Levoleucovorin disodium
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From MedlinePlus, U.S. National Library of Medicine
Dosing in kidney impairment
Impaired Methotrexate Elimination or Renal Impairment Decreased methotrexate elimination or renal impairment which are clinically important but less severe than the abnormalities described in Table 1 can occur following methotrexate administration. If toxicity associated with methotrexate is observed, in subsequent courses extend KHAPZORY rescue for an additional 24 hours (total of 14 doses over 84 hours).
| Clinical Situation | Laboratory Findings | Recommendation |
| Normal methotrexate elimination | Serum methotrexate level approximately 10 micromolar at 24 hours after administration, 1 micromolar at 48 hours, and less than 0.2 micromolar at 72 hours. | Administer 7.5 mg by intravenous infusion every 6 hours for 60 hours (10 doses starting at 24 hours after start of methotrexate infusion). |
| Delayed late methotrexate elimination | Serum methotrexate level remaining above 0.2 micromolar at 72 hours, and more than 0.05 micromolar at 96 hours after administration. | Continue 7.5 mg by intravenous infusion every 6 hours, until methotrexate level is less than 0.05 micromolar. |
| Delayed early methotrexate elimination and/or evidence of acute renal injury* | Serum methotrexate level of 50 micromolar or more at 24 hours, or 5 micromolar or more at 48 hours after administration, OR 100% or greater increase in serum creatinine level at 24 hours after methotrexate administration (e.g., an increase from 0.5 mg/dL to a level of 1 mg/dL or more). | Administer 75 mg by intravenous infusion every 3 hours until methotrexate level is less than 1 micromolar; then 7.5 mg by intravenous infusion every 3 hours until methotrexate level is less than 0.05 micromolar. |
Preparation and administration
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Important Use Information KHAPZORY is indicated for intravenous administration only . Do not administer intrathecally . KHAPZORY consists of levoleucovorin in the form of a disodium salt, which makes it compatible with fluorouracil. This allows KHAPZORY and fluorouracil to be combined in the same infusion bag for intravenous administration without catheter occlusion or precipitation for up to 72 hours at 20°C to 25°C (68°F to 77°F).
Preparation Reconstitution Reconstitute 175 mg KHAPZORY vial with 3.6 mL of 0.9% Sodium Chloride Injection, USP, to a concentration of 50 mg/mL. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The reconstituted solution should be clear, colorless to slight yellow and free of visible particles.
Discard the reconstituted solution with visible particulate matter or discoloration. If not used immediately, store the reconstituted solution for up to 12 hours at room temperature at 20°C to 25°C (68°F to 77°F). Protect from light. Dilution Withdraw the required volume of the reconstituted solution from the vial and dilute with 0.9% Sodium Chloride for Injection, USP or 5% Dextrose Injection, USP to a final concentration of 0.5 mg/mL to 5 mg/mL.
Discard any unused portion remaining in the single-dose vial(s). Store the diluted solution for up to 12 hours at room temperature at 20°C to 25°C (68°F to 77°F) if not used immediately. Protect from light. Visually inspect the diluted solution for particulate matter and discoloration prior to administration. Discard if particulate matter or discoloration is observed.
| Clinical Situation | Laboratory Findings | Recommendation |
| Normal methotrexate elimination | Serum methotrexate level approximately 10 micromolar at 24 hours after administration, 1 micromolar at 48 hours, and less than 0.2 micromolar at 72 hours. | Administer 7.5 mg by intravenous infusion every 6 hours for 60 hours (10 doses starting at 24 hours after start of methotrexate infusion). |
| Delayed late methotrexate elimination | Serum methotrexate level remaining above 0.2 micromolar at 72 hours, and more than 0.05 micromolar at 96 hours after administration. | Continue 7.5 mg by intravenous infusion every 6 hours, until methotrexate level is less than 0.05 micromolar. |
| Delayed early methotrexate elimination and/or evidence of acute renal injury* | Serum methotrexate level of 50 micromolar or more at 24 hours, or 5 micromolar or more at 48 hours after administration, OR 100% or greater increase in serum creatinine level at 24 hours after methotrexate administration (e.g., an increase from 0.5 mg/dL to a level of 1 mg/dL or more). | Administer 75 mg by intravenous infusion every 3 hours until methotrexate level is less than 1 micromolar; then 7.5 mg by intravenous infusion every 3 hours until methotrexate level is less than 0.05 micromolar. |
Drug interactions
Check levoleucovorin disodium against a medication listLabel text (3 paragraphs)
7 DRUG INTERACTIONS
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 )] .
Contraindications
4 CONTRAINDICATIONS 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 )
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary There are limited data with levoleucovorin use in pregnant women. Animal reproduction studies have not been conducted with levoleucovorin. Levoleucovorin is administered in combination with methotrexate or fluorouracil, which can cause embryo-fetal harm. Refer to methotrexate or fluorouracil prescribing information for additional information. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
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Therapeutic equivalence (Orange Book)
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