From the Guidelines
Medications such as methotrexate, sulfasalazine, azathioprine, and 6-mercaptopurine can contribute to macrocytosis, primarily by interfering with folate metabolism or causing myelosuppression, as reported in the most recent study 1. When evaluating macrocytosis, it's essential to review the patient's complete medication list, as drug-induced causes should be considered before pursuing more extensive workup for vitamin B12 or folate deficiencies, liver disease, or myelodysplastic syndromes. Some key medications that can cause macrocytosis include:
- Methotrexate, which inhibits dihydrofolate reductase, an enzyme that catalyzes the reduction of dihydrofolic acid to tetrahydrofolic acid 1
- Sulfasalazine, which can cause folate malabsorption 1
- Azathioprine and 6-mercaptopurine, which can induce macrocytosis through myelosuppressive activity 1 Laboratory evaluation typically reveals an elevated mean corpuscular volume (MCV) greater than 100 fL, and peripheral blood smear may show large, normally hemoglobinized red blood cells. It's crucial to note that folic acid supplementation can help prevent macrocytosis in patients taking certain medications, such as methotrexate, and the ECCO-ESPGHAN guidelines recommend oral administration of folate in patients on methotrexate 1. Additionally, other medications like anticonvulsants, trimethoprim, and certain antibiotics can also contribute to macrocytosis, as mentioned in other studies 1. However, the most recent and highest-quality study 1 provides the most relevant information on medications contributing to macrocytosis.
From the FDA Drug Label
Macrocytosis was reported in the majority of pediatric subjects receiving zidovudine 180 mg per m2 every 6 hours in open-label trials.
Zidovudine can contribute to macrocytosis, as it was reported in the majority of pediatric subjects receiving the medication in open-label trials 2.
From the Research
Medications Contributing to Macrocytosis
- Macrocytosis, a condition characterized by larger than normal red blood cells, can be caused by various medications, including:
- Methotrexate, a drug used to treat rheumatoid arthritis, as evidenced by a study published in the Journal of rheumatic diseases 3
- Zidovudine, an antiretroviral medication used to treat HIV infection, as shown in a study published in AIDS patient care and STDs 4
- Stavudine, another antiretroviral medication, as mentioned in the same study 4
- These medications can cause macrocytosis by interfering with DNA synthesis or folate metabolism, leading to the production of abnormally large red blood cells
- The occurrence of macrocytosis can be used as a marker to assess medication adherence, as seen in the case of zidovudine 4
- Macrocytosis can also be a predictor of hematologic toxicity due to methotrexate therapy, as demonstrated in a study published in Arthritis and rheumatism 5
Mechanisms and Associations
- The mechanisms by which these medications contribute to macrocytosis are complex and involve the inhibition of DNA synthesis or the depletion of folate, a crucial nutrient for red blood cell production
- Macrocytosis can be associated with other conditions, such as myelodysplastic syndrome, liver dysfunction, and hypothyroidism, as discussed in a review published in the Journal of general and family medicine 6
- The diagnosis and treatment of macrocytic anemias, including those caused by medications, require a comprehensive approach that takes into account the underlying cause and the patient's overall health status 6