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Divalproex and Phenytoin Extended-Release Capsules

Determining the interaction of Divalproex and Phenytoin Extended-Release Capsules and the possibility of their joint administration.

Check result:

Divalproex <> Phenytoin Extended-Release Capsules

Relevance: 25.04.2023 Reviewer: Shkutko P.M., M.D., in

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Consumer:

Before taking phenytoin, tell your doctor if you also use divalproex sodium. You may need dose adjustments or special tests in order to safely take both medications together. You should notify your doctor if you have symptoms such as drowsiness, visual problems, changes in behavior, nausea, or poor muscle coordination. It is important that you tell your healthcare provider about all other medications that you are using including vitamins and herbs. Do not stop using your medications without first talking to your doctor first.

Professional:

MONITOR: Valproic acid (and its derivatives) may increase the pharmacologic effects of phenytoin. Toxicity may result, despite normal phenytoin levels. The mechanism may be related to displacement of phenytoin from plasma proteins. Also, phenytoin may induce the CYP450 metabolism of valproic acid. Similar interactions may occur with other hydantoins.

MANAGEMENT: Patients on combination therapy should be closely monitored for clinical and laboratory evidence of altered phenytoin and valproate effects. It may be more useful to monitor plasma free-phenytoin levels than to monitor total plasma concentrations. Patients should be advised to notify their physician if they experience symptoms of toxicity (e.g., drowsiness, visual disturbances, change in mental status, seizures, nausea, or ataxia).

References

Bourgeois BF "Pharmacologic interactions between valproate and other drugs." Am J Med 84 (1988): 29-33
Perucca E, Hebdige S, Frigo GM, et al "Interaction between phenytoin and valproic acid: plasma protein binding and metabolic effects." Clin Pharmacol Ther 28 (1980): 779-89
Riva R, Albani F, Contin M, Baruzzi A "Pharmacokinetic interactions between antiepileptic drugs. Clinical considerations." Clin Pharmacokinet 31 (1996): 470-93
May T, Rambeck B "Fluctuations of unbound and total phenytoin concentrations during the day in epileptic patients on valproic acid comedication." Ther Drug Monit 12 (1990): 124-8
Lai ML, Huang JD "Dual effect of valproic acid on the pharmacokinetics of phenytoin." Biopharm Drug Dispos 14 (1993): 365-70
Bruni J, Gallo JM, Lee CS, et al "Interactions of valproic acid with phenytoin." Neurology 30 (1980): 1233-6
Riva R, Albani F, Contin M, Perucca E, Ambrosetto G, Gobbi G "Time-dependent interaction between phenytoin and valproic acid." Neurology 35 (1985): 510-5
Palm R, Silseth C, Alvan G "Phenytoin intoxication as the first symptom of fatal liver damage induced by sodium valproate." Br J Clin Pharmacol 17 (1984): 597-9
Pospisil J, Perlik F "Binding parameters of phenytoin during monotherapy and polytherapy." Int J Clin Pharmacol Ther Toxicol 30 (1992): 24-8
Sallustio BC, Morris RG "Unbound plasma phenytoin concentrations measured using enzyme immunoassay technique on the cobas MIRA analyser: in vivo effect of valproic acid." Ther Drug Monit 14 (1992): 9-13
Rodin EA, DeSoussa G, Haidukewych D, et al "Dissociation between free and bound phenytoin levels in presence of valproate sodium." Arch Neurol 38 (1981): 240-2
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
Kerrick JM, Wolff DL, Graves NM "Predicting unbound phenytoin concentrations in patients comedicated with valproate." Epilepsia 34 Suppl (1993): 112
Sackellares JC, Sato S, Dreifuss FE, Penry JK "Reduction of steady-state valproate levels by other antiepileptic drugs." Epilepsia 22 (1981): 437-41
Suzuki Y, Nagai T, Mano T, Arai H, Kodaka R, Matsuoka T, Itagaki Y, Ono J, Okada S "Interaction between valproate formulation and phenytoin concentrations." Eur J Clin Pharmacol 48 (1995): 61-3

Divalproex

Generic Name: divalproex sodium

Brand name: Depakote ER, Depakote Sprinkles, Depakote, Depakene, Depacon

Synonyms: Divalproex sodium

What is Divalproex?

Phenytoin Extended-Release Capsules

Generic Name: phenytoin

Brand name: Dilantin, Phenytek, Dilantin Infatabs, Phenytoin Sodium, Prompt

Synonyms: Phenytoin

What is Phenytoin Extended-Release Capsules?

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In the course of checking the drug compatibility and interactions, data from the following reference sources was used: Drugs.com, Rxlist.com, Webmd.com, Medscape.com.

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