Monitoring patients exhibiting symptoms of carbamazepine toxicity whose serum carbamazepine concentration is within the therapeutic range, but who may be producing significant levels of the active metabolite epoxide
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Carbamazepine is a common antiepileptic drug. It is a first-line drug for treatment of partial seizures and trigeminal neuralgia.
Carbamazepine is metabolized by the liver to carbamazepine-10,11-epoxide (CBZ10-11) which is pharmacologically active and potentially toxic. CBZ10-11 is, in turn, inactivated by hepatic conversion to a transdiol derivative.
CBZ10-11 may be responsible for the congenital abnormalities that are sometimes associated with the use of carbamazepine during early pregnancy. There have been cases of severe seizures exacerbation when serum epoxide levels were increased. Toxic levels of CBZ10-11 can occur during:
-Concomitant administration of other drugs that induce hepatic oxidizing enzymes (eg, most antiepileptic drugs [with the exception of valproic acid and the benzodiazepines], propoxyphene)
-Concomitant administration of drugs that inhibit its breakdown such as valproic acid, felbamate, and lamotrigine
-High-dose carbamazepine therapy, especially in combination with the above conditions
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Therapeutic concentration: 4.0-12.0 mcg/mL
Toxic concentration: > or =15.0 mcg/mL
Therapeutic concentration: 0.4-4.0 mcg/mL
Toxic concentration: > or =8.0 mcg/mL
The clinically acceptable serum concentration of carbamazepine-10,11-epoxide (CBZ10-11) is not well established, but 4.0 mcg/mL has often been used as an upper limit for its therapeutic range.
The ratio of CBZ10-11 to carbamazepine is usually < or =0.2 mcg/mL in symptomatic adults and < or =0.3 mcg/mL in children.
Clinical correlation is aided by comparing values obtained when the patient is symptomatic with those obtained when the patient has improved.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Routine determination of carbamazepine-10,11-epoxide (CBZ10-11) is not clinically indicated. It should be considered when the source of treatment in associated symptoms is not obvious.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Theodore WH, Narang PK, Holmes MD, et al: Carbamazepine and its epoxide: relation of plasma levels to toxicity and seizure control. Ann Neurol 1989;25:194-196
2. Tomson T, Almkvist O, Nilsson BY, et al: Carbamazepine-10, 11-epoxide in epilepsy. A pilot study. Arch Neurol 1990;47:888-892
3. McKauge L, Tyrer JH, Eadie MI: Factors influencing simultaneous concentrations of carbamazepine and its epoxide in plasma. Ther Drug Monit 1981;3:63-70
4. Brodie MJ, Forrest G, Rapeport WG: Carbamazepine-10,11-epoxide concentrations in epileptics of carbamazepine alone and in combination with other anticonvulsants. Br J Clin Pharmacol 1983;16:747-749
5. Shoeman JF, Elyas AA, Brett EM, Lascelles PT: Correlation between plasma carbamazepine-10,11-epoxide concentration and drug side-effects in children with epilepsy. Dev Med Child Neurol 1984;26:756-764