Calcium Leucovorin is the calcium salt of leucovorin, a reduced form of folic acid (folinic acid). It is a biologically active metabolite that bypasses the inhibition of dihydrofolate reductase, making it a critical antidote for folic acid antagonists like methotrexate and a chemoprotectant/modulator in fluorouracil (5-FU) based chemotherapy. It is also used to treat megaloblastic anemias due to folate deficiency when folic acid is not suitable.
Adult: **Methotrexate Rescue:** Dose, route, and duration are based on serum methotrexate levels. A common regimen: 15 mg (approx. 10 mg/m²) IV/IM/orally every 6 hours until methotrexate level is <0.05 micromolar. **5-FU Modulation (e.g., de Gramont regimen):** 200 mg/m² IV infusion over 2 hours, followed by 5-FU bolus and infusion. **Megaloblastic Anemia:** Up to 1 mg daily; 15mg dose is not typical for this indication.
Note: **Oral:** Can be taken without regard to meals. **Parenteral:** For IV use, can be administered as a slow IV push (not exceeding 160 mg/min) or diluted in infusion fluids (e.g., 5% Dextrose, 0.9% Sodium Chloride). For IM use, inject into a large muscle mass. The 15mg tablet is often used for oral rescue after initial IV/IM loading in methotrexate therapy.
Leucovorin is a 5-formyl derivative of tetrahydrofolic acid. It does not require reduction by dihydrofolate reductase (DHFR) to become metabolically active. It serves as a ready source of reduced folate cofactors (e.g., 5,10-methylenetetrahydrofolate) which are essential for the synthesis of purines, thymidylate, and amino acids. In methotrexate rescue, it replenishes the folate pools depleted by DHFR inhibition. In combination with 5-FU, it stabilizes the binding of fluorodeoxyuridine monophosphate (FdUMP) to thymidylate synthase, enhancing the cytotoxic effect of 5-FU.
Pregnancy: **Category C.** Animal reproduction studies have not been conducted. Leucovorin is used in pregnant women as part of cancer chemotherapy regimens when clearly needed. Benefits should outweigh risks.
Driving: Unlikely to affect the ability to drive or use machines. However, patients should be cautioned about potential side effects like dizziness or fatigue.
| Fluorouracil (5-FU) | Leucovorin potentiates the toxicity and antitumor activity of 5-FU. The combination is standard but requires careful monitoring for severe gastrointestinal (diarrhea, mucositis) and hematologic toxicity. | Major |
| Phenytoin, Phenobarbital, Primidone | Leucovorin may decrease serum levels and anticonvulsant efficacy of these drugs, potentially leading to increased seizure frequency. | Moderate |
| Sulfamethoxazole-Trimethoprim (Co-trimoxazole) | Leucovorin may antagonize the antibacterial effect in certain organisms (e.g., *Pneumocystis jirovecii*), but is used to reduce hematologic toxicity. | Moderate |
| Methotrexate | Leucovorin is the antidote. Timing is critical. Administration too early can interfere with methotrexate's antitumor effect. Dosing is based on methotrexate serum levels. | Critical |
Same composition (Calcium Leucovorin (15mg)), different brands: