Statin Toxicity From Macrolide Antibiotic Coprescription

  title={Statin Toxicity From Macrolide Antibiotic Coprescription},
  author={Amit M. Patel and Salimah Z. Shariff and David G Bailey and David N Juurlink and Sonja Gandhi and Muhammad M Mamdani and Tara Gomes and Jamie L Fleet and Y. Joseph Hwang and Amit X. Garg},
  journal={Annals of Internal Medicine},
  pages={869 - 876}
BACKGROUND Clarithromycin and erythromycin, but not azithromycin, inhibit cytochrome P450 isoenzyme 3A4 (CYP3A4), and inhibition increases blood concentrations of statins that are metabolized by CYP3A4. OBJECTIVE To measure the frequency of statin toxicity after coprescription of a statin with clarithromycin or erythromycin. DESIGN Population-based cohort study. SETTING Ontario, Canada, from 2003 to 2010. PATIENTS Continuous statin users older than 65 years who were prescribed… 

Comparing two types of macrolide antibiotics for the purpose of assessing population-based drug interactions

Clarithromycin can be used to assess drug interactions in population-based studies with azithromyzin serving as a control group, however, any differences in mortality observed between the two antibiotic groups in the setting of other drug use may be partially attributable to factors beyond the inhibition of drug metabolising enzymes and transporters.

Interaction Potential between Clarithromycin and Individual Statins - a Systematic Review.

Concurrent use of clarithromycin and CYP3A4-metabolized statins to be associated with a doubled risk of hospitalisation with rhabdomyolysis or other statin-related adverse events as compared with azithromyquin-statin co-administration.

Co-Medication of Statins with Contraindicated Drugs

The proportion of co-medication of statins with contraindicated drugs was relatively lower than that of previous studies; however, the co-Medication occurring by different medical institutions was not managed appropriately.

Risk of adverse events among older adults following co-prescription of clarithromycin and statins not metabolized by cytochrome P450 3A4

Among older adults taking a statin not metabolized by CYP3A4, co-prescription of clarithromycin versus azithromyzin was associated with a modest but statistically significant increase in the 30-day absolute risk of adverse outcomes.

Risks of Adverse Events Following Coprescription of Statins and Calcium Channel Blockers

Patients who received CYP3A4-metabolized statins had significantly higher risk of acute kidney injury, hyperkalemia, acute myocardial infarction, and acute ischemic stroke than those who received non-CYP3A 4-metabolic statins.

Clinical manifestation of macrolide antibiotic toxicity in CKD and dialysis patients

Two cases of end-stage renal disease (ESRD) patients who developed hallucinations such as vivid images of worms after taking clarithromycin were reported, similar to previous case reports of clarityromycin neurotoxicity.

Rhabdomyolysis Associations with Antibiotics: A Pharmacovigilance Study of the FDA Adverse Event Reporting System (FAERS)

This study confirms prior evidence for rhabdomyolysis associations with daptomycin, macrolides, trimethoprim-sulfamethoxazole, linezolid, fluoroquinolones, and cefdinir, and identifies previously unknown rhabDomyolytic associations with meropenem, cefditoren,cefaclor, and piperacillin-tazobactam.

Statin-Related Myotoxicity: A Comprehensive Review of Pharmacokinetic, Pharmacogenomic and Muscle Components

Further research is required, including stringent phenotyping of mild SRM through N-of-1 trials coupled to systems pharmacology omics- approaches to identify novel risk factors and provide mechanistic insight.

The clinical significance of statins-macrolides interaction: comprehensive review of in vivo studies, case reports, and population studies

Understanding the different characteristics of each statin and macrolide, as well as key patients’ risk factors, will enable health care providers to utilize both groups effectively without compromising patient safety.



Risk Management of Simvastatin or Atorvastatin Interactions with CYP3A4 Inhibitors

Nine out of ten physicians changed prescriptions or monitored potential adverse effects when informed by community pharmacists about the risk associated with co-prescription of CYP3A4 inhibitors with simVastatin or atorvastatin suggests that an important risk factor for myotoxicity due to these statins could be minimized through interdisciplinary co-operation.

Statin–macrolide interaction risk: a population-based study throughout a general practice database

Most GPs occasionally prescribed statin/macrolide at high interaction risk on the same date, despite the availability of therapeutic alternatives, and prevention strategies targeted to increase awareness of health professionals about the interaction risks of widely prescribed drugs are needed.

A Study of the Interaction Potential of Azithromycin and Clarithromycin with Atorvastatin in Healthy Volunteers

The data suggest that while azithromycin appears to be safe to coadminister with atorvastatin, clarithromyzin should be avoided in patients taking this and similarly metabolized HMG‐CoA inhibitors.

Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs.

Rhabdomyolysis risk was similar and low for monotherapy with atorvastatin, pravastsatin, and simvastsatin; combined statin-fibrate use increased risk, especially in older patients with diabetes mellitus.

A cautionary tale: delayed onset rhabdomyolysis due to erythromycin/simvastatin interaction.

An 80-year-old gentleman was admitted with a one-week history of myalgia and inability to walk, Investigations revealed an elevated AST, myoglobinuria, and high creatine kinase and he subsequently developed renal failure requiring haemofiltration.

Erythromycin Coadministration Increases Plasma Atorvastatin Concentrations

The effect of erythromycin on the pharmacokinetics of atorvastatin, an inhibitor of HMG‐CoA reductase, was investigated in 12 healthy volunteers and it was found that mean terminal half‐life was similar following each atorVastatin dose.

Prevalence of Potentially Severe Drug-Drug Interactions in Ambulatory Patients with Dyslipidaemia Receiving HMG-CoA Reductase Inhibitor Therapy

CYP3A4 inhibitors are the most frequent cause of potential drug interactions with statins, and clinicians should be aware of the most frequently observed drug-statin interactions and how these interactions can be avoided.

Steady‐State Pharmacokinetic Interactions of Darunavir/Ritonavir With Lipid‐Lowering Agent Rosuvastatin

Rosuvastatin levels increase in the presence of darunavir/ritonavir coadministration, whereas the lipid‐lowering benefits are blunted, and the clinical significance of these changes requires further investigation.

Age-Related Differences in the Prevalence of Potential Drug-Drug Interactions in Ambulatory Dyslipidaemic Patients Treated with Statins

The more frequent prescription of cardiovascular drugs with a high potential for pDDIs in patients aged ≥75 years was mainly responsible for the observed increases in statin and non-statin p DDIs in this age group.

Drug interactions with lipid‐lowering drugs: Mechanisms and clinical relevance