Medication Guide App

Label Changes for:

Tegretol (carbamazepine) Tablets, Chewable Tablets, Oral Suspension, and Tegretol-XR (carbamazepine extended-release) Tablets

March 2013

Changes have been made to the WARNINGS and PRECAUTIONS sections of the safety label.

Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)

 

March 2013

WARNINGS

Hypersensitivity Reactions and HLA-A*3101 Allele
  • Retrospective case-control studies in patients of European, Korean, and Japanese ancestry have found a moderate association between the risk of developing hypersensitivity reactions and the presence of HLAA*3101, an inherited allelic variant of the HLA-A gene, in patients using carbamazepine. These hypersensitivity reactions include SJS/TEN, maculopapul Systemic Symptoms.
  • HLA-A*3101 is expected to be carried by more than 15% of patients of Japanese, Native American, Southern Indian (for example, Tamil Nadu) and some Arabic ancestry; up to about 10% in patients of Han Chinese, Korean, European, Latin Aamerican, and other Indian ancestry; and up to about 5% in African-Americans and  patients of Thai, Taiwanese, and Chinese (Hong Kong) ancestry.
  • The risks and benefits of Tegretol therapy should be weighed before considering Tegretol in patients known to be positive for HLA-A*3101.
  • Application of HLA genotyping as a screening tool has important limitations and must never substitute for appropriate clinical vigilance and patient management. Many HLA-B*1502-positive and HLA-A*3101-positive patients treated with Tegretol will not develop SJS/TEN or other hypersensitivity reactions, and these reactions can still occur infrequently in HLA-B*1502-negative and HLA-A*3101-negative patients of any ethnicity. The role of other possible factors in the development of, and morbidity from, SJS/TEN and other hyper sensitivity reactions, such as antiepileptic drug (AED) dose, compliance, concomitant medications, comorbidities, and the level of dermatologic monitoring, have not been studied.
Drug Interactions

Agents That May Affect Tegretol Plasma Levels

  • …. Drugs that have been shown, or would be expected, to increase plasma carbamazepine levels include:
    • Aprepitant….
Effect of Tegretol on Plasma Levels of Concomitant
  • Cyclophosphamide is an inactive prodrug and is converted to its active metabolite in part by CYP3A. The rate of metabolism and the leukopenic activity of cyclophosphamide reportedly are increased by chronic administration of high doses of another CYP3A4 inducer. There is a potential for increased cyclophosphamide toxicity when coadministered with carbamazepine.
  • When carbamazepine is added to aripiprazole therapy, the aripiprazole dose should be doubled. Additional dose increases should be based on clinical evaluation. When carbamazepine is withdrawn from the combination therapy, the aripiprazole dose should be reduced When carbamazepine is used with tacrolimus, monitoring of tacrolimus blood concentrations and appropriate dosage adjustments are recommended.
  • CYP3A4 inducers such as carbamazepine should be avoided with temsirolimus.
  • The use of carbamazepine with lapatinib should generally be avoided. Dosage adjustment should be considered if lapatinib is coadministered with carbamazepine. If carbamazepine is started in a patient already taking lapatinib, the dose of lapatinib should be gradually titrated up. If carbamazepine is discontinued, the lapatinib dose should be reduced.
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