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Drug Interactions between Phenytoin Sodium, Prompt and Tritec

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

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Interactions between your drugs

Moderate

phenytoin raNITIdine bismuth citrate

Applies to: Phenytoin Sodium, Prompt (phenytoin) and Tritec (ranitidine bismuth citrate)

MONITOR: Coadministration with famotidine or ranitidine may rarely increase the plasma concentrations of phenytoin, resulting in toxicity. The mechanism of interaction is unknown. Neither famotidine nor ranitidine has been shown to significantly inhibit CYP450-mediated oxidative metabolism at therapeutic dosages. In addition, no effects on clearance or plasma levels of phenytoin were reported during coadministration with famotidine or ranitidine in separate pharmacokinetic studies. Data suggesting a potential interaction are limited to isolated case reports of phenytoin toxicity shortly after initiation or dosage increase of the H2-receptor antagonist. In at least a couple cases, the patient was elderly and had underlying conditions that may have contributed to the development of toxicity (e.g., renal dysfunction, hypoalbuminemia).

MANAGEMENT: Until more information is available, caution is advised if phenytoin is prescribed in combination with famotidine or ranitidine, particularly in elderly patients. Clinicians should be alert for signs and symptoms of phenytoin toxicity such as ataxia, incoordination, tremor, nystagmus, hypotension, slurred speech, lethargy, nausea, vomiting, mental confusion, and psychosis. The possibility of an interaction should be considered if toxicity occurs shortly (e.g., within a month) after initiation or change of dosage of the H2-receptor antagonist. Both phenytoin and the H2-receptor antagonist may need to be withdrawn until the patient recovers.

References

  1. Richards DA "Comparative pharmacodynamics and pharmacokinetics of cimetidine and ranitidine." J Clin Gastroenterol 5 (1983): 81-90
  2. Karlstadt RG, Palmer RH, Shinn AF "Unrecognized drug interactions with famotidine and nizatidine." Arch Intern Med 151 (1991): 610, 614-5
  3. Smith SR, Kendall MJ "Ranitidine versus cimetidine: a comparison of their potential to cause clinically important drug interactions." Clin Pharmacokinet 15 (1988): 44-56
  4. Bramhall D, Levine M "Possible interaction of ranitidine with phenytoin." Drug Intell Clin Pharm 22 (1988): 979-80
  5. Humphries TJ "Famotidine: a notable lack of drug interactions." Scand J Gastroenterol Suppl 134 (1987): 55-60
  6. "Product Information. Pepcid (famotidine)." Merck & Co., Inc PROD (2002):
  7. "Product Information. Zantac (ranitidine)." Glaxo Wellcome PROD (2001):
  8. Tse CS, Iagmin P "Phenytoin and ranitidine interaction." Ann Intern Med 120 (1994): 892-3
  9. Powell JR, Donn KH "Histamine H2-antagonist drug interactions in perspective: mechanistic concepts and clinical implications." Am J Med 77 (1984): 57-84
  10. Williams D, Kelly A, Feely J "Drug interactions avoided - a useful indicator of good prescribing practice." Br J Clin Pharmacol 49 (2000): 369-72
  11. Khan AY, Kalimuddin MN, Gorman JM "Neuropsychiatric manifestations of phenytoin toxicity in an elderly patient." J Psychiatr Pract 13 (2007): 49-54
  12. Sambol NC, Upton RA, Chremos AN, Lin ET, Williams RL "A comparison of the influence of famotidine and cimetidine on phenytoin elimination and hepatic blood flow." Br J Clin Pharmacol 27 (1989): 83-7
  13. Watts RW, Hetzel DJ, Bochner F, Hallpike JF, Hann CS, Shearman DJ "Lack of interaction between ranitidine and phenytoin." Br J Clin Pharmacol 15 (1983): 499-500
View all 13 references

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Drug and food interactions

Moderate

phenytoin food

Applies to: Phenytoin Sodium, Prompt (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 "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

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.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.