5-FU IV Injection or Infusion Uses
5-Fluorouracil is indicated alone or in combination for carcinoma of the colon or rectum, carcinoma of the stomach and exocrine pancreas, carcinoma of the liver, carcinoma of the breast (an especially aggressive form of breast cancer), carcinoma of the bladder, carcinoma of the lung, epithelial ovarian carcinoma andcervical carcinoma.
5-Fluorouracil works by inhibiting the enzyme thymidylate kinase which results in reduced formation of thymidine and thus DNA. The active metabolite FdUMP appears to form a stable complex with the folate cofactor N-5, 10-methylene tetrahydrofolate which inactivates thymidylate kinase. 5-Fluril as FdUMP is also incorporated into RNA which results in fluorination of RNA. The effect of fluorouracil on living cells is limited mainly to those in the proliferative phase but while cells in the G2 and S phase are most affected there may be effects at any stage of the cell cycle.
5-FU IV Injection or Infusion Doses
Various protocols exist-
- 500 mg/m2 IV on Days 1-5, OR
- 450-600 mg/m2 IV weekly, OR
- 200-400 mg/m2 IV continuous infusion qD
- Not to exceed 800 mg/day
The commonest schedules being 500 mg/m2 daily for 5 days repeated at 4-weekly intervals.
5-FU IV Injection or Infusion Side Effects
Mild to moderate cardiac effects, hepatic effects, hematological effects, neurological effects, allergic reaction, decreased bone marrow function, hand-foot syndrome, severe vomiting, diarrhoea, frequent bowel movements or watery stools, sores in the mouth or throat may occur.
Dose should be reduced in patients with compromised liver function. For intra-arterial infusion, 5000 U of L.M. heparin should be added to 1 L of 5% dextrose in water together with the daily dose of fluorouracil. Ulcer-like pain or other significant gastrointestinal symptoms are indications to discontinue intra-arterial therapy, as hemorrhage or perforation may occur. Precipitation may occur when leucovorin and fluorouracil are mixed in the same bag.
Pre-treatment with cimetidine for 4 weeks lead to increased plasma concentrations of fluorouracil following intravenous and oral administration. The effect was probably due to a combination of hepatic enzyme inhibition and reduced hepatic blood flow.
Its use should be avoided in patients receiving drugs known to modulate dihydropyrimidine dehydrogenase (such as the antiviral drug sorivudine). It may also increase the INR and prothrombin times in patients on warfarin. Fluoruracil's efficacy is decreased when used alongside allopurinol which can be used to decrease fluoruracil induced stomatitis through use of allopurinol mouthwash.
5-FU Uses During Pregnancy
Pregnancy category D. There are no data on the excretion of fluorouracil into human milk. Because fluorouracil inhibits DNA, RNA and protein synthesis, mothers should not nurse while receiving this drug.
5-FU Accute Overdose
There is very little difference between the minimum effective dose and maximum tolerated dose of 5-FU, and the drug exhibits marked individual pharmacokinetic variability. Therefore, an identical dose of 5-FU may result in a therapeutic response with acceptable toxicity in some patients and unacceptable and possibly life-threatening toxicity in others. Both overdosing and underdosing are of concern with 5-FU, although several studies have shown that the majority of colorectal cancer patients treated with 5-FU are underdosed based on today's dosing standard, body surface area (BSA). The limitations of BSA-based dosing prevent oncologists from being able to accurately titer the dosage of 5-FU for the majority of individual patients, which results in sub-optimal treatment efficacy or excessive toxicity.
Numerous studies have found significant relationships between concentrations of 5-FU in blood plasma and both desirable or undesirable effects on patients. Studies have also shown that dosing based on the concentration of 5-FU in plasma can greatly increase desirable outcomes while minimizing negative side effects of 5-FU therapy. One such test that has been shown to successfully monitor 5-FU plasma levels and which "may contribute to improved efficacy and safety of commonly used 5-FU-based chemotherapies" is the My 5-FU test.
It is contraindicated in patients that are severely debilitated or in patients with bone marrow suppression due to either radiotherapy or chemotherapy. It is likewise contraindicated in pregnant or breastfeeding women. It should also be avoided in patients that do not have malignant illnesses.
5-FU Uses Direction
Intravenous 5-FU can be delivered by rapid intravenous bolus injection or slow infusion. The vial contents can rapidly be injected directly into a peripheral vein. Slow intravenous infusion requires the drug to be diluted in 500 mL of dextrose 5% solution, then infused over 2-3 hours on 5 successive days.
5-FU Storage Condition
Product should be stored below 25℃, without freezing and protected from light.