Which special population should be considered before prescribing Tegretol (Carbamazepine)?

From the Guidelines

Before prescribing Tegretol (carbamazepine), patients with Asian ancestry, particularly those of Han Chinese, Thai, Malaysian, Filipino, and Indian descent, should undergo genetic testing for the HLA-B*1502 allele due to the significantly increased risk of Stevens-Johnson syndrome and toxic epidermal necrolysis. This is based on the most recent evidence, which highlights the importance of genetic testing in these populations to minimize the risk of severe adverse reactions 1.

When considering the use of Tegretol, several special populations require careful consideration, including:

• Pregnant women, who should be monitored closely as Tegretol can cause fetal malformations and developmental delays
• Elderly patients, who often require lower doses due to decreased drug clearance and increased sensitivity to side effects
• Patients with liver or kidney impairment, who need dose adjustments since these organs are responsible for metabolizing and eliminating the drug
• Individuals with cardiac conduction disorders, who should be evaluated carefully as Tegretol can exacerbate heart block
• Those with a history of bone marrow suppression or blood disorders, who require regular blood count monitoring
• Patients taking other medications, who should be screened for potential drug interactions, as Tegretol is both a substrate and inducer of the cytochrome P450 enzyme system, which can affect the metabolism of many medications.

It is essential to weigh the benefits and risks of Tegretol in these special populations and to closely monitor them for any adverse effects, as the risk of morbidity and mortality can be significant if not properly managed 1.

From the FDA Drug Label

WARNINGS Serious Dermatologic Reactions Serious and sometimes fatal dermatologic reactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), have been reported with carbamazepine treatment. The risk of these events is estimated to be about 1 to 6 per 10,000 new users in countries with mainly Caucasian populations However, the risk in some Asian countries is estimated to be about 10 times higher. Prior to initiating carbamazepine therapy, testing for HLA-B1502 should be performed in patients with ancestry in populations in which HLA-B1502 may be present HLA-B1502 is present in less than 1% of the population in Japan and Korea. HLA-B1502 is largely absent in individuals not of Asian origin (e. g., Caucasians, African-Americans, Hispanics, and Native Americans). Consideration should be given to avoiding use of other drugs associated with SJS/TEN in HLA-B1502 positive patients, when alternative therapies are otherwise equally acceptable 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 HLA-A3101, an inherited allelic variant of the HLA-A gene, in patients using carbamazepine 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;

The special populations to consider before prescribing Tegretol are:

• Asian patients, especially those from countries with higher frequencies of the HLA-B*1502 allele, such as Hong Kong, Thailand, Malaysia, and parts of the Philippines.
• Patients of Chinese ancestry, due to the strong association between the risk of developing SJS/TEN and the presence of HLA-B*1502.
• Patients with ancestry in populations where HLA-B*1502 may be present, such as South Asians, including Indians.
• Patients with Japanese, Native American, Southern Indian, or Arabic ancestry, due to the moderate association between the risk of developing hypersensitivity reactions and the presence of HLA-A*3101. 2 2

From the Research

Special Population Considerations for Tegretol (Carbamazepine) Prescription

Before prescribing Tegretol, also known as carbamazepine, it is essential to consider the following special population:

• Pregnant women:
  • The risk of major congenital malformations is higher with carbamazepine exposure during pregnancy, especially at higher doses 3, 4.
  • The prevalence of major congenital malformations was 2.6% with carbamazepine monotherapy, which is lower than valproate but still a consideration 3.
  • Polytherapy with valproate and carbamazepine increases the risk of malformations 5, 6.
• Women of childbearing potential:
  • Carbamazepine may be a safer alternative to valproate for women of childbearing potential 6.
  • Preconception counseling is crucial to discuss the risks and benefits of carbamazepine treatment during pregnancy 7.