Phenytoin and a number of statins are metabolized by the superfamily of cytochrome p450 cyp isoenzymes present in the intestines, liver, lung, kidney and brain. Pharmacogenomicsdrug disposition, drug targets, and side effects. Dec 01, 2018 drug interactions hmg coa reductase inhibitors. If concomitant therapy is necessary, the patient should be observed for symptoms of. Recommendations for management of clinically significant drugdrug interactions with statins and select agents used in patients with cardiovascular disease. Pharmacodynamic relationships of atorvastatin, an hmg. Case reports in medicine hindawi publishing corporation. Pharmacokinetic pharmacodynamic drug interactions with hmg coa reductase inhibitors.
In healthy adult subjects, concomitant administration of cubicin and simvastatin had no effect on plasma trough concentrations of simvastatin, and there were no reports of skeletal myopathy see clinical pharmacology 12. Pharmacokinetic and pharmacodynamic assessments of hmgcoa. The aim of this study was to investigate the incidence of. Request pdf drug interactions with hmgcoa reductase inhibitors statins. Boc and tpv are both substrates and inhibitors of the hepatic enzyme, cytochrome p450 3a, and the drug transporter, p. Statins and ciprofloxacin are both commonly prescribed drugs. Dec 15, 2003 hmg coa reductase inhibitors the statins are an important class of cholesterol lowering medications that act by competitive inhibition of 3hydroxy3methylglutaryl coenzyme a hmg coa reductase.
Clinically relevant drug interactions between statins and. The role of cytochrome p450mediated drugdrug interactions in determining the. These drugs are effective and widely prescribed for the treatment of hypercholesterolemia and prevention of cardiovascular morbidity and mortality. Coa reductase inhibitors are metabolized in the liver by the cyp450 enzymes 1 see table 1. The hmgcoa reductase inhibitors statins are effective in both the primary and secondary prevention of ischaemic heart disease. This article was sponsored by kowa pharmaceuticals america. Major temporarily suspend hmg coa reductase inhibitors in patients taking daptomycin as cases of rhabdomyolysis have been reported with concomitant use. The 3hydroxy3methylglutaryl coenzyme a hmg coa reductase inhibitors statins are generally well tolerated as monotherapy. Although safe when used alone, in combination with other drugs the likelihood of adverse drug reactions increases significantly. Pharmacokineticpharmacodynamic drug interactions with hmgcoa reductase inhibitors. To support the development of these agents statins as potential hypocholesterolemic drugs, a variety of preclinical studies were conducted in several animal species. This leads to the possibility of pharmacokinetic drug interactions, given the well.
Recommendations for management of clinically significant drug. The metabolism of statins is complex, with extensive conversion between the lactone, openacid, and glucuronidated forms as well as other less common metabolites. Atorvastatin and hmgcoa reductase inhibitors are the most frequently used medication in the world due to very few adverse toxic side effects. Statins or hmgcoa reductase inhibitors represent a class of drugs used to. Pharmacokinetic and pharmacodynamic assessments of. Pharmacogenetic considerations for statin drugdrug interactions. Pharmacodynamic pd drugdrug interactions ddis are unlikely to occur as statins are highly selective inhibitors of hmgcoa reductase with no relevant effect on other.
Everolimus c max was reduced by 9% and 10% with atorvastatin and pravastatin coadministration. Common side effects include joint pain, diarrhea, heartburn, nausea, and muscle pains. Drug drug interactions and interindividual differences in transporter and metabolic enzyme functions. The objectives of the present study were to develop a population pharmacokineticpharmacodynamic pk.
Atorvastatin and hmg coa reductase inhibitors are the most frequently used medication in the world due to very few adverse toxic side effects. Dec 27, 2016 atorvastatin and hmg coa reductase inhibitors are the most frequently used medication in the world due to very few adverse toxic side effects. Hmg coa reductase catalyzes the reduction of 3hydroxy3methylglutarylcoenzyme a hmg coa to mevalonate, which is the ratelimiting step in hepatic cholesterol biosynthesis. Coa reductase with no relevant effect on other enzymes or receptor systems.
Both atorvastatin and lovastatin are metabolized by cyp3a4 and danazol is reported to be a cyp3a4 inhibitor 2. Oct 22, 2007 phenytoin and a number of statins are metabolized by the superfamily of cytochrome p450 cyp isoenzymes present in the intestines, liver, lung, kidney and brain. Multiple drug interactions induced serotonin syndrome. Clinical pharmacokinetics of pravastatin springer for. May 24, 20 the hmg coa reductase inhibitors are a class of drugs also known as statins. Hmgcoa reductase inhibitors, more commonly known as the statins. Safety issues with statin therapy journal of the american. Coadministration with the hmgcoa reductase inhibitors that are primarily metabolized through cyp3a4 e. Pharmacokinetic drug interactions between hmgcoa reductase inhibitors fluvastatin with concomitantl. As a group, these drugs a adverse effects with statins are frequently associated with drug interactions because of their longterm use in older patients who are likely to be exposed to polypharmacy. Coa reductase inhibitor, is widely used for the treatment of hyperlipidaemia. The american heart association has estimated that more than 70 million americans have some form of cardiovascular disease, the most common manifestations of which are high blood pressure 65 million, coronary heart disease chd million, stroke 5. Recommendations for management of clinically significant. In cardiovascular research, evidence points toward the benefits of increasingly low levels of lowdensity lipoprotein cholesterol ldlc, the socalled bad cholesterol.
The risk of myopathy and rhabdomyolysis increases when fluconazole is coadministered with hmgcoa reductase inhibitors metabolised through cyp3a4, such as atorvastatin and simvastatin, or through cyp2c9, such as fluvastatin. The risk of myopathy and rhabdomyolysis increases when fluconazole is coadministered with hmg coa reductase inhibitors metabolised through cyp3a4, such as atorvastatin and simvastatin, or through cyp2c9, such as fluvastatin. The patient in our case who previously had cardiac insufficiency, atrial. Inflammation, immunity, and hmgcoa reductase inhibitors. Drug interactions with hmgcoa reductase inhibitors statins. Drugdrug interactions ddis are a well known risk factor for adverse drug reactions. A pharmacokinetic and pharmacodynamic drug interaction. Cubicin rf daptomycin dose, indications, adverse effects. Hansten 11regarding drug drug interactions and myopathy risk with statins provide important additional information to guidelines issued last year on the use of these agents 22. Pharmacokineticpharmacodynamic drug interactions with hmgcoa reductase. The discovery that 3hydroxy3methyglutaryl coenzyme a reductase was a ratedetermining step in the biosynthesis of cholesterol led to the discovery of inhibitors of this enzyme. The metabolism of statins is complex, with extensive conversion between the lactone, openacid, and glucuronidated. Statins and phenytoin interact a case history tan 2008.
Statins also called hmgcoa reductase inhibitors block an enzyme called hmgcoa reductase 3hydroxy3methylglutaryl coenzyme a reductase that is involved in the synthesis of mevalonate, a naturally occurring substance that is then used by the body to make sterols, including cholesterol. The pharmacokinetics of all three drugs and total hmg. Clinically, drugdrug interactions may lead to severe toxicity and may force. May 2018 research journal of pharmacy and technology roshan sayeed. Comparative tolerability of the hmg coa reductase inhibitors. Pharmacodynamics and pharmacokinetics of the hmgcoa.
Major temporarily suspend hmgcoa reductase inhibitors in patients taking daptomycin as cases of rhabdomyolysis have been reported with concomitant use. Clinical decision making on statin drug interactions jacc. Hmgcoa reductase inhibitors statins are a cornerstone in the treatment of dyslipidaemia and patients with dyslipidaemia are concomitantly treated with a variety of additional drugs. A scientific statement from the american heart association. Absence of interaction between atorvastatin or other. The hmgcoa reductase inhibitors are a class of drugs also known as statins. For the prevention of cardiovascular disease, statins are a firstline treatment. Interaction between amlodipine and simvastatin in patients. Pharmacokinetic and pharmacodynamic alterations of 3hydroxy. Chemical, pharmacokinetic and pharmacodynamic properties. Major dietdrug interactions affecting the kinetic characteristics and. In healthy subjects, concomitant administration of cubicin and simvastatin had no effect on plasma trough concentrations of simvastatin, and there were no reports of skeletal myopathy see clinical pharmacology 12. Statin drug interactions and related adverse reactions. Myopathy is most likely to occur when statins are administered with other drugs.
Both agents can cause myopathy and rhabdomyolysis when given alone and the risk may be increased when given together. Severe rhabdomyolysis as complication of interaction. Pravastatin, one of the 3hydroxy3methylglutarylcoenzyme a hmgcoa reductase inhibitors statins widely used in the management of hypercholesterolaemia, has unique pharmacokinetic characteristics among the members of this class. Review and management of drug interactions with boceprevir and telaprevir. Chemical, pharmacokinetic and pharmacodynamic properties of statins. As with other statins, atorvastatin is a competitive inhibitor of hmg coa reductase. Pharmacogenomics drug disposition, drug targets, and side effects. Pharmacokinetic and pharmacodynamic assessments of hmgcoa reductase inhibitors when coadministered with everolimus article in the journal of clinical pharmacology 422. Concurrent use of verapamil or diltiazem and hmgcoa reductase inhibitors increases the risk of muscle related adrs introduction the hmgcoa reductase inhibitors statins are effective in both the primary and secondary prevention of ischaemic heart disease. Hmgcoa reductase inhibitors the statins are an important class of cholesterol lowering medications that act by competitive inhibition of 3hydroxy3. Sep 14, 2012 the hmg coa reductase inhibitors statins are effective in both the primary and secondary prevention of ischaemic heart disease.
Multiple drug interactionsinduced serotonin syndrome. Hansten 1 regarding drugdrug interactions and myopathy risk with statins provide important additional information to guidelines issued last year on the use of these agents 2. One potentially life threatening adverse effect is caused by clinically significant statin induced rhabdomyolysis, either independently or in combination with fusidic acid. Pd model for simvastatin and to evaluate its usefulness in predicting the doseresponse relationship of simvastatin in patients with hyperlipidaemia. A population pharmacokineticpharmacodynamic model for. Pharmacokinetic and pharmacodynamic alterations of 3hydroxy3methylglutaryl coenzyme a hmgcoa reductase inhibitors.
Select statindrug interactions discussed in the article that do not. Drugdrug interactions and interindividual differences in transporter and metabolic enzyme functions. Comparative tolerability of the hmgcoa reductase inhibitors. Pharmacodynamics and pharmacokinetics of the hmgcoa reductase inhibitors. Since ddis are associated with adverse reactions, we performed a crosssectional study to assess the. Pharmacokinetic evaluation of the interaction between the hcv protease inhibitor boceprevir and the hmgcoa reductase inhibitors atorvastatin. As a result, the number of individuals requiring lipidlowering medications has increased, and the most commonly used agents, the hmgcoa reductase inhibitors or statins, are used aggressively in some patients to. Background some, but not all, post hoc analyses have suggested that the antiplatelet effects of clopidogrel are inhibited by atorvastatin. However, the literature contains confusing data concerning the degree of liver versus tissue selectivity.
Concurrent use of verapamil or diltiazem and hmgcoa. Prevalence of potentially severe drugdrug interactions in. Pharmacokinetic and pharmacodynamic assessments of hmg. Statins 3hydroxy3methylglutarylcoenzyme a hmgcoa reductase inhibitors are effective in both the primary and. Nov 03, 2014 a pharmacokinetic and pharmacodynamic drug interaction between rosuvastatin and valsartan in healthy subjects jin ah jung,1 sooyun lee,2 jungryul kim,1 jaewook ko,1,2 seong bok jang,3 su youn nam,3 wooseong huh1,41department of clinical pharmacology and therapeutics, samsung medical center, 2department of health sciences and technology, samsung advanced institute for health sciences and. Different degrees of liver selectivity have been claimed for the hmgcoa reductase inhibitors. Pharmacodynamic pd drug drug interactions ddis are unlikely to occur as statins are highly selective inhibitors of hmgcoa reductase with no relevant effect on other. The 3hydroxy3methylglutaryl coenzyme a hmgcoa reductase inhibitors statins are generally well tolerated as monotherapy. Unlike most others, however, it is a completely synthetic compound. Performance of community pharmacy drug interaction software. Statins are associated with two important adverse effects, asymptomatic elevation in liver enzymes and myopathy. Recommendations for management of clinically significant drug drug interactions with statins and select agents used in patients with cardiovascular disease. The role of cytochrome p450mediated drug drug interactions in determining the. Expanded clinical evaluation of lovastatin excel study results.
Pharmacokinetic and pharmacodynamic alterations of 3. Additionally, their routes of metabolism and transport predispose them to drug drug interactions. Hmg coa reductase catalyses the conversion of hmg coa to mevalonate, the. As a group, these drugs are well tolerated apart from two uncommon but potentially serious adverse effects. Pharmacokineticpharmacodynamic drug interactions with hmg. Severe rhabdomyolysis as complication of interaction between. Mar 26, 2020 coadministration with the hmg coa reductase inhibitors that are primarily metabolized through cyp3a4 e. Statins are cholesterollowering drugs widely used for cardiovascular prevention.
A drug whose affinity for cyp3a4 is greater than that of a statin blocks the. Concomitant administration of statins with food may alter statin pharmacokinetics or pharmacodynamics, incre asing the risk of adverse reactions such as. As a group, these drugs are well tolerated apart from two. Interactions between grapefruit juice and hmgcoa reducatase. The exposure of the bulgarian population to coprescriptions leading to potential statindrug interactions is currently unknown. Review and management of drug interactions with boceprevir. Coadministration with the hmg coa reductase inhibitors that are primarily metabolized through cyp3a4 e. Hmgcoa reductase inhibitors statins are widely used for the.
The statins have distinctive pharmacodynamic and pharmacokinetic properties that. Atorvastatin, sold under the brand name lipitor among others, is a statin medication used to prevent cardiovascular disease in those at high risk and treat abnormal lipid levels. For example, the hmgcoa reductase inhibitors lovastatin and cerivastatin diminish the expression of the integrin dimer cd11b mac1, the cognate ligand of icam1 on endothelium and other cells on monocytes and inhibit adhesion of leukocytes to ecs. Drugdrug interactions between hmgcoa reductase inhibitors. Pharmacodynamic pd drug drug interactions ddis are unlikely to occur as statins are highly selective inhibitors of hmg coa reductase with no relevant effect on other. Concurrent use of verapamil or diltiazem and hmg coa reductase inhibitors increases the risk of muscle related adrs introduction the hmg coa reductase inhibitors statins are effective in both the primary and secondary prevention of ischaemic heart disease. Hansten regarding drugdrug interactions and myopathy risk with statins provide important additional information to guidelines issued last year on the use of these agents. Pdf pharmacokinetic drug drug interactions between. Though these agents represent an important advance in the treatment of chronic hcv, they present new treatment challenges to the hepatology community. On the basis of clinical trial evidence, the most commonly prescribed lipidmodifying therapies are the hydroxymethylglutarylcoenzyme a hmg coa reductase inhibitors, more commonly known as the statins. A pharmacokinetic and pharmacodynamic drug interaction between rosuvastatin and valsartan in healthy subjects jin ah jung,1 sooyun lee,2 jungryul kim,1 jaewook ko,1,2 seong bok jang,3 su youn nam,3 wooseong huh1,41department of clinical pharmacology and therapeutics, samsung medical center, 2department of health sciences and technology, samsung advanced. Dujovne ca, chremos an, pool jl, schnaper h, bradford rh, shear cl et al. Clinical decision making on statin drug interactions.