khapzory

For intravenous administration only. Do not administer intrathecally. ( 2.1 ) Rescue After High-Dose Methotrexate Therapy Rescue recommendations are based on a methotrexate dose of 12 grams/ m 2 administered by intravenous infusion over 4 hours. Initiate rescue at a dose of 7.5 mg (approximately 5 mg/m 2 ) every 6 hours, 24 hours after the beginning of the methotrexate infusion. ( 2.2 ) Continue until the methotrexate level is below 5 x 10 -8 M (0.05 micromolar). Adjust dose if necessary, based on methotrexate elimination; refer to Full Prescribing Information. ( 2.2 ) Overdosage of Folic Acid Antagonists or Impaired Methotrexate Elimination Start as soon as possible after methotrexate overdosage or within 24 hours of delayed methotrexate elimination. ( 2.3 ) Administer KHAPZORY 7.5 mg (approximately 5 mg/m 2 ) intravenously every 6 hours until methotrexate level is less than 5 x 10 -8 M (0.05 micromolar). ( 2.3 ) Metastatic Colorectal Cancer in Combination with Fluorouracil The following regimens have been used for the treatment of colorectal cancer. o KHAPZORY 100 mg/m 2 by intravenous injection over a minimum of 3 minutes, followed by fluorouracil 370 mg/m 2 once daily for 5 consecutive days. ( 2.4 ) o KHAPZORY 10 mg/m 2 by intravenous injection followed by fluorouracil 425 mg/m 2 once daily for 5 consecutive days. ( 2.4 ) The above five-day courses may be repeated every 4…

The following clinical significant adverse reactions are described elsewhere in the labeling: • Increased gastrointestinal toxicities with fluorouracil [see Warnings and Precautions ( 5.1 )] The most common adverse reactions (≥ 20%) in patients receiving high-dose methotrexate therapy with levoleucovorin rescue are stomatitis and vomiting. ( 6.1 ) The most common adverse reactions (>50%) in patients receiving levoleucovorin in combination with fluorouracil for metastatic colorectal cancer are stomatitis, diarrhea, and nausea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Acrotech Biopharma Inc at 1-888-292-9617 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. High-Dose Methotrexate Therapy Table 2 presents the frequency of adverse reactions which occurred during the administration of 58 courses of high-dose methotrexate 12 grams/m 2 followed by levoleucovorin rescue, for osteosarcoma, in 16 patients aged 6 to 21 years. Most patients received levoleucovorin 7.5 mg every 6 hours for 60 hours or longer, beginning 24 hours after completion of methotrexate administration. Table 2…

KHAPZORY is contraindicated in patients who have had severe hypersensitivity to leucovorin products, folic acid, or folinic acid [see Adverse Reactions ( 6.2 )] . Patients who have had severe hypersensitivity reactions to leucovorin products, folic acid, or folinic acid. ( 4 )

7.1 Effects of Leucovorin Products on Other Drugs Antiepileptic Drugs Folic acid in large amounts may counteract the antiepileptic effect of phenobarbital, phenytoin and primidone and increase the frequency of seizures in susceptible children. It is not known whether folinic acid has the same effects; however, both folic and folinic acids share some common metabolic pathways. Monitor patients taking folinic acid in combination with antiepileptic drugs. Fluorouracil Leucovorin products increase the toxicity of 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 the diarrhea has resolved, as rapid deterioration leading to death can occur [see Warnings and Precautions ( 5.1 )] . Trimethoprim-Sulfamethoxazole The concomitant use of d, l -leucovorin with trimethoprim-sulfamethoxazole for the acute treatment of Pneumocystis jiroveci pneumonia in patients with HIV infection was associated with increased rates of treatment failure and morbidity in a placebo-controlled study [see Warnings and Precautions ( 5.2 )] .