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Drug Interactions between Epitol and fosphenytoin

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

carBAMazepine fosphenytoin

Applies to: Epitol (carbamazepine) and fosphenytoin

MONITOR: Hydantoins may decrease carbamazepine levels, and carbamazepine may have variable effects on hydantoin levels. The mechanism may be related to induction of CYP450 hepatic metabolism of carbamazepine and alteration of hydantoin metabolism.

MANAGEMENT: Close observation for clinical and laboratory evidence of altered effects is recommended, particularly when one drug is started or discontinued. Patients should be advised to notify their physician if they experience loss of seizure control or symptoms of hydantoin toxicity (drowsiness, visual disturbances, change in mental status, nausea, or ataxia).

References

  1. Zielinski JJ, Haidukewych D, Leheta BJ (1985) "Carbamazepine-phenytoin interaction: elevation of plasma phenytoin concentrations due to carbamazepine comedication." Ther Drug Monit, 7, p. 51-3
  2. Zielinski JJ, Haidukewych D (1987) "Dual effects of carbamazepine-phenytoin interaction." Ther Drug Monit, 9, p. 21-3
  3. Ramsay RE, McManus DQ, Guterman A, et al. (1990) "Carbamazepine metabolism in humans: effect of concurrent anticonvulsant therapy." Ther Drug Monit, 12, p. 235-41
  4. Hansen JM, Siersbaek-Nielsen K, Skovsted L (1971) "Carbamazepine-induced acceleration of diphenylhydantoin and warfarin metabolism in man." Clin Pharmacol Ther, 12, p. 539-43
  5. Perucca E, Richens A (1980) "Reversal by phenytoin of carbamazepine-induced water intoxication: a pharmacokinetic interaction." J Neurol Neurosurg Psychiatry, 43, p. 540-5
  6. Gratz ES, Theodore WH, Newmark ME, Kupferberg HJ, Porter RJ, Qu Z (1982) "Effect of carbamazepine on phenytoin clearance in patients with complex partial seizures." Neurology, 32, a223
  7. Morris JC, Dodson E, Hatlelid JM, Ferrendelli JA (1987) "Phenytoin and carbamazepine, alone and in combination: anticonvulsant and neurotoxic effects." Neurology, 37, p. 1111-8
View all 7 references

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Drug and food interactions

Moderate

carBAMazepine food

Applies to: Epitol (carbamazepine)

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of carbamazepine. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

In a small, randomized, crossover study, the administration of carbamazepine with grapefruit juice (compared to water) increased plasma drug concentrations by approximately 40%. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

MANAGEMENT: Patients receiving carbamazepine should be advised to avoid or limit consumption of alcohol. Given the drug's narrow therapeutic index, patients receiving carbamazepine therapy should preferably avoid the regular consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels. Patients should be advised to report signs of carbamazepine toxicity (nausea, visual disturbances, dizziness, or ataxia) to their physicians.

References

  1. (2002) "Product Information. Tegretol (carbamazepine)." Novartis Pharmaceuticals
  2. Garg SK, Kumar N, Bhargava VK, Prabhakar SK (1998) "Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther, 64, p. 286-8
  3. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

See also

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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