Carbamazepine and Erythromycin

Carbamazepine serum levels can very rapidly rise to toxic concentrations if erythromycin is given concurrently. Intoxication has been described in many reports. Erythromycin appears not to interact with phenytoin.

Clinical evidence
A girl of eight taking 50 mg phenobarbitone and 800 mg carba-mazepine daily was additionally given 500 mg and later 1000 mg erythromycin daily. Within two days she began to experience balancing difficulties and ataxia which were eventually attributed to carbamazepine intoxication. Her serum carbamazepine levels were found to have risen from a little below 10 /jg/ ml to over 25 jig/ ml (therapeutic range 2-10 uglml).

Marked rises m serum carbamazepine levels11 and/or intoxication following the addition of erythromycin have been described. At least 24 cases of carbamazepine intoxication have been reported.3-1013~16 A study in eight normal subjects showed that 1 g erythromycin daily for five days reduced the clearance of carbamazepine by an average of 20% (range 5-41%). Another study confirmed this interaction.

Mechanism
It is suggested that erythromycin has a high affinity for the active site on the liver enzymes concerned with the metabolism of the carbamazepine so that the metabolism of the latter is rapidly and markedly inhibited, resulting in its rapid accumulation which leads to toxicity.

Importance and management
A well-documented and established interaction. Its incidence is uncertain. Concurrent use should be avoided unless the effects can be very closely monitored (measurement of serum carbamazepine levels) and suitable dosage reductions made Toxic symptoms (ataxia, vertigo, drowsiness, lethargy, confusion, diplopia) can develop very rapidly (within 24 h), and serum carbamazepine levels can return to normal within 8-12 h of withdrawing the antibiotic.10 It has been suggested that the interaction may be more intense at higher erythromycin dosing rates (for instance 500 mg every six hours). Erythromycin appears not to interact with phenytoin.

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