Volibris Special Precautions

Ambrisentan has not been studied in a sufficient number of patients to establish the benefit/risk balance in WHO functional class I PAH.
The efficacy of ambrisentan as monotherapy has not been established in patients with WHO functional class IV PAH. Therapy that is recommended at the severe stage of the disease (e.g. epoprostenol) should be considered if the clinical condition deteriorates.
Liver function: Liver function abnormalities have been associated with PAH. Cases consistent with autoimmune hepatitis, including possible exacerbation of underlying autoimmune hepatitis, hepatic injury and hepatic enzyme elevations potentially related to therapy have been observed with ambrisentan (see Adverse Reactions and Pharmacology: Pharmacodynamics under Actions). Therefore hepatic aminotransferases (ALT and AST) should be evaluated prior to initiation of ambrisentan and treatment should not be initiated in patients with baseline values of ALT and/or AST>3xULN (see Contraindications).
Patients should be monitored for signs of hepatic injury and monthly monitoring of ALT and AST is recommended. If patients develop sustained, unexplained, clinically significant ALT and/or AST elevation, or if ALT and/or AST elevation is accompanied by signs or symptoms of hepatic injury (e.g. jaundice), ambrisentan therapy should be discontinued.
In patients without clinical symptoms of hepatic injury or of jaundice, re-initiation of ambrisentan may be considered following resolution of hepatic enzyme abnormalities. The advice of a hepatologist is recommended.
Haemoglobin concentration: Reductions in haemoglobin concentrations and haematocrit have been associated with endothelin receptor antagonists (ERAs) including ambrisentan. Most of these decreases were detected during the first 4 weeks of treatment and haemoglobin generally stabilised thereafter. Mean decreases from baseline (ranging from 0.9 to 1.2 g/dL) in haemoglobin concentrations persisted for up to 4 years of treatment with ambrisentan in the long-term open-label extension of the pivotal Phase 3 clinical studies. In the post-marketing period, cases of anaemia requiring blood cell transfusion have been reported (see Adverse Reactions).
Initiation of ambrisentan is not recommended for patients with clinically significant anaemia. It is recommended that haemoglobin and/or haematocrit levels are measured during treatment with ambrisentan, for example at 1 month, 3 months and periodically thereafter in line with clinical practice. If a clinically significant decrease in haemoglobin or haematocrit is observed, and other causes have been excluded, dose reduction or discontinuation of treatment should be considered.
Fluid retention: Peripheral oedema has been observed with ERAs including ambrisentan. Most cases of peripheral oedema in clinical studies with ambrisentan were mild to moderate in severity, although it appeared to occur with greater frequency and severity in patients ≥65 years. Peripheral oedema was reported more frequently with 10 mg ambrisentan in short-term clinical studies (see Adverse Reactions).
Post-marketing reports of fluid retention occurring within weeks after starting ambrisentan have been received and, in some cases, have required intervention with a diuretic or hospitalisation for fluid management or decompensated heart failure. If patients have pre-existing fluid overload, this should be managed as clinically appropriate prior to starting ambrisentan.
If clinically significant fluid retention develops during therapy with ambrisentan, with or without associated weight gain, further evaluation should be undertaken to determine the cause, such as ambrisentan or underlying heart failure, and the possible need for specific treatment or discontinuation of ambrisentan therapy.
Women of child-bearing potential: Volibris treatment must not be initiated in women of child-bearing potential unless the result of a pre-treatment pregnancy test is negative and reliable contraception is practiced. If there is any doubt on what contraceptive advice should be given to the individual patient, consultation with a gynaecologist should be considered. Monthly pregnancy tests during treatment with ambrisentan are recommended (see Contraindications and Use in Pregnancy & Lactation).
Pulmonary veno-occlusive disease: Cases of pulmonary oedema have been reported with vasodilating medicinal products, such as ERAs, when used in patients with pulmonary veno-occlusive disease. Consequently, if PAH patients develop acute pulmonary oedema when treated with ambrisentan, the possibility of pulmonary veno-occlusive disease should be considered.
Concomitant use with other medicinal products: Patients on ambrisentan therapy should be closely monitored when starting treatment with rifampicin (see Interactions and Pharmacology: Pharmacokinetics under Actions).
Excipients: Volibris tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Volibris tablets contain the azo colouring agent Allura red AC Aluminium Lake (E129), which can cause allergic reactions.
Volibris tablets contain lecithin derived from soya. If a patient is hypersensitive to soya, ambrisentan must not be used (see Contraindications).
Volibris tablets contain less than 1 mmol sodium (23 mg), which is essentially 'sodium-free'.
Effects on ability to drive and use machines: Ambrisentan has minor or moderate influence on the ability to drive and use machines. The clinical status of the patient and the adverse reaction profile of ambrisentan (such as hypotension, dizziness, asthenia, fatigue) should be borne in mind when considering the patient's ability to perform tasks that require judgement, motor or cognitive skills (see Adverse Reactions). Patients should be aware of how they might be affected by ambrisentan before driving or using machines.