KHAPZORY administration in combination with fluorouracil for metastatic colorectal cancer.

The following regimens have been used for the treatment of colorectal cancer:

This five-day course may be repeated every 4 weeks for 2 courses, then every 4-5 weeks, if the patient has recovered from toxicity from the prior course. Do not adjust KHAPZORY dosage for toxicity.

Refer to fluorouracil prescribing information for information on fluorouracil dosage and dosage modifications for adverse reactions.

Important Administration Information

KHAPZORY is indicated for intravenous administration only. Do not administer intrathecally.

Reconstitution and Infusion Instructions¹

KHAPZORY for Injection is supplied in single-dose vials containing 175 mg and 300 mg of levoleucovorin as a sterile, white to yellowish lyophilized powder in a single-dose vial for reconstitution.

Preparation

• Reconstitute the 175 mg and 300 mg vial contents with 3.6 mL and 6.2 mL of 0.9% Sodium Chloride Injection, USP, respectively to obtain a clear, colorless to yellowish solution (resultant concentration 50 mg per mL levoleucovorin). Reconstitution with a sodium chloride solution with preservatives (e.g. benzyl alcohol) has not been studied. Do not store reconstituted solution for more than 12 hours at room temperature. Protect from light.
• Dilute reconstituted solution immediately (if possible), to concentrations of 0.5 mg/mL to 5 mg/mL in 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP. Do not store diluted reconstituted solution for more than 12 hours at room temperature. Protect from light.
• Visually inspect parenteral drug products for particulate matter and discoloration prior to administration. Discard if particulate matter or discoloration is observed.

Storage

• Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature].
• Store vial in original carton until contents are used. Protect solutions from light.

Indications and Usage

KHAPZORY^TM is a folate analog indicated for:

• Rescue after high-dose methotrexate therapy in patients with osteosarcoma.
• Diminishing the toxicity associated with overdosage of folic acid antagonists or impaired methotrexate elimination.
• Treatment of patients with metastatic colorectal cancer in combination with fluorouracil.

Limitations of Use

KHAPZORY is not indicated for the treatment of pernicious anemia and megaloblastic anemia secondary to lack of vitamin B₁₂ because of the risk of progression of neurologic manifestations despite hematologic remission.

Important Safety Information

Contraindications

• KHAPZORY is contraindicated in patients who have had severe hypersensitivity to leucovorin products, folic acid, or folinic acid.

Warnings and Precautions

• Increased gastrointestinal toxicities with fluorouracil: Gastrointestinal toxicities, including stomatitis and diarrhea, occur more commonly and may be of greater severity and of prolonged duration. Deaths from severe enterocolitis, diarrhea, and dehydration have occurred in elderly patients receiving weekly d,l-leucovorin and fluorouracil. Do not initiate or continue therapy with KHAPZORY and fluorouracil in patients with symptoms of gastrointestinal toxicity until those symptoms have resolved. Monitor patients with diarrhea until it has resolved as rapid deterioration leading to death can occur.
• Drug interaction with trimethoprim-sulfamethoxazole: Concomitant use of d,l-leucovorin with trimethoprim-sulfamethoxazole for the acute treatment of Pneumocystis jiroveci pneumonia in patients with HIV infection increased treatment failure and morbidity.

Adverse Reactions

• The most common adverse reactions (≥20%) in patients receiving high-dose methotrexate therapy with levoleucovorin rescue were stomatitis (38%) and vomiting (38%).
• The most common adverse reactions (>50%) in patients receiving levoleucovorin in combination with fluorouracil for metastatic colorectal cancer were stomatitis (72%), diarrhea (70%), and nausea (62%).

Drug Interactions

Leucovorin products increase the toxicity of fluorouracil.

Use in Specific Populations

Levoleucovorin is administered in combination with methotrexate or fluorouracil, which can cause embryo-fetal harm. Refer to methotrexate and fluorouracil prescribing information for additional information.

Please click here to see full Prescribing Information for KHAPZORY.

ISI-PP-KAP-00-0001

Reporting of Suspected Adverse Reactions

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

Reference:

1. KHAPZORY [package insert]. Irvine, CA: Spectrum Pharmaceuticals, Inc.