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Drug Interactions between Di-Phen and Stavzor

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

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Interactions between your drugs

Moderate

valproic acid phenytoin

Applies to: Stavzor (valproic acid) and Di-Phen (phenytoin)

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

  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
View all 15 references

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Drug and food interactions

Moderate

valproic acid food

Applies to: Stavzor (valproic acid)

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

  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
View all 4 references

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Moderate

phenytoin food

Applies to: Di-Phen (phenytoin)

ADJUST DOSING INTERVAL: Phenytoin bioavailability may decrease to subtherapeutic levels when the suspension is given concomitantly with enteral feedings. The mechanism may be related to phenytoin binding to substances in the enteral formula (e.g., calcium, protein) and/or binding to the tube lumen. Data have been conflicting and some studies have reported no changes in phenytoin levels, while others have reported significant reductions.

MONITOR: Acute consumption of alcohol may increase plasma phenytoin levels. Chronic consumption of alcohol may decrease plasma phenytoin levels. The mechanism of this interaction is related to induction of phenytoin metabolism by ethanol during chronic administration. Other hydantoin derivatives may be similarly affected by ethanol.

MANAGEMENT: Some experts have recommended interrupting the feeding for 2 hours before and after the phenytoin dose, giving the phenytoin suspension diluted in water, and flushing the tube with water after administration; however, this method may not entirely avoid the interaction and is not always clinically feasible. Patients should be closely monitored for clinical and laboratory evidence of altered phenytoin efficacy and levels upon initiation and discontinuation of enteral feedings. Dosage adjustments or intravenous administration may be required until therapeutic serum levels are obtained. In addition, patients receiving phenytoin therapy should be warned about the interaction between phenytoin and ethanol and they should be advised to notify their physician if they experience worsening of seizure control or symptoms of toxicity, including drowsiness, visual disturbances, change in mental status, nausea, or ataxia.

References

  1. Sandor P, Sellers EM, Dumbrell M, Khouw V (1981) "Effect of short- and long-term alcohol use on phenytoin kinetics in chronic alcoholics." Clin Pharmacol Ther, 30, p. 390-7
  2. Holtz L, Milton J, Sturek JK (1987) "Compatibility of medications with enteral feedings." JPEN J Parenter Enteral Nutr, 11, p. 183-6
  3. Sellers EM, Holloway MR (1978) "Drug kinetics and alcohol ingestion." Clin Pharmacokinet, 3, p. 440-52
  4. (2001) "Product Information. Dilantin (phenytoin)." Parke-Davis
  5. Doak KK, Haas CE, Dunnigan KJ, et al. (1998) "Bioavailability of phenytoin acid and phenytoin sodium with enteral feedings." Pharmacotherapy, 18, p. 637-45
  6. Rodman DP, Stevenson TL, Ray TR (1995) "Phenytoin malabsorption after jejunostomy tube delivery." Pharmacotherapy, 15, p. 801-5
  7. Au Yeung SC, Ensom MH (2000) "Phenytoin and enteral feedings: does evidence support an interaction?" Ann Pharmacother, 34, p. 896-905
  8. Ozuna J, Friel P (1984) "Effect of enteral tube feeding on serum phenytoin levels." J Neurosurg Nurs, 16, p. 289-91
  9. Faraji B, Yu PP (1998) "Serum phenytoin levels of patients on gastrostomy tube feeding." J Neurosci Nurs, 30, p. 55-9
  10. Marvel ME, Bertino JS (1991) "Comparative effects of an elemental and a complex enteral feeding formulation on the absorption of phenytoin suspension." JPEN J Parenter Enteral Nutr, 15, p. 316-8
  11. Fleisher D, Sheth N, Kou JH (1990) "Phenytoin interaction with enteral feedings administered through nasogastric tubes." JPEN J Parenter Enteral Nutr, 14, p. 513-6
  12. Haley CJ, Nelson J (1989) "Phenytoin-enteral feeding interaction." DICP, 23, p. 796-8
  13. Guidry JR, Eastwood TF, Curry SC (1989) "Phenytoin absorption in volunteers receiving selected enteral feedings." West J Med, 150, p. 659-61
  14. Krueger KA, Garnett WR, Comstock TJ, Fitzsimmons WE, Karnes HT, Pellock JM (1987) "Effect of two administration schedules of an enteral nutrient formula on phenytoin bioavailability." Epilepsia, 28, p. 706-12
  15. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  16. Cerner Multum, Inc. "Australian Product Information."
View all 16 references

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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.

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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.

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