Pharmacokinetic-Pharmacodynamic Drug Interactions with HMG-CoA Reductase Inhibitors

  title={Pharmacokinetic-Pharmacodynamic Drug Interactions with HMG-CoA Reductase Inhibitors},
  author={David Williams and John Feely},
  journal={Clinical Pharmacokinetics},
The HMG-CoA reductase inhibitors (statins) are effective in both the primary and secondary prevention of ischaemic heart disease. As a group, these drugs are well tolerated apart from two uncommon but potentially serious adverse effects: elevation of liver enzymes and skeletal muscle abnormalities, which range from benign myalgias to life-threatening rhabdomyolysis. Adverse effects with statins are frequently associated with drug interactions because of their long-term use in older patients who… 
Drug–Drug Interactions Between HMG-CoA Reductase Inhibitors (Statins) and Antiviral Protease Inhibitors
Simvastatin and lovastatin have the highest potency for drug–drug interaction with potent CYP3A inhibitors such as ritonavir- or cobicistat-boosted HIV-PI or the hepatitis C virus, telaprevir or boceprevir, and therefore their coadministration is contraindicated.
Drug–drug interactions that interfere with statin metabolism
The pharmacokinetic aspects of the drug–drug interaction with statins and genetic polymorphisms in CYPs, which are involved in the metabolism of statins, are discussed and the importance of establishing a system utilizing electronic medical information practically to avoid adverse drug reactions is highlighted.
Genetic Polymorphisms in Cytochrome P450 Enzymes
  • A. Vermes, I. Vermes
  • Biology, Medicine
    American journal of cardiovascular drugs : drugs, devices, and other interventions
  • 2004
Genotyping may help to select the appropriate HMG-CoA reductase inhibitor and the optimal dosage during the start of the treatment and will allow for more efficient individual therapy.
Statins and their interactions with other lipid-modifying medications: safety issues in the elderly
  • C. Ho, S. Walker
  • Biology, Medicine
    Therapeutic advances in drug safety
  • 2012
The major adverse events associated with statin use, with particular reference to the elderly patient, are summarized, including factors which might increase the risk of adverse effects.
Role of P‐glycoprotein in Statin Drug Interactions
Drug interaction studies involving statins and digoxin support a role for P‐gp, an efflux protein located in the gastrointestinal tract, placenta, kidneys, brain, and liver, and many additional drugs such as diltiazem, verapamil, itraconazoles, ketoconazole, and cyclosporine, interact with statin and are modulators of both CYP3A4 and P‐ gp.
Drug interactions with statins
Possible adverse effects of statins can occur due to interactions in concomitant use of drugs that substantially inhibit or induce their methabolic pathway.
Lipid lowering inefficacy of high-dose statin therapy due to concurrent use of phenytoin.
A case of a patient on multiple lipid-lowering medications, including high-dose atorvastatin whose LDL cholesterol improved significantly after discontinuation of phenytoin is presented, and a review of the literature for similar cases is discussed.
Cytochrome P450-mediated cardiovascular drug interactions
  • A. Scheen
  • Biology, Medicine
    Expert opinion on drug metabolism & toxicology
  • 2011
Clinicians are encouraged to develop their knowledge of CYP-mediated DDIs so that they can choose safe drug combination regimens, adjust drug dosages appropriately and conduct therapeutic drug monitoring for drugs with narrow therapeutic indices.
Lipid-lowering therapies and liver enzymes
Concerns surrounding the safety of lipid-lowering therapy as it affects liver function are focused on, and when statin therapy is needed the lowest effective dose should be prescribed in adults at risk for liver problems.
Statin-induced rhabdomyolysis.


Interactions with hydroxymethylglutaryl-coenzyme A reductase inhibitors.
  • W. Garnett
  • Biology, Medicine
    American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists
  • 1995
Although the HMG-CoA reductase inhibitors rarely have severe adverse effects, they may interact, in some cases dangerously, with other drugs, with food, and with disease states.
Drug interactions and the statins.
  • R. Herman
  • Medicine, Biology
    CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne
  • 1999
The pharmacology of drug interactions that can occur with hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) is reviewed to illustrate the scope of the problem and the ways in which physicians may manage this important therapeutic class of drugs.
Differential metabolism of statins: importance in drug-drug interactions
The pharmacokinetic properties of the statins and how they affect the use of these agents in clinical practice are described here.
Pharmacokinetic-Pharmacodynamic Consequences and Clinical Relevance of Cytochrome P450 3A4 Inhibition
The clinical importance of any drug interaction depends on factors that are drug-, patient- and administration-related and is likely to be dependent on interindividual differences in CYP3A4 tissue content, pre-existing medical conditions and, possibly, age.
HMG-CoA Reductase Inhibitors and Myotoxicity
It is important that the potentially serious adverse reactions are recognised and correctly diagnosed so that the HMG-CoA reductase inhibitor may at once be withdrawn to prevent further muscular damage.
The Use of HMG-CoA Reductase Inhibitors to Prevent Accelerated Graft Atherosclerosis in Heart Transplant Patients
Although the risk of musculoskeletal toxicity exists at any HMG-CoA reductase inhibitor dosage, most patients should be able to tolerate daily dosages of up to 20 mg of lovastatin, 10 mg of simvastatin and 40 mg of pravastatin.
Antihyperlipidaemic Agents
With the HMG-CoA reductase inhibitors, relatively new agents for which clinical data are still being accumulated, the major problems appear to be rhabdomyolysis, associated with the concomitant use of cyclosporin, fibric acid derivatives or erythromycin and mild, intermittent hepatic abnormalities that may be potentiated by other hepatotoxic drugs.
Drug Interactions of Lipid-Altering Drugs
In order to use lipid-altering drugs in the most effective, and safest manner, it is important for the clinician to have an understanding of the mechanisms of potential drug interactions.
Pharmacodynamics and Pharmacokinetics of the HMG-CoA Reductase Inhibitors
The liver is the target organ for the statins, since it is the major site of cholesterol biosynthesis, lipoprotein production and LDLcatabolism, and the adverse effects of HMG-reductase inhibitors during long term treatment may depend in part upon the degree to which they act in extrahepatic tissues.