Carbamazepine/Phenytoin; Anticonvulsant Barbiturates Interactions

This information is generalized and not intended as specific medical advice. Consult your healthcare professional before taking or discontinuing any drug or commencing any course of treatment.

Medical warning:

Moderate. These medicines may cause some risk when taken together. Contact your healthcare professional (e.g. doctor or pharmacist) for more information.

How the interaction occurs:

When these two medicines are taken together, the way your body processes each medicine may change.

What might happen:

Your blood levels of medicine could decrease, reducing the beneficial effects of this medicine, or increase and cause toxic effects.

What you should do about this interaction:

Let your healthcare professional (e.g. doctor or pharmacist) know that you are taking these medicines together. If you notice decreased effectiveness of your medicine (e.g. increase in seizures, migraine headaches, or unstable mood) or if you experience symptoms of high blood levels such as drowsiness, headache, dizziness, slowed/difficult breathing, confusion, or difficulty with coordination, contact your doctor. Your doctor may check medicine blood levels and may need to adjust the dose of one or both medicines.Your healthcare professionals (e.g. doctor or pharmacist) may already be aware of this interaction and may be monitoring you for it. Do not start, stop, or change the dosage of any medicine before checking with them first.

  • 1.Lakehal F, Wurden CJ, Kalhorn TF, Levy RH. Carbamazepine and oxcarbazepine decrease phenytoin metabolism through inhibition of CYP2C19. Epilepsy Res 2002 Dec;52(2):79-83.
  • 2.McKee PJ, Blacklaw J, Forrest G, Gillham RA, Walker SM, Connelly D, Brodie MJ. A double-blind, placebo-controlled interaction study between oxcarbazepine and carbamazepine, sodium valproate and phenytoin in epileptic patients. Br J Clin Pharmacol 1994 Jan;37(1):27-32.
  • 3.Hansen JM, Siersboek-Nielsen K, Skovsted L. Carbamazepine-induced acceleration of diphenylhydantoin and warfarin metabolism in man. Clin Pharmacol Ther 1971 May-Jun;12(3):539-43.
  • 4.Windorfer A Jr, Sauer W. Drug interactions during anticonvulsant therapy in childhood: diphenylhydantoin, primidone, phenobarbitone, clonazepam, nitrazepam, carbamazepin and dipropylacetate. Neuropadiatrie 1977 Feb; 8(1):29-41.
  • 5.Zielinski JJ, Haidukewych D, Leheta BJ. Carbamazepine-phenytoin interaction: elevation of plasma phenytoin concentrations due to carbamazepine comedication. Ther Drug Monit 1985;7(1):51-3.
  • 6.Zielinski JJ, Haidukewych D. Dual effects of carbamazepine-phenytoin interaction. Ther Drug Monit 1987;9(1):21-3.
  • 7.Perucca E, Richens A. Reversal by phenytoin of carbamazepine-induced water intoxication: a pharmacokinetic interaction. J Neurol Neurosurg Psychiatry 1980 Jun;43(6):540-5.
  • 8.Christiansen J, Dam M. Influence of phenobarbital and diphenylhydantoin on plasma carbamazepine levels in patients with epilepsy. Acta Neurol Scand 1973;49(4):543-6.
  • 9.Lander CM, Eadie MJ, Tyrer JH. Interactions between anticonvulsants. Proc Aust Assoc Neurol 1975;12:111-6.
  • 10.Lander CM, Eadie MJ, Tyrer JH. Factors influencing plasma carbamazepine concentrations. Clin Exp Neurol 1977;14:184-93.
  • 11.Cereghino JJ, Brock JT, Van Meter JC, Penry JK, Smith LD, White BG. The efficacy of carbamazepine combinations in epilepsy. Clin Pharmacol Ther 1975 Dec;18(6):733-41.
  • 12.McKauge L, Tyrer JH, Eadie MJ. Factors influencing simultaneous concentrations of carbamazepine and its epoxide in plasma. Ther Drug Monit 1981;3(1):63-70.
  • 13.Dam M, Jensen A, Christiansen J. Plasma level and effect of carbamazepine in grand mal and psychomotor epilepsy. Acta Neurol Scand Suppl 1975; 60:33-8.
  • 14.Rane A, Hojer B, Wilson JT. Kinetics of carbamazepine and its 10,11-epoxide metabolite in children. Clin Pharmacol Ther 1976 Mar; 19(3):276-83.
  • 15.Liu H, Delgado MR. Interactions of phenobarbital and phenytoin with carbamazepine and its metabolites' concentrations, concentration ratios, and level/dose ratios in epileptic children. Epilepsia 1995 Mar; 36(3):249-54.
  • 16.Venci JV, Rowcliffe MM, Wollenberg L, Rainka MM, Gengo FM. Pharmacokinetic simulation of fatal carbamazepine intoxication in 23-month old child following phenytoin discontinuation. Forensic Sci Med Pathol 2013 Mar;9(1):73-6.
  • 17.Fukuoka N, Tsukamoto T, Uno J, Kimura M, Morita S. Effects of concomitant antiepileptic drugs on serum carbamazepine concentration in epileptic patients: quantitative analysis based on extracellular water volume as a transforming factor. Yakugaku Zasshi 2003 Jan;123(1):35-42.
  • 18.Sennoune S, Iliadis A, Bonneton J, Barra Y, Genton P, Mesdjian E. Steady state pharmacokinetics of carbamazepine-phenobarbital interaction in patients with epilepsy. Biopharm Drug Dispos 1996 Mar;17(2):155-64.
  • 19.Chapron DJ, LaPierre BA, Abou-Elkair M. Unmasking the significant enzyme-inducing effects of phenytoin on serum carbamazepine concentrations during phenytoin withdrawal. Ann Pharmacother 1993 Jun; 27(6):708-11.
  • 20.Spina E, Martines C, Fazio A, Trio R, Pisani F, Tomson T. Effect of phenobarbital on the pharmacokinetics of carbamazepine-10,11-epoxide, an active metabolite of carbamazepine. Ther Drug Monit 1991 Mar; 13(2):109-12.
  • 21.Ichikou N, Ieiri I, Higuchi S, Hirata K, Yamada H, Aoyama T. Analysis of the factors influencing anti-epileptic drug concentrations--carbamazepine. J Clin Pharm Ther 1990 Oct;15(5):337-49.
  • 22.Benetello P, Furlanut M. Primidone-carbamazepine interaction: clinical consequences. Int J Clin Pharmacol Res 1987;7(2):165-8.

Selected from data included with permission and copyrighted by First Databank, Inc. This copyrighted material has been downloaded from a licensed data provider and is not for distribution, except as may be authorized by the applicable terms of use.

CONDITIONS OF USE: The information in this database is intended to supplement, not substitute for, the expertise and judgment of healthcare professionals. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for you or anyone else. A healthcare professional should be consulted before taking any drug, changing any diet or commencing or discontinuing any course of treatment.