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Drug Interactions between Depakote and Tegretol

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

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Interactions between your drugs

Moderate

carBAMazepine divalproex sodium

Applies to: Tegretol (carbamazepine) and Depakote (divalproex sodium)

MONITOR: Carbamazepine usually decreases valproate levels, and valproate may alter carbamazepine levels in unpredictable ways. Additionally, valproate may prolong the elimination half-life of carbamazepine epoxide. Multiple complex mechanisms may be involved.

MANAGEMENT: Patients who must take both drugs should be carefully monitored for clinical and laboratory evidence of altered effects, particularly when the dosage of either drug is changed.

References

  1. Levy RH, Moreland TA, Morselli PH, et al. "Carbamazepine/valproic acid interaction in man and rhesus monkey." Epilepsia 25 (1984): 338-45
  2. Jann MW, Fidone GS, Israel MK, Bonadero P "Increased valproate serum concentrations upon carbamazepine cessation." Epilepsia 29 (1988): 578-81
  3. Sackellares JC, Sato S, Dreifuss FE, Penry JK "Reduction of steady-state valproate levels by other antiepileptic drugs." Epilepsia 22 (1981): 437-41
  4. Pisani F, Caputo M, Fazio A, et al. "Interaction of carbamazepine, with valproate: a pharmacokinetic study." Epilepsia 31 (1990): 339-42
  5. Kondo T, Otani K, Hirano T, et al. "The effects of phenytoin and carbamazepine on serum concentrations of mono-unsaturated metabolites of valproic acid." Br J Clin Pharmacol 29 (1990): 116-9
  6. Ahuja YR "Chromosone-damaging action of isoniazid and thiacetazone on human lymphocyte cultures in vivo." Hum Genet 57 (1981): 321-2
  7. Koup JR, Toothaker RD, Posvar E, et al. "Theophylline dosage adjustment during enoxacin coadministration." Antimicrob Agents Chemother 34 (1990): 803-7
  8. Henriksen O, Johannessen SI "Clinical and pharmacokinetic observations on sodium valproate: a 5-year follow-up study in 100 children with epilepsy." Acta Neurol Scand 65 (1982): 504-23
  9. Adams DJ, Luders H, Pippenger C "Sodium valproate in the treatment of intractable seizure disorders: a clinical and electroencephalographic study." Neurology 28 (1978): 152-7
  10. Tohen M, Castillo J, Pope HG, Herbstein J "Concomitant use of valproate and carbamazepine in bipolar and schizoaffective disorders." J Clin Psychopharmacol 14 (1994): 67-70
  11. Riva R, Albani F, Contin M, Baruzzi A "Pharmacokinetic interactions between antiepileptic drugs. Clinical considerations." Clin Pharmacokinet 31 (1996): 470-93
View all 11 references

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Drug and food interactions

Moderate

carBAMazepine food

Applies to: Tegretol (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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Moderate

divalproex sodium food

Applies to: Depakote (divalproex sodium)

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

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References

  1. Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc. (1990):
  3. "Product Information. Fycompa (perampanel)." Eisai Inc (2012):
  4. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):
View all 4 references

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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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