Verapamil-Induced Carbamazepine Neurotoxicity

Abstract

Two patients with signs of carbamazepine neurotoxicity after combined treatment with verapamil showed complete recovery after discontinuation of the calcium entry blocker. Use of verapamil in combination with carbamazepine should either be avoided or prescribed only with appropriate adjustment of the carbamazepine dose (usually reduction of the carbamazepine dose by one half).

Drug Metabolism

“…The reaction of enzymatic conversion is presented in Figure 2.67: When tested in animals, low toxicity was registered for cefuroxime axetil [163].…”

“…Penicillins phenytoin possible phenytoin toxicity (decreased metabolism) [153] digoxin possible digoxin toxicity (decreased gut metabolism and increased absorption) [154] lithium lithium toxicity (decreased renal excretion) [155] phenytoin decreased doxycycline effect (increased metabolism) [156] theophyllines possible theophylline toxicity (mechanism not established) [157] Tetracyclines zinc decreased tetracycline effect (decreased absorption) [158] azathioprine possible azathioprine toxicity with sulfasalazine (decreased metabolism) [159] cyclosporin nephrotoxicity (synergism) [160] dapsone dapsone toxicity, methemoglobinemia (probably decreased metabolism) [161] Trimethoprim digoxin possible digoxin toxicity (decreased renal excretion and possibly decreased metabolism) [162] carbamazepine carbamazepine toxicity (decreased metabolism) [163] clonidine A-V Block (possible synergy) [164] Verapamil digoxin digoxin toxicity (probably decreased biliary excretion) [165] Chapter 8…”

Calcium Antagonists

“…Neurotoxicity associated with carbamazepine has been seen with concomitant treatment with either diltiazem [4][5][6][7][8][9] or verapamiI.l9, 13,14) Both these drugs produce significant inhibition of hepatic cytochrome P450 oxidative metabolism. The frequency with which symptoms are seen in patients taking these drug combinations suggests that diltiazem and verapamil inhibit the metabolism of carbamazepine to an extent likely to have important clinical repercussions.…”

“…Beattie et al [13] advocated careful monitoring of serum carbamazepine concentrations when diltiazem or veraparnil are initiated, and Macphee et al [14] stated that judicious monitoring of patients receiving carbamazepine in combination with either verapamil or diltiazem, both clinically and biochemically, may prevent toxic effects.…”

Antiepileptic Drugs

“…Verapamil and diltiazem can almost double carbamazepine serum concentrations resulting in adverse effects, while nifedipine does not exhibit any significant interaction (Bahls et al 1991;Beattie et al 1988;Macphee et al 1986). Verapamil and diltiazem can almost double carbamazepine serum concentrations resulting in adverse effects, while nifedipine does not exhibit any significant interaction (Bahls et al 1991;Beattie et al 1988;Macphee et al 1986).…”