HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use TRACLEER® safely and effectively. See full prescribing information for TRACLEER. TRACLEER® (bosentan) tablets, for ...
These highlights do not include all the information needed to use TRACLEER® safely and effectively. See full prescribing information for TRACLEER.
TRACLEER® (bosentan) tablets, for oral use
Initial U.S. Approval: 2001
WARNING: RISKS OF HEPATOTOXICITY and EMBRYO-FETAL TOXICITY
See full prescribing information for complete boxed warning.
Tracleer is available only through a restricted distribution program called the Tracleer REMS Program because of these risks (5.2):
Elevations of liver aminotransferases (ALT, AST) and liver failure have been reported with Tracleer (5.1).
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Measure liver aminotransferases prior to initiation of treatment and then monthly (5.1).
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Discontinue Tracleer if aminotransferase elevations are accompanied by signs or symptoms of liver dysfunction or injury or increases in bilirubin ≥2 × ULN (2.2, 5.1).
Based on animal data, Tracleer is likely to cause major birth defects if used during pregnancy (4.1, 8.1).
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Must exclude pregnancy before and during treatment (4.1, 8.1).
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To prevent pregnancy, females of reproductive potential must use two reliable forms of contraception during treatment and for one month after stopping Tracleer (4.1, 8.1).
RECENT MAJOR CHANGES
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Boxed Warning |
12/2015 |
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Dosage and Administration (2, 2.3) |
12/2015 |
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Contraindications (4.1, 4.4) |
10/2016 |
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Warnings and Precautions (5.2) |
12/2015 |
INDICATIONS AND USAGE
Tracleer is an endothelin receptor antagonist indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise ability and to decrease clinical worsening. Studies establishing effectiveness included predominantly patients with NYHA Functional Class II-IV symptoms and etiologies of idiopathic or heritable PAH (60%), PAH associated with connective tissue diseases (21%), and PAH associated with congenital heart disease with left-to-right shunts (18%) (1.1).
Considerations for use:
Consider whether benefits offset the risk of hepatotoxicity in WHO Class II patients. Early hepatotoxicity may preclude future use as disease progresses (1.1).
DOSAGE AND ADMINISTRATION
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Initiate at 62.5 mg twice daily with or without food for 4 weeks, and then increase to 125 mg twice daily (2.1).
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Patients with low body weight (<40 kg) and >12 years old: Initial and maintenance dose is 62.5 mg twice daily (2.4).
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Reduce the dose and closely monitor patients developing aminotransferase elevations >3 × ULN (2.2).
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Discontinue Tracleer 36 hours prior to initiation of ritonavir. Patients on ritonavir: Initiate Tracleer at 62.5 mg once daily or every other day (2.5).
DOSAGE FORMS AND STRENGTHS
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Tablet: 62.5 mg and 125 mg (3)
CONTRAINDICATIONS
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Pregnancy (4.1)
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Use with Cyclosporine A (4.2)
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Use with Glyburide (4.3)
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Hypersensitivity (4.4)
WARNINGS AND PRECAUTIONS
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Pre-existing hepatic impairment: Avoid use in moderate and severe impairment (5.3).
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Fluid retention: May require intervention (5.4).
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Pulmonary veno-occlusive disease (PVOD): If signs of pulmonary edema occur, consider the diagnosis of associated PVOD and consider discontinuing Tracleer (5.5)
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Decreased sperm counts (5.6)
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Decreases in hemoglobin and hematocrit: Monitor hemoglobin levels after 1 and 3 months of treatment, then every 3 months thereafter (5.7).
ADVERSE REACTIONS
Common adverse reactions (≥3% more than placebo) are respiratory tract infection and anemia (6.1).
To report SUSPECTED ADVERSE REACTIONS, contact Actelion at 1-866-228-3546 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
DRUG INTERACTIONS
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Hormonal contraceptives: Tracleer use decreases contraceptive exposure and reduces effectiveness (7.2).
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Simvastatin and other CYP3A-metabolized statins: Combination use decreases statin exposure and may reduce efficacy (7.6).
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Rifampin: Alters bosentan exposure. Monitor hepatic function weekly for 4 weeks, followed by normal monitoring (7.7).
USE IN SPECIFIC POPULATIONS
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Nursing mothers: Choose breastfeeding or Tracleer (8.3).
See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.
Revised: 10/2016
FULL PRESCRIBING INFORMATION: CONTENTS*
Table of Contents
1. INDICATIONS AND USAGE
1.1 Pulmonary Arterial Hypertension - Tracleer® is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise ability and ...
1.1 Pulmonary Arterial Hypertension
Tracleer® is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise ability and to decrease clinical worsening. Studies establishing effectiveness included predominantly patients with NYHA Functional Class II-IV symptoms and etiologies of idiopathic or heritable PAH (60%), PAH associated with connective tissue diseases (21%), and PAH associated with congenital heart disease with left-to-right shunts (18%) [see Clinical Studies (14.1)].
Considerations for use
Patients with WHO Class II symptoms showed reduction in the rate of clinical deterioration and a trend for improvement in walk distance. Physicians should consider whether these benefits are sufficient to offset the risk of hepatotoxicity in WHO Class II patients, which may preclude future use as their disease progresses.
2. DOSAGE AND ADMINISTRATION
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 [see ...
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 [see Warnings and Precautions (5.2)].
2.1 Adult Dosage
Initiate treatment at 62.5 mg twice daily for 4 weeks and then increase 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 hepatotoxicity.
Tracleer should be administered in the morning and evening with or without food.
2.2 Dosage Adjustments for Patients Developing Aminotransferase Elevations
Measure liver aminotransferase levels prior to initiation of treatment and then monthly. If aminotransferase levels increase, revise the monitoring and treatment plan. The table below summarizes the dosage adjustment and monitoring recommendations for patients who develop aminotransferase elevations >3 × ULN during therapy with Tracleer. 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 increases in bilirubin ≥ 2 × ULN. There is no experience with the reintroduction of Tracleer in these circumstances.
2.3 Pregnancy Testing in Females of Reproductive Potential
Initiate treatment with Tracleer in females of reproductive potential only after a negative pregnancy test. Obtain monthly pregnancy test during treatment [see Use in Specific Populations (8.1)].
2.4 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 [see Use in Specific Populations (8.4)].
