Atorvastatin Interactions: What Drugs to Avoid When Using Atorvastatin?

Atorvastatin Interactions Atorvastatin Interactions

Atorvastatin Interactions: What Drugs to Avoid When Using Atorvastatin?

Atherosclerosis is a process in which fats and cholesterol accumulate on the arteries’ walls alongside inflammatory cells, smooth muscle cells, and connective tissue creating plaques, limiting blood flow and oxygen supply to the heart, brain, or other organs. These plaques may suddenly rupture and block flow resulting in heart disease, chest pain, heart attack, or stroke.

Atorvastatin is a medication that slows down the production of cholesterol and helps stabilize plaques, preventing rupture and preventing these life-threatening conditions. Still, atorvastatin interacts with many medications, requiring monitoring or dose adjustment. (1-2)

However, some interactions may cause serious complications such as muscle pain, tenderness, weakness, and even damage to the muscle tissue. Due to the severity of these interactions, atorvastatin is not recommended for use with cyclosporine, ritonavir, and other medications. (1)

This article covers atorvastatin interactions with drugs and food. Keep reading to learn about the interactions of the medication you should use for a long time and what combination to avoid.

1. Cyclosporine or Gemfibrozil

Cyclosporine and gemfibrozil significantly increase atorvastatin plasma levels and the risk of myopathy and rhabdomyolysis; therefore, the concomitant use of these medications is not recommended. (1)

Cytochrome P450 3A4 (CYP3A4) plays a vital role in atorvastatin breakdown. It is present in the liver and intestine and, aside from atorvastatin, is crucial for the metabolism of about half of the marketed drugs. (2-3)

Gemfibrozil is another medication used to lower triglycerides and cholesterol. By this mechanism, gemfibrozil prevents heart attacks and reduces the risk of pancreatitis due to hypertriglyceridemia. When used alone, gemfibrozil may cause myopathy; however, the risk is much higher if coadministered with a statin. (4)

Patients who have undergone organ transplantation may need to take cyclosporine, a medication that helps the body not to reject the transplanted organ. While suppressing the immune system, cyclosporine, at the same time, inhibits CYP3A4. (1, 5)

Atorvastatin, when used as a monotherapy, may cause the following side effects:

Myopathy – a condition where the skeletal muscles are affected. The enzyme creatine kinase levels increase due to muscle damage, alongside muscle pain, tenderness, or weakness; (6)

Rhabdomyolysis – extreme amounts of proteins (especially myoglobin) and electrolytes are released in the blood from the damaged muscle tissue. This can lead to kidney damage. (7)

The risk of myopathy and rhabdomyolysis increases when the atorvastatin plasma levels are increased due to concomitant use with cyclosporine or gemfibrozil. For this reason, cyclosporine and gemfibrozil are not recommended to be used with atorvastatin. (1)

2. Other Fibrates

Gemfibrozil belongs to fibrates, a class of lipid-regulating medications. Similar to gemfibrozil, other fibrates may cause myopathy when given alone. When atorvastatin is used with other fibrates, the risk of myopathy and rhabdomyolysis increases. (1, 4)

If your doctor considers that the combination treatment of atorvastatin and other fibrates is more beneficial than the risk of myopathy and rhabdomyolysis, concomitant use is acceptable. If so, your doctor will monitor your condition for signs and symptoms of myopathy, especially when initiating therapy and titrating the dose of both drugs. (1)

Statin-induced muscle pain and myopathy are typically symmetric and proximal (closer to the torso). As such, shoulders, upper arms, hips, and thighs are commonly affected, and there may be functional impairments such as difficulty raising arms above the head, standing from a seated position, or climbing stairs. (8)

Talk to your doctor about your symptoms if any of the above occur.

3. Antiviral Medications

Antiviral medications treat viral infections like AIDS (HIV), Cold Sores (Herpes), Ebola, or COVID-19 (SARS-CoV-2). Some antiviral drugs can inhibit CYP3A4 and/or drug transporters (e.g., BCRP, OATP1B1/1B3, P-gp, MRP2, and/or OAT2). This effect can significantly increase atorvastatin plasma levels, leading to myopathy and rhabdomyolysis. (1, 9)

The effect varies among different antiviral medications, and so the recommendations:

Ritonavir or glecaprevir plus pibrentasvir are not recommended for concomitant use with atorvastatin;

The risk/benefit ratio should be considered in patients taking:

  • Lopinavir plus ritonavir, or
  • Ledipasvir plus sofosbuvir,
  • Simeprevir.

Atorvastatin dose should be limited in patients taking:

  • Saquinavir plus ritonavir;
  • Darunavir plus ritonavir;
  • Fosamprenavir;
  • Fosamprenavir plus ritonavir,
  • Elbasvir plus grazoprevir, or
  • Letermovir.

The atorvastatin dose should also be limited in patients taking nelfinavir. (1)

All patients who take particular antivirals and atorvastatin should be cautious of any signs and symptoms that may appear during the initiation of the therapy and dose increase. (1)

4. Several Azole Antifungals or Macrolide Antibiotics

Some azole antifungals or macrolide antibiotics are other CYP3A4 inhibitors that increase atorvastatin plasma levels.

Azole antifungal drugs that eliminate fungal pathogens and inhibit cytochrome P450-dependent enzymes are:

  • Fluconazole;
  • Itraconazole;
  • Clotrimazole;
  • Miconazole; and
  • Ketoconazole. (10)

Macrolides are a class of antibiotics that treat specific bacterial infections which can cause pneumonia, sinusitis, pharyngitis, tonsillitis, uncomplicated skin infections, and otitis media (ear infection). Macrolide antibiotics also inhibit CYP3A4. Inhibitory effects of macrolides or select azole antifungals significantly increase atorvastatin plasma levels, which may cause myopathy. (11-121)

Therefore, your doctor will adjust your dose when taken with clarithromycin or itraconazole. For the other medications, your doctor will consider the risk/benefit ratio and monitor if myopathy symptoms appear. (1)

5. Food: Niacin and Grapefruit Juice

Niacin, aka vitamin B3, helps convert nutrients into energy and supports making “good” cholesterol. It is available in food sources such as:

  • Milk;
  • Meat;
  • Yeast;
  • Cereals.

Niacin is a water-soluble vitamin, so if you consume more than the body needs, it will be excreted in the urine. Niacin can also be prescribed in high doses to help lower cholesterol. High doses of prescribed niacin can cause side effects and interact with medications, including atorvastatin. (13)

There are reports of myopathy and rhabdomyolysis cases when ≥1 gram/day of niacin was taken with atorvastatin. (14)

Your doctor may consider that the benefit of the concomitant use of atorvastatin outweighs the increased risk of side effects. If you take niacin and atorvastatin, be aware of myopathy’s signs and symptoms explained earlier. (1)

While niacin co-administration can be acceptable, high quantities of grapefruit juice are not recommended. (1)

Grapefruit juice is generally healthy and safe in your diet. It is also rich in vitamin C and potassium. However, it interacts with many medications, including atorvastatin, because it blocks the CYP3A4 enzyme activity. The result is an increased level of atorvastatin in the body and a higher risk of side effects. (15)

Additionally, the Food and Drug Administration recommends avoiding Seville oranges, pomelos, and tangelos because of the same effect they have as grapefruit juice. (15)

6. Rifampin

The interactions explained above are due to the inhibition of the CYP3A4 enzyme. Unlike the above medications, rifampin induces cytochrome P450 3A4 but inhibits OATP1B1. This effect can lead to the opposite, a reduction of atorvastatin plasma concentrations or an increase in atorvastatin concentrations. (16, 17)

Rifampin is an antibiotic used for tuberculosis and meningitis. If atorvastatin is taken later after rifampin, atorvastatin plasma concentrations significantly reduce. Because of that, the recommendation is to take atorvastatin and rifampin simultaneously. (1, 18)

7. Oral Contraceptives

Aside from drug interactions where other drugs affect atorvastatin, there are cases where atorvastatin affects co-administered medications. Oral contraceptives are an example where the medication can be affected by atorvastatin.

Atorvastatin can interact with oral contraceptives containing norethindrone and ethinyl estradiol hormones. This interaction increases plasma concentrations of norethindrone and ethinyl estradiol and the risk of side effects.

Norethindrone is a progestin, a medication used to prevent pregnancy, as well as treat endometriosis and abnormal periods or bleeding. The most common side effects of norethindrone are:

  • Menstrual irregularity;
  • Frequent and irregular bleeding;
  • Breast tenderness;
  • Headache;
  • Nausea; and
  • Dizziness. (19)

Ethinyl estradiol also prevents ovulation and pregnancy. You may find a long list of reported side effects. Inform your doctor if you experience some of the following events:

  • Allergic reaction;
  • Chest pain;
  • Pain or swelling in the leg;
  • Swollen fingers, hands, or ankles;
  • Severe stomach pain, nausea, and vomiting;
  • Increase blood pressure;
  • Loss of appetite;
  • Color change of the stool;
  • Breast pain or tenderness. (20)

Read the Medication Guide to find out all possible side effects of the contraceptive you take. Consult your doctor about the contraceptives you should take. Your doctor will consider the possible interaction with atorvastatin. Other contraceptives, such as condoms, vaginal rings, or patches, can be an option.

8. Digoxin

Digoxin is another medication affected by atorvastatin. Studies showed that after multiple doses of co-administered atorvastatin and digoxin, the blood levels of digoxin increased. Atorvastatin inhibits the elimination of digoxin from the body and increases digoxin levels. (1)

Digoxin is used for the treatment of abnormal heart rhythms and heart failure. It helps control the health condition, but it is not a cure. Therefore, digoxin therapy is long-term. (21)

Because of this drug-drug interaction, your doctor will monitor you while using both medications.


Atorvastatin helps in cholesterol regulation in the body. However, its safety profile can be affected by certain medications.

Tell your doctor the medications you currently take; some may interact with atorvastatin and are not recommended for concomitant use. Avoid grapefruit juice, Seville oranges, pomelos, and tangelos while taking atorvastatin.

Be aware of the signs and symptoms of myopathy. Pay attention if any event occurs, especially when beginning atorvastatin treatment or titrating the dose.

See Also

Drug Interaction Checker

Bupropion Interactions

Bupropion Side Effects

Sertraline Interactions

Sertraline Side Effects

Amlodipine Interactions

Pantoprazole Interactions

Metronidazol Interactions

Meloxicam Interactions

Biljana is a Master of Pharmacy, with a Healthcare Management specialization. Over 20 years of professional engagement to enable access to innovative treatments for patients in need.
Biljana is dedicated to upgrading health education evidence-based, promoting a healthy lifestyle, and embedding healthy habits.

Franco Cuevas is a physician who graduated from the National University of Córdoba, Argentina. He practices general medicine in the Emergency Department at Sanatorio de la Cañada, Córdoba. His focus is on writing medical content to improve physicians' access to relevant medical information for daily practice. He has participated in some research projects and has a special joy in teaching and writing about medical concepts.

Dr. Baran Erdik is an M.D. with further specialization in Internal Medicine/Cardiology. He traveled the world, working as a physician in New Zealand, Germany and Washington State.
After earning his Master’s in Healthcare Administration and Policy from Washington State University, graduating summa cum laude, he decided to make a turn in his career. His master’s degree opened the door for him to a different aspect of the healthcare industry which highly piqued his interest. He found his new passion in consulting for hospitals and medical practices, where he could leverage his physician experience – understanding the needs of the clinicians – as well as his studies in healthcare administration.

He has now settled down in Atlanta, consulting for healthcare facilities, and helps CSR on a wide range of issues: mergers and acquisitions, policy compliance, and savings and efficiency, among others. What he enjoys most in his work is the need to constantly adapt to challenges and changes. It makes every day different and worth going to work for.
He has also done research on evidence-based medicine, focused on how big data can be used in medicine and consulting.

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