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Drug Interactions between divalproex sodium and fosphenytoin

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

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Interactions between your drugs

Moderate

divalproex sodium fosphenytoin

Applies to: divalproex sodium and fosphenytoin

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 (15)
  1. Perucca E, Hebdige S, Frigo GM, et al. (1980) "Interaction between phenytoin and valproic acid: plasma protein binding and metabolic effects." Clin Pharmacol Ther, 28, p. 779-89
  2. Bruni J, Gallo JM, Lee CS, et al. (1980) "Interactions of valproic acid with phenytoin." Neurology, 30, p. 1233-6
  3. Sackellares JC, Sato S, Dreifuss FE, Penry JK (1981) "Reduction of steady-state valproate levels by other antiepileptic drugs." Epilepsia, 22, p. 437-41
  4. Rodin EA, DeSoussa G, Haidukewych D, et al. (1981) "Dissociation between free and bound phenytoin levels in presence of valproate sodium." Arch Neurol, 38, p. 240-2
  5. May T, Rambeck B (1990) "Fluctuations of unbound and total phenytoin concentrations during the day in epileptic patients on valproic acid comedication." Ther Drug Monit, 12, p. 124-8
  6. Sallustio BC, Morris RG (1992) "Unbound plasma phenytoin concentrations measured using enzyme immunoassay technique on the cobas MIRA analyser: in vivo effect of valproic acid." Ther Drug Monit, 14, p. 9-13
  7. Pospisil J, Perlik F (1992) "Binding parameters of phenytoin during monotherapy and polytherapy." Int J Clin Pharmacol Ther Toxicol, 30, p. 24-8
  8. Henriksen O, Johannessen SI (1982) "Clinical and pharmacokinetic observations on sodium valproate: a 5-year follow-up study in 100 children with epilepsy." Acta Neurol Scand, 65, p. 504-23
  9. Palm R, Silseth C, Alvan G (1984) "Phenytoin intoxication as the first symptom of fatal liver damage induced by sodium valproate." Br J Clin Pharmacol, 17, p. 597-9
  10. Riva R, Albani F, Contin M, Perucca E, Ambrosetto G, Gobbi G (1985) "Time-dependent interaction between phenytoin and valproic acid." Neurology, 35, p. 510-5
  11. Bourgeois BF (1988) "Pharmacologic interactions between valproate and other drugs." Am J Med, 84, p. 29-33
  12. Lai ML, Huang JD (1993) "Dual effect of valproic acid on the pharmacokinetics of phenytoin." Biopharm Drug Dispos, 14, p. 365-70
  13. Kerrick JM, Wolff DL, Graves NM (1993) "Predicting unbound phenytoin concentrations in patients comedicated with valproate." Epilepsia, 34 Suppl, p. 112
  14. Suzuki Y, Nagai T, Mano T, Arai H, Kodaka R, Matsuoka T, Itagaki Y, Ono J, Okada S (1995) "Interaction between valproate formulation and phenytoin concentrations." Eur J Clin Pharmacol, 48, p. 61-3
  15. Riva R, Albani F, Contin M, Baruzzi A (1996) "Pharmacokinetic interactions between antiepileptic drugs. Clinical considerations." Clin Pharmacokinet, 31, p. 470-93

Drug and food interactions

Moderate

divalproex sodium food

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

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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