62.5 & 125 mg film-coated tabletsPRESCRIBING INFORMATION
ACTIVE INGREDIENT(S): Bosentan
Please refer to the Summary of Product Characteristics (SmPC) before prescribing.
INDICATION(S): Treatment of pulmonary arterial hypertension (PAH) to improve exercise capacity and symptoms in patients with WHO functional class III. Efficacy shown in: Primary (idiopathic and heritable) PAH, PAH secondary to scleroderma without significant interstitial pulmonary disease, PAH associated with congenital systemic-to-pulmonary shunts and Eisenmenger’s physiology. Some improvements shown in patients with PAH functional class II. Tracleer is also indicated to reduce the number of new digital ulcers in patients with systemic sclerosis (SS) and ongoing digital ulcer disease.
DOSAGE & ADMINISTRATION: Treatment should only be initiated and monitored by physician experienced in the treatment of PAH or SS. Before and during treatment with Tracleer, patients need to be aware of the important safety information provided in the patient safety card included in the Tracleer pack. Adults: Initial dose 62.5mg twice daily (b.d.) for 4 weeks, maintenance dose 125mg b.d. Take with or without food. Managing clinical deterioration of PAH. If clinical deterioration occurs despite bosentan treatment for ≥ 8 weeks, consider alternative therapies. Some PAH patients showing no response after 8 weeks, may respond favourably after an additional 4 to 8 weeks of treatment. Patients not responding well to 125mg b.d. may slightly improve their exercise capacity by increasing dose to 250mg b.d. A careful benefit/risk assessment should be made. Paediatrics: Recommended starting and maintenance dose in children with PAH aged 1 year and older is 2 mg/kg morning and evening. There are no data on the safety and efficacy in patients under 18 years in systemic sclerosis with ongoing digital ulcer. Hepatic impairment: Mild: No dose adjustment required. Moderate/severe: Contraindicated. Renal impairment: No dose adjustment required or in patients undergoing dialysis. Elderly patients: No dose adjustment required in patients >65 years.
CONTRAINDICATIONS: Hypersensitivity to the active substance or excipients. Moderate to severe hepatic impairment. Baseline values of liver aminotransferases (AST and/or ALT), greater than 3 times the upper limit of normal (ULN). Concomitant use of cyclosporine A. Pregnancy, women of childbearing potential not using reliable methods of contraception.
SPECIAL WARNINGS & PRECAUTIONS: Tracleer should only be initiated if the systemic systolic BP >85 mmHg. Efficacy of Tracleer not established in patients with severe PAH. Transfer to a therapy that is recommended at the severe stage of the disease (e.g. epoprostenol) should be considered if clinical condition deteriorates. Benefit/risk balance of bosentan not established in patients with WHO class I functional status of PAH. Liver function: Liver aminotransferase levels must be measured prior to initiation of treatment and subsequently at monthly intervals for duration of treatment. In addition, aminotransferase levels must be measured 2 weeks after any dose increase. If confirmed rise in aminotransferases, (>3 and ≤5 x ULN) a decision should be made on an individual basis whether to continue treatment, possibly at a reduced dose, or to stop treatment. Continue to monitor levels every 2 weeks. Stop treatment if aminotransferase levels are >5 and ≤8 x ULN. Consider re-introduction if potential benefits outweigh potential risks, and when aminotransferase levels are within pre-treatment values. Advice of a hepatologist is recommended. AST/ALT levels must be checked within 3 days after re-introduction, then again after 2 weeks, and thereafter according to the recommendations above. In case of associated clinical symptoms of liver injury, or a >8 x ULN rise in aminotransferases, stop treatment and do not re-introduce bosentan.
Haemoglobin (Hgb) concentration: Bosentan has been associated with dose-related decreases in Hgb concentration. Hgb concentrations should be checked prior to initiation of treatment, and monthly for the first 4 months and quarterly thereafter. Pulmonary veno-occlusive disease (PVOD): Should signs of pulmonary oedema occur in PAH patients, consider possibility of associated veno-occlusive disease. PAH patients with concomitant left ventricular failure: monitor patients for signs of fluid retention. Should this occur, treat with diuretics, or increase the dose of existing diuretics. Treatment with diuretics should be considered in patients with evidence of fluid retention before starting Tracleer treatment. PAH associated with HIV infection: Due to potential for interactions related to the inducing effect of bosentan on CYP450, monitor patients carefully regarding their HIV infection and HIV therapy. Combination with nevirapine not recommended due to its marked hepatotoxicity which could add to bosentan liver toxicity. PH secondary to chronic obstructive pulmonary disease: A small, 12-week study, showed an increase in minute ventilation and decrease in oxygen saturation; most frequent adverse event was dyspnoea which resolved with discontinuation of bosentan. Ability to drive and use machines: Bosentan may cause dizziness, which could affect ability to drive or use machines.
SIDE EFFECTS: Very common: headache, abnormal liver function test, oedema and fluid retention. Common: anaemia, Haemoglobin decrease, hypersensitive reactions, syncope, palpations, flushing, hypotension, nasal congestion, gastro-oesophageal reflux, diarrhoea, erythema. Other side effects: anaemia or haemoglobin decreases requiring red blood cell transfusion, thrombocytopenia, neutropenia, leukopenia, aminotransferase elevations associated with hepatitis and/or jaundice, anaphylaxis and/or angioedema, liver cirrhosis and liver failure have been reported. Refer to SmPC for other side effects.
PREGNANCY & FERTILITY: Tracleer is contraindicated in pregnancy. Women of child-bearing potential must not use hormonal contraceptives as sole method of contraception. Before initiation of bosentan, women of child-bearing potential must have a confirmed negative pre-treatment pregnancy test. Monthly pregnancy tests are recommended to allow early detection of pregnancy. Animal studies showed testicular effects. Bosentan may have a detrimental effect on spermatogenesis in men. In male children, a long term impact on fertility after treatment with bosentan cannot be excluded.
LACTATION: Breast feeding is not recommended during treatment with Tracleer.
INTERACTIONS: Bosentan induces cytochrome P450 isoenzymes, CYP2C9 and CYP3A4, and is metabolised by these enzymes. Concomitant administration of bosentan with CYP3A4 inhibitors or CYP2C9 inhibitors is not recommended: includes cyclosporine A, tacrolimus, sirolimus, glibenclamide, fluconazole, ketoconazole, nevirapine and rifampicin. Bosentan may render hormonal contraceptives ineffective. Caution advised with co-administration of simvastatin, sildenafil, tadalafil or lopinavir + ritonavir and other ritonavir-boosted protease inhibitors. Refer to SmPC for full details of interactions.
LEGAL CATEGORY: Prescription Only Medicine (POM)
PRESENTATIONS, PACK SIZES, MARKETING AUTHORISATION NUMBER(S) & BASIC NHS COSTS
|PRESENTATIONS||PACK SIZES||MARKETING AUTHORISATION NUMBER(S)||BASIC NHS COSTS|
|Tracleer 62.5mg||56 Tablets||EU/1/02/220/002||£1,510.21|
|Tracleer 125mg||56 Tablets||EU/1/02/220/004||£1,510.21|
MARKETING AUTHORISATION HOLDER: Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Belgium.
FURTHER INFORMATION IS AVAILABLE FROM: Janssen-Cilag Limited, 50-100 Holmers Farm Way, High Wycombe, Buckinghamshire, HP12 4EG UK.
Prescribing information last revised: April 2020