Pyrimethamine megaloblastic anemia with

Folic acid deficiency can be caused by drugs. Methotrexate and, to a lesser extent, trimethoprim and pyrimethamine, inhibit dihydrofolate reductase and may result in a deficiency of folate cofactors and ultimately in megaloblastic anemia. Long-term therapy with phenytoin can also cause folate deficiency, but only rarely causes megaloblastic anemia. 

With the combination of pyrimethamine plus trimethoprim the risk of megaloblastic anemia is higher than with pjrimethamine alone, which on theoretical grounds might be expected. Concomitant administration of folic acid has been recommended (SEDA-11, 590), but the effect of folic acid on efficacy is not known. 

Although the hematological complications of pyrimethamine are generally a consequence of therapeutic use, long-term prophylactic treatment with pyrimethamine and dapsone in malaria could well involve an increased risk of megaloblastic anemia in patients whose nutritional state is not optimal (SEDA-13, 812). 

Pyrimethamine (Daraprim) 25-mg tablet Malaria (see pyrimethamine-sulfadoxime) Gl Abdominal pain, vomiting, glossitis Hemat. Megaloblastic anemia, hemolytic anemia Recommended that folinic acid 1-5 mg/day be concurrently administered can cause hemolysis in patients with GbPO deficiency 9, 24, 25... 

Antimalarial doses of pyrimethamine alone cause little toxicity except occasional rashes and depression of hematopoiesis. Excessive doses produce a megaloblastic anemia that responds to drug withdrawal or treatment with folinic acid. At high doses, pyrimethamine is teratogenic in animals, and in humans, trimethoprim-sulfamethoxazole therapy is associated with birth defects, but such toxicity has not been studied systematically for pyrimethamine in humans. 

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