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Drug Interactions between Butisol Sodium and carbamazepine

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

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Interactions between your drugs

Minor

carBAMazepine butabarbital

Applies to: carbamazepine and Butisol Sodium (butabarbital)

Coadministration with a barbiturate may decrease the plasma concentrations of carbamazepine and increase concentrations of its active 10,11-epoxide metabolite. The mechanism is barbiturate induction of CYP450 3A4, the isoenzyme responsible for the metabolism of carbamazepine to carbamazepine-10,11-epoxide (CBZ-E). In clinical and pharmacokinetic studies, carbamazepine levels were typically lower when the drug was administered with phenobarbital than when administered alone, and CBZ-E levels generally higher. However, one study reported an increased clearance and reduced half-life of single-dose CBZ-E in six epileptic patients who were receiving phenobarbital compared to six drug-free healthy volunteers, which would seem to suggest an induction of CBZ-E metabolism also. The clinical significance of these changes are unknown, particularly since the anticonvulsant activity of CBZ-E relative to the parent compound has not been established. Until more data are available, it may be reasonable to monitor serum carbamazepine levels more closely whenever a barbiturate (if used for more than a few days) is added to or withdrawn from therapy.

References

  1. Dam M, Jensen A, Christiansen J (1975) "Plasma level and effect of carbamazepine in grand mal and psychomotor epilepsy." Acta Neurol Scand, S75, p. 33-8
  2. Eichelbaum M, Kothe KW, Hoffmann F, von Unruh GE (1979) "Kinetics and metabolism of carbamazepine during combined antiepileptic drug therapy." Clin Pharmacol Ther, 26, p. 366-71
  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. Cereghino JJ, Brock JT, Van Meter JC, et al. (1975) "The efficacy of carbamazepine combinations in epilepsy." Clin Pharmacol Ther, 18, p. 733-41
  5. Spina E, Martines C, Fazio A, Trio R, Pisani F, Tomson T (1991) "Effect of phenobarbital on the pharmacokinetics of carbamazepine-10, 11-epoxide, an active metabolite of carbamazepine." Ther Drug Monit, 13, p. 109-12
  6. (2002) "Product Information. Tegretol (carbamazepine)." Novartis Pharmaceuticals
  7. Tomson T, Spina E, Wedlund JE (1987) "Minor additive inducing effects of phenobarbital on carbamazepine clearance in patients on combined carbamazepine-phenytoin therapy." Ther Drug Monit, 9, p. 117-9
  8. Benetello P, Furlanut M (1987) "Primidone-carbamazepine interaction: clinical consequences." Int J Clin Pharmacol Res, 7, p. 165-8
  9. Liu H, Delgado MR (1995) "Interactions of phenobarbital and phenytoin with carbamazepine and its metabolites' concentrations, concentration ratios, and level dose ratios in epileptic children." Epilepsia, 36, p. 249-54
View all 9 references

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Drug and food interactions

Major

butabarbital food

Applies to: Butisol Sodium (butabarbital)

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

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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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