RD, a 64-year old female was recently diagnosed with methicillin-resistant Staphylococcus aureus while post-op for a right hip arthroplasty. The patient underwent debridement for the infection and has retained hardware. The physician has decided to order rifampin in combination with vancomycin to definitively treat the infection. RD’s laboratory findings and vitals are listed below:

Outpatient medications:

Warfarin 7.5 mg PO daily

Metoprolol 100 mg XL PO daily

Labs/Vitals:

Ht: 5’4 ft

Wt: 125 lbs

BP: 140/83 mmHg

HR: 83 BPM

Temp: 101.2 F

Glucose: 95 mg/dL (70-130 mg/dL)

Scr: 1.1 mg/dL (0.5-1.2 mg/dL)

Na: 144 mEq/L (135-145 mEq/L)

Cl: 98 mEq/L (95-105 mEq/L)

K: 3.7 mEq/L (3.5-5 mEq/L)

Ca: 9.6 mg/dL (8.5-10.5 mg/dL)

Mg: 2.1 mg/dL (1.7-2.2 mg/dL)

Overall, what effect can we expect rifampin to have on warfarin? Select all that apply. 

A. Increased anticoagulation effect

B. Decreased anticoagulation effect

C. Increased INR

D. Decreased INR

E. No effect on INR

Answer with rationale:

Rifampin is an effective antibiotic that can be used to treat infections such as tuberculosis, methicillin-resistant Staphylococcus aureus (MRSA), and is especially helpful for infections such as osteomyelitis involving retained hardware. Due to the potential resistance that can occur from monotherapy use, rifampin should only be initiated in combination with additional antibiotics. Rifampin can have significant effects on the metabolism of many medications including warfarin, specifically by inducing cytochrome P450 enzymes, including CYP2C9. CYP2C9 is the enzyme responsible for metabolizing the more potent S-warfarin isomer.

Answer A is incorrect. Rifampin speeds up the metabolism of warfarin resulting in a reduced concentration of warfarin. This causes a decreased anticoagulation effect and places the patient at a higher risk for developing a thrombus.

Answer B is correct. Rifampin does not enhance the blood-thinning effects of warfarin but promotes a quicker breaker down of the drug. Rifampin may decrease the effectiveness of warfarin and increase the chance of clot formation due to insufficient anticoagulation. Patients on warfarin and rifampin often need their warfarin dosage increased.

Answer C is incorrect. Rifampin may cause an increased clearance of warfarin from the body. This results in a decreased anticoagulation effect and thus decreases INR levels.

Answer D is correct. Rifampin is a strong inducer of CYP2C9- the enzyme responsible for metabolizing warfarin. This would cause a decrease in warfarin's effect and therefore decrease the INR, not increase it. 

Answer E is incorrect. See rationale in answers C and D. 

Brand/generics Covered: Rifadin (Rifampin), Vancocin (Vancomycin), Coumadin (Warfarin), Metoprolol succinate (Toprol XL)

Naplex Competencies Covered:

1. A. 2 – Pharmacokinetics, pharmacodynamics, or pharmacogenomics
2. A – Medication history, allergy history, and reconciliation
3. A. 3 – Interactions
4. D – Therapeutic monitoring, plan development, evaluation, and modifications