The Potential Drug Interactions
The combination of simvastatin and gemfibrozil, both medications the patient was taking at the time of his presentation, can lead to rhabdomyolysis. Simvastatin combined with clarithromycinalso presents a potential for this potentially serious adverse event. Rhabdomyolysis rarely occurs as a result of administration of a statin only; this complication is almost always seen in patients taking multiple drugs that can interact with a statin and increase the potential for this life-threatening adverse event.
There are several drugs[2] that increase the risk for statin toxicity, including rhabdomyolysis:Fibrates: Interactions between statins and drugs in the fibrate class occur much more frequently with gemfibrozil than with fenofibrate.[3] However, even with gemfibrozil, less than 1% of patients on the combination of gemfibrozil and a statin drug will experience rhabdomyolysis.
Azole antifungals: All drugs in this class are known to increase the potential for statin toxicity.
Amiodarone: An interaction with this drug is more likely with simvastatin and lovastatin.
Macrolide antibiotics: This effect is most pronounced with erythromycin and clarithromycin. The other drug in this antibiotic class, azithromycin, is not known to increase risk for statin toxicity.
Protease inhibitors: Protease inhibitors, especially ritonavir, have an important effect.
Protease inhibitors: Protease inhibitors, especially ritonavir, have an important effect.
Calcium-channel blockers: Verapamil and diltiazem have significant interactions with statins. Amlodipine and nifedipine, although still presenting some risk, are less likely than the other drugs in this class to cause statin toxicity.
Which statins are the least likely to cause interactions with other drugs? The fewest drug interactions occur with pravastatin because it is metabolized differently from the other statins, which are metabolized by the CYP3A4 isoenzyme.[2] The most interactions are found with simvastatin and lovastatin.If use of a drug with a potential interaction with a statin is unavoidable, nonconcurrent dosing can help to minimize interactions. Giving the drug doses, if possible, 12 hours apart will prevent the possibility of peak drug levels of the 2 agents occurring at the same time.
It should also be noted that amlodipine, a drug also taken by this patient, when combined with clarithromycin creates an increased risk for hypotension and acute renal injury -- providing yet another reason to avoid this antibiotic.