Are there prescription medicines to avoid if I am taking statins?

Manufacturers’ package inserts of the statin medications prescribed in the US identify specific medications to be avoided or used with caution when taking statins.^1–7 The majority of the drugs that interact with statins are called CYP3A4 inhibitors.⁸ When taken simultaneously with some statins, these high-risk drug combinations predictably cause an increase in statin levels in the body which, in turn, can increase the risk of toxicity of the statin, including myopathy and liver toxicity.^9,10 Simvastatin, lovastatin, and to a lesser degree, atorvastatin, have the highest risk of a CYP34A system drug-drug interaction because they are metabolized by the enzyme CYP3A4 and should be avoided in patients taking CYP34A inhibitors.

CYP34A inhibitors that may interact with a statin include cyclosporine, amiodarone, some calcium channel blockers (CCBs), azole antifungals agents, macrolide antibiotics, and protease inhibitors.^9,11,12 While not an inhibitor, colchicine may affect the CYP34A pathway and concomitant use with statins may increase concentrations of both drugs.¹¹ Patients taking atorvastatin, simvastatin, or lovastatin who require any of these high-risk medications, may need to switch to lower-risk statins like rosuvastatin, pravastatin, or pitavastatin. In some cases, the dose of the statin need only be limited to avoid a drug-drug interaction with CYP34A inhibitors.^1–7 The drug-drug interaction between the dihydropyridine CCB amlodipine has only a minor increase in exposure to simvastatin and lovastatin, so this combination may be considered.¹¹

Gemfibrozil is a fibric acid derivative that is used to treat complex dyslipidemias or hypertriglyceridemia. A scientific statement from the American Heart Association warns that the combination of gemfibrozil with lovastatin, pravastatin, or simvastatin is potentially harmful and should be avoided.¹¹ If clinically indicated, gemfibrozil can be used safely with atorvastatin, pitavastatin, fluvastatin, and rosuvastatin.

As with colchicine, concomitant use of statins with other drugs can increase the bioavailability of the non-statin drugs.^1–7,11 Drugs combinations in this category include digoxin-atorvastatin, warfarin with fluvastatin, lovastatin, rosuvastatin, or simvastatin, glyburide-fluvastatin, and phenytoin-fluvastatin.  Monitoring of the drug effects is recommended but does not preclude concomitant use.

^References

1. Rosuvastatin [package insert]. Wilmington DE: AstraZeneca Pharmaceticals; 2010.
2. Atorvastatin [package insert]. Dublin Ireland: Pfizer Parke-Davis; 2009.
3. Simvastatin [package insert]. Cramlington UK: Merck, Sharpe & Dohne, LTD;2010.
4. Lovastatin [package insert]. Morgantown WV: Mylan Pharmaceuticals.
5. Fluvastatin [package insert]. East Hanover NJ: Novartis Pharmaceuticals; 2012.
6. Pitavastatin [package insert]. Tokyo, Japan: Kowa Pharmaceuticals; 2012.
7. Pravastatin[package insert]. Princeton, NJ: Bristol Myers Squib.
8. Vuppalanchi R. Metabolism of Drugs and Xenobiotics: Cytochrome P450 Enzymes. In: Practical Hepatic Pathology: A Diagnostic Approach. 2nd ed. Elsevier Inc; 2018:319-326.
9. Wooten JM. A brief drug class review: considerations for statin use, toxicity, and drug interactions. South Med J 2018; 111 (1): 39-44.
10. Bellosta S, Corsini A. Statin drug interactions and related adverse reactions : an update. Expert Opin Drug Saf 2018; 17 (1): 25-37.
11. Wiggins B, Saseen J, Page R et al. Recommendations for management of clinically significant drug-drug interactions with statins and select agents used in patients with cardiovascular disease. Circulation 2016; 134 : e468-95.
12. Gravatt L, Flurie R, Lajthia E, Dixon D. Clinical guidance for managing statin and antimicrobial drug-drug interactions. Curr Atheroscler Rep 2017; 19 (46).