FDA information on Tegretol
Tegretol which is an anticonvulsant drug was first approved by FDA in March 1996. After some time, FDA also approved the drug to be used amongst children below six years of age. Tegretol is mostly used as a first step during the treatment of seizures in children and adults. These seizures can be either of partial or secondary generalized or can also be of generalized tonic-clonic category.
On 12th December 2007, FDA issued an alert to all the healthcare professionals, informing them about the dangerous and sometimes fatal side effects of carbamazepine, for which Tegretol happens to be one of the brand names. The fatal skin reactions included Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The patients who are suffering from a particular human leukocyte antigen (HLA) allele, HLA-B*1502, happen to be at higher risks to develop these disorders as a result of carbamazepine therapy. The genetic tests of HLA-B*1502 show that patients who have a family history of this leukocyte antigen, should first be tested for HLA-B*1502 before starting with Tegretol treatment. And in case, the patient is tested positive for the latter leukocyte antigen, then carbamazepine, should be given only if the practitioner is of the opinion that no other treatment can benefit the patient. If the patient is on this medication for more than few months, and has not developed any of the side effects, then the likelihood of developing them at a later stage during the treatment is bleak. This also holds true for patients suffering from any kind of human leukocyte antigen or ethnicity or genotype.
FDA approved this medicine to cure epilepsy, mania/bipolar disorder, and neuropathic pain. Post its commercial use, harmful health ailments like SJS & TEN were associated with this drug. These ailments could cause permanently disabling blistering reactions of the skin or mucous membranes. However these ailments were very country specific. The risk in Caucasian populations was reported as low as 1- 6 per 10,000 new users in comparison to some Asian countries, where it was reported 10 times higher by the manufacturers and the post- marketing adverse event reports to the WHO. Studies from Taiwan, Europe and Hong- Kong further suggested that the increased risk of SJS and TEN was mainly associated with HLA-B*1502, which was found exclusively across broad areas of Asia, including some individuals in South Asia, India and not in areas in and around Caucasus As a result the risk of these fatal ailments was low amongst Caucasian population and hence less number of cases were reported from these areas.
After all this information, FDA again reviewed the:
- Manufacturer’s information
- All the published studies
- Post- marketing adverse event reports
To reach to the conclusion that carbamazepine labeling information required amendments. These amendments covered the inclusion of the drug’s association with SJS/TEN, and information to guide testing for the HLAB*1502 allele in at-risk populations to the already existing boxed warning and to the sections of the guide educating about warnings, laboratory tests, and adverse reactions.