prolong cardiac repolarization when its metabolic elimination was impaired, such as by liver disease or drugs that inhibit the 3A family of cytochrome P450. In vitro studies indicate that this action is due to blockade of one or more of the cardiac potassium channels that determine the duration of the action potential.

Pharmacodynamics

Astemizole is a second generation H₁-receptor antagonist. It does not significantly cross the blood brain barrier and therefore does not cause drowsiness or CNS depression at normal doses.