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Interactions

Selected Anticonvulsants/Barbiturates; Hydantoins

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 experience symptoms of high blood levels such as drowsiness, headache, dizziness, slowed/difficult breathing, confusion, or difficulty with coordination, or if you notice decreased effectiveness of your medicine (e.g. increase in seizures, migraine headaches, or unstable mood) 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.

References:

1.Depakote (divalproex sodium) US prescribing information. AbbVie Inc. June, 2013.

2.Patel IH, Levy RH, Cutler RE. Phenobarbital--valproic acid interaction. Clin Pharmacol Ther 1980 Apr;27(4):515-21.

3.Bruni J, Wilder BJ, Perchalski RJ, Hammond EJ, Villarreal HJ. Valproic acid and plasma levels of phenobarbital. Neurology 1980 Jan;30(1):94-7.

4.Windorfer A Jr, Sauer W, Gadeke R. Elevation of diphenylhydantoin and primidone serum concentration by addition of dipropylacetate, a new anticonvulsant drug. Acta Paediatr Scand 1975 Sep;64(5):771-2.

5.Bardy A, Hari R, Lehtovaara R, Majuri H. Valproate may lower serum-phenytoin. Lancet 1976 Dec 11;2(7998):1297-8.

6.Patsalos PN, Lascelles PT. Valproate may lower serum-phenytoin. Lancet 1977 Jan 1;1(8001):50-1.

7.Patsalos PN, Lascelles PT. Effect of sodium valproate on plasma protein binding of diphenylhydantoin. J Neurol Neurosurg Psychiatry 1977 Jun; 40(6):570-4.

8.Wilder BJ, Willmore LJ, Bruni J, Villarreal HJ. Valproic acid: interaction with other anticonvulsant drugs. Neurology 1978 Sep;28(9 Pt 1):892-6.

9.Dahlqvist R, Borga O, Rane A, Walsh Z, Sjoqvist F. Decreased plasma protein binding of phenytoin in patients on valproic acid. Br J Clin Pharmacol 1979 Dec;8(6):547-52.

10.Reunanen MI, Luoma P, Myllyla VV, Hokkanen E. Low serum valproic acid concentrations in epileptic patients on combination therapy. Curr Ther Res 1980 Sep;28(3):456-62.

11.Sansom LN, Beran RC, Schapel GJ. Interaction between phenytoin and valproate. Med J Aust 1980 Aug 23;2(4):212.

12.Monks A, Richens A. Effect of single doses of sodium valproate on serum phenytoin levels and protein binding in epileptic patients. Clin Pharmacol Ther 1980 Jan;27(1):89-95.

13.Bruni J, Gallo JM, Lee CS, Perchalski RJ, Wilder BJ. Interactions of valproic acid with phenytoin. Neurology 1980 Nov;30(11):1233-6.

14.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 1982 May;65(5):504-23.

15.Palm R, Silseth C, Alvan G. Phenytoin intoxication as the first symptom of fatal liver damage induced by sodium valproate. Br J Clin Pharmacol 1984 May;17(5):597-9.

16.Riva R, Albani F, Contin M, Perucca E, Ambrosetto G, Gobbi G, Santucci M, Procaccianti G, Baruzzi A. Time-dependent interaction between phenytoin and valproic acid. Neurology 1985 Apr;35(4):510-5.

17.Miles MV, Snead OC 3rd, Thorn MD. Predictability of unbound antiepileptic drug concentrations in children treated with valproic acid and phenytoin. Clin Pharm 1988 Sep;7(9):688-93.

18.Haidukewych D, Rodin EA, Zielinski JJ. Derivation and evaluation of an equation for prediction of free phenytoin concentration in patients co-medicated with valproic acid. Ther Drug Monit 1989;11(2):134-9.

19.Johnson GJ, Kilpatrick CJ, Bury RW, Fullinfaw RO, Moulds RF. Unbound phenytoin plasma concentrations in patients comedicated with sodium valproate--the predictive value of plasma albumin concentration. Br J Clin Pharmacol 1989 Jun;27(6):843-9.

20.May T, Rambeck B. Fluctuations of unbound and total phenytoin concentrations during the day in epileptic patients on valproic acid comedication. Ther Drug Monit 1990 Mar;12(2):124-8.

21.Trileptal (oxcarbazepine) US prescribing information. Novartis Pharmaceuticals Corporation July, 2014.

22.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.

23.Aptiom (eslicarbazepine) US prescribing information. Sunovian Pharmaceuticals Inc. November, 2013.

24.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.

25.Felbatrol (felbamate) US prescribing information. MedPoint Pharmaceuticals Inc. August 27, 2012.

26.Fuerst RH, Graves NM, Leppik IE, Brundage RC, Holmes GB, Remmel RP. Felbamate increases phenytoin but decreases carbamazepine concentrations. Epilepsia 1988 Jul-Aug;29(4):488-91.

27.Graves NM, Holmes GB, Fuerst RH, Leppik IE. Effect of felbamate on phenytoin and carbamazepine serum concentrations. Epilepsia 1989 Mar-Apr; 30(2):225-9.

28.Wagner ML, Graves NM, Marienau K, Holmes GB, Remmel RP, Leppik IE. Discontinuation of phenytoin and carbamazepine in patients receiving felbamate. Epilepsia 1991 May-Jun;32(3):398-406.

29.Reidenberg P, Glue P, Banfield CR, Colucci RD, Meehan JW, Radwanski E, Mojavarian P, Lin CC, Nezamis J, Guillaume M, et al. Effects of felbamate on the pharmacokinetics of phenobarbital. Clin Pharmacol Ther 1995 Sep; 58(3):279-87.

30.Kelley MT, Walson PD, Cox S, Dusci LJ. Population pharmacokinetics of felbamate in children. Ther Drug Monit 1997 Feb;19(1):29-36.

31.Gidal BE, Zupanc ML. Potential pharmacokinetic interaction between felbamate and phenobarbital. Ann Pharmacother 1994 Apr;28(4):455-8.

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, expect 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.

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