Tracleer

Method of administration Tablets are to be taken orally morning and evening, with or without food. The film-coated tablets are to be swallowed with water. Patients should be advised not to swallow the desiccant found in the white high-density polyethylene bottles.

Posology Pulmonary arterial hypertension Treatment should only be initiated and monitored by a physician experienced in the treatment of PAH. A Patient Alert Card providing important safety information that patients need to be aware of before and during treatment with Tracleer is included in the pack.

5 mg twice daily for 4 weeks and then increased to the maintenance dose of 125 mg twice daily. 4). 2). Increasing the dose or the dosing frequency will likely not result in additional clinical benefit. Based on these pharmacokinetic results, when used in children with PAH aged 1 year and older, the recommended starting and maintenance dose is 2 mg/kg morning and evening.

In neonates with persistent pulmonary hypertension of the newborn (PPHN), the benefit of bosentan has not been shown in the standard-of-care treatment. 2). , decrease in 6-minute walk test distance by at least 10% compared with pre-treatment measurement) despite Tracleer treatment for at least 8 weeks (target dose for at least 4 weeks), alternative therapies should be considered.

However, some patients who show no response after 8 weeks of treatment with Tracleer may respond favourably after an additional 4 to 8 weeks of treatment. , after several months of treatment), the treatment should be re-assessed. Some patients not responding well to 125 mg twice daily of Tracleer may slightly improve their exercise capacity when the dose is increased to 250 mg twice daily.

1). 4 Discontinuation of treatment There is limited experience with abrupt discontinuation of Tracleer in patients with PAH. No evidence for acute rebound has been observed. However, to avoid the possible occurrence of harmful clinical deterioration due to potential rebound effect, gradual dose reduction (halving the dose for 3 to 7 days) should be considered.

Intensified monitoring is recommended during the discontinuation period. If the decision to withdraw Tracleer is taken, it should be done gradually while an alternative therapy is introduced. Systemic sclerosis with ongoing digital ulcer disease Treatment should only be initiated and monitored by a physician experienced in the treatment of systemic sclerosis.

In 20 placebo-controlled studies, conducted in a variety of therapeutic indications, a total of 2 486 patients were treated with bosentan at daily doses ranging from 100 mg to 2 000 mg and 1 838 patients were treated with placebo. The mean treatment duration was 45 weeks.

5% more than on placebo. 9%). 4). Adverse reactions observed in 20 placebo-controlled studies and post-marketing experience with bosentan are ranked according to frequency using the following convention: 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); not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. No clinically relevant differences in adverse reactions were observed between the overall dataset and the approved indications. 4) Rare Liver cirrhosis, liver failure1 Skin and subcutaneous disorders Common Erythema General disorders and administration site conditions Very common Oedema, fluid retention5 1 Data derived from post-marketing experience, frequencies based on statistical modelling of placebo-controlled clinical trial data.

1% of patients on placebo. 8% of patients on placebo. 4 These types of reactions can also be related to the underlying disease. 9% of patients on placebo. In the post-marketing period rare cases of unexplained hepatic cirrhosis were reported after prolonged therapy with Tracleer in patients with multiple co-morbidities and therapies with medicinal products.

There have also been rare reports of liver failure. 4). Paediatric population Uncontrolled clinical studies in paediatric patients The safety profile in the first paediatric uncontrolled study performed with the film-coated tablet (BREATHE-3: n = 19, median age 10 years [range 3–15 years], open-label bosentan 2 mg/kg twice daily; treatment duration 12 weeks) was similar to that observed in the pivotal trials in adult patients with PAH.

The efficacy of Tracleer has not been established in patients with severe PAH. 2). The benefit/risk balance of bosentan has not been established in patients with WHO class I functional status of PAH. Tracleer should only be initiated if the systemic systolic blood pressure is higher than 85 mmHg.

Tracleer has not been shown to have a beneficial effect on the healing of existing digital ulcers. , aspartate and alanine aminotransferases (AST and/or ALT), associated with bosentan are dose dependent. 8). These increases may be partly due to competitive inhibition of the elimination of bile salts from hepatocytes but other mechanisms, which have not been clearly established, are probably also involved in the occurrence of liver dysfunction.

The accumulation of bosentan in hepatocytes leading to cytolysis with potentially severe damage of the liver, or an immunological mechanism, are not excluded. 5), are co-administered with bosentan, but limited data are available. Liver aminotransferase levels must be measured prior to initiation of treatment and subsequently at monthly intervals for the duration of treatment with Tracleer.

In addition, liver aminotransferase levels must be measured 2 weeks after any dose increase. 2). Monitoring of aminotransferase levels should be continued at least every 2 weeks. If the aminotransferase levels return to pre-treatment values continuing or re- introducing Tracleer according to the conditions described below should be considered.

> 5 and  8  ULN The result should be confirmed by a second liver test; if confirmed, treatment should be stopped and aminotransferase levels monitored at least every 2 weeks. If the aminotransferase levels return to pre-treatment values re- introducing Tracleer according to the conditions described below should be considered.

6 > 8  ULN Treatment must be stopped and re-introduction of Tracleer is not to be considered. , nausea, vomiting, fever, abdominal pain, jaundice, unusual lethargy or fatigue, flu-like syndrome (arthralgia, myalgia, fever), treatment must be stopped and re-introduction of Tracleer is not to be considered.

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