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Drug Interactions between carbamazepine and Mysoline

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

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Interactions between your drugs

Moderate

carBAMazepine primidone

Applies to: carbamazepine and Mysoline (primidone)

MONITOR: Coadministration with primidone may decrease the plasma concentrations of carbamazepine and increase concentrations of its active 10,11-epoxide metabolite. The mechanism is primidone induction of CYP450 3A4, the isoenzyme responsible for the metabolism of carbamazepine to carbamazepine-10,11-epoxide (CBZ-E). In one case report, carbamazepine levels were persistently low and subtherapeutic in a 15-year-old boy receiving carbamazepine and primidone for the treatment of partial complex seizures. Increasing the carbamazepine dosage only modestly increased serum levels but did not control the seizures. Adequate control was achieved only after gradual withdrawal of primidone, which led to a substantial increase in carbamazepine serum levels, a reduction in CBZ-E levels, and a 60% reduction in total carbamazepine clearance. Conversely, carbamazepine has also been reported to decrease the plasma concentrations of primidone and increase levels of phenobarbital derived from primidone. In clinical and pharmacokinetic studies, primidone levels were typically lower when the drug was administered with carbamazepine than when administered alone, and phenobarbital levels generally higher. The proposed mechanism is carbamazepine induction of the metabolism of primidone to phenobarbital.

MANAGEMENT: Serum drug levels and seizure control should be monitored more closely when carbamazepine or primidone is added to or withdrawn from a stabilized anticonvulsant regimen, and the dosages adjusted as necessary.

References

  1. Battino D, Avanzini G, Bossi L, Croci D, Cusi C, Gomeni C, Moise A "Plasma levels of primidone and its metabolite phenobarbital: effect of age and associated therapy." Ther Drug Monit 5 (1983): 73-9
  2. "Product Information. Tegretol (carbamazepine)." Novartis Pharmaceuticals PROD (2002):
  3. Windorfer A Jr, Sauer W "Drug interactions during anticonvulsant therapy in childhood: diphenylhydantoin, primidone, phenobarbitone, clonazepam, nitrazepam, carbamazepin and dipropylacetate." Neuropadiatrie 8 (1977): 29-41

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Drug and food interactions

Major

primidone food

Applies to: Mysoline (primidone)

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.

References

  1. Gupta RC, Kofoed J "Toxological statistics for barbiturates, other sedatives, and tranquilizers in Ontario: a 10-year survey." Can Med Assoc J 94 (1966): 863-5
  2. Misra PS, Lefevre A, Ishii H, Rubin E, Lieber CS "Increase of ethanol, meprobamate and pentobarbital metabolism after chronic ethanol administration in man and in rats." Am J Med 51 (1971): 346-51
  3. Saario I, Linnoila M "Effect of subacute treatment with hypnotics, alone or in combination with alcohol, on psychomotor skills related to driving." Acta Pharmacol Toxicol (Copenh) 38 (1976): 382-92
  4. Stead AH, Moffat AC "Quantification of the interaction between barbiturates and alcohol and interpretation of fatal blood concentrations." Hum Toxicol 2 (1983): 5-14
  5. Seixas FA "Drug/alcohol interactions: avert potential dangers." Geriatrics 34 (1979): 89-102
View all 5 references

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Moderate

carBAMazepine food

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