MANAGING ADULT PATIENTS
TRACLEER ADULT DOSAGE AND ADMINISTRATION

Managing Adult Patients

Setting patient expectations

When starting a patient on TRACLEER^® (bosentan), it is important to set expectations. Setting patient expectations is essential in a chronic disease such as pulmonary arterial hypertension (PAH) because you and your patient will be working together closely to evaluate outcomes during treatment with TRACLEER.

Responsible monitoring

The safe use of TRACLEER requires ongoing monthly monitoring of liver function test (LFT) results and, if applicable, pregnancy test results. You must counsel your patients about the importance of monthly testing and ensure that test results are obtained and reviewed by your office.

LFT monitoring algorithm

Elevated monthly LFT results do not always preclude treatment with TRACLEER. The table below provides recommendations on the management of patients taking TRACLEER with elevated LFT results.

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 × ULN, treatment should be stopped. There is no experience with the reintroduction of TRACLEER in these circumstances.

TRACLEER: Management of aminotransferase (ALT/AST) elevations¹
ALT/AST levels	Treatment and monitoring recommendations
>3 and ≤5 × ULN	Confirm by another aminotransferase test; if confirmed, - in adults and pediatric patients >12 years and >40 kg, reduce the daily dose to 62.5 mg twice daily or interrupt treatment, and monitor aminotransferase levels at least every 2 weeks. If the aminotransferase levels return to pretreatment values, treatment may continue or be reintroduced at 62.5 mg twice daily, with reassessment of aminotransferase levels within 3 days. - in all other pediatric patients, interrupt treatment with no prior dose reduction. If the aminotransferase levels return to pretreatment values, reintroduce at the dose used prior to treatment interruption, with reassessment of aminotransferase levels within 3 days.
>5 to ≤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, - in adults and pediatric patients >12 years and >40 kg, consider reintroduction of treatment at 62.5 mg twice daily, with reassessment of aminotransferase levels within 3 days. - in all other pediatric patients, consider reintroduction at the dose used prior to treatment interruption, with reassessment of aminotransferase levels within 3 days.
>8 × ULN	Stop treatment permanently. There is no experience with reintroduction of TRACLEER in these circumstances.

ALT: alanine aminotransferase; AST: aspartate aminotransferase; ULN: upper limit of normal.

*If TRACLEER is reintroduced, it should be at the starting dose; aminotransferase levels should be checked within three days and thereafter according to the recommendations above.

Test confirmation

The specialty pharmacy will confirm with your patients that monthly LFTs and, if applicable, pregnancy tests have been obtained. If a patient does not confirm having the monthly tests or becomes pregnant, the pharmacy will contact you.

Please notify Janssen and/or FDA of any pregnancies or adverse events, including hepatotoxicity, by calling toll-free at 1-800-Janssen (1-800-526-7736), or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

TRACLEER^® Adult Dosage and Administration

TRACLEER adult dosing¹

Healthcare professionals who prescribe TRACLEER must enroll in the TRACLEER REMS Program and must comply with the required monitoring to minimize the risks associated with TRACLEER.

Initiate at 62.5 mg twice daily (BID) 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 × upper limit of normal (ULN).
Discontinue TRACLEER 36 hours prior to initiation of ritonavir. Patients on ritonavir: Initiate TRACLEER at 62.5 mg once daily or every other day.

Indicate centered image — Tablets should be administered in the 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.