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Drug Interactions between ethotoin and Nabi-HB

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

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Interactions between your drugs

Moderate

ethotoin hepatitis B immune globulin

Applies to: ethotoin and Nabi-HB (hepatitis b immune globulin)

MONITOR: A possible interaction between phenytoin and intravenous immunoglobulin (IVIG) was suspected in a case of fatal hypersensitivity myocarditis. The mechanism of interaction has not been described. The case patient was a 43-year-old man with a past history of alcohol abuse who had been receiving phenytoin for the treatment of partial epilepsy for eight years. He was given intravenous immunoglobulin 0.4 g/kg for 5 days for suspected Guillain-Barre syndrome. On the second day after the last administration, the patient complained of abdominal pain, aching shoulders, and backache. He subsequently developed hypotension and died after attempts at resuscitation. An autopsy confirmed Guillain-Barre syndrome and revealed signs of a slight hepatitis with eosinophils as well as hypersensitivity (eosinophilic) myocarditis. There were no signs of alcoholic cardiomyopathy. Since phenytoin alone has been associated with hypersensitivity myocarditis, a contributory role for IVIG could not be established. Moreover, IVIG has been used successfully in some cases to treat anticonvulsant hypersensitivity syndrome, including that associated with phenytoin.

MANAGEMENT: Due to the serious nature of the possible interaction, clinicians should consider monitoring hematologic parameters such as eosinophil counts as well as blood pressure and ECG tracings if immunoglobulins are used in patients receiving phenytoin.

References

  1. Fenoglio JJ, McAllister HA, Mullick FG "Drug related myocarditis: I. Hypersensitivity myocarditis." Hum Pathol 12 (1981): 900-7
  2. Koehler PJ, Koudstaal J "Lethal hypersensitivity myocarditis associated with the use of intravenous gammaglobulin for Guillan-Barre syndrome, in combination with phenytoin." J Neurol 243 (1996): 366-7
  3. Mostella J, Pieroni R, Jones R, Finch CK "Anticonvulsant hypersensitivity syndrome: treatment with corticosteroids and intravenous immunoglobulin." South Med J 97 (2004): 319-21
  4. Cumbo-Nacheli G, Weinberger J, Alkhalil M, Thati N, Baptist AP "Anticonvulsant hypersensitivity syndrome: is there a role for immunomodulation?" Epilepsia 49 (2008): 2108-12
View all 4 references

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Drug and food interactions

Moderate

ethotoin food

Applies to: ethotoin

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 "Effect of short- and long-term alcohol use on phenytoin kinetics in chronic alcoholics." Clin Pharmacol Ther 30 (1981): 390-7
  2. Holtz L, Milton J, Sturek JK "Compatibility of medications with enteral feedings." JPEN J Parenter Enteral Nutr 11 (1987): 183-6
  3. Sellers EM, Holloway MR "Drug kinetics and alcohol ingestion." Clin Pharmacokinet 3 (1978): 440-52
  4. "Product Information. Dilantin (phenytoin)." Parke-Davis PROD (2001):
  5. Doak KK, Haas CE, Dunnigan KJ, et al. "Bioavailability of phenytoin acid and phenytoin sodium with enteral feedings." Pharmacotherapy 18 (1998): 637-45
  6. Rodman DP, Stevenson TL, Ray TR "Phenytoin malabsorption after jejunostomy tube delivery." Pharmacotherapy 15 (1995): 801-5
  7. Au Yeung SC, Ensom MH "Phenytoin and enteral feedings: does evidence support an interaction?" Ann Pharmacother 34 (2000): 896-905
  8. Ozuna J, Friel P "Effect of enteral tube feeding on serum phenytoin levels." J Neurosurg Nurs 16 (1984): 289-91
  9. Faraji B, Yu PP "Serum phenytoin levels of patients on gastrostomy tube feeding." J Neurosci Nurs 30 (1998): 55-9
  10. Marvel ME, Bertino JS "Comparative effects of an elemental and a complex enteral feeding formulation on the absorption of phenytoin suspension." JPEN J Parenter Enteral Nutr 15 (1991): 316-8
  11. Fleisher D, Sheth N, Kou JH "Phenytoin interaction with enteral feedings administered through nasogastric tubes." JPEN J Parenter Enteral Nutr 14 (1990): 513-6
  12. Haley CJ, Nelson J "Phenytoin-enteral feeding interaction." DICP 23 (1989): 796-8
  13. Guidry JR, Eastwood TF, Curry SC "Phenytoin absorption in volunteers receiving selected enteral feedings." West J Med 150 (1989): 659-61
  14. Krueger KA, Garnett WR, Comstock TJ, Fitzsimmons WE, Karnes HT, Pellock JM "Effect of two administration schedules of an enteral nutrient formula on phenytoin bioavailability." Epilepsia 28 (1987): 706-12
  15. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  16. Cerner Multum, Inc. "Australian Product Information." O 0
View all 16 references

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Therapeutic duplication warnings

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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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