What medications can cause folic acid deficiency?

Medications That Cause Folic Acid Deficiency

Several medications can cause folic acid deficiency by various mechanisms including impaired absorption, increased metabolism, or direct antagonism of folate metabolism. Understanding these medications is crucial for preventing deficiency-related complications such as megaloblastic anemia and neurological symptoms.

Common Medications That Cause Folic Acid Deficiency

Antifolate Medications

• Trimethoprim/Sulfamethoxazole (TMP-SMX): Directly interferes with folate metabolism by inhibiting dihydrofolate reductase, an enzyme that converts dihydrofolic acid to tetrahydrofolic acid (the active form of folate) 1, 2
• Methotrexate: Potent inhibitor of dihydrofolate reductase, commonly used in rheumatologic conditions and psoriasis 1, 3
• Pyrimethamine: Antimalarial that inhibits dihydrofolate reductase 3
• Triamterene: Potassium-sparing diuretic that can act as a folate antagonist 3

Anticonvulsants

• Phenytoin: Causes folate deficiency through multiple mechanisms including impaired absorption and altered metabolism 4
• Phenobarbital: May interfere with folate absorption and metabolism 1, 3
• Carbamazepine: Associated with reduced folate levels 3

Anti-inflammatory Drugs

• Sulfasalazine: Impairs folate absorption and metabolism, particularly important in patients with inflammatory bowel disease or rheumatoid arthritis 1, 5, 6

Other Medications

• Oral contraceptives: May reduce folate levels through uncertain mechanisms 3
• Cholestyramine: Bile acid sequestrant that can bind to folate and reduce its absorption 1
• Colestipol: Similar to cholestyramine, may interfere with folate absorption 1

Risk Factors for Medication-Induced Folate Deficiency

• Elderly patients: More susceptible to folate deficiency due to age-related changes in absorption 2
• Malnutrition: Inadequate dietary intake compounds medication effects 2
• Malabsorption syndromes: Further impair folate absorption 2
• Chronic alcoholism: Alcohol itself can contribute to folate deficiency 2
• Pregnancy: Increased folate requirements 2

Clinical Implications and Management

• Monitor for deficiency: Patients on high-risk medications should be monitored for signs of folate deficiency including macrocytic anemia, fatigue, and neurological symptoms 1
• Prophylactic supplementation: Consider prophylactic folic acid supplementation for patients on methotrexate (1-5 mg daily) 1 and sulfasalazine 1
• Treatment dosing: For established folate deficiency, treatment with oral folic acid 5 mg daily for a minimum of 4 months is recommended 1
• Caution with B12 deficiency: Always check and treat vitamin B12 deficiency before initiating folate supplementation to avoid precipitating subacute combined degeneration of the spinal cord 1

Special Considerations

• Trimethoprim: FDA labeling specifically lists "documented megaloblastic anemia caused by folate deficiency" as a contraindication 2
• Bariatric surgery patients: Those on medications like methotrexate, sulfasalazine, or anticonvulsants require special attention to folate status 1
• Inflammatory bowel disease: Patients on sulfasalazine should receive prophylactic folic acid supplementation 1
• Drug interactions: When administering folate supplements, be aware of potential interactions with anticonvulsants and other medications 4

By recognizing medications that cause folate deficiency and implementing appropriate monitoring and supplementation strategies, clinicians can prevent the potentially serious consequences of folate deficiency in at-risk patients.