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Drug Interactions between fosphenytoin and Tritec

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

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Moderate

fosphenytoin raNITIdine bismuth citrate

Applies to: fosphenytoin 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 Both phenytoin and the H2-receptor antagonist may need to be withdrawn until the patient recovers.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

No alcohol/food interactions were found. However, this does not necessarily mean no interactions exist. Always consult your healthcare provider.

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

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