Medication-Induced Macrocytosis

Introduction to Medication-Induced Macrocytosis

Medications such as azathioprine, 6-mercaptopurine, methotrexate, phenytoin, valproate, zidovudine, and other immunosuppressive agents can cause macrocytosis, as recommended by the European Crohn’s and Colitis Organisation and the American College of Clinical Pharmacy 1, 2, 3
Thiopurine users, including those on azathioprine and 6-mercaptopurine, may exhibit macrocytosis as an early sign of bone marrow toxicity, according to the American Gastroenterological Association and the European Crohn’s and Colitis Organisation 1

Azathioprine and 6-mercaptopurine cause bone marrow suppression, affecting bone marrow function in patients, as stated by the European Crohn’s and Colitis Organisation 1
Methotrexate inhibits dihydrofolate reductase, preventing conversion of dihydrofolic acid to tetrahydrofolic acid, leading to macrocytosis in patients on this medication 2, 3
Sulfasalazine causes folate malabsorption, resulting in macrocytosis in patients taking this drug 2, 3
Hydroxyurea affects DNA synthesis and can contribute to macrocytosis in patients, as noted by the American Academy of Dermatology 4

Macrocytosis from medications may occur with or without anemia in patients, as noted by the American College of Clinical Pharmacy 1
Regular CBC monitoring is necessary for patients on medications that can cause macrocytosis, such as methotrexate, hydroxyurea, and azathioprine, to detect early signs of bone marrow toxicity 2, 3, 4

For patients on methotrexate, the American College of Clinical Nutrition recommends regular CBC monitoring and considers folate supplementation (5 mg once weekly 24-72 hours after methotrexate, or 1 mg daily for 5 days per week) to prevent macrocytosis 2, 3
For patients on sulfasalazine, monitoring for folate deficiency and supplementation with either folic or folinic acid may be needed to mitigate macrocytosis 2
The American Academy of Dermatology suggests that for patients on hydroxyurea, regular monitoring of CBC is necessary due to the risk of macrocytosis 4