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Serious Dermatologic Reactions and HLA-B*1502 Allele
• Serious and sometimes fatal dermatologic reactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), reported in patients receiving carbamazepine therapy.
• Such reactions are estimated to occur in 1–6 per 10,000 new users of carbamazepine in countries with mainly Caucasian populations; however, risk in some Asian countries estimated to be approximately 10 times higher.
• Retrospective, case-control studies in patients of Asian ancestry have demonstrated a strong association between risk of developing SJS and TEN and presence of human leukocyte antigen (HLA)-B*1502, an inherited allelic variant of the HLA-B gene. The HLA-B*1502 allele is found almost exclusively in patients with ancestry across broad areas of Asia.
• Screen patients with ancestry in genetically at-risk populations for presence of HLA-B*1502 prior to initiating carbamazepine therapy. Patients testing positive for the allele should not receive carbamazepine therapy unless benefit clearly outweighs risk. (See Serious Dermatologic Reactions and HLA-B*1502 Allele under Cautions.)

Hematologic Effects
• Aplastic anemia and agranulocytosis reported.
• Risk of aplastic anemia or agranulocytosis in patients receiving carbamazepine appears to be 5–8 times greater than that in general population, but overall risk of these reactions in untreated general population is low (about 6 or 2 cases per million population year for agranulocytosis or aplastic anemia, respectively).
• Transient or persistent minor hematologic changes (e.g., decreased leukocyte or platelet counts) are not uncommon, but, in most cases, have not progressed to more serious conditions (e.g., aplastic anemia, agranulocytosis).
• Determine baseline hematologic function before initiation of therapy; closely monitor patients exhibiting abnormalities during therapy. Most hematologic changes observed during periodic monitoring are unlikely to signal occurrence of aplastic anemia or agranulocytosis.
• Consider discontinuance if evidence of substantial bone marrow depression develops.

REMS:

FDA approved a REMS for carbamazepine to ensure that the benefits of a drug outweigh the risks. The REMS may apply to one or more preparations of carbamazepine and consists of the following: medication guide. See the FDA REMS page ([Web]) or the ASHP REMS Resource Center ([Web]).