Statin drug interactions and related adverse reactions: an update

ABSTRACT

Introduction: Statins reduce the risk of cardiovascular morbidity and mortality in patients with or at risk for cardiovascular disease and their use is expanding, especially in elderly. Statins are prescribed on a long-term basis and may undergo drug–drug interactions (DDIs) with other drugs. Statins have different safety and tolerability, and this might affect the possibility of DDIs with other cardiovascular drugs, increasing the risk of statin-associated myopathy and hepatotoxicity. Polypharmacy and pharmacogenetic variability are potential causes of statin DDIs. Thus, the safety and adverse effects of statins, particularly in patients receiving multiple medications at risk of DDIs, are a matter of special concern.

Areas covered: The purpose of this manuscript is to give an update on the potential statin DDIs and related adverse drug reactions (myopathy and hepatotoxicity), with special considerations on polypharmacy in elderly population, HIV patients, cardiovascular drugs and liver toxicities. The potential DDIs among statins and monoclonal antibodies including the recently approved PCSK9 inhibitors are also extensively discussed in the present review.

Expert opinion: A better understanding of the incidence and clinical significance of statin DDIs will help physicians in fine-tuning the lipid-lowering therapeutic interventions thus providing their patients with an evidence-based, safe and cost-effective clinical support.

KEYWORDS:

• Dabigatran
• elderly patients
• HIV patients
• ivabradine
• liver toxicity
• PCSK9 inhibitors antibodies
• polypharmacy
• sacubitril
• ticagrelor
• tocilizumab

Article highlights

• Patients with multiple comorbidities receive concomitant multiple medications and are exposed to increased risk of adverse events, including SAMS and statin-induced hepatotoxicity, due to increased exposure to statins caused by DDIs with co-prescribed drugs.

• Statins have different PK properties. Many clinically significant DDIs are on a PK basis and the risk of DDIs varies among different statins thus affecting differently statin safety and tolerability

• Pharmacogenetics and molecular studies have highlighted that several inter-individual variations in the activity of CYP450 enzymes and transport proteins exist and may contribute to statin disposition and DDIs.

• Some therapeutic mAbs may exert an indirect effect on hepatic clearance pathways involved in the metabolism of conventional drugs. On the other hand, drugs affecting the expression of the molecular target of a specific mAb (i.e. PCSK9 inhibitors) may also influence the target-mediated clearance of mAbs.

• Older patients, due to the highest prevalence of chronic diseases and comorbidities, require multiple drug therapies and are the major consumers of medications in most developed countries thus increasing the potential risk of DDIs.

• Physicians should make a careful evaluation of possible DDI risks when co-administering drugs in patients receiving a statin therapy. This will allow them to balance the potential clinical benefits versus the risks of statin treatment, thus improving overall outcomes and provide patients with a safe and cost-effective pharmacological therapy.

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Declaration of interest

S. Bellosta received an honorarium from Novartis for a giving a lecture. A. Corsini, PhD has received research grants and/or honoraria from or having been a consultant for Astra Zeneca, Merck and Co, Pfizer Inc., Kowa, Recordati, AMGEM, Sanofi Aventis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.