When it comes to improving cardiovascular health, managing hypertension and cholesterol levels are paramount. Amlodipine, a widely prescribed calcium channel blocker, helps control blood pressure, while statins effectively lower cholesterol. However, when (some of) these medications are used together, there’s a potential for drug interactions that need careful consideration. We will break down important amlodipine and statin interactions and what you should do about them.

When amlodipine and certain statins are taken together, there’s a potential for drug interactions since both medications are metabolized in the liver by the cytochrome P450 enzyme system, particularly CYP3A4. Of the seven available statins, only three are metabolized by CYP3A4; simvastatin, atorvastatin, and lovastatin. These are the three statins to remember when it comes to drug interactions with amlodipine but there are even more subtleties that than.

When amlodipine is taken together with simvastatin or lovastatin, it inhibits the metabolism of the statins, leading to higher-than-intended levels of statins in the bloodstream. This could increase the risk of statin-related side effects such as muscle pain (myopathy), rhabdomyolysis, or liver toxicity. When using simvastatin with amlodipine, it is recommended to limit the dose to a maximum of 20 mg per day. Interestingly, the American Heart Association has a recommendation to limit the dose of lovastatin to 20 mg per day as well but other references do not mention this recommendation.

Atorvastatin is much more commonly used nowadays compared to simvastatin and lovastatin. It is also metabolized by CYP3A4 but is less prone to interaction due to its structural properties and has not shown any clinically significant interaction with amlodipine based on current data (Gundlach et al.). It should be noted that there have been case reports (like this one) of atorvastatin and amlodipine causing rhabdomyolysis but in trials, there have been no clinically significant changes in concentration. 

Now, the awesome part of amlodipine and statin interactions…some don’t interact! The remaining four statins, fluvastatin, pitavastatin, pravastatin, and rosuvastatin, which are not metabolized by CYP3A4, do not interact with amlodipine. Fluvastatin undergoes metabolism via CYP2C9, and rosuvastatin is metabolized, to a lesser extent, by both CYP2C9 and CYP2C19 enzymes. While the OATP1B (organic anion-transporting polyprotein) plays a role in eliminating pitavastatin, and pravastatin. 

Common Sense Guidance – Amlodipine and Statin Interactions

1. Don’t worry if the patient is taking fluvastatin, pitavastatin, pravastatin, or rosuvastatin with amlodipine. 
2. Consider reducing the dose of simvastatin and possibly lovastatin to a maximum of 20 mg per day and also monitor for signs/symptoms of statin toxicity when starting amlodipine. 
3. It is reasonable to pay a little closer attention and monitor for statin toxicity when starting amlodipine in a patient taking atorvastatin but blanket dose reductions do not seem warranted at this time. 

Want to know which statins interact with grapefruit juice? We’ve covered that in the past as well!

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This article was written by Jack Mageto, PharmD Candidate in collaboration with Eric Christianson, PharmD, BCPS, BCGP

References 

• Khan S, Khan I, Novak M, Regmi A, Difilippo W. The Concomitant Use of Atorvastatin and Amlodipine Leading to Rhabdomyolysis. Cureus. 2018 Jan 3;10(1):e2020. doi: 10.7759/cureus.2020. PMID: 29531873; PMCID: PMC5837234.
• Orekhov AN, Tertov VV, Sobenin IA, Akhmetzhanov NM, Pivovarova EM. Antiatherosclerotic and antiatherogenic effects of a calcium antagonist plus statin combination: amlodipine and lovastatin. Int J Cardiol. 1997 Dec 31;62 Suppl 2:S67-77. doi: 10.1016/s0167-5273(97)00243-x. PMID: 9488197.
• Jellinger PS, Handelsman Y, Rosenblit PD, et al. American Association of Clinical Endocrinologists and American College of Endocrinology guidelines for management of dyslipidemia and prevention of cardiovascular disease. Endocr Pract. 2017;23(suppl 2):1-87.
• Zhou YT, Yu LS, Zeng S, Huang YW, Xu HM, Zhou Q. Pharmacokinetic drug-drug interactions between 1,4-dihydropyridine calcium channel blockers and statins: factors determining interaction strength and relevant clinical risk management. Ther Clin Risk Manag. 2014;10:17-26. doi: 10.2147/TCRM.S55512. Epub 2013 Dec 20. PMID: 24379677; PMCID: PMC3873236.
• Gundlach K, Wolf K, Salem I, Randerath O, Seiler D. Safety of candesartan, amlodipine, and atorvastatin in combination: interaction study in healthy subjects. Clin Pharmacol Drug Dev. 2021;10(2):190-197. [PubMed 32388918]