Megaloblastosis may be caused by drugs. In most cases discontinuation of the offending drug reverses the changes in the erythrocytes.


Causes of megaloblastosis due to drugs:

(1) interference with vitamin B12 absorption or metabolism

(2) interference with folate absorption or metabolism

(3) acute interference with DNA synthesis

(4) chemotherapy-induced myelodysplasia


Drugs interfering with vitamin B12 (cobalamin) absorption include:

(1) neomycin

(2) metformin or other biguanides

(3) omeprazole or other proton pump inhibitors (PPI)


Chemicals interfering with vitamin B12 metabolism:

(1) nitrous oxide


Drugs interfering with folate absorption or metabolism include:

(1) phenyotin

(2) methotrexate

(3) trimethoprim and trimethroprim-sulfamethoxazole

(4) sulfasalazine

(5) triamterene

(6) pyrimethamine

(7) cholestyramine


Drugs interfering acutely with DNA synthesis:

(1) hydroxyurea

(2) methotrexate

(3) zidovudine

(4) azathioprine

(5) cladribine, fludarabine or other purine nucleoside analogs

(6) chemotherapeutic agents


Drugs causing myelodysplasia:

(1) alkylating agents or other chemotherapeutic agents with or without radiation


Differential diagnosis:

(1) myelodysplastic syndrome not due to medications

(2) alcohol abuse

(3) other causes of vitamin B12 or folate deficiency


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