Pulmoten 62.50 mg (Tablet)

Indications

• Treatment of pulmonary arterial hypertension (PAH)
• Improvement of exercise capacity
• Symptoms in patients with WHO functional class III
• Improvements for patients with PAH WHO functional class II

Pharmacology

• Dual endothelin receptor antagonist (ERA)
• Affinity for both endothelin A and B (ETA and ETB) receptors
• Decreases pulmonary and systemic vascular resistance
• Increases cardiac output without increasing heart rate
• Potent vasoconstrictor
• Promotes fibrosis, cell proliferation, cardiac hypertrophy, and remodelling
• Mediated by endothelin binding to ETA and ETB receptors
• Absorption: Absolute bioavailability approximately 50%
• Distribution: Highly bound (>98%) to plasma proteins, mainly albumin
• Elimination: Eliminated by biliary excretion
• Metabolism in the liver by the cytochrome P450 isoenzymes, CYP2C9 and CYP3A4
• Plasma concentrations attained within 3-5 hours

Dosage & Administration

• Oral administration
• Morning and evening dosage
• Tablets
• Initial dose of 62.5 mg twice daily for 4 weeks
• Maintenance dose of 125 mg twice daily
• Optimal maintenance dose not defined for pediatric patients

Interactions

• Increased levels with CYP3A4 inhibitors (e.g. ketoconazole, ritonavir, diltiazem)
• Increased levels with CYP2C9 inhibitors (e.g. amiodarone, fluconazole)
• Increased levels with tacrolimus
• Rifampicin initially increases but subsequently decreases concentration
• May decrease plasma levels of warfarin, statins, hormonal contraceptives, sildenafil, tadalafil

Contraindications

• Hypersensitivity to the active substance or excipients
• Moderate to severe hepatic impairment (Child-Pugh class B or C)
• Baseline values of liver aminotransferases greater than 3 times the upper limit of normal
• Concomitant use of cyclosporine A
• Pregnancy

Side Effects

• Dose-dependent elevations in liver aminotransferases
• Decreases in hemoglobin concentration
• Other side effects: Anaemia, Thrombocytopenia, Neutropenia, Leucopenia, Hypersensitivity reactions, Headache, Syncope, Palpitations, Flushing, Hypotension, Gastroesophageal reflux disease, Aminotransferase elevations, Liver cirrhosis, Liver failure, Erythema, Diarrhoea, Oedema, Fluid retention

Pregnancy & Lactation

• Contraindicated in pregnancy
• Unknown excretion into human breast milk
• Not recommended during breast-feeding

Precautions & Warnings

• Consider discontinuation if pulmonary edema occurs
• Avoid abrupt withdrawal and consider dose reduction to minimize risk of clinical deterioration
• Potential for causing dizziness
• Impairment of ability to drive or use machines

Use in Special Populations

• No dose adjustment in mild hepatic impairment
• Contraindicated in moderate to severe liver dysfunction
• No dose adjustment in renal impairment or elderly patients
• No relevant changes in pharmacokinetics in mildly impaired liver function
• No dose adjustment in patients undergoing dialysis

Therapeutic Class

• Anti-hypertensive
• Endothelin receptor antagonist

Storage Conditions

• Store below 30°C
• Cool and dry place
• Protected from light
• Keep out of children’s reach

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