Leucovorin

🔴 RED FLAG (IMPORTANT) INFORMATION

(Most critical safety points)

• Must NOT be used alone to treat pernicious anaemia or vitamin B12 deficiency — blood counts may improve while irreversible neurological damage progresses.

• Markedly increases toxicity of 5-fluorouracil (5-FU) — 5-FU dose reduction is mandatory. Do NOT start or continue leucovorin/5-FU if any gastrointestinal toxicity is present. Fatal diarrhoea, enterocolitis and dehydration have been reported, especially in elderly patients.

• Can reduce the antineoplastic effect of intrathecal methotrexate if given concurrently.

• High-dose methotrexate rescue requires specialist supervision with close monitoring of methotrexate levels and renal function.

• Renal impairment or pleural/peritoneal effusions may delay methotrexate elimination, increasing toxicity risk.

• May reduce seizure control by lowering blood levels of certain anticonvulsants (barbiturates, hydantoins, primidone).

• Avoid benzyl-alcohol–containing diluents in premature and newborn infants.

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1. BASIC INFORMATION

• Generic name: Leucovorin (calcium leucovorin)

• Brand name: Leucovorin ABIC®

• Pharmacological class: Erythopoietics (Haematinics)

• Formulation: Solution for injection

• Strengths:

  • 100 mg / 10 mL

  • 200 mg / 20 mL

  • 300 mg / 30 mL
    (10 mg/mL)

• Scheduling status: S1

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2. INDICATIONS

• Calcium leucovorin rescue to reduce toxicity and counteract folic acid antagonists such as methotrexate during cytotoxic therapy

• Megaloblastic anaemias due to folate deficiency, where vitamin B12 deficiency has been excluded

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3. DOSING & ADMINISTRATION

Megaloblastic anaemia (folate deficiency)

• 1–15 mg daily, intramuscularly

Methotrexate rescue

• Dose based on plasma methotrexate concentration

• Typical regimens include:

  • 10–15 mg/m² every 6 hours for 48–72 hours, or

  • Higher doses (30–100 mg/m²) when methotrexate levels are elevated

• In some regimens:

  • Up to 120 mg divided over 12–24 hours, followed by

  • 12–15 mg IM or 15 mg orally every 6 hours for 48 hours

• Leucovorin must be started after methotrexate, usually within 36–42 hours

Routes

• Intramuscular

• Intravenous bolus or infusion (e.g. diluted in normal saline)

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4. DOSE MODIFICATIONS

• Increase dose and/or duration if:

  • Methotrexate levels remain elevated

  • Renal function deteriorates

• Continue until methotrexate concentration falls to safe levels

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5. CO-MEDICATIONS

Important interactions

• 5-Fluorouracil: significantly increased gastrointestinal and systemic toxicity

• Anticonvulsants: reduced effectiveness with possible increase in seizure frequency

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6. CONTRAINDICATIONS

• Hypersensitivity to leucovorin

• Pernicious anaemia or other megaloblastic anaemias caused by vitamin B12 deficiency

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7. MONITORING REQUIREMENTS

During methotrexate rescue

• Plasma methotrexate levels

• Serum creatinine and renal function

• Clinical signs of methotrexate toxicity

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8. SIDE EFFECTS

• Hypersensitivity reactions:

  • Fever

  • Rash

  • Urticaria

  • Pruritus

  • Wheezing

• Thrombocytosis (reported with intra-arterial methotrexate and leucovorin)

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9. DRUG INTERACTIONS

• 5-Fluorouracil: enhanced toxicity

• Anticonvulsants: reduced seizure control

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10. USE IN SPECIAL POPULATIONS

• Renal impairment: use with caution

• Pleural or peritoneal effusions: increased risk of delayed methotrexate elimination

• Neonates and premature infants: avoid benzyl-alcohol–containing diluents

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11. DURATION OF USE / WHEN TO STOP

• Duration depends on methotrexate levels and renal function

• Continue until methotrexate has been adequately cleared

• Discontinue if serious hypersensitivity occurs

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12. TOXICITY MANAGEMENT (SIMPLIFIED)

• Methotrexate toxicity: increase leucovorin dose and extend duration

• Hypersensitivity reactions: supportive and symptomatic treatment

• Overdose: supportive care

 

https://pi-pil-repository.sahpra.org.za/wp-content/uploads/2024/10/Leucovorin-Abic-PI.pdf