5 FU PhaRes IV Injection

5 FU PhaRes IV Injection is used for: Palliation of malignant neoplasms, Superficial basal cell carcinoma, Oesophageal carcinoma, Carcinoma of Colon, Carcinoma of Breast, Carcinoma of Ovary, Carcinoma of Liver, Carcinoma of Pancreas, Carcinoma of Rectum, Carcinoma of Stomach

Adult: IV Palliation of malignant neoplasms 12 mg/kg/day (max: 0.8-1g/day) for 3-4 days, if no toxicity occurs, may be followed after 1 day w/ 6 mg/kg on alternate days for another 3-4 doses. May repeat course 4-6 wk later or maintenance doses of 5-15 mg/kg (max: 1 g) may be given wkly. Cancers of Colon, Breast, Ovary, Liver, Pancreas, Rectum, Stomach Various protocols exist 500 mg/sq.meter IV on Days 1-5, OR 450-600 mg/sq.meter IV weekly, OR 200-400 mg/sq.meter IV continuous infusion qD Not to exceed 800 mg/day As an infusion: 15 mg/kg/day (max: 1 g/day), continue until toxicity occurs or a total of 12-15 g is given. May repeat course 4-6 wk later. Intra-arterial Palliation of malignant neoplasms 5-7.5 mg/kg/day as continuous infusion (regional perfusion). Hepatic impairment: Dose reduction may be required.

Child: Safety & efficacy not established.

Renal impairment: Dose reduction may be required.

IV Preparation IV Push: dose/syringe (concentration: 50 mg/mL); max syringe size for IVP is 30 mL syringe and syringe should be <75% full Continuous IV Infusion/IVPB: dose/50-1000 mL D5W or NS; syringe and solution are stable for 72 hr at 4 to 25°C IV Administration Direct IV push injection (50 mg/mL solution needs no further dilution) or by IV infusion Toxicity may be reduced by giving the drug as a constant infusion Bolus doses may be administered by slow IVP or IVPB Warm to body temperature before using Continuous IV infusion may be administered in D5W or NS Solution should be protected from direct sunlight 5-FU may also be administered intra-arterially or intra-hepatically Use plastic IV containers for continuous infusions (stable in plastic IV bags than in glass bottles)

Topical application on mucous membranes, exposure to sunlight, hypersensitivity. Depressed bone marrow function, poor nutritional status, potentially serious infections. Pregnancy and lactation.

Serious Adverse Reactions from Dihydropyrimidine Dehydrogenase (DPD) Deficiency: Patients with certain homozygous or compound heterozygous variants in the DPYD gene are at increased risk for acute early-onset toxicity and serious, including fatal, adverse reactions due to fluorouracil (e.g., mucositis, diarrhea, neutropenia, and neurotoxicity). Fluorouracil is not recommended for use in patients known to have certain homozygous or compound heterozygous DPYD variants that result in complete absence of DPD activity. Withhold or permanently discontinue based on clinical assessment. No fluorouracil dose has been proven safe in patients with complete absence of DPD activity. Cardiotoxicity: Fluorouracil can cause cardiotoxicity, including angina, myocardial infarction/ischemia, arrhythmia, and heart failure. Withhold fluorouracil for cardiac toxicity. Hyperammonemic Encephalopathy: Altered mental status, confusion, disorientation, coma, or ataxia with elevated serum ammonia level can occur within 72 hours of initiation of fluorouracil. Withhold fluorouracil and initiate ammonia-lowering therapy. Neurologic Toxicity: Fluorouracil can cause acute cerebellar syndrome, confusion, disorientation, ataxia, or visual disturbances. Withhold fluorouracil for neurologic toxicity. Diarrhea: Fluorouracil can cause severe diarrhea. Withhold fluorouracil for severe diarrhea until resolved. Palmar-Plantar Erythrodysesthesia (Hand-Foot Syndrome): Fluorouracil can cause hand-foot syndrome. If severe, discontinue fluorouracil until resolved or decreased to Grade 1, then resume at a reduced dose. Myelosuppression: Fluorouracil can cause severe and fatal myelosuppression. Withhold fluorouracil until severe myelosuppression resolves, then resume at a reduced dose. Mucositis: Fluorouracil can cause severe mucositis. Discontinue fluorouracil until resolved or decreased to Grade 1, then resume at a reduced dose. Increased Risk of Elevated INR with Warfarin: Concurrent administration with warfarin can result in clinically significant increases in coagulation parameters: Closely monitor INR and prothrombin time. Embryofetal Toxicity: Fluorouracil can cause fetal harm. Advise females and males of reproductive potential of the potential risk to a fetus. Monitoring Parameter: Regularly monitor CBC, blood counts, renal function tests, LFT's, INR, and prothrombin time. Monitor cardiac function regularly.

Pregnancy There are no adequate and well-controlled studies with fluorouracil in pregnant women; based on its mechanism of action, the drug can cause fetal harm when administered to a pregnant woman If this drug is used during pregnancy, or patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to a fetus Contraception Females: Based on mechanism of action, drug can cause fetal harm when administered to a pregnant woman; advise females of reproductive potential to use effective contraception during treatment with fluorouracil and for up to 3 months following cessation of therapy Males: Fluorouracil may damage spermatozoa; advise males with female partners of reproductive potential to use effective contraception during and for 3 months following cessation of therapy Infertility Females: Advise females of reproductive potential that, based on animal data, fertility may be impaired while receiving fluorouracil Males: Advise males of reproductive potential that, based on animal data, fertility may be impaired while receiving fluorouracil Animal data Administration to rats and mice during selected periods of organogenesis, at doses lower than a human dose of 12 mg/kg, caused embryolethality and teratogenicity; malformations included cleft palate and skeletal defects In monkeys, maternal doses of fluorouracil higher than an approximate human dose of 12 mg/kg resulted in abortion Lactation Not known whether fluorouracil or its metabolites are present in human milk; because many drugs are present in human milk and because of potential for serious adverse reactions in nursing infants from fluorouracil, a decision should be made whether to discontinue nursing or to discontinue drug, taking into account importance of drug to the mother

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. Contraindicated (0) Serious - Use Alternative (19) • adenovirus types 4 and 7 live, oral • axicabtagene ciloleucel • brexucabtagene autoleucel • ciltacabtagene autoleucel • deferiprone • erdafitinib • etrasimod • germanium • givinostat • idecabtagene vicleucel • influenza virus vaccine quadrivalent, adjuvanted • influenza virus vaccine trivalent, adjuvanted • lisocabtagene maraleucel • palifermin • ropeginterferon alfa 2b • siponimod • tinidazole • tisagenlecleucel • tofacitinib

Side effects of 5-Fluorouracil (5-FU) : 1-10% Loss of appetite,Headache,Nausea,Vomiting,Diarrhea,Mucositis,Myelosuppression,Alopecia,Photosensitivity,Hand-foot syndrome,Maculopapular eruption (pruritic) Frequency Not Defined Angina,Coronary arteriosclerosis,Thrombophlebitis,Darkening of veins,Gastrointestinal ulcer,Increased alkaline phosphatase,Increased LFTs,Hyperbilirubinemia,Hypercholesterolemia (increased LDH),Anaphylaxis,Nystagmus,Ophthalmic findings Potentially Fatal: Central neurotoxicity, myocardial ischaemia.

Fluorouracil interferes with DNA synthesis by blocking the conversion of deoxyuridylic acid to thymidylic acid. It also interferes with RNA synthesis. This results in an unbalanced growth of the cells. Fluorouracil exerts greater effect on rapidly growing cells as they take up the drug at a faster rate.

5 FU PhaRes 25 mg/ml IV Injection manufactured by ZAS Corporation. Its generic name is 5-Fluorouracil (5-FU). 5 FU PhaRes is availble in Bangladesh. Farmaco BD drug index information on 5 FU PhaRes IV Injection is not intended for diagnosis, medical advice or treatment; neither intended to be a substitute for the exercise of professional judgment.