DOSAGE AND ADMINISTRATION
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. Doses above 125 mg twice daily did not appear to confer additional benefit sufficient to offset the increased risk of liver injury.
Tablets should be administered morning and evening with or without food.
Liver aminotransferase levels must be measured prior to initiation of treatment and then monthly. If elevated aminotransferase levels are seen, changes in monitoring and treatment must be initiated.
Dosage Adjustments for Patients Developing Aminotransferase Elevations
The table below summarizes the dosage adjustment and monitoring recommendations for patients who develop aminotransferase elevations >3 X ULN during therapy with Tracleer. If liver aminotransferase elevations are accompanied by clinical symptoms of liver injury (such as nausea, vomiting, fever, abdominal pain, jaundice, or unusual lethargy or fatigue) or increases in bilirubin ≥ 2 — ULN, treatment with Tracleer should be stopped. There is no experience with the re-introduction of Tracleer in these circumstances.
Table 1: Dosage Adjustment and Monitoring in Patients Developing Aminotransferase Elevations >3 — ULN
|ALT/AST levels ||Treatment and monitoring recommendations |
|> 3 and ≤ 5 — ULN ||Confirm by another aminotransferase test; if confirmed, 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 pre-treatment values, continue or re-introduce the treatment as appropriate (see below). |
|> 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 pre-treatment values, consider re-introduction of the treatment (see below). |
|> 8 — ULN ||Treatment should be stopped and re-introduction of Tracleer should not be considered. There is no experience with re-introduction of Tracleer in these circumstances. |
If Tracleer is re-introduced it should be at the starting dose; aminotransferase levels should be checked within 3 days and thereafter according to the recommendations above.
Use in Females of Childbearing Potential
Initiate treatment in females of child-bearing potential only after a negative pregnancy test and only in females who are using two reliable methods of contraception. Females who have had a tubal sterilization or a 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. Females should seek contraceptive advice as needed from a gynecologist or similar expert. Urine or serum pregnancy tests should be obtained monthly in females of childbearing potential taking Tracleer [see Boxed Warning, Contraindications, Drug Interactions].
Use in Patients with Pre-existing Hepatic Impairment
Tracleer should generally be avoided in patients with moderate or severe liver impairment. There are no specific data to guide dosing in hepatically impaired patients; caution should be exercised in patients with mildly impaired liver function [see Warnings and Precautions].
Patients with Low Body Weight
In patients with a body weight below 40 kg but who are over 12 years of age the recommended initial and maintenance dose is 62.5 mg twice daily. There is limited information about the safety and efficacy of Tracleer in children between the ages of 12 and 18 years.
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 62.5 mg once daily or every other day based upon individual tolerability [see Drug Interactions].
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 62.5 mg once daily or every other day based upon individual tolerability [see Dosage and Administration and Drug Interactions].
There is limited experience with abrupt discontinuation of Tracleer. No evidence for acute rebound has been observed. Nevertheless, to avoid the potential for clinical deterioration, gradual dose reduction (62.5 mg twice daily for 3 to 7 days) should be considered.
DOSAGE FORMS AND STRENGTHS
Tracleer is available as 62.5 mg and 125 mg film-coated, unscored tablets for oral administration.
62.5 mg tablets: film-coated, round, biconvex, orange-white tablets, embossed with identification marking "62,5"
125 mg tablets: film-coated, oval, biconvex, orange-white tablets, embossed with identification marking "125"