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Drug Interactions between fluorouracil and levofloxacin

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

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Interactions between your drugs

Minor

fluorouracil levoFLOXacin

Applies to: fluorouracil and levofloxacin

Limited data suggest that chemotherapy with antineoplastic agents may reduce the plasma concentrations of oral quinolone antibiotics. The proposed mechanism is decreased quinolone absorption secondary to alteration of intestinal mucosa by cancer chemotherapy. In six patients with newly diagnosed hematologic malignancy, treatment with various antineoplastic agents (cyclophosphamide, cytarabine, daunorubicin, doxorubicin, mitoxantrone, prednisolone, vincristine) decreased the mean peak serum concentration (Cmax) and area under the concentration-time curve (AUC 0 to 4 hours) of ciprofloxacin by approximately 46% each. Data are not available for other quinolone antibiotics.

References

  1. Johnson EJ, MacGowan AP, Potter MN, et al. (1990) "Reduced absorption of oral ciprofloxacin after chemotherapy for haematological malignancy." J Antimicrob Chemother, 25, p. 837-42

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Drug and food interactions

Major

fluorouracil food

Applies to: fluorouracil

MONITOR CLOSELY: Coadministration with folate therapy may potentiate the pharmacologic effects of 5-fluorouracil (5-FU). The exact mechanism of interaction is unknown. Although enhancement of 5-FU cytotoxicity may be used to advantage in some cancer patients, increased toxicity should also be considered. Deaths from severe enterocolitis, diarrhea, and dehydration have been reported in elderly patients receiving weekly leucovorin and fluorouracil. In a clinical study consisting of 148 patients with advanced untreated colorectal cancer, weekly administration of 5-FU (600 mg/m2) in combination with leucovorin (500 mg/m2) was associated with a higher response rate than 5-FU alone (23% versus 8%). However, the combination was also more toxic than 5-FU alone, as evidenced by a higher incidence of grade 3 to 4 diarrhea (19.5% versus 8.5%) and conjunctivitis (26.5% versus 5.6%), as well as one recorded toxic death versus none. No differences in median survival and time to progression were observed between the two groups. Similar results were observed in another study with capecitabine, a prodrug of 5-FU. The interaction has also been reported with folic acid. A published case report describes two patients who were hospitalized for presumed 5-FU toxicity (anorexia, severe mouth ulceration, bloody diarrhea, vaginal bleeding) during concomitant treatment with a multivitamin containing folic acid (0.5 mg in one and 5 mg in the other). Both patients tolerated subsequent courses of 5-FU at the previous dosage following discontinuation of the multivitamin. Another published report describes a breast cancer patient who died during treatment with capecitabine (2500 mg/m2 daily for 14 days every 3 weeks) while taking folic acid 15 mg/day. The patient developed diarrhea, vomiting, and hand-foot syndrome eight days after starting capecitabine therapy. Her condition improved briefly following discontinuation of capecitabine and then folic acid, but she subsequently developed necrotic colitis and died from septic shock and vascular collapse.

MANAGEMENT: Caution is advised if 5-FU or any of its prodrugs (e.g., capecitabine, tegafur) are prescribed in combination with leucovorin. A lower dosage of 5-FU or the prodrug may be required. Therapy with leucovorin and fluorouracil should not be initiated or continued in patients with symptoms of gastrointestinal toxicity until such symptoms have resolved. Closely monitor patients with diarrhea until it resolves. Monitor for other potential toxicities of 5-FU such as neutropenia, thrombocytopenia, stomatitis, cutaneous reactions, and neuropathy. Patients should be instructed to avoid taking folic acid supplementation or multivitamin preparations containing folic acid without first speaking with their physician.

References

  1. Schalhorn A, Kuhl M (1992) "Clinical pharmacokinetics of fluorouracil and folinic acid." Semin Oncol, 19, p. 82-92
  2. Nobile MT, Rosso R, Sertoli MR, Rubagotti A, Vidili MG, Guglielmi A, Venturini M, Canobbio L, Fassio T, Gallo L, et al. (1992) "Randomised comparison of weekly bolus 5-fluorouracil with or without leucovorin in metastatic colorectal carcinoma." Eur J Cancer, 28a, p. 1823-7
  3. Mainwaring P, Grygiel JJ (1995) "Interaction of 5-fluorouracil with folates." Aust N Z J Med, 25, p. 60
  4. "Product Information. Wellcovorin (leucovorin)." Glaxo Wellcome, Research Triangle Park, NC.
  5. (2001) "Product Information. Xeloda (capecitabine)." Roche Laboratories
  6. Clippe C, Freyer G, Milano G, Trillet-Lenoir V (2003) "Lethal toxicity of capecitabine due to abusive folic acid prescription?" Clin Oncol (R Coll Radiol), 15, p. 299-300
  7. EMEA. European Medicines Agency (2007) EPARs. European Union Public Assessment Reports. http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/medicines/medicines_landingpage.jsp&mid
  8. (2008) "Product Information. Levoleucovorin (levoleucovorin)." Spectrum Chemical
  9. (2022) "Product Information. Khapzory (LEVOleucovorin)." Acrotech Biopharma LLC
View all 9 references

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Moderate

levoFLOXacin food

Applies to: levofloxacin

ADJUST DOSING INTERVAL: Food may reduce the oral absorption and bioavailability of levofloxacin. According to the drug product labeling, administration of levofloxacin 500 mg with food prolonged the time to peak concentration by 1 hour and decreased the Cmax decreased by 25% following administration of the oral solution and by 14% following administration of the oral tablet.

MANAGEMENT: To ensure maximal and consistent oral absorption, levofloxacin oral solution should be taken at least one hour before or two hours after meals. For administration of the oral solution with continuous enteral nutrition, some experts recommend that the tube feeding should be interrupted for one hour before and two hours after the dose of levofloxacin. The oral tablets may be taken without regard to food.

References

  1. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT (2009) "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm, 66, p. 1438-67

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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.