DAV and Simvastatin
Diltiazem, Amlodipine and Verapamil (DAV) and their interactions with Simvastatin
Today I would like to share a tiny bit of information on Diltiazem, Amlodipine and Verapamil (DAV) and their interactions with Simvastatin.
The use of statin may induce myopathy as one of its side effects. High dose of Simvastatin (>80mg) has been associated with increased risk of myopathy.
One may experience muscle-related symptoms such as fatigue, muscle pain or weakness, cramps and it may be aggravated by physical exertion.
Simvastatin is metabolized by CYP3A4 enzyme in the body. The DAVs are all CYP3A4 enzyme inhibitors. Concomitant use of the drugs may lead to increased plasma concentration of Simvastatin, which in turn, increases the risk of myopathy.
Findings from multiple studies has shown that the coadministration of Amlodipine 10mg and Simvastatin has the potential to increase the plasma concentration of Simvastatin by approximately 2-fold.
On the other hand, diltazem may increase simvastatin exposure up to 3-fold.
So what can recommendations can be done?
1. Limit the maximum daily dose of Simvastatin to 20mg, if use concurrently with Amlodipine.
(The exposure to Simvastatin will be similar to taking Simvastatin 40mg)
2. Switching to alternative statins such as Pravastatin or Rosuvastatin
3. Maintain current dose of there is no sign and symptoms of adverse reaction, but discuss with patients regarding the possible risk that they might be facing.
References:
1. Sivakumar S., et al. (2008). Statin induced myopathy, British Medical Journal, 337(a2286).
2. Barbara S. W., et al. (2016). Recommendations for Management of Clinically Significant Drug-Drug Interactions With Statins and Select Agents Used in Patients With Cardiovascular Disease: A Scientific Statement From the American Heart Association, Circulation,134:e468–e495.
3. Medicines and Healthcare Products Regulatory Agency. (2012). Simvastatin: dose limitations with concomitant amlodipine or diltiazem, Drug Safety Update October 2012, vol 6(3): H1.