Carbamazepine drug hypersensitivity

The DRESS syndrome is an acronym for Drug Rash with Eosinophilia and Systemic Symptoms. It is also known as the Drug-Induced Pseudolymphoma and Drug Hypersensitivity Syndrome. The symptoms of DRESS syndrome usually begin I to 8 weeks after exposure to the offending drug. Common causes include carbamazepine, phenobarbital, phenytoin, terbinafine, and valproic acid. 

The carbamazepine-HLA-B 15 02 interaction has also recently been used by S-1 Hung and collaborators in Taiwan as a model for the study of the pathologic role of HLA in delayed-type drug hypersensitivity. No intracellular metabolism or antigen processing was detected in the interaction between carbamazepine and HLA-B 15 02 in patients with the bullons skin... 

In the Han Chinese population, genetic polymorphisms at HLA-B 1502 are associated with an increased risk for carbamazepine (CBZ)-induced Stevens-Johnson syndrome (SJS), while HLA-A 3101 polymorphisms are associated with an increased risk for drug hypersensitivity to CBZ [1 ]. Studies on Caucasian populations did not consistently reproduce the same associations [2,3 ] although a more recent multiethnic study population in Canada demonstrated similar associations to those seen in the Han Chinese population In addition, HLA-A 2402 allele is linked... 

Mebendazole is contraindicated in patients witii known hypersensitivity. Mebendazole is also contraindicated during pregnancy (Category C). The drug, like albendazole, has exhibited embryotoxic and teratogenic effects in experimental animals. Administration of mebendazole with tiie hydantoins and carbamazepine may reduce plasma levels of mebendazole. 

Oxcarbazepine Modulate sodium channels Loading dose Not recommended due to excessive adverse effects Maintenance dose 600-1200 mg/day. Start at 300 mg twice daily and titrate upward as indicated by response Half-life Not established Parent drug 2 hours 1 0-monohydroxy metabolite 9 hours Apparent volume of distribution 0.5-0.7 L/kg Protein binding 40% Primary elimination route Hepatic Diplopia, dizziness, somnolence Hyponatremia, 25-30% cross sensitivity in patients with hypersensitivity to carbamazepine... 

Oxcarbazepine Hyponatremia (serum sodium concentrations less than 125 mEq/L) has been reported and occurs more frequently during the first 3 months of therapy serum sodium concentrations should be monitored in patients receiving drugs that lower serum sodium concentrations (e.g., diuretics or drugs that cause inappropriate antidiuretic hormone secretion) or in patients with symptoms of hyponatremia (e.g., confusion, headache, lethargy, and malaise). Hypersensitivity reactions have occurred in approximately 25-30% of patients with a history of carbamazepine hypersensitivity and requires immediate discontinuation. 

Coadministration with cisapride, pimozide, or carbamazepine (see Warnings and Drug Interactions) patients who were withdrawn from nefazodone because of evidence of liver injury (see Warning box. Warnings) hypersensitivity to nefazodone or other phenylpiperazine antidepressants. 

Carbamazepine causes a variety of rashes and other allergic reactions including fever, hepatosplenomegaly, and lymphadenopathy, but the incidence of serious hypersensitivity reactions is rare. Systemic lupus erythematosus can occur, but discontinuation of the drug leads to eventual disappearance of the symptoms. Idiosyncratic hematological reactions to carbamazepine... 

Cholestatic hepatitis may occur when drug therapy lasts longer than 10 days or repeated courses are prescribed. The hepatitis is characterized by fever, enlarged and tender liver, hyperbilirubinemia, dark urine, eosinophilia, elevated serum bilirubin, and elevated transaminase levels. Hepatitis has been associated with the estolate salt of erythromycin but not with other formulations. Although the hepatitis usually occurs 10 to 20 days after the initiation of therapy, it can occur within hours in a patient who has had such a reaction in the past. The hepatitis is believed to be the result of both a hepatotoxic effect and a hypersensitivity reaction this latter effect is reversible on withdrawal of the drug. Erythromycin and derivatives induce hepatic microsomal enzymes and interfere with the actions of various drugs, including theophylline and carbamazepine. 

Geriatric Considerations - Summary Well-tolerated in older adults. Adjust dose based on creatinine clearance. Autoinduction of metabolism does not occur as seen with carbamazepine, but drug interactions are still an issue. Many of the CNS effects occur early in treatment and are transitory. One-third of patients with hypersensitivity reactions to carbamazepine will experience cross-sensitivity to oxcarbazepine. 

Oxcarbazepine is less potent than carbamazepine, both in animal models of epilepsy and in epileptic patients clinical doses of oxcarbazepine may need to be 50% higher than those of carbamazepine to obtain equivalent seizure control. Some studies report fewer hypersensitivity reactions to oxcarbazepine, and cross-reactivity with carbamazepine does not always occur. Furthermore, the drug appears to induce hepatic enzymes to a lesser extent than carbamazepine, minimizing drug interactions. Although hyponatremia may occur more commonly with oxcarbazepine than with carbamazepine, most adverse effects that occur with oxcarbazepine are similar in character to reactions reported with carbamazepine. 

A skin rash occurs in 5-20% of patients started on carbamazepine, and is a common cause of early drug withdrawal. The rash is usually erythematous or maculopapular and may accompany systemic manifestations of hypersensitivity. Exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis are relatively rare (SED-13, 148) (55,56). 

Cross-sensitivity among aromatic antiepileptic drugs occurs in about 50% of patients with a hypersensitivity reaction. It has previously been described on first exposure to each of the offending drugs (57). However, this patient developed an allergic rash on his second exposure to phenytoin, having previously tolerated it for 6 months. This suggests that carbamazepine may have altered his response to phenytoin. 

Hypersensitivity to barbiturates can result in a life-threatening syndrome called the Drug, Rash with Eosinophilia and Systemic Symptoms (DRESS) Syndrome with a mortality of 10%. In persons developing hypersensitivity to barbiturates, there is a potential of cross-sensitivity with other aromatic antiepileptics, such as phenytoin and carbamazepine. 

Hypersensitivity to the drug and to carbamazepine, alcohol. Recommend additional nonhormonal forms of contraception. 

Carbamazepine has a similar tricyclic structure to these drugs and may precipitate a hypersensitivity reaction. 

Naisbitt DJ, Britschgi M, Wong G, Earrell J, Depta JP, Chadwick DW, Pichler WJ, Pirmohamed M, Park BK (2003a) Hypersensitivity reactions to carbamazepine characterization of the specificity, phenotype, and cytokine profile of drug-specific T cell clones. Mol Pharmacol 63 732-741... 

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