Digoxin-Simvastatin Interaction
Coadministration of digoxin with simvastatin is reasonable and safe if clinically indicated, but requires monitoring of digoxin levels when simvastatin is initiated, as simvastatin may elevate plasma digoxin concentrations. 1, 2
Key Interaction Mechanism
- Simvastatin can increase digoxin plasma concentrations, requiring vigilance when initiating therapy. 2
- The FDA drug label for simvastatin explicitly states that concomitant use may result in elevated plasma digoxin concentrations and mandates monitoring digoxin levels when simvastatin is initiated. 2
- This interaction differs from atorvastatin, which shows a dose-dependent effect (20% increase in Cmax and 15% increase in AUC at 80 mg, but no effect at 10 mg doses). 1
Clinical Recommendations
- The American Heart Association guidelines state that digoxin coadministration with any statin, including simvastatin, is reasonable if clinically indicated. 1
- Monitor digoxin levels when initiating simvastatin therapy to detect any clinically significant elevation in digoxin concentrations. 2
- Serial monitoring of serum electrolytes (especially potassium and magnesium) and renal function remains mandatory regardless of statin choice, as digoxin can cause arrhythmias particularly with hypokalemia. 1
Target Therapeutic Range
- Maintain digoxin serum concentration at 0.5-0.9 ng/mL (or 0.6-1.2 ng/mL per some guidelines) to minimize toxicity risk while preserving efficacy. 3
- Digoxin concentrations ≥1.2 ng/mL are associated with a 56% increased hazard of mortality and should be avoided. 4
Practical Implementation
- Start with conservative digoxin dosing: 0.125 mg daily (or every other day) in elderly patients (>70 years), those with renal impairment, or low lean body mass. 3
- Use 0.25 mg daily only in younger adults with normal renal function. 3
- Check digoxin level early during chronic therapy after adding simvastatin, but routine serial measurements are not necessary once stable. 3
Critical Safety Considerations
- Absolute contraindications to digoxin include second- or third-degree heart block without permanent pacemaker, pre-excitation syndromes (Wolff-Parkinson-White), and previous digoxin intolerance. 3, 5, 6
- Be aware that multiple other drugs (amiodarone, diltiazem, verapamil, certain antibiotics, quinidine) also increase plasma digoxin levels and require dose reduction by 50% if added to therapy. 3, 5, 6, 2
- Monitor for signs of digoxin toxicity including sinoatrial and AV block, atrial and ventricular arrhythmias (especially with hypokalemia), confusion, nausea, anorexia, and disturbance of color vision. 3
Evidence Quality Note
The guideline evidence is robust and consistent across multiple American Heart Association statements from 2016, with FDA drug labeling corroborating the interaction. 1, 2 The interaction is clinically manageable with appropriate monitoring, distinguishing it from more problematic combinations like simvastatin with dronedarone (which requires limiting simvastatin to 10 mg daily). 1