• Home
  • A-B index
  • Pharmacological Index
  • Drug Classes
  • Active Ingredients
  • Companies
  • News
  • Volibris
    / GSK


    Active Ingredient
    Ambrisentan 5 mg, 10 mg

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Film Coated Tablets

    30 x 5 mg

    partial basket chart 78755 22299

    Film Coated Tablets

    30 x 10 mg

    partial basket chart 78756 22300

    Related information


    Dosage

    Special populations
    Elderly patients: No dose adjustment is required in patients over the age of 65.
    Patients with renal impairment: No dose adjustment is required in patients with renal impairment. There is limited experience with ambrisentan in individuals with severe renal impairment (creatinine clearance <30 ml/min); therapy should be initiated cautiously in this subgroup and particular care taken if the dose is increased to 10 mg ambrisentan.
    Patients with hepatic impairment: Ambrisentan has not been studied in individuals with hepatic impairment (with or without cirrhosis). Since the main routes of metabolism of ambrisentan are glucuronidation and oxidation with subsequent elimination in the bile, hepatic impairment would be expected to increase exposure (Cmax and AUC) to ambrisentan. Therefore ambrisentan must not be initiated in patients with severe hepatic impairment, or clinically significant elevated hepatic aminotransferases (greater than 3 times the Upper Limit of Normal (>3xULN)
    Paediatric population: The safety and efficacy of ambrisentan in children and adolescents aged below 18 years has not been established. No data are available.
    For full details see prescribing information.


    Indications

    For the treatment of pulmonary arterial hypertension (PAH) classified as WHO functional class II and III, to improve exercise capacity, decrease the symptoms of PAH, and delay clinical worsening.


    Contra-Indications

    Hypersensitivity to the active substance, to soya, or to any of the excipients. Pregnancy and lactation. Women of child-bearing potential who are not using reliable contraception. Severe hepatic impairment (with or without cirrhosis). Baseline values of hepatic aminotransferases (aspartate aminotransferases (AST) and/or alanine aminotransferases (ALT)) >3xULN.
    For full details see prescribing information.


    Special Precautions

    Volibris 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 Volibris 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 Volibris. Therefore hepatic aminotransferases (ALT and AST) should be evaluated prior to initiation of Volibris and treatment should not be initiated in patients with baseline values of ALT and/or AST>3xULN.
    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), Volibris therapy should be discontinued.
    In patients without clinical symptoms of hepatic injury or of jaundice, re-initiation of Volibris 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 ERAs including Volibris. 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 hemoglobin 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. Initiation of Volibris is not recommended for patients with clinically significant anaemia. It is recommended that haemoglobin and/or haematocrit levels are measured during treatment with Volibris, 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 ambrisentanPost-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 Volibris are recommended .
    Pulmonary veno-occlusive disease: Cases of pulmonary oedema have been reported with vasodilating agents, such as endothelin receptor antagonists, 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:  Rifampicin: Patients on ambrisentan therapy should be closely monitored when starting treatment with rifampicin.


    Side Effects

    Safety of Volibris has been evaluated in clinical trials of more than 483 patients with PAH. Adverse drug reactions (ADR) identified from 12 week placebo controlled clinical trial data are included below by system organ class and frequency. With longer observation in uncontrolled studies (mean observation of 79 weeks), the safety profile was similar to that observed in the short term studies. Post marketing data are also presented. Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000). For dose-related adverse reactions the frequency category reflects the higher dose of Volibris. Frequency categories do not account for other factors including varying study duration, pre-existing conditions and baseline patient characteristics. Adverse reaction frequency categories assigned based on clinical trial experience may not reflect the frequency of adverse events occurring during normal clinical practice. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
    For full details see prescribing information.


    Drug interactions

    Ambrisentan does not inhibit or induce phase I or II drug metabolizing enzymes at clinically relevant concentrations in in vitro and in vivo non-clinical studies, suggesting a low potential for ambrisentan to alter the profile of medicinal products metabolized by these pathways. The potential for ambrisentan to induce CYP3A4 activity was explored in healthy volunteers with results suggesting a lack of inductive effect of ambrisentan on the CYP3A4 isoenzyme. Co-administration of ambrisentan with a phosphodiesterase inhibitor, either sildenafil or tadalafil (both substrates of CYP3A4) in healthy volunteers did not significantly affect the pharmacokinetics of the phosphodiesterase inhibitor or ambrisentan. Steady-state administration of ketoconazole (a strong inhibitor of CYP3A4) did not result in a clinically significant increase in exposure to ambrisentan.
    Ambrisentan had no effects on the steady-state pharmacokinetics and anti-coagulant activity of warfarin in a healthy volunteer study. Warfarin also had no clinically significant effects on the pharmacokinetics of ambrisentan. In addition, in patients, ambrisentan had no overall effect on the weekly warfarin-type anticoagulant dose, prothrombin time (PT) and international normalized ratio (INR).
    For full details see prescribing information.


    Pregnancy and Lactation

    Pregnancy: Volibris is contraindicated in pregnancy. Animal studies have shown that ambrisentan is teratogenic. There is no experience in humans.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. Monthly pregnancy tests during treatment with Volibris are recommended. Women receiving Volibris must be advised of the risk of foetal harm and alternative therapy initiated if pregnancy occurs.
    Lactation: It is not known whether ambrisentan is excreted in human breast milk. The excretion of ambrisentan in milk has not been studied in animals. Therefore lactation is contraindicated in patients taking Volibris.
    Male fertility:  The development of testicular tubular atrophy in male animals has been linked to the chronic administration of ERAs, including ambrisentan. Although no clear evidence of a detrimental effect of ambrisentan long-term exposure on sperm count was found in ARIES-E study, chronic administration of ambrisentan was associated with changes in markers of spermatogenesis. A decrease in plasma inhibin-B concentration and an increase in plasma FSH concentration were observed. The effect on male human fertility is not known but a deterioration of spermatogenesis cannot be excluded. Chronic administration of ambrisentan was not associated with a change in plasma testosterone in clinical studies.


    Overdose

    There is no experience in PAH patients of Volibris at daily doses greater than 10 mg. In healthy volunteers, single doses of 50 and 100 mg (5 to 10 times the maximum recommended dose) were associated with headache, flushing, dizziness, nausea and nasal congestion.
    Due to the mechanism of action, an overdose of Volibris could potentially result in hypotension. In the case of pronounced hypotension, active cardiovascular support may be required. No specific antidote is available.


    Manufacturer
    Patheon Inc. Canada
    CLOSE