Calcium Leucovorin is the calcium salt of leucovorin (folinic acid), a reduced form of folic acid. It is a crucial antidote for folic acid antagonists like methotrexate and pyrimethamine, and a chemoprotectant/modulator in oncology. It serves as a source of active folate, bypassing the dihydrofolate reductase (DHFR) enzyme blockade, allowing for the synthesis of thymidylate and purines essential for DNA/RNA synthesis. In India, it is a critical drug in oncology, hematology, and toxicology protocols.
Adult: **Highly variable.** Methotrexate Rescue: Typically 15 mg (approx. 10 mg/m2) IV/IM/PO every 6 hours starting 24 hours after methotrexate infusion, continued until methotrexate level <0.05 micromolar. Dosing guided by methotrexate levels and creatinine. **Colorectal Cancer with 5-FU:** Various regimens, e.g., 200 mg/m2 IV over 2 min followed by 5-FU bolus, or 20 mg/m2 IV before 5-FU. **Folate Antagonist Overdose:** 10 mg/m2 IV/IM/PO, then 10 mg/m2 orally every 6 hours.
Note: **Oral:** Can be taken without regard to meals, but food may decrease bioavailability. Tablets can be crushed. **IV:** Can be administered as a slow IV push (over 1-3 min for rescue doses) or as a short infusion (over 10-15 min for high doses with 5-FU). **IM:** Deep intramuscular injection. **DO NOT ADMINISTER INTRATHECALLY.** For methotrexate rescue, timing relative to methotrexate dose is critical.
Leucovorin is a 5-formyl derivative of tetrahydrofolic acid (THF). It is readily converted intracellularly to other reduced folate cofactors, including 5,10-methylenetetrahydrofolate. This bypasses the metabolic block induced by dihydrofolate reductase (DHFR) inhibitors like methotrexate. By providing a source of reduced folates, it 'rescues' normal cells from the toxic effects of these antagonists, allowing for continued synthesis of thymidylate, purines, and ultimately DNA/RNA.
Pregnancy: US FDA Category C. Animal studies are inconclusive. Use only if clearly needed, such as in methotrexate rescue for maternal malignancy. Benefits must outweigh risks.
Driving: Unlikely to affect ability. However, fatigue or other side effects of concomitant chemotherapy may impair reactions.
| Methotrexate | Leucovorin rescues normal cells from methotrexate toxicity. However, if given concurrently or too early, it can interfere with methotrexate's antitumor efficacy. | Major |
| Fluorouracil (5-FU) | Leucovorin potentiates the cytotoxicity and toxicity (e.g., diarrhea, stomatitis, myelosuppression) of 5-FU by stabilizing its active complex. | Major |
| Phenytoin, Phenobarbital, Primidone | Anticonvulsants may reduce serum folate levels. Leucovorin may decrease serum levels of these anticonvulsants, potentially leading to increased seizure frequency. Monitor levels closely. | Moderate |
| Sulfamethoxazole-Trimethoprim (Co-trimoxazole) | Trimethoprim is a DHFR inhibitor. Leucovorin may counteract its antibacterial effect in certain infections (e.g., Pneumocystis jirovecii pneumonia). | Moderate |
| Pyrimethamine | Leucovorin is used to counteract its hematologic toxicity in toxoplasmosis treatment without impairing its antiparasitic effect at appropriate doses. | Moderate |
Same composition (Calcium Leucovorin (50mg)), different brands: