Ambrisentan

INTRODUCTION

Indications

Pulmonary arterial hypertension.

Action

Antagonizes endogenous endothelin, resulting in vasodilation. Therapeutic Effects: Improved exercise capacity and delayed clinical worsening.

Adverse Reactions/Side Effects

CNS: headache. GI: HEPATOTOXICITY. F and E: fluid retention. Hemat: ↓ hemoglobin. Misc: ↓ sperm count.

PHYSICAL THERAPY IMPLICATIONS

Examination and Evaluation

• Be alert for signs of hepatotoxicity including anorexia, abdominal pain, severe nausea and vomiting, yellow skin or eyes, fever, sore throat, malaise, weakness, facial edema, lethargy, and unusual bleeding or bruising. Report these signs to the physician immediately.

• Assess exercise tolerance, and document possible benefits of drug therapy in reducing pulmonary hypertension and improving exercise capacity.

Interventions

• Design and implement aerobic exercise and endurance training programs as tolerated to improve exercise tolerance, reduce pulmonary impairments, and augment the effects of drug therapy.

Patient/Client-related Instruction

• Instruct patient or family/caregivers to report other troublesome side effects such as severe or prolonged headache or fluid retention.

Pharmacokinetics

Absorption: Absorbed following oral administration, Bioavailability unknown.

Distribution: Unknown.

Protein Binding: 99%.

Metabolism and Excretion: Highly metabolized.

Half-life: 15 hr (effective half-life 9 hr).

Contraindications/Precautions

Contraindicated in: OB: Pregnancy or lactation; Moderate/severe hepatic impairment.

Use Cautiously in: Mild hepatic impairment; Concurrent use of cyclosporine or strong inhibitors of CYP2C19 and CYP3A; Pedi: safety and efficacy in children has not been established.

Interactions

Drug-Drug: Blood levels may be ↑ by cyclosporine, strong CYP3A inhibitors including ketoconazole and strong 2C19 inhibitors including omeprazole.

Route/Dosage

PO (Adults): 5 mg once daily, may be increased to 10 mg once daily.

Availability

Tablets: 5 mg, 10 mg.