Megaloblastic anemia drug-induced

The resnlts of folic acid measnrements may vary depending on the assay method nsed. Decreased serum folic acid levels indicate a folate deficiency megaloblastic anemia that may coexist with a vitamin B12 deficiency anemia. An erythrocyte folic acid level is less volatile than sernm levels, as it is slow to decrease in an acnte process such as drug-induced folic acid deficiency, and slow to increase with oral folic acid replacement. However, the clinical ntflity of determining the erythrocyte folic acid level is qnestionable, and the procedure should be reserved for cases in which the clinician snspects folic acid depletion and the serum folic acid may be falsely elevated or depleted. 

Several drugs (e.g., sulfasalazine, trimethoprim-sulfamethoxazole, and methotrexate) have been reported to cause a fohc acid deficiency megaloblastic anemia. These drugs either interfere with folate absorption or inhibit the dihydrofolate reductase enzyme necessary for conversion of dihydrofolate to its active tetrahydrofolate form (see Chap. 102, on drug-induced blood dyscrasias). 

The most common drug-induced hematologic disorders in- elude aplastic anemia, agranulocytosis, megaloblastic anemia, thrombocytopenia, and hemolytic anemia. 

When drug-induced megaloblastic anemia is related to chemotherapy, no real therapeutic option is available, and the anemia becomes an accepted side effect of therapy. If drug-induced megaloblastic anemia results from cotrimoxazole, a trial course of folinic acid, 5 to 10 mg up to four times a day, may correct the anemia. Folic acid supplementation of 1 mg every day often corrects the drug-induced megaloblastic anemia produced by either phenytoin or phenobarbital, but some clinicians suggest that supplementation of folic acid may decrease the effectiveness of the antiepileptic medications. ... 

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