What are the recommended dosages of vitamin D and vitamin K supplements for patients taking rifampin?

Vitamin D and K Supplementation During Rifampin Therapy

Patients taking rifampin should receive vitamin D supplementation of 800-2000 IU daily and vitamin K supplementation of 1-10 mg weekly to prevent deficiency-related complications, as rifampin accelerates the metabolism of both vitamins through hepatic enzyme induction.

Vitamin D Supplementation with Rifampin

Mechanism and Rationale

• Rifampin is a potent inducer of CYP3A4, which provides an alternative pathway for vitamin D inactivation, leading to accelerated metabolism and clearance of vitamin D metabolites 1
• This enzyme induction can significantly lower serum 25-hydroxyvitamin D levels, potentially causing deficiency even in patients with adequate baseline stores 1

Recommended Dosing

• Standard supplementation: 800-2000 IU daily is recommended for patients on rifampin therapy 2
• For patients with documented vitamin D deficiency at baseline, higher repletion doses may be needed: a cumulative dose of at least 600,000 IU administered over several weeks (not as a single dose) to replenish stores 3
• Avoid single large doses of 300,000-500,000 IU, as these have been associated with adverse outcomes 2
• Target serum 25(OH)D level: 30-50 ng/mL during rifampin therapy 2

Monitoring

• Measure baseline 25-hydroxyvitamin D levels before starting rifampin 2
• Recheck levels 2-3 months after initiating rifampin therapy to assess adequacy of supplementation
• Vitamin D3 (cholecalciferol) is preferred over D2 (ergocalciferol) for supplementation 2

Vitamin K Supplementation with Rifampin

Mechanism and Rationale

• Rifampin inhibits vitamin K epoxide reductase, interfering with the recycling and reuse of vitamin K, which can lead to severe coagulopathy 4
• This effect is dose-dependent and duration-dependent, with prolongation of prothrombin time observed in experimental models 4
• Severe vitamin K deficiency coagulopathy has been documented in children and adults on rifampin, manifesting as hemorrhagic complications including cerebral hemorrhage 5, 6

Recommended Dosing

• Prophylactic vitamin K: 1-10 mg orally once weekly during rifampin therapy 5, 4
• For patients with documented coagulopathy (elevated INR/PT): immediate administration of vitamin K 10 mg IV/PO plus fresh frozen plasma if actively bleeding 5
• Pyridoxine (vitamin B6) 50 mg daily should also be given when rifampin is used with isoniazid to prevent peripheral neuropathy 2

Monitoring

• Check baseline prothrombin time (PT/INR) before starting rifampin
• Monitor PT/INR monthly during rifampin therapy, or more frequently if the patient has risk factors for bleeding
• Watch for clinical signs of coagulopathy: easy bruising, ecchymoses, mucosal bleeding 5

Special Populations

Patients with Malabsorption

• Patients with small intestinal dysfunction or those on total enteral nutrition are at particularly high risk for vitamin K deficiency on rifampin 4
• Consider higher vitamin K doses (10 mg weekly) and more frequent monitoring in these patients 4

Pregnant Women

• Rifampin is considered safe in pregnancy, but vitamin supplementation becomes even more critical 2
• Continue both vitamin D (800-2000 IU daily) and vitamin K (5-10 mg weekly) supplementation throughout pregnancy 2

Children

• Infants and young children may be at higher risk due to immature vitamin K metabolism and absorption 6
• Use weight-based dosing for vitamin K (0.1-0.3 mg/kg weekly, maximum 10 mg) 6

Common Pitfalls to Avoid

• Do not assume dietary intake is sufficient during rifampin therapy—the accelerated metabolism overcomes normal dietary sources 4, 1
• Do not give single massive doses of vitamin D (>300,000 IU at once)—use divided dosing over weeks 3
• Do not wait for symptoms to develop before supplementing—prophylactic supplementation is essential as severe coagulopathy can occur suddenly 5
• Do not forget pyridoxine when rifampin is combined with isoniazid 2