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Drug Interactions between Adrucil and Te Anatoxal Berna

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

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Interactions between your drugs

Moderate

fluorouracil tetanus toxoid

Applies to: Adrucil (fluorouracil) and Te Anatoxal Berna (tetanus toxoid)

MONITOR: The administration of inactivated, killed, or otherwise noninfectious vaccines to immunosuppressed patients is generally safe but may be associated with a diminished or suboptimal immunologic response due to antibody inhibition. Such patients may include those who have recently received or are receiving immunosuppressive agents, antilymphocyte globulins, 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.

MANAGEMENT: In general, the U.S. Department of Public Health Advisory Committee on Immunization Practices (ACIP) recommends that inactivated or killed vaccines be administered to non-HIV immunosuppressed patients according to the same guidelines as for healthy patients. However, higher dosages, more frequent boosters, and/or serological testing may be required in some cases. Local guidelines and prescribing information for individual vaccines should be consulted. For Haemophilus influenzae b vaccine, some experts recommend that it be administered at least 2 weeks before starting or 3 months after discontinuing chemotherapy when used in patients with Hodgkin's disease. For rabies vaccine, some authorities suggest that immunosuppressive agents should generally be avoided during postexposure therapy except when absolutely necessary for the treatment of other conditions. For SARS-CoV-2 (COVID-19) vaccines, vaccination should generally be completed at least 2 weeks before initiation or resumption of immunosuppressive therapies; however, decisions to delay or temporarily withhold immunosuppressive therapy to complete COVID-19 vaccination should consider the individual's risks relative to their underlying condition. Some authorities recommend administering the COVID-19 vaccine approximately 4 weeks prior to the next scheduled therapy for those on B-cell-depleting therapies on a continuing basis. Additional shots, boosters, and even revaccination may be appropriate depending on age, prior COVID-19 vaccine formulation(s) received, current or planned immunosuppressive therapy, and other factors in individuals with moderate to severe immune compromise due to medical conditions or immunosuppressive medications or treatments (e.g., solid organ transplant recipients on immunosuppressive therapy; patients on active treatment for solid tumor and hematologic malignancies). Vaccines may generally be administered to patients receiving corticosteroids as replacement therapy (e.g., for Addison's disease).

References

  1. "Product Information. Fluzone (influenza virus vaccine, inactivated)." Connaught Laboratories Inc
  2. "Product Information. Omnihib (haemophilus b conjugate vaccine (obsolete))." SmithKline Beecham PROD
  3. "Product Information. Havrix (HepA) (hepatitis A adult vaccine)." SmithKline Beecham PROD
  4. CDC. Centers for Disease Control and Prevention/ "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) (1993): 1-18
  5. "Product Information. Imovax Rabies (rabies vaccine, human diploid cell)." sanofi pasteur (2022):
  6. "Product Information. Biothrax (anthrax vaccine adsorbed)." Emergent BioSolutions Inc. (2003):
  7. Cerner Multum, Inc. "Australian Product Information." O 0
  8. "Product Information. Influenza Virus Vaccine, H5N1, Inactivated (influenza virus vaccine, H5N1, inactivated)." GlaxoSmithKline (2022):
  9. CDC Centers for Disease Control and Prevention "General Best Practice Guidelines for Immunization: Altered Immunocompetence. https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/immunocompetence.pdf" (2019):
  10. Department of Health. National Health Service "Immunisation Against Infectious Disease - "The Green Book". Chapter 6: Contraindications and special considerations. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/655225/Greenbook_chapter_6.pdf" (2019):
  11. CDC Centers for Disease Control and Prevention "Interim Clinical Considerations for Use of COVID-19 Vaccines Currently Approved or Authorized in the United States. https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html" (2022):
  12. Centers for Disease Control and Prevention "Use of COVID-19 vaccines in the U.S. https://www.cdc.gov/vaccines/covid-19/clinical-considerations/interim-considerations-us.html" (2023):
  13. UK Health Security Agency "COVID-19: the green book, chapter 14a https://www.gov.uk/government/publications/covid-19-the-green-book-chapter-14a" (2023):
  14. Public Health Agency of Canada "Immunization of immunocompromised persons: Canadian immunization guide https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-3-vaccination-specific-populations/page-8-immunization-immunocompromised-p" (2023):
  15. Public Health Agency of Canada "COVID-19 vaccines: Canadian immunization guide. https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-26-covid-19-vaccine.html" (2023):
  16. Australian Government. Department of Health and Aged Care "Australian immunisation handbook: COVID-19. https://immunisationhandbook.health.gov.au/contents/vaccine-preventable-diseases/covid-19" (2023):
View all 16 references

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Drug and food interactions

Major

fluorouracil food

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

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