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Fluorouracil Intravenous, Injection and Foltanx

Determining the interaction of Fluorouracil Intravenous, Injection and Foltanx and the possibility of their joint administration.

Check result:
Fluorouracil Intravenous, Injection <> Foltanx
Relevance: 09.12.2023 Reviewer: Shkutko P.M., M.D., in

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Consumer:

Consumer information for this interaction is not currently available.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) is prescribed in combination with leucovorin. A lower dosage of 5-FU or the prodrug may be required. Patients should be monitored closely for potential toxicities of 5-FU such as neutropenia, thrombocytopenia, stomatitis, gastrointestinal hemorrhage, severe diarrhea, vomiting, 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 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 "Product Information. Xeloda (capecitabine)." Roche Laboratories, Nutley, NJ. "Product Information. Levoleucovorin (levoleucovorin)." Spectrum Chemical, Gardena, CA. EMEA. European Medicines Agency "EPARs. European Union Public Assessment Reports. Available from: URL: http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/medicines/medicines_landingpage.jsp&mid." 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 Schalhorn A, Kuhl M "Clinical pharmacokinetics of fluorouracil and folinic acid." Semin Oncol 19 (1992): 82-92 "Product Information. Wellcovorin (leucovorin)." Glaxo Wellcome, Research Triangle Park, NC. Mainwaring P, Grygiel JJ "Interaction of 5-fluorouracil with folates." Aust N Z J Med 25 (1995): 60 View all 8 references

Professional:

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) is prescribed in combination with leucovorin. A lower dosage of 5-FU or the prodrug may be required. Patients should be monitored closely for potential toxicities of 5-FU such as neutropenia, thrombocytopenia, stomatitis, gastrointestinal hemorrhage, severe diarrhea, vomiting, 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
  • 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
  • "Product Information. Xeloda (capecitabine)." Roche Laboratories, Nutley, NJ.
  • "Product Information. Levoleucovorin (levoleucovorin)." Spectrum Chemical, Gardena, CA.
  • EMEA. European Medicines Agency "EPARs. European Union Public Assessment Reports. Available from: URL: http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/medicines/medicines_landingpage.jsp&mid."
  • 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
  • Schalhorn A, Kuhl M "Clinical pharmacokinetics of fluorouracil and folinic acid." Semin Oncol 19 (1992): 82-92
  • "Product Information. Wellcovorin (leucovorin)." Glaxo Wellcome, Research Triangle Park, NC.
  • Mainwaring P, Grygiel JJ "Interaction of 5-fluorouracil with folates." Aust N Z J Med 25 (1995): 60
Fluorouracil Intravenous, Injection

Generic Name: fluorouracil

Brand name: Adrucil

Synonyms: Fluorouracil (injection), Fluorouracil (Systemic)

Foltanx

Generic Name: l-methylfolate

Brand name: Deplin, L-Methylfolate Formula, XaQuil XR, L-Methylfolate Formula 75

Synonyms: L-methylfolate, Methylfolate

In the course of checking the drug compatibility and interactions, data from the following reference sources was used: Drugs.com, Rxlist.com, Webmd.com, Medscape.com.

Interaction with food and lifestyle