Use of Bosentan in Pediatric Pulmonary Hypertension
Use of Bosentan in Pediatric Pulmonary Hypertension
The recommended starting dose for bosentan in adults is 62.5 mg twice daily for 4 weeks, followed by an increase to 125 mg twice daily for maintenance therapy. Based on the available literature, an initial dose of 1–2 mg/kg twice daily appears appropriate for children. After 4 weeks, the dose may be increased to 2–4 mg/kg twice daily. Bosentan may be taken with or without food.
In children requiring less than a full tablet, the tablet may be split with a pill cutter. Split tablets are stable for up to 4 weeks if stored in the original manufacturer's bottle. Because of the risk for teratogenic effects, splitting tablets or handling of split tablets should not be performed by women who are or may be pregnant. Bosentan tablets should not be crushed. For children unable to swallow tablets, or who require smaller doses, the tablet can be placed in 5–25 mL of water and allowed to disintegrate. The resulting suspension can be used to prepare an aliquot providing the correct dose. The suspension is stable at room temperature for up to 24 hrs. Bosentan should not be dissolved or mixed with acidic liquids such as fruit juices.
Although limited information exists on the potential for rebound PAH with abrupt discontinuation, the manufacturer suggests reducing the dose by 50% for 3–7 days prior to discontinuation. Dosing must also be adjusted in patients with elevated liver transaminases. In those with transaminases 3–5 times the upper limit of normal, testing should be repeated and if the results are confirmed, the dose should be reduced to 62.5 mg twice daily in adults, half the starting dose in children, or stopped. Liver transaminases should be repeated every two weeks; therapy can be reintroduced when values return to baseline. In patients with transaminases 5–8 times the upper limit of normal, therapy should be stopped and not restarted until values are at baseline. When bosentan is re-introduced, it should be at the patient's initial dose. If transaminases are over 8 times the upper limit of normal, therapy should be discontinued.
Dosing Recommendations
The recommended starting dose for bosentan in adults is 62.5 mg twice daily for 4 weeks, followed by an increase to 125 mg twice daily for maintenance therapy. Based on the available literature, an initial dose of 1–2 mg/kg twice daily appears appropriate for children. After 4 weeks, the dose may be increased to 2–4 mg/kg twice daily. Bosentan may be taken with or without food.
In children requiring less than a full tablet, the tablet may be split with a pill cutter. Split tablets are stable for up to 4 weeks if stored in the original manufacturer's bottle. Because of the risk for teratogenic effects, splitting tablets or handling of split tablets should not be performed by women who are or may be pregnant. Bosentan tablets should not be crushed. For children unable to swallow tablets, or who require smaller doses, the tablet can be placed in 5–25 mL of water and allowed to disintegrate. The resulting suspension can be used to prepare an aliquot providing the correct dose. The suspension is stable at room temperature for up to 24 hrs. Bosentan should not be dissolved or mixed with acidic liquids such as fruit juices.
Although limited information exists on the potential for rebound PAH with abrupt discontinuation, the manufacturer suggests reducing the dose by 50% for 3–7 days prior to discontinuation. Dosing must also be adjusted in patients with elevated liver transaminases. In those with transaminases 3–5 times the upper limit of normal, testing should be repeated and if the results are confirmed, the dose should be reduced to 62.5 mg twice daily in adults, half the starting dose in children, or stopped. Liver transaminases should be repeated every two weeks; therapy can be reintroduced when values return to baseline. In patients with transaminases 5–8 times the upper limit of normal, therapy should be stopped and not restarted until values are at baseline. When bosentan is re-introduced, it should be at the patient's initial dose. If transaminases are over 8 times the upper limit of normal, therapy should be discontinued.
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