Folinic acid, also known as leucovorin, is a medication used to decrease the toxic effects of methotrexate and pyrimethamine. It is also used in combination with 5-fluorouracil to treat colorectal cancer, may be used to treat folate deficiency that results in anemia, and methanol poisoning. It is taken by mouth, injection into a muscle, or injection into a vein. Folinic acid, also known as leucovorin, is a medication used to decrease the toxic effects of methotrexate and pyrimethamine. It is also used in combination with 5-fluorouracil to treat colorectal cancer, may be used to treat folate deficiency that results in anemia, and methanol poisoning. It is taken by mouth, injection into a muscle, or injection into a vein. Side effects may include trouble sleeping, allergic reactions, or fever. Use in pregnancy or breastfeeding is generally regarded as safe. When used for anemia it is recommended that pernicious anemia as a cause be ruled out first. Folinic acid is a form of folic acid that does not require activation by dihydrofolate reductase to be useful to the body. Folinic acid was first made in 1945. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. In the United Kingdom it costs the NHS about 4.62 pounds per 30 mg vial. Folinic acid is given following methotrexate as part of a total chemotherapeutic plan, where it may protect against bone marrow suppression or gastrointestinal mucosa inflammation. No apparent effect is seen on pre-existing methotrexate-induced nephrotoxicity. Folinic acid can be taken as a pill (orally) or injected into a vein (intravenously) or muscle (intramuscularly). While not specifically an antidote for methotrexate, folinic acid may also be useful in the treatment of acute methotrexate overdose. Different dosing protocols are used, but folinic acid should be redosed until the methotrexate level is less than 5 x 10−8 M. Additionally, folinic acid is sometimes used to reduce the side effects of methotrexate in rheumatoid arthritis patients. This includes reductions in nausea, abdominal pain, abnormal liver blood tests, and mouth sores. Folinic acid is also used in combination with the chemotherapy agent 5-fluorouracil in treating colon cancer. In this case, folinic acid is not used for 'rescue' purposes; rather, it enhances the effect of 5-fluorouracil by inhibiting thymidylate synthase. Folinic acid is also sometimes used to prevent toxic effects of high doses of antimicrobial dihydrofolate reductase inhibitors such as trimethoprim and pyrimethamine. It may be prescribed in the treatment of toxoplasmosis retinitis, in combination with the folic acid antagonists pyrimethamine and sulfadiazine. Folinic acid is also used in the treatment of cerebral folate deficiency, a syndrome in which the use of folic acid cannot normalize cerebrospinal fluid levels of 5-MTHF.