Hydantoins/Valproic Acid (mono deleted 12/26/2013)
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.
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, valproic acid may interfere with your phenytoin and phenytoin may interfere with your valproic acid.
What might happen:
Your blood levels of phenytoin may increase and your blood levels of valproic acid may decrease.
What you should do about this interaction:
If you experience a seizure, loss of coordination, constant unintentional eye movements, drowsiness, or mental changes, contact your doctor. It may be necessary to adjust the dose of either medicine.Your healthcare professionals (e.g. doctor or pharmacist) may already be aware of this drug interaction and may be monitoring you for it. Do not stop, start, or change the dosage of any medicine before checking with them first.
1.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.
2.Bardy A, Hari R, Lehtovaara R, Majuri H. Valproate may lower serum-phenytoin. Lancet 1976 Dec 11;2(7998):1297-8.
3.Patsalos PN, Lascelles PT. Valproate may lower serum-phenytoin. Lancet 1977 Jan 1;1(8001):50-1.
4.Patsalos PN, Lascelles PT. Effect of sodium valproate on plasma protein binding of diphenylhydantoin. J Neurol Neurosurg Psychiatry 1977 Jun; 40(6):570-4.
5.Wilder BJ, Willmore LJ, Bruni J, Villarreal HJ. Valproic acid: interaction with other anticonvulsant drugs. Neurology 1978 Sep;28(9 Pt 1):892-6.
6.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.
7.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.
8.Sansom LN, Beran RC, Schapel GJ. Interaction between phenytoin and valproate. Med J Aust 1980 Aug 23;2(4):212.
9.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.
10.Bruni J, Gallo JM, Lee CS, Perchalski RJ, Wilder BJ. Interactions of valproic acid with phenytoin. Neurology 1980 Nov;30(11):1233-6.
11.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.
12.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.
13.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.
14.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.
15.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.
16.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.
17.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.