VOLIBRIS

What it is

VOLIBRIS contains ambrisentan and is available as film-coated tablets in 5 mg and 10 mg strengths .

Approved indications

VOLIBRIS is indicated for the treatment of idiopathic pulmonary arterial hypertension (PAH) and pulmonary arterial hypertension associated with connective tissue disease (PAH-CTD), in patients with WHO functional class II, III or IV symptoms. VOLIBRIS in combination with tadalafil is indicated for the treatment of WHO Group 1 pulmonary arterial hypertension in patients with WHO functional class II, III or IV symptoms.

Dosing overview

VOLIBRIS should be taken orally at a dose of 5 mg once daily, with additional benefit obtainable by increasing the dose to 10 mg once daily. When used in combination with tadalafil, the VOLIBRIS starting dose of 5 mg should be titrated to 10 mg once daily, as tolerated. When co-administered with cyclosporin A, the dose of ambrisentan should be limited to 5 mg once daily.

Key safety warnings

VOLIBRIS may cause birth defects and is contraindicated in pregnancy. Hepatic enzyme elevations have been observed with endothelin receptor antagonists, with cumulative incidence of serum aminotransferase abnormalities greater than 3 times the Upper Limit of Normal in clinical studies being 3.5% of subjects. Hepatic function should be evaluated prior to initiation of ambrisentan, and if aminotransferases are greater than 3 times the Upper Limit of Normal, initiation is contraindicated; monthly monitoring of aminotransferases is warranted for the first 6 months after treatment is initiated. Reductions in haemoglobin concentrations and haematocrit have been associated with VOLIBRIS, with decreases observed within the first few weeks of therapy and generally stabilising thereafter; the mean decrease in haemoglobin from baseline to end of treatment was 0.8 g/dL in 12-week studies. Haemoglobin should be measured prior to initiation of VOLIBRIS, again at 1 month and periodically thereafter; initiation is not recommended for patients with clinically significant anaemia. Peripheral oedema has been observed with VOLIBRIS, and may also be a clinical consequence of PAH; most cases in clinical studies were mild to moderate although it occurred with greater frequency and severity in elderly patients. Post-marketing reports of fluid retention occurring within weeks after starting VOLIBRIS have been received and, in some cases, have required intervention with a diuretic or hospitalisation; if clinically significant fluid retention develops during therapy, further evaluation should be undertaken to determine the cause and the possible need for specific treatment or discontinuation.

Contraindications

VOLIBRIS is contraindicated in pregnancy. VOLIBRIS is contraindicated in women of child-bearing potential who are not using reliable contraception. VOLIBRIS is contraindicated in patients with severe hepatic impairment (with or without cirrhosis). VOLIBRIS is contraindicated in patients with baseline values of hepatic aminotransferases (aspartate aminotransferase and/or alanine aminotransferase) greater than 3 times the Upper Limit of Normal. VOLIBRIS is contraindicated in patients with idiopathic pulmonary fibrosis with or without secondary pulmonary hypertension. VOLIBRIS is contraindicated in patients who exhibit or may exhibit hypersensitivity to ambrisentan or to any of the excipients.

PBS listing

No source document provides information on PBS listing for VOLIBRIS.

Regulatory history

VOLIBRIS was first listed on the ARTG on 24 November 2008, with two registrations for the 5 mg and 10 mg tablet formulations. On 9 February 2016, the TGA approved an extension of indications for VOLIBRIS, allowing its use in combination with tadalafil for the treatment of WHO Group 1 pulmonary arterial hypertension in patients with WHO functional class II, III or IV symptoms.