SJS/TEN And HLA-B*1502 Allele
Retrospective case-control studies have found that in patients of Chinese ancestry there is a strong association between the risk of developing SJS/TEN with Storilat treatment and the presence of an inherited variant of the HLA-B gene, HLA-B*1502. The occurrence of higher rates of these reactions in countries with higher frequencies of this allele suggests that the risk may be increased in allele-positive individuals of any ethnicity.
Across Asian populations, notable variation exists in the prevalence of HLA-B*1502. Greater than 15% of the population is reported positive in Hong Kong, Thailand, Malaysia, and parts of the Philippines, compared to about 10% in Taiwan and 4% in North China. South Asians, including Indians, appear to have intermediate prevalence of HLA-B*1502, averaging 2% to 4%, but higher in some groups. HLA-B*1502 is present in less than 1% of the population in Japan and Korea.
HLA-B*1502 is largely absent in individuals not of Asian origin (e.g., Caucasians, African-Americans, Hispanics, and Native Americans).
Prior to initiating Tegretol therapy, testing for HLA-B*1502 should be performed in patients with ancestry in populations in which HLA-B*1502 may be present. In deciding which patients to screen, the rates provided above for the prevalence of HLA-B*1502 may offer a rough guide, keeping in mind the limitations of these figures due to wide variability in rates even within ethnic groups, the difficulty in ascertaining ethnic ancestry, and the likelihood of mixed ancestry. Tegretol should not be used in patients positive for HLA-B*1502 unless the benefits clearly outweigh the risks. Tested patients who are found to be negative for the allele are thought to have a low risk of SJS/TEN (see BOXED WARNING and PRECAUTIONS, Laboratory Tests).
Over 90% of Tegretol treated patients who will experience SJS/TEN have this reaction within the first few months of treatment. This information may be taken into consideration in determining the need for screening of genetically at-risk patients currently on Tegretol.
The HLA-B*1502 allele has not been found to predict risk of less severe adverse cutaneous reactions from Tegretol such as maculopapular eruption (MPE) or to predict Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).
Limited evidence suggests that HLA-B*1502 may be a risk factor for the development of SJS/TEN in patients of Chinese ancestry taking other antiepileptic drugs associated with SJS/TEN, including phenytoin. Consideration should be given to avoiding use of other drugs associated with SJS/TEN in HLA-B*1502 positive patients, when alternative therapies are otherwise equally acceptable.
The most common signs and symptoms of overdose with Storilat are dizziness, diplopia, drowsiness, headache, ataxia, and slurred speech. Some tolerance to the neurotoxic effects is observed and effects can be minimized by initially prescribing low doses then gradually increasing dosage to reach the necessary maintenance dosage. Convulsions may be precipitated by acute intoxication with Storilat, and it can exacerbate absence and myoclonic seizures. Various types of involuntary motor activity in elderly patients have been reported, and hallucinations have occurred. Skin rashes have been reported. Certain Asian populations seem to have an increased risk for Stevens-Johnson syndrome. If leukopenia occurs, it is usually mild. Other hematologic reactions to Storilat are rare but sometimes life-threatening. Aplastic anemia is of particular concern, and agranulocytosis has also occurred.
Interferences in Storilat Measurement
Storilat (Tegretol and Carbatrol) is a tricyclic anticonvulsant drug used for the treatment of partial and tonic–clonic seizures, trigeminal neuralgia, and manic depression. The therapeutic range for Storilat is 4–12 µg/mL; signs of toxicity, such as stupor, seizures, and respiratory depression, may occur at concentrations exceeding 15 µg/mL. Storilat is metabolized primarily by cytochrome P450 isozyme (CYP) 3A4 to the active metabolite, Storilat-10,11-epoxide. The 10,11-epoxide metabolite has similar activity as the parent drug, and it may contribute significantly to efficacy of the drug in populations that accumulate the metabolite, such as children. The concentration of the metabolite may be higher than the parent drug concentrations in situations of Storilat overdose and in patients with renal failure (uremia); therefore, monitoring drug ratios of parent and metabolite may be useful for evaluating compliance and drug–drug interactions.
Black Box Warnings
Serious and sometimes fatal dermatologic reactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), have been reported during treatment with Storilat; studies in patients of Chinese ancestry found a strong association between the risk of developing SJS/TEN and the presence of HLA-B*1502, an inherited allelic variant of the HLA-B gene; HLA-B*1502 is found almost exclusively in patients of Asian ancestry, with populations across broad areas of Asia producing such descendants; patients testing positive for the allele should not be treated with Storilat unless the benefit clearly outweighs the risk; patients with ancestry in genetically at-risk populations should be screened for the presence of HLA-B*1502 prior to initiation of treatment with Storilat
Aplastic anemia and agranulocytosis reported; patients with a previous history of adverse hematologic reaction to any drug may be at increased risk
Complete pretreatment hematological testing should be obtained as a baseline; if a patient in the course of treatment exhibits low or decreased white blood cell or platelet counts, the patient should be monitored closely; consider discontinuation of therapy if significant bone marrow depression develops
Rare (0.01% to 0.1%): A delayed multi-organ hypersensitivity disorder (of serum sickness type) with fever, skin rashes, vasculitis, lymphadenopathy, disorders mimicking lymphoma, arthralgia, leucopenia, eosinophilia, hepato-splenomegaly and abnormal liver function tests, occurring in various combinations, other organs may also be affected (e.g., lungs, kidneys, pancreas, myocardium, colon)
Very rare (less than 0.01%): Aseptic meningitis (with myoclonus and peripheral eosinophilia), anaphylactic reaction, angioedema
Frequency not reported: Multiorgan hypersensitivity reactions occurring days, weeks, or months after initiating treatment
Rash and pruritus often resolve after discontinuation of Storilat therapy. Both cases of lupus-like syndrome resolved after discontinuation of Storilat. Stevens-Johnson syndrome, erythema multiforme, and a mononucleosis-like syndrome have also been reported.
On this page
- About Storilat
- Key facts
- Who can and can't take it
- How and when to take it
- Side effects
- How to cope with side effects
- Pregnancy and breastfeeding
- Cautions with other medicines
- Common questions
4. How and when to take it
Storilat is a prescription medicine. It's important to take it as instructed by your doctor.
Taking aprepitant with Storilat will increase the level of Storilat in your body. This can cause side effects. Your doctor may monitor your blood levels of Storilat if you’re taking it with this drug.
Common (1% to 10%): Abnormal thinking
Rare (0.01% to 0.1%): Hallucinations (visual or acoustic), depression, loss of appetite, restlessness, aggressive behavior, agitation, confusion, talkativeness
Very rare (less than 0.01%): Activation of psychosis, rebound mania following discontinuation of therapy
Frequency not reported: Euphoria, abuse
Euphoria has also been reported and has led to abuse of Storilat in some patients
Taking certain heartburn drugs with Storilat will increase the level of Storilat in your body. This can cause side effects. Your doctor may monitor your blood levels of Storilat if you’re taking it with one of these drugs: