Pfizer" on one side and "LLN 100" on the other side
4CONTRAINDICATIONS
LORBRENA is contraindicated in patients taking strong CYP3A inducers, due to the potential for serious hepatotoxicity [see Warnings and Precautions (5.1)].
5WARNINGS AND PRECAUTIONS
5.1Risk of Serious Hepatotoxicity with Concomitant Use of Strong CYP3A Inducers
Severe hepatotoxicity occurred in 10 of 12 healthy subjects receiving a single dose of LORBRENA with multiple daily doses of rifampin, a strong CYP3A inducer. Grade 4 alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations occurred in 50% of subjects, Grade 3 ALT or AST elevations occurred in 33% and Grade 2 ALT or AST elevations occurred in 8%. ALT or AST elevations occurred within 3 days and returned to within normal limits after a median of 15 days (7 to 34 days); the median time to recovery was 18 days in subjects with Grade 3 or 4 ALT or AST elevations and 7 days in subjects with Grade 2 ALT or AST elevations.
LORBRENA is contraindicated in patients taking strong CYP3A inducers. Discontinue strong CYP3A inducers for 3 plasma half-lives of the strong CYP3A inducer prior to initiating LORBRENA.
Avoid concomitant use of LORBRENA with moderate CYP3A inducers. If concomitant use of moderate CYP3A inducers cannot be avoided, monitor AST, ALT, and bilirubin 48 hours after initiating LORBRENA and at least 3 times during the first week after initiating LORBRENA.
Depending upon the relative importance of each drug, discontinue LORBRENA or the CYP3A inducer for persistent Grade 2 or higher hepatotoxicity [see Clinical Pharmacology (12.3)].
5.2Central Nervous System Effects
A broad spectrum of central nervous system (CNS) effects can occur in patients receiving LORBRENA. These include seizures, hallucinations, and changes in cognitive function, mood (including suicidal ideation), speech, mental status, and sleep. Overall, CNS effects occurred in 54% of patients receiving LORBRENA [see Adverse Reactions (6.1)]. Cognitive effects occurred in 29% of the 332 patients who received LORBRENA at any dose in Study B7461001; 2.1% of these events were severe (Grade 3 or 4). Mood effects occurred in 24% of patients; 1.8% of these events were severe. Speech effects occurred in 14% of patients; 0.3% of these events were severe. Hallucinations occurred in 7% of patients; 0.6% of these events were severe. Mental status changes occurred in 2.1% of patients; 1.8% of these events were severe. Seizures occurred in 3% of patients, sometimes in conjunction with other neurologic findings. Sleep effects occurred in 10% of patients. The median time to first onset of any CNS effect was 1.2 months (1 day to 1.7 years). Overall, 1.5% of patients required permanent discontinuation of LORBRENA for a CNS effect; 9% required temporary discontinuation and 8% required dose reduction.
Withhold and resume at the same dose or at a reduced dose or permanently discontinue LORBRENA based on severity [see Dosage and Administration (2.2)].
5.3Hyperlipidemia
Increases in serum cholesterol and triglycerides can occur in patients receiving LORBRENA [see Adverse Reactions (6.1)]. Grade 3 or 4 elevations in total cholesterol occurred in 17% and Grade 3 or 4 elevations in triglycerides occurred in 17% of the 332 patients who received LORBRENA in Study B7461001. The median time to onset was 15 days for both hypercholesterolemia and hypertriglyceridemia. Approximately 7% of patients required temporary discontinuation and 3% of patients required |
