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Drug Interactions between fluorouracil and influenza virus vaccine, live

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

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Interactions between your drugs

Major

fluorouracil influenza virus vaccine, live

Applies to: fluorouracil and influenza virus vaccine, live

GENERALLY AVOID: The administration of live, attenuated virus or bacterial vaccines during immunosuppressant or intense antineoplastic therapy may be associated with a risk of disseminated infection due to enhanced replication of vaccine virus or bacteria in the presence of diminished immune competence. Patients may be immunosuppressed if they have recently received or are receiving alkylating agents, antimetabolites, radiation, some antirheumatic agents, high dosages of corticosteroids or adrenocorticotropic agents (e.g., greater than or equal to 2 mg/kg/day or 20 mg/day of prednisone or equivalent for 14 consecutive days or more), or long-term topical or inhaled corticosteroids. These patients may also have increased adverse reactions and decreased or suboptimal immunologic response to vaccines. Data concerning the use of live influenza virus vaccines in immunosuppressed patients are limited. In a study consisting of 57 HIV-infected subjects with a median CD4 cell count of 541 cells/mm3 and 54 HIV-negative adults aged 18 to 58 years, no serious adverse events were reported during the one-month follow-up period after administration of a live influenza virus vaccine (FluMist intranasal spray). Vaccine strain (type B) virus was detected in 1 of 28 HIV-infected subjects on day 5 only and none of the HIV-negative vaccine recipients. No adverse effects on HIV viral load or CD4 counts were identified following vaccine administration. The effectiveness of live influenza virus vaccines in preventing influenza illness in HIV-infected individuals has not been evaluated.

MANAGEMENT: Administration of live influenza virus vaccines to immunocompromised persons should be based on careful consideration of potential benefits and risks. In general, live attenuated vaccines should preferably not be used in patients receiving immunosuppressive therapy or cancer chemotherapy. Vaccination should be deferred until after such therapy is discontinued and immune function has been restored, usually 4 to 12 weeks after stopping immunosuppressive therapy. A longer waiting period may be necessary following treatment with agents that have a prolonged elimination half-life (e.g., leflunomide, teriflunomide). Current local immunization guidelines should be consulted for recommendations. In patients who have recently been vaccinated, such therapy should not be initiated for at least 2 weeks (may be longer in some cases; refer to individual product labeling). However, the decision to vaccinate with a live influenza virus vaccine should be considered on an individual basis. Use of the inactivated form of the vaccine may be a safer alternative in some patients. Vaccines may generally be administered to patients receiving corticosteroids as replacement therapy (e.g., for Addison's disease).

References

  1. Braunwald E, Hauser SL, Kasper DL, Fauci AS, Isselbacher KJ, Longo DL, Martin JB, eds., Wilson JD (1998) "Harrison's Principles of Internal Medicine." New York, NY: McGraw-Hill Health Professionals Division
  2. CDC. Centers for Disease Control and Prevention/ (1993) "Recommendations of the advisory committtee on immunization practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence." MMWR Morb Mortal Wkly Rep, 42(RR-04), p. 1-18
  3. (2022) "Product Information. FluMist (influenza virus vaccine, live)." Medimmune Inc
  4. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  5. (2022) "Product Information. Influenza Virus Vaccine, H1N1, Live (influenza virus vaccine, H1N1, live)." Medimmune Inc
  6. CDC Centers for Disease Control and Prevention (2019) General Best Practice Guidelines for Immunization: Altered Immunocompetence. https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/immunocompetence.pdf
View all 6 references

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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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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.