Adrucil

Tell your doctor if you are breastfeeding or plan to breastfeed. It is not known if fluorouracil is excreted in human breast milk or if it will harm your nursing baby.

Pyrimidine antagonist; antimetabolite; antineoplastic agent.205 a

Fluorouracil belongs to the group of medicines known as antimetabolites. It is used to treat cancer of the colon, rectum, breast, stomach, and pancreas. It may also be used to treat other kinds of cancer, as determined by your doctor.

Fluorouracil interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal body cells may also be affected by fluorouracil, other effects will also occur. Some of these may be serious and must be reported to your doctor. Other effects, like hair loss, may not be serious but may cause concern. Some effects may not occur for months or years after the medicine is used.

Before you begin treatment with fluorouracil, you and your doctor should talk about the good this medicine will do as well as the risks of using it.

Fluorouracil is to be administered only by or under the immediate supervision of your doctor.

• If you need to store this medicine at home, talk with your doctor, nurse, or pharmacist about how to store it.

Anticoagulants and CYP 2C9 Substrates

Elevated coagulation times have been reported in patients taking fluorouracil concomitantly with warfarin. While pharmacokinetic data are not available to assess the effect of fluorouracil administration on warfarin pharmacokinetics, the elevation of coagulation times that occurs with the fluorouracil prodrug capecitabine is accompanied by an increase in warfarin concentrations. Thus, the interaction may be due to inhibition of cytochrome P450 2C9 by fluorouracil or its metabolites.

Mechanism of Action

Fluorouracil is a nucleoside metabolic inhibitor that interferes with the synthesis of deoxyribonucleic acid (DNA) and to a lesser extent inhibits the formation of ribonucleic acid (RNA); these affect rapidly growing cells and may lead to cell death. Fluorouracil is converted to three main active metabolites: 5-fluoro-2′-deoxyuridine-5′-monophosphate (FdUMP), 5-fluorouridine-5′-triphosphate (FUTP) and 5-fluoro-2′-deoxyuridine-5′-triphosphate (FdUTP). These metabolites have several effects including the inhibition of thymidylate synthase by FdUMP, incorporation of FUTP into RNA and incorporation of FdUTP into DNA.

Pharmacokinetics

Distribution

Following bolus intravenous injection, fluorouracil distributes throughout the body including the intestinal mucosa, bone marrow, liver, cerebrospinal fluid and brain tissue.

Elimination

Following bolus intravenous injection, 5 to 20 % of the parent drug is excreted unchanged in the urine in six hours. The remaining percentage of the administered dose is metabolized, primarily in the liver. The metabolites of fluorouracil (e.g., urea and α-fluoro-ß-alanine) are excreted in the urine over 3 to 4 hours.

Following bolus intravenous injection of fluorouracil, as a single agent, the elimination half-life increased with dose from 8 to 20 minutes.

"OSHA Hazardous Drugs." OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html

Adrucil® (fluorouracil injection USP) 50 mg/mL, 10 x 10 mL Single Dose Vial Carton Label Text

Adrucil®

(fluorouracil injection USP)

500 mg/10 mL

(50 mg/mL)

For Intravenous Use Only

CAUTION: Cytotoxic Agent

10 mL Single Dose Vial

10 Vials

TEVA

Pregnancy Category: D

Lactation: excretion in milk unknown; do not nurse

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.