Tracleer® Dosage and Administration
- Initiate at 62.5 mg twice daily with or without food for four weeks; then increase to 125 mg twice daily.
- Patients with low body weight (<40 kg) and >12 years old: initial and maintenance dose is 62.5 mg twice daily.
- Reduce the dose or interrupt treatment and closely monitor patients developing aminotransferase elevations >3 x ULN.
- Discontinue Tracleer (bosentan) 36 hours prior to initiation of ritonavir. Patients on ritonavir: initiate Tracleer at 62.5 mg once daily or every other day.
Tablets should be administered morning and evening with or without food. Doses above 125 mg twice daily did not appear to confer additional benefit sufficient to offset increased risk of hepatotoxicity.
Required monitoring—liver aminotransferase levels
Liver aminotransferase levels must be measured prior to initiation of treatment and monitored on a monthly basis.1
- If elevated aminotransferase levels are seen, changes in monitoring and treatment must be initiated.
- If liver aminotransferase elevations are accompanied by clinical symptoms of hepatotoxicity (such as nausea, vomiting, fever, abdominal pain, jaundice, or unusual lethargy or fatigue) or increases in bilirubin ≥ 2 x ULN, treatment with Tracleer should be stopped. There is no experience with reintroduction of Tracleer in these circumstances.
Tracleer should generally be avoided in patients with moderate or severe liver impairment.1 There are no specific data to guide dosing in hepatically impaired patients; caution should be exercised in patients with mildly impaired liver function.1
Prescribing Tracleer for females of childbearing potential
Initiate Tracleer in females of childbearing potential only after negative pregnancy test and only in females who are using two reliable methods of contraception.1
- Females who have had tubal sterilization or Copper T 380A IUD or LNg-20 IUS inserted do not require other forms of contraception.
- Effective contraception must be practiced throughout treatment and for one month after stopping Tracleer.
- Pregnancy tests should be obtained monthly in females of childbearing potential taking Tracleer.
- Tracleer is contraindicated for use with cyclosporine A and glyburide.
- Tracleer is metabolized by CYP2C9 and CYP3A.
- Co-administration with agents that are metabolized by these pathways may affect plasma concentrations of one or both agents.
- When initiating lopinavir/ritonavir and other ritonavir-containing HIV regimens, dosage adjustment of Tracleer is necessary.
- When co-administered with simvastatin, or other statins that are CYP3A substrates, dosage adjustment of such statins may need to be considered.
- When co-administered with rifampicin, a CYP3A inducer, liver function should be monitored weekly for the first four weeks before reverting to normal monitoring.
- Co-administration of tacrolimus and bosentan resulted in markedly increased plasma concentrations of bosentan in animals; caution should be exercised if they are used together.
- When co-administered with ketoconazole, a potent CYP3A inhibitor, no dose adjustment of bosentan is necessary, but increased effects of Tracleer may need to be considered.
- There are no clinically relevant interactions between Tracleer and warfarin, digoxin, nimodipine, losartan, or sildenafil.
- Tracleer has no significant interaction with iloprost.
- Dose adjustments are not necessary with Tracleer and sildenafil.
Gradual dose reduction (62.5 mg twice daily for three to seven days) should be considered to avoid the potential for clinical deterioration as there is limited experience with abrupt discontinuation of Tracleer.1 No evidence for acute rebound has been observed.1