Page 631 - Williams Hematology ( PDFDrive )

606 Part VI: The Erythrocyte Chapter 41: Folate, Cobalamin, and Megaloblastic Anemias 607

TABLE 41–5. Drugs That Cause Megaloblastic Anemia
Agents Comments Reference
ANTIFOLATES
Methotrexate Very potent inhibitor of dihydrofolate reductase 425
Aminopterin Treat overdose with folinic acid 380
Pyrimethamine Much weaker than methotrexate and aminopterin
Trimethoprim Treat with folinic acid or by withdrawing the drug 426, 427
Sulfasalazine Can cause acute megaloblastic anemia in susceptible patients, especially those with 428
low folate stores
Chlorguanide (Proguanil) 429
Triamterene Use of folate and cobalamin during pemetrexed treatment reduces toxicity
Pemetrexed (Alimta) 430
PURINE ANALOGUES
6-Mercaptopurine Megaloblastosis precedes hypoplasia, usually mild 431
6-Thioguanine Responds to folinic acid but not folate 432
Azathioprine 433
Acyclovir Megaloblastosis at high doses 434
PYRIMIDINE ANALOGUES
5-Fluorouracil Mild megaloblastosis 435
Floxuridine (5-fluorodeoxyuridine) 435
6-Azauridine Blocks uridine monophosphate production by inhibiting orotidylic decarboxylase; 436
occasional megaloblastosis with orotic acid and orotidine in urine
Zidovudine (AZT) Severe megaloblastic anemia is the major side effect 383
RIBONUCLEOTIDE REDUCTASE INHIBITORS
Hydroxyurea Marked megaloblastosis within 1–2 days of starting therapy; quickly reversed by 437
withdrawing drug
Cytarabine (cytosine arabinoside) Early megaloblastosis is routine 438
ANTICONVULSANTS
Phenytoin (diphenylhydantoin) Occasional megaloblastosis, associated with low folate levels; responds to high-dose 439–441
folate (1–5 mg/day); how anticonvulsants cause low folate is not understood, but
may be related to a drug-induced rise in cytochrome P450
Phenobarbital 439
Primidone 439
Carbamazepine 442
OTHER DRUGS THAT DEPRESS FOLATES
Oral contraceptives Occasional megaloblastosis; sometimes dysplasia of uterine cervix, corrected with 443
folate
Glutethimide
Cycloserine
H /K -ATPASE INHIBITORS
+
+
Omeprazole Long-term use causes decreased serum cobalamin levels 386
Lansoprazole
MISCELLANEOUS
N O See “Acute Megaloblastic Anemia” in text 368
2
p-Aminosalicylic acid Causes cobalamin malabsorption with occasional mild megaloblastic anemia 444
Metformin 445
Phenformin Causes cobalamin malabsorption but not anemia
Colchicine 446
Neomycin 447
Arsenic Causes myelodysplastic hematopoiesis, sometimes with megaloblastic changes 448

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