Source: European Medicines Agency (EU) Revision Year: 2019 Publisher: Janssen-Cilag International NV, Turnhoutseweg 30, B-2340, Beerse, Belgium
Treatment of pulmonary arterial hypertension (PAH) to improve exercise capacity and symptoms in patients with WHO functional class III. Efficacy has been shown in:
Some improvements have also been shown in patients with pulmonary arterial hypertension WHO functional class II (see section 5.1).
Tracleer is also indicated to reduce the number of new digital ulcers in patients with systemic sclerosis and ongoing digital ulcer disease (see section 5.1).
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.
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.
In adult patients, Tracleer treatment should be initiated at a dose of 62.5 mg twice daily for 4 weeks and then increased to the maintenance dose of 125 mg twice daily. The same recommendations apply to re-introduction of Tracleer after treatment interruption (see section 4.4).
Paediatric pharmacokinetic data have shown that bosentan plasma concentrations in children with PAH aged from 1 year to 15 years were on average lower than in adult patients and were not increased by increasing the dose of Tracleer above 2 mg/kg body weight or by increasing the dosing frequency from twice daily to three times daily (see section 5.2). 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. No recommendation on a posology can be made (see sections 5.1 and 5.2).
In the event of clinical deterioration (e.g. 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.
In the event of late clinical deterioration despite treatment with Tracleer (i.e. 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. A careful benefit/risk assessment should be made, taking into consideration that the liver toxicity is dose dependent (see sections 4.4 and 5.1).
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.
Treatment should only be initiated and monitored by a physician experienced in the treatment of systemic sclerosis. 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.
Tracleer treatment should be initiated at a dose of 62.5 mg twice daily for 4 weeks and then increased to the maintenance dose of 125 mg twice daily. The same recommendations apply to re-introduction of Tracleer after treatment interruption (see section 4.4).
Controlled clinical study experience in this indication is limited to 6 months (see section 5.1). The patient’s response to treatment and need for continued therapy should be re-evaluated on a regular basis. A careful benefit/risk assessment should be made, taking into consideration the liver toxicity of bosentan (see sections 4.4 and 4.8).
There are no data on the safety and efficacy in patients under the age of 18 years. Pharmacokinetic data are not available for Tracleer in young children with this disease.
Tracleer is contraindicated in patients with moderate to severe liver dysfunction (see sections 4.3, 4.4 and 5.2). No dose adjustment is needed in patients with mild hepatic impairment (i.e., Child-Pugh class A) (see section 5.2).
No dose adjustment is required in patients with renal impairment. No dose adjustment is required in patients undergoing dialysis (see section 5.2).
No dose adjustment is required in patients over the age of 65 years.
Bosentan has been administered as a single dose of up to 2,400 mg to healthy subjects and up to 2,000 mg/day for 2 months in patients with a disease other than pulmonary hypertension. The most common adverse reaction was headache of mild to moderate intensity.
Massive overdose may result in pronounced hypotension requiring active cardiovascular support. In the post-marketing period there was one reported overdose of 10,000 mg of Tracleer taken by an adolescent male patient. He had symptoms of nausea, vomiting, hypotension, dizziness, sweating and blurred vision. He recovered completely within 24 hours with blood pressure support. Note: bosentan is not removed through dialysis.
4 years.
For white high-density polyethylene bottles, use within 30 days after the first opening.
For PVC/PE/PVDC/aluminium-blisters: Do not store above 30°C.
For white high-density polyethylene bottles: This medicinal product does not require any special storage conditions. For storage conditions after first opening of the medicinal product, see section 6.3.
Tracleer 62.5 mg film-coated tablets:
PVC/PE/PVDC/aluminium-blisters containing 14 film-coated tablets. Cartons contain 14, 56 or 112 film-coated tablets.
White high-density polyethylene bottles with a silica gel desiccant containing 56 film-coated tablets. Cartons contain 56 film-coated tablets.
Tracleer 125 mg film-coated tablets:
PVC/PE/PVDC/aluminium-blisters containing 14 film-coated tablets. Cartons contain 56 or 112 film-coated tablets.
White high-density polyethylene bottles with a silica gel desiccant containing 56 film-coated tablets. Cartons contain 56 film-coated tablets.
Not all pack sizes may be marketed.
No special requirements for disposal.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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