Simvastatin interactions to avoid

In this article:

• Simvastatin drug interactions
• Simvastatin food interactions
• Other simvastatin interactions
• How to minimize the risk of simvastatin interactions

In this article

• Simvastatin drug interactions
• Simvastatin food interactions
• Other simvastatin interactions
• How to minimize the risk of simvastatin interactions

Simvastatin (generic Zocor) is an oral medication approved by the Food and Drug Administration (FDA) to lower cholesterol levels. This statin is generally safe and effective in treating high cholesterol, but taking it with certain other medications, drinks, or foods may increase the risk of serious side effects like liver or muscle damage. It is important to be aware of these interactions and tell your healthcare provider and pharmacist about all of the prescriptions and supplements you’re taking, especially since about 22% of people who take simvastatin also take a medication that could potentially interact with it. 

Simvastatin drug interactions

Many patients with cardiovascular disease may need statins as well as other medications, especially if they have other related health conditions. However, some of those medications can affect how the body absorbs, distributes, metabolizes, and excretes statins. As such, severe side effects can occur, including myopathy (muscle weakness), rhabdomyolysis (breakdown of muscle tissue), and hepatic disease (liver damage). 

Some types of medication are more likely to interact with simvastatin than others. 

Strong CYP3A4 inhibitors

Cytochrome P450 3A4 (CYP3A4) is an enzyme that helps the body break down many medications, including simvastatin. However, some medications inhibit CYP3A4 (prevent it from working), which can cause too much simvastatin to build up in a person’s bloodstream. When that happens, liver damage, muscle weakness (myopathy), and muscle breakdown (rhabdomyolysis) may occur. 

Medications that significantly prevent the breakdown of simvastatin are called “strong CYP3A4 inhibitors.” Your healthcare provider may choose to prescribe a different type of statin if you currently take a strong CYP3A4 inhibitor. 

There are dozens of strong CYP3A4 inhibitors, including:   

• An androgen called danazol
• An antidepressant called nefazodone
• Antifungal azoles like fluconazole, itraconazole, ketoconazole, levoketoconazole, posaconazole, and voriconazole
• A progesterone blocker called mifepristone
• Certain antibiotics like clarithromycin, erythromycin, rifampin, telithromycin, and troleandomycin
• Certain cancer medications, including adagrasib, ceritinib, idelalisib, lenalidomide, lonafarnib, pexidartinib, and tucatinib
• Heart medications like amiodarone, dronedarone, and ranolazine
• HIV protease inhibitors such as amprenavir, atazanavir, boceprevir, cobicistat, darunavir, delavirdine, fosamprenavir, indinavir, letermovir, nelfinavir, ritonavir, saquinavir, and tipranavir
• Other high cholesterol medications, including lomitapide and mipomersen
• Some immunosuppressive drugs, like cyclosporine and leflunomide
• Some high blood pressure medications, including amlodipine, diltiazem, levamlodipine, mibefradil, and verapamil

Many other drugs also inhibit CYP3A4, but less significantly. 

If it’s impossible to avoid taking one of these medications, your healthcare provider may lower your dose of simvastatin or recommend discontinuing it temporarily. 

Fibrates

Like statins, fibrates are a drug class used to treat high cholesterol (hypercholesterolemia). They’re associated with an increased risk of muscle weakness, even when taken with no other medications. Combining fibrates with a simvastatin may increase the risk of muscle weakness. 

Fibrates include:

• Gemfibrozil 
• Fenofibrate
• Simfibrate
• Ciprofibrate
• Clofibrate
• Bezafibrate

According to the Zocor (simvastatin) prescribing information, it’s best to completely avoid taking fibrates with simvastatin. However, there may be cases where a healthcare provider believes the benefits of the two medications outweigh their potential risks. 

Coumadin anticoagulants

Taking a Coumadin anticoagulant with simvastatin may cause blood to clot more slowly, which could increase your risk of bleeding. Your healthcare provider should monitor your blood clotting speed before and after you begin taking simvastatin and make any necessary adjustments.

Coumadin anticoagulants include:

• Warfarin
• Acenocoumarol
• Phenprocoumon

Morphine

Normally, a protein called P-glycoprotein (P-gp) slows down the absorption of morphine in the body. Taking simvastatin, a P-gp inhibitor, allows more morphine to enter the bloodstream. This may increase the risk of morphine’s adverse effects, including extreme sedation, difficulty breathing, and death. 

Colchicine 

Used to treat and prevent gout, colchicine (generic Colcrys) carries a risk of myopathy. When colchicine is combined with simvastatin or other drugs known as HMG-CoA reductase inhibitors, that risk increases. 

Digoxin

Simvastatin may cause an increased concentration of digoxin (generic Digitek) in the blood when these medications are taken simultaneously. Too much digoxin can cause symptoms like nausea, vomiting, and heart problems, and it may also result in death. 

Resmetirom

Resmetirom (generic Rezdiffra) isn’t a CYP3A4 inhibitor, but it has basically the same effect: It increases simvastatin levels in the blood. If your healthcare provider prescribes resmetirom and simvastatin together, they may limit the doses of both medications to prevent serious side effects. 

Teriflunomide 

Liver damage is a possible side effect of simvastatin and teriflunomide (generic Aubagio), and taking them together increases the risk of liver damage. Your healthcare provider may decide to prescribe both medications and routinely check for elevated liver enzymes to make sure your liver remains healthy. 

Simvastatin food interactions

Large quantities of some drinks, foods, and herbs may increase the risk of liver or muscle damage when taken with simvastatin. While complete abstinence may not be necessary, your health care provider should assess your risk factors and suggest dietary changes. 

Grapefruit juice

Grapefruit juice is a strong CYP3A4 inhibitor. “Simvastatin [blood] levels can surge by up to 260% when taken with grapefruit juice, potentially increasing the risk of adverse effects like rhabdomyolysis,” says Isaac Tawfik, Chief of Cardiology at Monmouth Medical Center, an RWJBarnabas Health Hospital. 

According to the simvastatin drug label, drinking 1 quart (4 cups) or less of grapefruit juice a day is safe, but it’s a good idea to talk to your healthcare provider before you sip this beverage.  

Alcohol

Because simvastatin and alcohol can both cause liver damage, it’s best to avoid alcoholic drinks while taking this medication. The prescribing label for simvastatin specifically recommends letting your healthcare provider know if you drink more than two glasses of alcohol daily before you take the medication. 

Green tea

Green tea is a CYP3A4 inhibitor, but not a strong one. The CYP3A4-inhibiting components in green tea are compounds called catechins, which are found in antioxidant-rich foods. Ask your healthcare provider about your risk of simvastatin interactions if you’re an avid green tea drinker or regularly consume other antioxidant-rich foods and drinks.

Parsley

A 2019 study found that when parsley and simvastatin were taken together, simvastatin blood levels doubled. 

Parsley contains compounds called flavonoids, and a specific flavonoid called apigenin is believed to be responsible for this herb’s CYP3A4-inhibiting properties. Parsley and thyme have higher levels of apigenin than other herbs and vegetables, but celery, rutabaga, and peppermint also contain a fair amount. 

Other simvastatin interactions

The following over-the-counter products may increase your risk of potential side effects when taken with simvastatin. 

Cigarettes

“No direct interaction has been established between smoking and statins, but tobacco use undermines the medication’s benefits,” Dr. Tawfik says. Smoking damages blood vessels and hardens the arteries. “This directly counteracts statins’ role in reducing atherosclerosis [hardening of the arteries] and stabilizing existing plaque.” 

Dr. Tawfik says quitting smoking will significantly improve the effectiveness of simvastatin, and researchers agree. 

Cannabidiol (CBD) and naltrexone

CBD and naltrexone can potentially cause liver damage, as can simvastatin. The risk of liver damage increases when CBD or naltrexone is taken with simvastatin. Your healthcare provider may weigh the therapeutic benefits of these drugs against the potential risks and choose to adjust your dose or closely monitor your liver enzymes. 

Herbal supplements

Some herbal supplements may increase the risk of simvastatin side effects or affect how well the drug works. For example:

• Ashwaganda and black cohosh may increase the risk of liver damage.
• Goldenseal is a CYP3A4 inhibitor that may increase the risk of muscle damage and weakness. 
• Echinacea and St. John’s wort are both CYP3A4 inhibitors and inducers. At certain doses, they may speed up the metabolism of simvastatin, making it less effective. At other doses, they may increase simvastatin plasma concentrations. 

This isn’t a complete list of herbs with the potential to interact with simvastatin. Talk to your healthcare provider and pharmacist before taking any supplements. 

Red yeast rice

Red yeast rice is a powdered over-the-counter supplement believed to be a natural alternative to statins, but taking red yeast rice with simvastatin may increase the risk of peripheral neuropathy (nerve damage in the feet and hands) and other simvastatin side effects. 

Niacin (Vitamin B3)

Niacin is another cholesterol-lowering remedy, but taking it in high doses (1 gram or more per day) with simvastatin increases the risk of myopathy. This risk appears to be greater in people of Chinese descent, according to the drug’s prescribing information. Most patients cannot tolerate the flushing that occurs with niacin. 

How to minimize the risk of simvastatin interactions

“To minimize interaction risks, start by providing a full list of medications and supplements to your healthcare provider,” Dr. Tawfik says. Be honest about recreational drug and alcohol use as well.  

Your healthcare provider will also consider other risk factors for simvastatin interactions, including uncontrolled hypothyroidism, uncontrolled kidney disease, and high doses of simvastatin. 

Bruce Haik, MD, Chief of the Division of Cardiology at Cooperman Barnabas Medical Center, an RWJBarnabas Health Hospital, says adults 65 and older are also at an increased risk of simvastatin interactions due to a slower drug metabolism. “As we age, our liver and kidneys don’t work quite as efficiently as they used to, and our muscle mass tends to decrease, which can make us more sensitive to side effects like muscle pain.”

If your healthcare provider sees that you take a drug or supplement that may interact with simvastatin or identifies other risk factors, they may do one or more of the following:

• Prescribe a lower dose of simvastatin.
• Change one of your other prescriptions to a medication with less interaction potential.
• Monitor your liver enzyme levels more frequently.
• Suggest taking simvastatin at a different time of day than other medications.
• Advise you to make dietary or lifestyle changes, or to stop using certain supplements.
• Advise you to look out for symptoms like muscle pain, weakness, and tingling.

RELATED: When is the best time to take statins?

Switching to a simvastatin alternative is another possibility. “Some alternatives, like Pravachol (pravastatin sodium) or Crestor (rosuvastatin calcium), tend to play nicer with other medications because they’re broken down differently in the body,” Dr. Haik says. “That means they’re less likely to cause problems if you’re also taking other prescriptions or supplements.”

Your healthcare provider can address any concerns you have about simvastatin interactions. If you have an urgent question and can’t reach your healthcare provider, call your pharmacy. For life-threatening emergencies or allergic reactions, call 911.