General Dosage Information

Adrucil is recommended for administration either as an intravenous bolus or as an intravenous infusion. 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.

Recommended Dosage for Adenocarcinoma of the Colon and Rectum

• The recommended dose of Adrucil, administered in an infusional regimen in combination with leucovorin alone, or in combination with leucovorin and oxaliplatin or irinotecan, is 400 mg/m2 by intravenous bolus on Day 1, followed by 2400 mg/m2 to 3000 mg/m2 intravenously as a continuous infusion over 46 hours every two weeks.
• The recommended dose of Adrucil, if administered in a bolus dosing regimen in combination with leucovorin, is 500 mg/m2 by intravenous bolus on Days 1, 8, 15, 22, 29, and 36 in 8-week cycles.

Recommended Dosage for Adenocarcinoma of the Breast

• The recommended dose of Adrucil, administered as a component of a cyclophosphamide-based multidrug regimen, is 500 mg/m2 or 600 mg/m2 intravenously on Days 1 and 8 every 28 days for 6 cycles.

Recommended Dosage for Gastric Adenocarcinoma

• The recommended dose of Adrucil, administered as a component of a platinum-containing multidrug chemotherapy regimen, is 200 mg/m2 to 1000 mg/m2 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 Adrucil and the specific regimen administered.

Recommended Dosage for Pancreatic Adenocarcinoma

• The recommended dose of Adrucil, administered as an infusional regimen in combination with leucovorin or as a component of a multidrug chemotherapy regimen that includes leucovorin, is 400 mg/m2 intravenous bolus on Day 1, followed by 2400 mg/m2 intravenously as a continuous infusion over 46 hours every two weeks.

Dose Modifications

Withhold Adrucil 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 Adrucil administration at a reduced dose.

There is no recommended dose for resumption of Adrucil administration following development of any of the following adverse reactions:

• Cardiac toxicity
• Hyperammonemic encephalopathy
• Acute cerebellar syndrome, confusion, disorientation, ataxia, or visual disturbances

Preparation for Administration

The 10 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.

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.

Administration

Do not administer in the same intravenous line concomitantly with other medicinal products.

For bolus administration, store undiluted Adrucil in the syringe for up to 4 hours at room temperature (25°C). Administer Adrucil as an intravenous bolus through an established intravenous line.

Store diluted solutions of Adrucil 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.