Fluorouracil

Product Type: HUMAN PRESCRIPTION DRUG

Route: INTRAVENOUS

Dosage Form:

NDC: 46708-779

Application: ANDA217676

Effective: 20231116

1 INDICATIONS & USAGE Fluorouracil is indicated for the treatment of patients with: Fluorouracil is a nucleoside metabolic inhibitor indicated for the treatment of patients with Adenocarcinoma of the Colon and Rectum (1.1) Adenocarcinoma of the Breast (1.2) Gastric Adenocarcinoma (1.3) Pancreatic Adenocarcinoma (1.4) 1.1. Adenocarcinoma of the Colon and Rectum . 1.2. Adenocarcinoma of the Breast . 1.3. Gastric Adenocarcinoma . 1.4. Pancreatic Adenocarcinoma .

2 DOSAGE & ADMINISTRATION Fluorouracil is recommended for administration either as an intravenous bolus or as an intravenous infusion. (2.1) See Full Prescribing Information for dose individualization (2.1) and dose modifications due to adverse reactions (2.6) See Full Prescribing Information for recommended doses of fluorouracil for adenocarcinoma of the colon and rectum (2.2) and for recommended doses of fluorouracil as a component of a chemotherapy regimen for adenocarcinoma of the breast (2.3), gastric adenocarcinoma (2.4), pancreatic adenocarcinoma (2.5) Pharmacy Bulk Package: Prepare doses for more than one patient in a Pharmacy Admixture Service under appropriate conditions for cytotoxic drugs. Do not inject entire contents of vial directly into patients. Use within 4 hours of puncture (2.7, 2.8) 2.1. General Dosage Information Fluorouracil is recommended for administration either as an intravenous bolus or as an intravenous infusion. Do not inject the entire contents of the vial directly into patients. Individualize the dose and dosing schedule of fluorouracil based on tumor type, the specific regimen administered, disease state, response to treatment, and patient risk factors. 2.2. Recommended Dosage for Adenocarcinoma of the Colon and Rectum The recommended dose of fluorouracil, administered in an infusional regimen in combination with leucovorin alone, or in combination with leucovorin and oxaliplatin or irinotecan, is 400 mg/m 2 by intravenous bolus on Day 1, followed by 2400 mg/m 2 to 3000 mg/m 2 intravenously as a continuous infusion over 46 hours every two weeks. The recommended dose of fluorouracil, if administered in a bolus dosing regimen in combination with leucovorin, is 500 mg/m 2 by intravenous bolus on Days 1, 8, 15, 22, 29, and 36 in 8-week cycles. 2.3. Recommended Dosage for Adenocarcinoma of the Breast The recommended dose of fluorouracil, administered as a component of a cyclophosphamide-based multidrug regimen, is 500 mg/m 2 or 600 mg/m 2 intravenously on Days 1 and 8 every 28 days for 6 cycles. 2.4. Recommended Dosage for Gastric Adenocarcinoma The recommended dose of fluorouracil, administered as a component of a platinum-containing multidrug chemotherapy regimen, is 200 mg/m 2 to 1000 mg/m 2 intravenously as a continuous infusion over 24 hours. The frequency of dosing in each cycle and the length of each cycle will depend on the dose of fluorouracil and the specific regimen administered. 2.5. Recommended Dosage for Pancreatic Adenocarcinoma The recommended dose of fluorouracil, administered as an infusional regimen in combination with leucovorin or as a component of a multidrug chemotherapy regimen that includes leucovorin, is 400 mg/m 2 intravenous bolus on Day 1, followed by 2400 mg/m 2 intravenously as a continuous infusion over 46 hours every two weeks. 2.6. Dose Modifications Withhold fluorouracil for any of the following: Development of angina, myocardial infarction/ischemia, arrhythmia, or heart failure in patients with no history of coronary artery disease or myocardial dysfunction [see Warnings and Precautions (5.2)] Hyperammonemic encephalopathy [see Warnings and Precautions (5.3)] Acute cerebellar syndrome, confusion, disorientation, ataxia, or visual disturbances [see Warnings and Precautions (5.4)] Grade 3 or 4 diarrhea [see Warnings and Precautions (5.5)] Grade 2 or 3 palmar-plantar erythrodysesthesia (hand-foot syndrome) [see Warnings and Precautions (5.6)] Grade 3 or 4 mucositis [see Warnings and Precautions (5.8)] Grade 4 myelosuppression [see Warnings and Precautions (5.7)] Upon resolution or improvement to Grade 1 diarrhea, mucositis, myelosuppression, or palmar-plantar erythrodysesthesia, resume fluorouracil administration at a reduced dose. There is no recommended dose for resumption of fluorouracil administration following development of any of the following adverse reactions: Cardiac toxicity Hyperammonemic encephalopathy Acute cerebellar syndrome, confusion, disorientation, ataxia, or visual disturbances 2.7. Preparation for Administration Fluorouracil is supplied in a pharmacy bulk package consisting of a vial. The pharmacy bulk package can be used to prepare doses for more than one patient. It is not supplied with a sterile transfer device, which is required for dispensing when multiple doses will be prepared from the single vial. The 100 mL vial is only intended for preparation in a Pharmacy Admixture Service under appropriate conditions for cytotoxic drugs [see References (15)] . Store vial at room temperature. Using aseptic conditions, penetrate the container closure once with a suitable sterile transfer device or dispensing set that allows measured distribution of the contents. Record the date and time the vial was opened on the vial label. Discard the pharmacy bulk package 4 hours after penetration of the container closure. Withdraw the calculated dose for an individual patient into a sterile syringe. Inspect the solution in syringe for particulate matter and discoloration prior to administration or further dilution. Discard syringe if the solution is discolored or contains particulate matter. 2.8. Administration Do not administer in the same intravenous line concomitantly with other medicinal products. For bolus administration, store undiluted fluorouracil in the syringe for up to 4 hours at room temperature (25°C). Administer fluorouracil as an intravenous bolus through an established intravenous line. Store diluted solutions of fluorouracil for up to 4 hours at room temperature (25°C) prior to administration to the patient. For intravenous infusion regimens, administer through a central venous line using an infusion pump.

4 CONTRAINDICATIONS None. None

Not available.

6 ADVERSE REACTIONS The following adverse reactions are discussed in more detail in other sections of the labeling: Increased risk of serious or fatal adverse reactions in patients with low or absent dipyrimidine dehydrogenase activity [see Warnings and Precautions (5.1)] Cardiotoxicity [see Warnings and Precautions (5.2)] Hyperammonemic encephalopathy [see Warnings and Precautions (5.3)] Neurologic toxicity [see Warnings and Precautions (5.4)] Diarrhea [see Warnings and Precautions (5.5)] Palmar-plantar erythrodysesthesia (hand-foot syndrome) [see Warnings and Precautions (5.6)] Myelosuppression [see Warnings and Precautions (5.7)] Mucositis [see Warnings and Precautions (5.8)] Increased risk of elevated INR when administrated with warfarin [see Warnings and Precautions (5.9)] To report SUSPECTED ADVERSE REACTIONS, contact Alembic Pharmaceuticals, Inc. at 1-866-210-9797 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.2. Postmarketing Experience The following adverse reactions have been identified during postapproval use of fluorouracil. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Hematologic: pancytopenia [see Warnings and Precautions (5.7)] Gastrointestinal: gastrointestinal ulceration, nausea, vomiting Allergic Reactions: anaphylaxis and generalized allergic reactions Neurologic: nystagmus, headache Dermatologic: dry skin; fissuring; photosensitivity, as manifested by erythema or increased pigmentation of the skin; vein pigmentation Ophthalmic: lacrimal duct stenosis, visual changes, lacrimation, photophobia Psychiatric: euphoria Miscellaneous: thrombophlebitis, epistaxis, nail changes (including loss of nails)