Carbamazepine liver toxicity

The macrolide antibacterials (including erythromycin, clarithromycin and telithromycin) are often implicated in interactions, most frequently as a result of inhibition of the CYP3A4 enzyme system in the liver and enterocytes. Erythromycin inhibits the metabolism of carbamazepine, ciclosporin and theophylline significant increases in serum levels and features of toxicity have been documented. Careful clinical and pharmacokinetic monitoring are required in a patient taking any of these drugs who requires concomitant erythromycin. 

Propoxyphene interacts with several drugs. The use of sedatives in combination with propoxyphene can be fatal. In addition, the metabolism of the drug is increased in smokers due to induction of liver enzymes. Thus, smokers may require a higher dose of the drug for pain relief. Propoxyphene enhances the effects of both warfarin and carbamazepine and may increase the toxicity associated with both drugs, such as bleeding and sedation, respectively. 

Because of the potential for hematological and hepatic toxicity, carbamazepine should not be administered to patients with liver disease or thrombocytopenia or to those at risk for agranulocytosis. For this reason, carbamazepine is strictly contraindicated in patients receiving clozapine. Because of reports of teratogenicity, including increased risks of spina bifida (Rosa 1991), microcephaly (Bertol-lini et al. 1987), and craniofacial defects (Jones et al. 1989), carbamazepine is relatively contraindicated in pregnant women. Pretreatment evaluation should include a complete blood count and determination of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. 

A related issue is the patient s ability to metabolize and eliminate drugs adequately. For example, lithium is excreted entirely by the kidneys, and if a patient suffers from significantly impaired renal function, high, potentially toxic levels could develop on standard doses. Although the dose could be adjusted to compensate for the decrease in drug clearance, it might be more appropriate to choose another mood stabilizer such as valproate or carbamazepine, because they are primarily metabolized through the liver. 

A week later he went home on full anti-tuberculosis drugs with stable liver function tests and carbamazepine and the addition of pyridoxine. The white count does not suggest resistance has emerged during this treatment gap but should be monitored over the full treatment course. Any acute liver insult on top of this treatment would be very difficult to resolve. Compliance with the pyridoxine is very important to prevent any toxicity. 

Hypersusceptibility reactions to carbamazepine are relatively common and range from cutaneous reactions (including Stevens-Johnson sjmdrome and toxic epidermal necrolysis, severe forms of erythema multiforme) to systemic reactions with fever, lymphadenopathy, and/or involvement of the bone marrow, the liver, the heart, the gastrointestinal system, the lungs, and other organs. 

The elderly appear to be at increased risk of blood dys-crasias and liver reactions (39). Age above 55 years was associated with a greater risk of toxicity after rapid switch-over to a carbamazepine dosage designed to jdeld a plasma concentration of 10 pg/ml (76). Moderately severe to severe adverse effects in the 11 patients in either subgroup included sedation, ataxia, and confusion. 

Transient elevations of the serum transaminases occur in 12% to 15% of patients receiving isoniazid and usually occur within the first 8 to 12 weeks of therapy. Overt hep ato toxicity, however, occurs in only 1% of cases. Risk factors for hepatotoxicity include patient age, preexisting liver disease, excessive alcohol intake, pregnancy, and the postpartum state. Isoniazid also may result in neurotoxicity, most frequently presenting as peripheral neuropathy or, in overdose, as seizures and coma. Patients with pyridox-ine deficiency, such as pregnant women, alcoholics, children, and the malnourished, are at increased risk. Isoniazid may inhibit the metabolism of phenytoin, carbamazepine, primidone, and warfarin." Patients who are being treated with these agents should be monitored closely, and appropriate dose adjustments should be made when necessary. 

Carbamazepine (Tegretol) Actions and indications similar to phenytoin. Theraputic serum levels are 4-12 pg/ml. Toxicity Vertigo, nausea, vomiting, aplastic anemia and agranulocytosis (rare but serious). Metab Induces its own metabolism (T P450 enzymes) in liver. One metabolite is active. 75% protein bound. 

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