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Patients taking the commonly prescribed drug simvastatin (FLOLIPID, VYTORIN, ZOCOR), 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 has approved simvastatin for use in combination with diet to, among other things, reduce the risk of death from cardiovascular disease and the risk of nonfatal heart attacks and strokes in...
Patients taking the commonly prescribed drug simvastatin (FLOLIPID, VYTORIN, ZOCOR), 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 has approved simvastatin for use in combination with diet to, among other things, reduce the risk of death from cardiovascular disease and the risk of nonfatal heart attacks and strokes in individuals at high risk of adverse heart events.[1] Such individuals are those with any of the following:
- Existing coronary artery disease
- Diabetes
- Peripheral vascular disease (blood-vessel disease leading to blockage of arteries outside the heart and brain
- A history of stroke or other blood-vessel disease in the brain
Drugs that increase risk of simvastatin toxicity[2],[3]
The Table below lists examples of oral drugs that, when taken concomitantly with (at the same time as) simvastatin, can cause toxic levels of simvastatin in the blood.
The list includes antibiotics, antifungal drugs, antiviral drugs for HIV infection, the antidepressant nefazodone (generic only) and drugs for abnormal heart rhythms.
Like many drugs, simvastatin 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 simvastatin, these CYP3A4-inhibiting drugs, because they decrease simvastatin breakdown, can thereby increase simvastatin levels in the blood to toxic levels.
High blood levels of simvastatin 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 and elderly patients are at increased risk of myopathy and rhabdomyolysis.
Examples of Oral Drugs That Increase the Risk of Simvastatin Toxicity
| Generic Name | Brand Name(s)† | Drug Class |
|---|---|---|
| Drugs that should not be taken concomitantly with simvastatin | ||
| atazanavir | REYATAZ | Antiviral drug for HIV infection |
| clarithromycin* | BIAXIN XL | Macrolide antibiotic |
| cyclosporine | GENGRAF, NEORAL, SANDIMMUNE | Immunosuppressant/organ transplant drug |
| danazol | generic only | Androgenic steroid |
| darunavir | PREZISTA | Antiviral drug for HIV infection |
| erythromycin | E.E.S., ERY-TAB, ERYC, ERYPED, ERYTHROCIN | Macrolide antibiotic |
| gemfibrozil** | LOPID | Blood-lipid-lowering drug |
| indinavir | CRIXIVAN | Antiviral drug for HIV infection |
| itraconazole*** | ONMEL, SPORANOX, TOLSURA | Antifungal drug |
| ketoconazole** | generic only | Antifungal drug |
| nefazodone** | generic only | Antidepressant |
| nelfinavir | VIRACEPT | Antiviral drug for HIV infection |
| posaconazole | NOXAFIL | Antifungal drug |
| ritonavir | NORVIR | Antiviral drug for HIV infection |
| saquinavir | INVIRASE | Antiviral drug for HIV infection |
| voriconazole | VFEND | Antifungal drug |
| Drugs that may require simvastatin dose reduction during concomitant use | ||
| amiodarone* | PACERONE | Abnormal heart rhythm drug |
| amlodipine* | KATERZIA, NORVASC | Calcium channel blocker, hypertension drug |
| azithromycin* | ZITHROMAX | Macrolide antibiotic |
| ciprofloxacin* | CIPRO | Fluoroquinolone antibiotic |
| diltiazem* | CARDIZEM, CARTIA XT, DILTZAC, TAZTIA XT, TIAZAC | Calcium channel blocker, hypertension drug |
| dronedarone** | MULTAQ | Abnormal heart rhythm drug |
| fluconazole | DIFLUCAN | Antifungal drug |
| lomitapide** | JUXTAPID | Cholesterol-lowering drug |
| niacin | NIACOR, NIASPAN** | Vitamin, cholesterol-lowering drug |
| ranolazine | RANEXA | Angina drug |
| risperidone* | RISPERDAL | Antipsychotic drug |
| verapamil | CALAN SR, VERELAN | Calcium channel blocker, hypertension drug |
†Combination drug that contains other active ingredients not listed
*Designated as Limited Use
**Designated as Do Not Use
***Designated as Do Not Use except for serious fungal infections
Other important drug interactions
Concomitant use of simvastatin and the anticoagulant (blood thinner) warfarin (COUMADIN, JANTOVEN) can increase blood levels of warfarin. This can increase the risk of bleeding complications. Patients who take warfarin should undergo more frequent monitoring of warfarin levels after starting, stopping or changing the dose of simvastatin.
Concomitant use of simvastatin with the heart drug digoxin (LANOXIN) may result in increased levels of digoxin, which could lead to digoxin toxicity. Symptoms of digoxin toxicity are loss of appetite, nausea, vomiting and fatigue. Patients taking digoxin should undergo more frequent monitoring of blood digoxin levels after starting or stopping digoxin.
What You Can Do
If you need treatment with simvastatin, 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 simvastatin, you may need a lower dose of, or your doctor may advise you to stop, either simvastatin or the interacting drug. Be aware that other drugs not listed in this article also may have dangerous interactions with simvastatin.
References
[1] Merck Sharp & Dohme. Label: simvastatin (ZOCOR). October 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/019766s100lbl.pdf. Accessed March 30, 2020.
[2] IBM Micromedex. Drug interactions. http://www.micromedexsolutions.com/home/dispatch. Search term: “simvastatin.” Accessed March 30, 2020.
[3] Merck Sharp & Dohme. Label: simvastatin (ZOCOR). October 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/019766s100lbl.pdf. Accessed March 30, 2020.
