What are the risks of using clarithromycin with statins, such as simvastatin (Zocor) and lovastatin (Mevacor), and how can they be mitigated?

From the Guidelines

Clarithromycin should not be used with simvastatin (Zocor) or lovastatin (Mevacor) due to the high risk of a dangerous drug interaction that can lead to severe muscle damage, as evidenced by recent guidelines 1. This interaction occurs because clarithromycin strongly inhibits the CYP3A4 enzyme that metabolizes these statins, causing their blood levels to rise dramatically, which can result in rhabdomyolysis, a serious condition where muscle breaks down, releasing proteins that can damage the kidneys and potentially lead to kidney failure, as noted in the 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA guideline 1. Some key points to consider when using clarithromycin with statins include:

• The risk of myopathy, including rhabdomyolysis, is increased when clarithromycin is used with statins that are extensively metabolized by CYP3A4, such as lovastatin or simvastatin, as stated in the european position paper on rhinosinusitis and nasal polyps 2020 1.
• To mitigate these risks, several approaches can be taken:
  • Temporarily stop the statin while taking clarithromycin
  • Switch to a different antibiotic if appropriate
  • Use an alternative statin like pravastatin, rosuvastatin, or fluvastatin that are less affected by this interaction
• If clarithromycin must be used, the prescribing physician should be consulted immediately to determine the best course of action, and patients should never stop taking their medications without medical guidance, as both statins and antibiotics serve important therapeutic purposes. It's also important to note that clarithromycin should not be given to patients with a history of QT prolongation or ventricular cardiac arrhythmia, and concomitant administration with certain medications, such as astemizole, cisapride, pimozide, and/or terfenadine, is contraindicated due to the risk of QT prolongation and cardiac arrhythmias, as mentioned in the european position paper on rhinosinusitis and nasal polyps 2020 1.

From the FDA Drug Label

Concomitant administration of clarithromycin with HMG-CoA reductase inhibitors (statins) that are extensively metabolized by CYP3A4 (lovastatin or simvastatin) is contraindicated, due to the increased risk of myopathy, including rhabdomyolysis [see Warnings and Precautions (5.4)and Drug Interactions (7)].

The use of clarithromycin with statins, such as simvastatin (Zocor) and lovastatin (Mevacor), is contraindicated due to the increased risk of myopathy, including rhabdomyolysis. To mitigate this risk, alternative antibiotics or statins that are not extensively metabolized by CYP3A4 should be considered. Key points to consider:

• Concomitant use is contraindicated: Clarithromycin should not be used with lovastatin or simvastatin.
• Increased risk of myopathy: The combination of clarithromycin and these statins increases the risk of myopathy, including rhabdomyolysis.
• Alternative treatments: Consider using alternative antibiotics or statins that are not contraindicated with clarithromycin 2 2.

From the Research

Risks of Using Clarithromycin with Statins

• The use of clarithromycin with statins, such as simvastatin and lovastatin, can increase the risk of rhabdomyolysis and other adverse events 3, 4, 5.
• Clarithromycin is a potent inhibitor of CYP3A4, which can increase the systemic exposure to simvastatin and lovastatin, leading to a higher risk of myopathy and rhabdomyolysis 3, 4.
• The risk of adverse events is higher when clarithromycin is co-administered with CYP3A4-metabolized statins, such as simvastatin, lovastatin, and atorvastatin 3, 6.

Mitigating the Risks

• Avoiding co-administration of clarithromycin with simvastatin, lovastatin, or atorvastatin is recommended 3.
• Withholding or dose-reducing pitavastatin may be necessary when co-administered with clarithromycin 3.
• Continuing pravastatin therapy with caution, limiting the dose to 40 mg daily, may be acceptable when co-administered with clarithromycin 3.
• Continuing fluvastatin or rosuvastatin with caution may be acceptable when co-administered with clarithromycin, as they are less likely to interact with clarithromycin 3, 7.

Special Considerations

• Patients with renal insufficiency or those taking other medications associated with myopathy may be at higher risk of adverse events when co-administered with clarithromycin and statins 4, 6.
• Clinicians should be aware of the potential risks and take steps to minimize them, such as monitoring patients for signs of myopathy or rhabdomyolysis 4, 5.