Drug-Drug Interaction

CARBAMAZEPINE/CIMETIDINE

MECHANISM OF ACTION
Inhibition of carbamazepine metabolism.

DISCUSSION
Elevated plasma carbamazepine concentrations and toxicity have been reported in patients stabilized on carbamazepine after cimetidine has been started. The effects of this interaction appear to dissipate within one week, at which time carbamazepine returns to the level observed prior to the addition of cimetidine. However, toxicity may still occur as long as these drugs are administered concomitantly.

CLINICAL EFFECTS
The pharmacologic and toxic effects of carbamazepine may be increased.

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

PATIENT MANAGEMENT
Monitor serum carbamazepine and observe the patient for signs of carbamazepine toxicity when starting, stopping or altering the dose of cimetidine. Administration of an alternative H-2 antagonist, such as famotidine or ranitidine, may circumvent this interaction.

PREDISPOSING FACTORS
None determined.

REFERENCES

  1. Telerman-Toppet N, Duret ME, Coers C. Cimetidine interaction with .Telerman-Toppet N, Duret ME, Coers C. Cimetidine interaction with carbamazepine. Ann Intern Med 1981 Apr;94(4 pt 1):544.
  2. Sonne J, Luhdorf K, Larsen NE, Andreasen PB. Lack of interaction between .Sonne J, Luhdorf K, Larsen NE, Andreasen PB. Lack of interaction between cimetidine and carbamazepine. Acta Neurol Scand 1983 Oct;68(4):253-6.
  3. Macphee GJ, Thompson GG, Scobie G, Agnew E, Park BK, Murray T, McColl KE, .Macphee GJ, Thompson GG, Scobie G, Agnew E, Park BK, Murray T, McColl KE, Brodie MJ. Effects of cimetidine on carbamazepine auto- and hetero-induction in man. Br J Clin Pharmacol 1984 Sep;18(3):411-9.
  4. Webster LK, Mihaly GW, Jones DB, Smallwood RA, Phillips JA, Vajda FJ. .Webster LK, Mihaly GW, Jones DB, Smallwood RA, Phillips JA, Vajda FJ. Effect of cimetidine and ranitidine on carbamazepine and sodium valproate pharmacokinetics. Eur J Clin Pharmacol 1984;27(3):341-3.
  5. Dalton MJ, Powell JR, Messenheimer JA. The influence of cimetidine on .Dalton MJ, Powell JR, Messenheimer JA. The influence of cimetidine on single dose carbamazepine pharmacokinetics. Clin Pharmacol Ther 1984 Fe; 35(2):233.
  6. Dalton MJ, Powell JR, Messenheimer JA Jr. The influence of cimetidine on .Dalton MJ, Powell JR, Messenheimer JA Jr. The influence of cimetidine on single-dose carbamazepine pharmacokinetics. Epilepsia 1985 Mar-Apr; 26(2):127-30.
  7. Levine M, Jones MW, Sheppard I. Differential effect of cimetidine on serum .Levine M, Jones MW, Sheppard I. Differential effect of cimetidine on serum concentrations of carbamazepine and phenytoin. Neurology 1985 Apr; 35(4):562-5.
  8. Dalton MJ, Powell JR, Messenheimer JA Jr. Ranitidine does not alter .Dalton MJ, Powell JR, Messenheimer JA Jr. Ranitidine does not alter single-dose carbamazepine pharmacokinetics in healthy adults. Drug Intell Clin Pharm 1985 Dec;19(12):941-4.
  9. Dalton MJ, Powell JR, Messenheimer JA Jr, Clark J. Cimetidine and .Dalton MJ, Powell JR, Messenheimer JA Jr, Clark J. Cimetidine and carbamazepine: a complex drug interaction. Epilepsia 1986 Sep-Oct; 27(5):553-8.