Atorvastatin (Lipitor, Atorvaliq) was the most commonly prescribed medication in the U.S. in 2023. It belongs to a group of drugs called statins, which can help lower “bad” cholesterol levels (called LDL) in the body and reduce the risk of heart attack, stroke, and even death in many individuals. Examples of other statins include rosuvastatin (Crestor), simvastatin (Zocor, FloLipid), and pravastatin.
With nearly half of U.S. adults aged 56 to 75 years old qualifying for statin treatment under current cholesterol guidelines, knowing about possible drug interactions is critical to avoiding preventable harm.
One medication worth highlighting is amiodarone (Pacerone), which is used to treat abnormal heart rhythms (arrhythmias).
Do Amiodarone and Atorvastatin Interact?
Yes, amiodarone and atorvastatin can interact. But the overall risk is low, and these medications are often prescribed together safely.
Regardless of whether you take amiodarone, it’s a good idea to watch for side effects like muscle pain, weakness and cramps if you take a statin. In rare cases, statins can cause a serious condition called rhabdomyolysis. This is when muscle breaks down, which may lead to other major health problems, such as kidney failure. Though it’s rare to experience rhabdomyolysis, a study published in 2023 looking at over 10,000 statin-related case reports found the risk was higher in those aged 75 or older, men, and in people taking medications that interact with statins (including amiodarone).
Most people won’t experience rhabdomyolysis, but knowing the signs and symptoms to watch for is important. If you have dark urine, are unable to complete workouts due to weakness or fatigue, and/or experience muscle pain, let your prescriber know immediately.
While atorvastatin and amiodarone are often combined without problems, other statins may require more careful management, says Jaclyn Hawn, PharmD, a cardiovascular pharmacy specialist and associate professor at the Medical University of South Carolina.
Why Do Amiodarone and Statins Interact?
Amiodarone can increase the amount of atorvastatin in your blood. The extent to which this happens varies from person to person, partly due to natural differences in how our bodies metabolize medications. For many people, the effects of this interaction are small and unlikely to cause problems.
The interaction between atorvastatin and amiodarone is due to the involvement of certain liver enzymes (proteins) called cytochrome P450s (CYPs). In fact, around 80% of all medications are metabolized by CYP enzymes.
Atorvastatin is metabolized (broken down) in the liver by a certain CYP called CYP3A4. Amiodarone inhibits (blocks) CYP3A4, which prevents atorvastatin from being cleared normally from the body. Amiodarone also blocks P-glycoprotein (Pgp), a protein that pumps atorvastatin out of cells.
The result? Atorvastatin may stick around in the body longer, increasing the risk of muscle-related side effects. Still, Dr. Hawn notes that evidence suggests the amiodarone-atorvastatin interaction isn’t usually serious enough to require changes to medication regimens.
What Does the Evidence Say?
Evidence on the atorvastatin–amiodarone interaction is limited and mostly comes from case reports, not large, well-designed studies. In the medical community, the interaction is considered well-documented, notes Dr. Andy Lee, a cardiologist and assistant clinical professor at the University of California, Irvine Health.
Besides case reports, one of the most cited pieces of research is a 2005 analysis of side effect reports of statin and amiodarone users. The study authors only looked at the three most commonly prescribed statins at the time: atorvastatin, simvastatin, and pravastatin. Here’s what the analysis showed:
- Out of thousands of reports mentioning statin-related side effects, 71 involved people also taking amiodarone.
- Among people taking amiodarone along with a statin, side effect reports were most often associated with those taking simvastatin, followed by atorvastatin; far fewer involved pravastatin. This makes sense because simvastatin and atorvastatin rely on CYP enzymes for metabolism, but pravastatin doesn’t.
- Most side effect reports involved muscle toxicity in men over 70 years old who took several other medications.
It’s also important to note that although many people attribute muscle aches and pains to their statins, large studies show that mild muscle-related symptoms may not be caused by statins. For instance, a 2022 meta-analysis of 19 clinical trials found that mild muscle pain rates were similar in people taking statins compared to those taking a placebo (a pill with no active drug in it).
Are Any Statins Safe to Take With Amiodarone?
Yes, several statins are safe to take with amiodarone. While atorvastatin is safe for many people taking amiodarone, rosuvastatin and pravastatin are even less likely to interact.
The statins most likely to interact with amiodarone are simvastatin and lovastatin, says Dr. Hawn. Both are metabolized by CYP3A4, which amiodarone can inhibit. Although atorvastatin is also metabolized by CYP3A4, it relies on this pathway less heavily than simvastatin and lovastatin. That’s why current guidance doesn’t recommend adjusting the atorvastatin dose when it’s taken with amiodarone. However, your prescriber may lower the dose of lovastatin or simvastatin if you’re taking either of these statins alongside amiodarone.
The table below illustrates the interactions between different statins and amiodarone.
| Medication | Interaction with amiodarone? | Primary mechanism | What could happen? |
| Atorvastatin | Yes | Amiodarone blocks CYP3A4, an enzyme that helps clear atorvastatin | Higher atorvastatin levels in the body, leading to muscle-related side effects; this is less likely to occur than with simvastatin and lovastatin |
| Simvastatin | Yes | Amiodarone blocks CYP3A4, an enzyme that helps clear simvastatin | Higher simvastatin levels in the body, leading to muscle-related side effects |
| Lovastatin | Yes | Amiodarone blocks CYP3A4, an enzyme that helps clear lovastatin | Higher lovastatin levels in the body, leading to muscle-related side effects |
| Pravastatin, Rosuvastatin, Pitavastatin (Livalo, Zypitamag), and Fluvastatin (Lescol XL) | No | No clinically significant interaction | No expected risk |
Keep in mind: Even though fluvastatin and rosuvastatin are also metabolized by CYPs, their interaction isn’t considered clinically significant. That said, case reports of interactions between rosuvastatin and amiodarone do exist, with other medications often involved. So, if you take amiodarone, it’s a good idea to watch for muscle-related side effects no matter which statin you take.
Statin Alternatives: Should I Try Another Cholesterol-Lowering Medication?
Statins are the gold standard medications for lowering cholesterol levels. Even though other medications, like PCSK9 inhibitors such as evolocumab (Repatha), are considered as (or more) effective than statins at lowering “bad” cholesterol, they’re not considered first-choice options. A few reasons for this include:
- They haven’t been consistently proven to reduce heart-related deaths, while statins have.
- Statins also have decades of robust clinical trial data to support their use. PCSK9 inhibitors have only been available since 2015, so long-term data is more limited.
- PCSK9 inhibitors are brand-name injections, while statins are available as oral generics
Other alternatives, such as Nexletol (bempedoic acid) or Nexlizet (bempedoic acid/ezetimibe), are also effective at lowering cholesterol. But they’re usually reserved for certain people who can’t take statins or for those whose LDL remains high despite taking statins.
The bottom line? Statins are typically preferred for lowering cholesterol. Most people who need both amiodarone and a statin can find a combination that’s safe and effective.
Your Safety Checklist for Talking To Your Healthcare Provider About Statins and Amiodarone
Taking amiodarone and a statin can help treat your abnormal heart rhythm and high cholesterol at the same time. Here are a few tips to help you manage these medications and approach your healthcare provider with any concerns:
- Share your medication list with your healthcare team. Give your healthcare provider or pharmacist a list of all prescription medications and over-the-counter products you take. Include vitamins and herbal supplements. If you’re at risk for several drug interactions, the risk-benefit ratio for taking a statin and amiodarone may change.
- Discuss your personal risk factors. Your age, other medications and health conditions can impact your risk of experiencing muscle-related side effects. In some cases, this may lead your prescriber to recommend a lower statin dose. Dr. Lee adds that he often considers lower doses for people with frailty, as well as for certain Asian populations who metabolize some statins more slowly.
- Don’t stop taking amiodarone or your statin without medical advice. Stopping either medication can be risky, so don’t make any changes without talking to your prescriber first.
- Ask your healthcare provider if your statin is the best choice. They may recommend a lower dose or switching to a statin that doesn’t interact with amiodarone, such as rosuvastatin, notes Dr. Lee.
- Watch for warning signs of an interaction. If you experience muscle pain, weakness or cramping, let your prescriber know promptly. Also watch for physical signs of kidney injury, such as dark urine.
- Know your monitoring plan. Ask whether you’ll need periodic blood tests to monitor for a potential interaction.
Want to learn more about how prescription and over-the-counter medications interact? Read the next article in our series: Can I Take Prilosec with Levothyroxine?
