Drug Detail:Tracleer (Bosentan [ boe-sen-tan ])
Generic Name: BOSENTAN 62.5mg
Dosage Form: tablet, film coated
Drug Class: Agents for pulmonary hypertension
Required Monitoring
Healthcare professionals who prescribe TRACLEER must enroll in the Bosentan REMS Program and must comply with the required monitoring to minimize the risks associated with TRACLEER [see Warnings and Precautions (5.3)] .
Obtain a pregnancy test in females of reproductive potential prior to TRACLEER treatment, monthly during treatment and one month after stopping TRACLEER. Initiate treatment with TRACLEER in females of reproductive potential only after a negative pregnancy test [see Boxed Warning, Contraindications (4.1), Warnings and Precautions (5.3), Use in Specific Populations (8.1, 8.3)] .
Measure liver aminotransferase levels prior to initiation of treatment and then monthly [see Warnings and Precautions (5.1)] .
Recommended Dosage
Administer TRACLEER orally following the dosing recommendations in Table 1. Doses above 125 mg twice daily did not appear to confer additional benefit sufficient to offset the increased risk of hepatotoxicity.
| Initial 4 weeks | Maintenance (after 4 weeks) | |
|---|---|---|
| Patients >12 years of age and >40 kg | 62.5 mg twice daily | 125 mg twice daily |
| Patients >12 years of age and <40 kg | 62.5 mg twice daily | 62.5 mg twice daily |
| Patients ≤12 years of age | ||
| ≥4–8 kg | 16 mg twice daily | 16 mg twice daily |
| >8–16 kg | 32 mg twice daily | 32 mg twice daily |
| >16–24 kg | 48 mg twice daily | 48 mg twice daily |
| >24–40 kg | 64 mg twice daily | 64 mg twice daily |
Administration
TRACLEER film-coated tablets and tablets for oral suspension (dispersible tablets) should be administered orally twice daily.
Disperse tablets for oral suspension, or dispersible tablet half, in a minimal amount of water immediately before administration.
Store divided dispersible tablet pieces at 20ºC to 25ºC (68ºF to 77ºF) in the opened blister for up to 7 days.
Dosage Adjustments for Aminotransferase Elevations
If aminotransferase levels increase, adjust monitoring and treatment plan according to Table 2.
Discontinue TRACLEER 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 bilirubin ≥2 ×Upper Limit of Normal (ULN). There is no experience with the reintroduction of TRACLEER in these circumstances.
| ALT/AST levels | Treatment and monitoring recommendations |
|---|---|
| >3 and ≤5 ×ULN | Confirm by another aminotransferase test; if confirmed,
|
| >5 and ≤8 ×ULN | Confirm by another aminotransferase test; if confirmed, stop treatment and monitor aminotransferase levels at least every 2 weeks. Once the aminotransferase levels return to pretreatment values,
|
| >8 ×ULN | Stop treatment permanently. There is no experience with reintroduction of TRACLEER in these circumstances. |
Use with Ritonavir
Co-administration of TRACLEER in Patients on Ritonavir
In patients who have been receiving ritonavir for at least 10 days, start TRACLEER at the recommended initial dose once daily or every other day based upon individual tolerability [see Cytochrome P450 Drug Interactions (7.1)] .
Co-administration of Ritonavir in Patients on TRACLEER
Discontinue use of TRACLEER at least 36 hours prior to initiation of ritonavir. After at least 10 days following the initiation of ritonavir, resume TRACLEER at the recommended initial dose once daily or every other day based upon individual tolerability [see Cytochrome P450 Drug Interactions (7.1)] .
Use in Patients with Pre-existing Hepatic Impairment
Avoid initiation of TRACLEER in patients with aminotransferases >3 ×ULN. No dose adjustment is required in patients with mildly impaired liver function [see Warnings and Precautions (5.3), Use in Specific Populations (8.6), Clinical Pharmacology (12.3)] .
