Drug-Drug Interaction

CARBAMAZEPINE/SELECTED CALCIUM CHANNEL BLOCKERS

MECHANISM OF ACTION
Diltiazem and verapamil may inhibit the metabolism of carbamazepine. Carbamazepine may induce the metabolism of felodipine.

DISCUSSION
Neurotoxicity has been reported during concurrent use of carbamazepine and diltiazem or verapamil. Diltiazem has been shown to increase carbamazepine levels by 40% to 72%. Verapamil has been shown to increase carbamazepine levels by 46%.

CLINICAL EFFECTS
Concurrent diltiazem or verapamil may result in elevated levels of and toxicity from carbamazepine.

SEVERITY LEVEL
3-Moderate Interaction: Assess the risk to the patient and take action as needed.

PATIENT MANAGEMENT
Monitor serum carbamazepine levels when starting, stopping, or altering the dose of diltiazem or verapamil. Adjust the dose of carbamazepine accordingly.

PREDISPOSING FACTORS
None determined.

REFERENCES

  1. Macphee GJ, McInnes GT, Thompson GG, Brodie MJ. Verapamil potentiates .Macphee GJ, McInnes GT, Thompson GG, Brodie MJ. Verapamil potentiates carbamazepine neurotoxicity: a clinically important inhibitory interaction. Lancet 1986 Mar 29;1(8483):700-3.
  2. Brodie MJ, MacPhee GJ. Carbamazepine neurotoxicity precipitated by .Brodie MJ, MacPhee GJ. Carbamazepine neurotoxicity precipitated by diltiazem. Br Med J (Clin Res Ed) 1986 May 3;292(6529):1170-1.
  3. Eimer M, Carter BL. Elevated serum carbamazepine concentrations following .Eimer M, Carter BL. Elevated serum carbamazepine concentrations following diltiazem initiation. Drug Intell Clin Pharm 1987 Apr;21(4):340-2.
  4. Price WA, DiMarzio LR. Verapamil-carbamazepine neurotoxicity. J Clin .Price WA, DiMarzio LR. Verapamil-carbamazepine neurotoxicity. J Clin Psychiatry 1988 Feb;49(2):80.
  5. Beattie B, Biller J, Mehlhaus B, Murray M. Verapamil-induced carbamazepine .Beattie B, Biller J, Mehlhaus B, Murray M. Verapamil-induced carbamazepine neurotoxicity. A report of two cases. Eur Neurol 1988;28(2):104-5.
  6. Gadde K, Calabrese JR. Diltiazem effect on carbamazepine levels in manic .Gadde K, Calabrese JR. Diltiazem effect on carbamazepine levels in manic depression. J Clin Psychopharmacol 1990 Oct;10(5):378-9.
  7. Ahmad S. Diltiazem-carbamazepine interaction. Am Heart J 1990 Dec;120(6 Pt .Ahmad S. Diltiazem-carbamazepine interaction. Am Heart J 1990 Dec;120(6 Pt 1):1485-6.
  8. Bahls FH, Ozuna J, Ritchie DE. Interactions between calcium channel .Bahls FH, Ozuna J, Ritchie DE. Interactions between calcium channel blockers and the anticonvulsants carbamazepine and phenytoin. Neurology 1991 May;41(5):740-2.
  9. Maoz E, Grossman E, Thaler M, Rosenthal T. Carbamazepine neurotoxic .Maoz E, Grossman E, Thaler M, Rosenthal T. Carbamazepine neurotoxic reaction after administration of diltiazem. Arch Intern Med 1992 Dec; 152(12):2503-4.
  10. Cardizem LA (diltiazem hcl extended release tablets) US prescribing .Cardizem LA (diltiazem hcl extended release tablets) US prescribing information. Kos Pharmaceuticals, Inc. April, 2007.
  11. Plendil (felodipine) US prescribing information. AstraZeneca .Plendil (felodipine) US prescribing information. AstraZeneca Pharmaceuticals LP November, 2003.
  12. Wijdicks EF, Arendt C, Bazzell MC. Postoperative ophthalmoplegia and .Wijdicks EF, Arendt C, Bazzell MC. Postoperative ophthalmoplegia and ataxia due to carbamazepine toxicity facilitated by diltiazem. J Neuroophthalmol 2004 Mar;24(1):95.
  13. Shaughnessy AF, Mosley MR. Elevated carbamazepine levels associated with .Shaughnessy AF, Mosley MR. Elevated carbamazepine levels associated with diltiazem use. Neurology 1992 Apr;42(4):937-8.