How to deal with statin interaction?

This topic will discuss the drug interaction with statins

Statin INRERACTION alerts continue to cause confusion. We know to watch for the more problematic statins: simvastatin, lovastatin, or atorvastatin since they're metabolized by CYP3A4 the most. But be familiar with some of the less cut-and-dried interactions...

Are all azole antifungals a big problem? No. Fluconazole is less risky. It's a moderate 3A4 inhibitor. Most others are strong inhibitors. Don't be too concerned about single-dose fluconazole. But advise patients to report muscle symptoms when longer fluconazole courses are used with simvastatin, lovastatin, or atorvastatin. For most other azoles (itraconazole, etc), hold simvastatin or lovastatin during the antifungal course and for about 3 days afterward. Also be careful with atorvastatin, depending on the azole.

Are all macrolides a problem? No. It's usually okay to use azithromycin. But avoid other macrolides with lovastatin or simvastatin.

Is fenofibrate as risky as gemfibrozil? No. But continue to advise patients on fenofibrate (Lipanthyl, Fenolip) plus any statin to report muscle problems. Use this as another reason to re-evaluate fibrate use, since there's no good evidence that adding a fibrate to a statin improves CV outcomes.

Does grapefruit juice need to be avoided with all statins? No. But advise patients on simvastatin or lovastatin to avoid it and patients on atorvastatin to keep to less than about 4 cups/day. Switch statins if a patient just has to have their grapefruit. Explain it usually isn't a problem to use any statin with grapefruit-flavored drinks, since they have very little juice.

References

Corsini, A. and Bellosta, S. (2008). Drug–drug interaction with statins. Expert Review of Clinical Pharmacology, 1(1), pp.105–113

Stump, A.L., Mayo, T. and Blum, A. (2019). Management of Grapefruit-Drug Interactions. American Family Physician, [online] 74(4), pp.605–608. Available at: https://www.aafp.org/afp/2006/0815/p605.html

Patel AM, Shariff S, Bailey DG, Juurlink DN, Gandhi S, Mamdani M, Gomes T, Fleet J, Hwang YJ, Garg AX. Statin toxicity from macrolide antibiotic coprescription: a population-based cohort study. Ann Intern Med. 2013 Jun 18;158(12):869-76. Available at: https://pubmed.ncbi.nlm.nih.gov/23778904