Statins and its Life Threatening Drug Interactions




  •  weigh risk/benefit when giving simvastatin with amiodarone as it increases the toxicity of this statin by decreasing metabolism and thus increasing the risks for myopathy and rhabdomyolysis. Use alternatives when possible and do not administer simvastatin more than 20mg/day.

Cardiac glycoside:

  • Digoxin: digoxin levels need to be monitored very closely with atorvastatin and simvastatin as both of these lipid lowering agents can increase the levels of digoxin by P-glycoprotein efflux transporter.


  • Warfarin: use of warfarin with fluvastatin, rosuvastatin, simvastatin, lovastatin requires caution and close monitoring as the combinations can increase INR.


  • Clarithromycin: clarithromycin and simvastatin use together is contraindicated due to the fact that this anti-biotic can increase the levels or effect of simvastatin by altering hepatic/intestinal CYP3A4 metabolism. Drugs that increase simvastatin systemic exposure can increase risks for rhabdomyolysis.

           Clarithromycin heightens the toxicity of atorvastatin. It is contra- indicated                              unless benefits prove to outweigh risks (not to exceed atorvastatin   more than                        20mg/day in such cases), if not, alternatives are used.

  • Erythromycin: erythromycin and simvastatin’s use is contra-indicated as it can increase simvastatin’s systemic exposure that could result in toxic reactions like rhabdomyolysis or myopathy. Erythromycin increases the effects of atorvastatin and ups the risks for toxicity by P-glycoprotein efflux transporter, so alternatives are preferred and in the case of absence of alternatives, it should be monitored closely. Erythromycin can also increase the toxicity of fluvastatin; OATP1B1 inhibitors may increase risk of myopathy.
  • Fusidic acid: concomitant use should be avoided and after 7 days of last fusidic acid dose.


  • Carbamazepine: carbamazepine use with simvastatin, atorvastatin or lovastatin can give rise to serious life-threatening interactions.
  • Phenytoin: phenytoin if given with atorvastatin, lovastatin or simvastatin requires the efficacy of these statins to be monitored properly as the combination can decrease the satin’s levels.


  • Itraconazole: use is contra-indicated with simvastatin and lovastatin as itraconazole increases levels and effects of these statins via affecting their metabolism and leads to rhabdomyolysis.
  • Ketoconazole: contra-indicated with simvastatin and lovastatin… increased risk of rhabdomyolysis.

Calcium channel blocker:

  • Amlodipine: weigh risk and benefit when to be given with simvastatin, better to go for an alternative. The combo can lead to elevated LFTs, myopathy, rhabdomyolysis.




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