Source: FDA, National Drug Code (US) Revision Year: 2020
KHAPZORY is indicated for:
KHAPZORY is not indicated for pernicious anemia and megaloblastic anemia secondary to the lack of vitamin B12 because of the risk of progression of neurologic manifestations despite hematologic remission.
KHAPZORY is indicated for intravenous administration only.
Do not administer intrathecally.
The recommended dosage for KHAPZORY is based on a methotrexate dose of 12 grams/m2 administered as intravenous infusion over 4 hours. Twenty-four hours after starting the methotrexate infusion, initiate KHAPZORY at a dose of 7.5 mg (approximately 5 mg/m2) as an intravenous infusion every 6 hours.
Monitor serum creatinine and methotrexate levels at least once daily. Continue KHAPZORY, hydration, and urinary alkalinization (pH of 7 or greater) until the methotrexate level is below 5 × 10-8 M (0.05 micromolar). Adjust the dose KHAPZORY or extend the duration as recommended in Table 1.
Table 1. Recommended Dosage for KHAPZORY based on Serum Methotrexate and Creatinine Levels:
| 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. |
* These patients are likely to develop reversible renal failure. In addition to appropriate KHAPZORY therapy, continue hydration and urinary alkalinization, and monitoring fluid and electrolyte status, until the serum methotrexate level has fallen to below 0.05 micromolar and the renal failure has resolved.
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).
Accumulation in a third space fluid collection (i.e., ascites, pleural effusion), renal insufficiency, or inadequate hydration can delay methotrexate elimination. Under such circumstances, higher doses of KHAPZORY or prolonged administration may be indicated.
Start KHAPZORY as soon as possible after an overdosage of methotrexate or within 24 hours of methotrexate administration when methotrexate elimination is impaired. As the time interval between methotrexate administration and KHAPZORY increases, the effectiveness of KHAPZORY to diminish methotrexate toxicity may decrease. Administer KHAPZORY 7.5 mg (approximately 5 mg/m2) as an intravenous infusion every 6 hours until the serum methotrexate level is less than 5 × 10-8 M (0.05 micromolar).
Monitor serum creatinine and methotrexate levels at least every 24 hours. Increase the dosage of KHAPZORY to 50 mg/m2 intravenously every 3 hours and continue KHAPZORY at this dosage until the methotrexate level is less than 5 × 10-8 M for the following:
Continue concomitant hydration (3 L per day) and urinary alkalinization with sodium bicarbonate. Adjust the bicarbonate dose to maintain urine pH at 7 or greater.
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 to 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.
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 the diluted reconstituted solution for more than 12 hours at room temperature. Protect from light.
Visually inspect the product for particulate matter and discoloration prior to administration. Discard if particulate matter or discoloration is observed.
Store at 20°C to 25°C (68°F to 77°F) in original carton until contents are used. Excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. Protect solutions from light.
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