Usual Adult Dose for Methotrexate Rescue

Rescue after high dose methotrexate therapy, based on a methotrexate (MTX) dose of 12 grams/m2 IV over 4 hours, depending on methotrexate clearance:

7.5 mg (approximately 5 mg/m2) IV every 6 hours for 10 doses

• Start 24 hours after beginning of methotrexate infusion.

Normal Methotrexate Clearance (serum MTX approximately 10 micromolar 24 hour after administration, 1 micromolar at 48 hours, less than 0.2 micromolar at 72 hours): Follow above dosing

Delayed Methotrexate Clearance (serum MTX above 0.2 micromolar at 72 hours, and more than 0.05 micromolar at 96 hours):
Continue 7.5 mg IV every 6 hours until MTX level is less than 0.05 micromolar

Delayed Early Methotrexate Elimination (serum MTX 50 micromolar or higher at 24 hours, or 5 micromolar or higher at 48 hours)
and/or
Evidence of Acute Renal Injury (100% or greater increase in serum creatinine at 24 hours after MTX administration; e.g. increase from 0.5 mg/dL to 1 mg/dL or above):
75 mg IV every 3 hours until MTX level is less than 1 micromolar; then 7.5 mg IV every 3 hours until MTX level is less than 0.05 micromolar

Comments:

• Measure serum creatinine and methotrexate levels at least once daily.
• Continue levoleucovorin, hydration, and urinary alkalinization (pH of 7.0 or higher) until methotrexate level is below 0.05 micromolar.
• Patients with delayed early methotrexate elimination are likely to develop reversible renal failure; continue hydration and urinary alkalinization, and closely monitor fluid and electrolyte status until MTX is under 0.05 micromolar and renal failure has resolved.
• If significant clinical toxicity is observed, continue levoleucovorin for an additional 24 hours (total of 14 doses over 84 hours) in subsequent courses of therapy.
• Consider that other medications that interact with methotrexate may be being used when laboratory abnormalities or clinical toxicities are seen.
• Delayed methotrexate excretion may be from accumulation in a third space fluid collection (i.e. ascites, pleural effusion), renal insufficiency, or inadequate hydration; higher levoleucovorin doses or prolonged administration may be indicated.
• Although this drug may ameliorate methotrexate's hematologic toxicity, it has no effect on other toxicities such as nephrotoxicity.

Use(s): As a rescue after high dose methotrexate therapy in osteosarcoma

Usual Adult Dose for Methotrexate Overdosage

7.5 mg IV every 6 hours until serum methotrexate is less than 0.01 micromolar

• If serum creatinine increased 50% over baseline, or methotrexate is over 5 micromolar at 24 hours or 0.9 micromolar at 48 hours, increase levoleucovorin dose to 50 mg/m2 IV every 3 hours until methotrexate level is less than 0.01 micromolar

Comments:

• Begin as soon as possible after the overdosage and within 24 hours of methotrexate when there is delayed excretion.
• As the time interval between methotrexate and levoleucovorin administration increases, the effectiveness of levoleucovorin decreases.
• Determine serum creatinine and methotrexate levels at 24 hour intervals.
• Use concomitant hydration (3 L/day) and urinary alkalinization to maintain a pH of 7.0 or greater.

Use(s): Inadvertent methotrexate overdosage

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Precautions

CONTRAINDICATIONS:

• Allergic reactions to folic acid or folinic acid

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• For intravenous administration only.
• Do not give intrathecally.
• Maximum infusion rate is 16 mL per minute.

IV compatibility:

• Do not mix with other agents in the same admixture.