Khapzory Side Effects Center

SIDE EFFECTS

The following clinically significant adverse reactions are described elsewhere in the labeling:

• Increased gastrointestinal toxicities with fluorouracil [see WARNINGS AND PRECAUTIONS]

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/m² 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 : Adverse Reactions with High-Dose Methotrexate Therapy

Combination With Fluorouracil In Colorectal Cancer

Table 3 presents the frequency of adverse reactions which occurred in 2 arms of a randomized controlled trial conducted by the North Central Cancer Treatment Group (NCCTG) in patients with metastatic colorectal cancer. The trial failed to show superior overall survival with fluorouracil + levoleucovorin compared to fluorouracil + d,l-leucovorin. Patients were randomized to fluorouracil 370 mg/m² intravenously and levoleucovorin 100 mg/m² intravenously, both daily for 5 days, or to fluorouracil 370 mg/m² intravenously and d,l-leucovorin 200 mg/m² intravenously, both daily for 5 days. Treatment was repeated week 4 and week 8, and then every 5 weeks until disease progression or unacceptable toxicity.

Table 3 : Adverse Reactions Occurring in ≥ 10% of Patients in Either Arm

Postmarketing Experience

The following adverse reactions have been identified during post approval use of levoleucovorin products. Because these adverse 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. The following have been reported:

• Dermatologic: pruritus, rash
• Respiratory: dyspnea
• Other Clinical Events: temperature change, rigors, allergic reactions

DRUG INTERACTIONS

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 Fusilev 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].

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].

Read the entire FDA prescribing information for Khapzory (Levoleucovorin Injection)