Important Drug Interactions for Cholesterol-Lowering Drug Atorvastatin (LIPITOR)

Patients taking the commonly prescribed drug atorvastatin, which is a member of the statin family of cholesterol-lowering drugs, should be aware that it has clinically important interactions with many other prescription medications.

The Food and Drug Administration (FDA) has approved atorvastatin under the brand name LIPITOR for use in combination with diet in order to, among other things, lower high blood cholesterol and triglyceride levels and to reduce the risk of heart attacks and strokes in certain individuals at high risk of such adverse heart events.[1]

The FDA also has approved a combination drug product marketed under the brand name CADUET that contains atorvastatin and the calcium channel blocker amlodipine, which is used to treat hypertension (high blood pressure).[2]

Drugs that increase risk of atorvastatin toxicity[3],[4]

The Table below lists examples of oral drugs that, when taken concomitantly with atorvastatin, increased the risk of atorvastatin muscle toxicity. The list includes certain macrolide antibiotics, antifungal drugs, antiviral drugs for HIV infection, calcium channel blockers used to treat hypertension and other blood-lipid-lowering drugs, the abnormal heart rhythm drug amiodarone (PACERONE) and the antidepressant nefazodone (available in generic only).

Like many drugs, atorvastatin is metabolized (broken down or chemically modified) by substances in the liver called enzymes. One important liver enzyme, known as CYP3A4, breaks down this drug. Most of the drugs listed in the Table inhibit CYP3A4. When taken concomitantly with atorvastatin, these CYP3A4-inhibiting drugs, because they decrease atorvastatin breakdown, can thereby increase atorvastatin levels in the blood to toxic levels. For example, studies of concomitant use of atorvastatin with cyclosporine (GENGRAF, NEORAL, SANDIMMUNE) for 28 days showed a nearly ninefold increase in overall atorvastatin blood levels.

High blood levels of atorvastatin increase the risk of myopathy (muscle damage). Symptoms of myopathy include muscle pain and weakness. In severe cases, this condition can progress to rhabdomyolysis, a life-threatening, muscle-destroying condition that can lead to sudden kidney failure and death. Patients with impaired kidney function or uncontrolled hypothyroidism (low thyroid hormone levels) and those who are age 65 or older or taking a high atorvastatin dosage are at most risk of myopathy and rhabdomyolysis due to higher blood levels of atorvastatin.

Examples of Oral Drugs That Increase the Risk of Atorvastatin Toxicity

†Combination drug that contains other active ingredients not listed
*Designated as Limited Use by Public Citizen’s Health Research Group
**Designated as Do Not Use by Public Citizen’s Health Research Group
***Designated as Do Not Use except for serious fungal infections by Public Citizen’s Health Research Group

Other important interactions[5],[6]

Colchicine (COLCRYS, GLOPERBA, MITIGARE)

Concomitant use of atorvastatin and the gout drug colchicine may result in increased levels of colchicine, which could lead to colchicine toxicity. Colchicine toxicity typically causes gastrointestinal symptoms, including abdominal pain, nausea, vomiting and diarrhea. It also can impair the bone marrow’s ability to make red and white blood cells, resulting in severe anemia and increasing the risk of serious infections, respectively.

Colchicine itself can cause myopathy or rhabdomyolysis with long-term treatment at recommended doses. Concomitant use of colchicine with atorvastatin can further increase the risk of these adverse muscle effects.

Digoxin (LANOXIN)

Concomitant use of atorvastatin with the heart drug digoxin, which is used to treat heart failure and control the heart rate in atrial fibrillation, may result in increased levels of digoxin, which could lead to digoxin toxicity. Symptoms of digoxin toxicity include loss of appetite, nausea, vomiting and fatigue.[7] Patients taking digoxin may need a dosage change and should undergo more frequent monitoring of blood digoxin levels after starting or stopping atorvastatin.

Oral contraceptives

Concomitant use of atorvastatin with oral contraceptives containing norethindrone and ethinyl estradiol (multiple brand names including ALYACEN 7/7/7, CYCLAFEM 7/7/7 and LOESTRIN) may increase the blood levels of norethindrone and ethinyl estradiol. This may increase the risk of adverse effects of these oral contraceptives, such as harmful blood clots in veins and arteries.

Grapefruit juice

Consumption of very large quantities of grapefruit juice (more than 1.3 quarts daily) when taking atorvastatin can raise blood levels of the drug and increase the risk of myopathy and rhabdomyolysis.

What You Can Do

If you need treatment with atorvastatin, review all your other medications with your doctor to assess your risk of potentially significant drug interactions. If you are taking certain medications that interact with atorvastatin, you may need a lower dose of, or your doctor may advise you to stop, either atorvastatin or the interacting drug. Be aware that other drugs not listed in this article also may have dangerous interactions with atorvastatin.
 

References

[1] Pfizer. Label: atorvastatin (LIPTIOR). November 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020702s077lbl.pdf. Accessed February 3, 2021.

[2] Pfizer. Label: amlodipine and atorvastatin (CADUET). January 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/021540s046lbl.pdf. Accessed February 3, 2021.

[3] IBM Micromedex. Drug interactions. http://www.micromedexsolutions.com/home/dispatch. Search term: “atorvastatin.” Accessed February 3, 2021.

[4] Pfizer. Label: atorvastatin (LIPTIOR). November 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020702s077lbl.pdf. Accessed February 3, 2021.

[5] IBM Micromedex. Drug interactions. http://www.micromedexsolutions.com/home/dispatch. Search term: “atorvastatin.” Accessed February 3, 2021.

[6] Pfizer. Label: atorvastatin (LIPTIOR). November 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020702s077lbl.pdf. Accessed February 3, 2021.

[7] Concordia Pharmaceuticals. Label: digoxin (LANOXIN). February 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020405s015lbl.pdf. Accessed February 3, 2021.