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Drug Interactions between Ergamisol and mephenytoin

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

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Interactions between your drugs

Moderate

levamisole mephenytoin

Applies to: Ergamisol (levamisole) and mephenytoin

MONITOR: Concomitant administration with levamisole and 5-fluorouracil (5-FU) has been reported to increase serum levels of phenytoin. No mechanism has been established for this interaction, and it is unknown whether levamisole or 5-FU, or both, is responsible. However, 5-FU alone was implicated in one case report. A 66-year-old man who had been stabilized on phenytoin for more than 4 years developed symptoms of toxicity in association with elevated phenytoin serum concentrations 11 weeks after starting 5-FU and leucovorin treatment. Symptoms resolved following a reduction in phenytoin dosage, and phenytoin levels were monitored and dosage adjusted accordingly throughout the remainder of chemotherapy treatment. After completion of chemotherapy, the phenytoin dosage was gradually increased to original levels without further incident. The authors suggested that 5-FU may inhibit the metabolism of phenytoin via CYP450 2C9.

MANAGEMENT: Pharmacologic response to phenytoin should be monitored more closely whenever levamisole, 5-FU, or capecitabine (which is metabolized to 5-FU in vivo) is added to or withdrawn from therapy, and the phenytoin dosage adjusted as necessary. Patients should be advised to notify their physician if they experience symptoms of phenytoin toxicity, including drowsiness, visual disturbances, mental status changes, seizures, nausea, or ataxia. It is uncertain whether this interaction may also occur with other hydantoins.

References

  1. "Product Information. Dilantin (phenytoin)." Parke-Davis PROD (2001):
  2. "Product Information. Ergamisol (levamisole)." Janssen Pharmaceuticals PROD (2001):
  3. "Product Information. Cerebyx (fosphenytoin)." Parke-Davis PROD (2001):
  4. Gilbar PJ, Brodribb TR "Phenytoin and fluorouracil interaction." Ann Pharmacother 35 (2001): 1367-70
View all 4 references

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Drug and food interactions

Moderate

mephenytoin food

Applies to: mephenytoin

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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Moderate

levamisole food

Applies to: Ergamisol (levamisole)

GENERALLY AVOID: Case histories have suggested that levamisole is associated with some side effects (including headache, fever, shivers, and dizziness) that suggest an disulfiram-like interaction with alcohol. These side effects could be alleviated by total abstinence from alcohol. No mechanism has been established for this interaction.

MANAGEMENT: Patients receiving levamisole should avoid alcohol.

References

  1. "Product Information. Ergamisol (levamisole)." Janssen Pharmaceuticals PROD (2001):
  2. Renoux G "The general immunopharmacology of levamisole." Drugs 19 (1980): 89-99
  3. Renoux G "Modulation of immunity by levamisole." Pharmacol Ther [B] 2 (1978): 397-422

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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.

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

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