Rosuvastatin

Generic Name
Rosuvastatin
Brand Names
Crestor, Ezallor, Roszet
Drug Type
Small Molecule
Chemical Formula
C22H28FN3O6S
CAS Number
287714-41-4
Unique Ingredient Identifier
413KH5ZJ73
Background

Rosuvastatin, also known as the brand name product Crestor, is a lipid-lowering drug that belongs to the statin class of medications, which are used to lower the risk of cardiovascular disease and manage elevated lipid levels by inhibiting the endogenous production of cholesterol in the liver. More specifically, statin medications competitively inhibit the enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) Reductase, which catalyzes the conversion of HMG-CoA to mevalonic acid and is the third step in a sequence of metabolic reactions involved in the production of several compounds involved in lipid metabolism and transport including cholesterol, low-density lipoprotein (LDL) (sometimes referred to as "bad cholesterol"), and very low-density lipoprotein (VLDL). Prescribing of statin medications is considered standard practice following any cardiovascular events and for people with a moderate to high risk of development of CVD, such as those with Type 2 Diabetes. The clear evidence of the benefit of statin use coupled with very minimal side effects or long term effects has resulted in this class becoming one of the most widely prescribed medications in North America.

Rosuvastatin and other drugs from the statin class of medications including atorvastatin, pravastatin, simvastatin, fluvastatin, and lovastatin are considered first-line options for the treatment of dyslipidemia. This is largely due to the fact that cardiovascular disease (CVD), which includes heart attack, atherosclerosis, angina, peripheral artery disease, and stroke, has become a leading cause of death in high-income countries and a major cause of morbidity around the world. Elevated cholesterol levels, and in particular, elevated low-density lipoprotein (LDL) levels, are an important risk factor for the development of CVD. Use of statins to target and reduce LDL levels has been shown in a number of landmark studies to significantly reduce the risk of development of CVD and all-cause mortality. Statins are considered a cost-effective treatment option for CVD due to their evidence of reducing all-cause mortality including fatal and non-fatal CVD as well as the need for surgical revascularization or angioplasty following a heart attack. Evidence has shown that even for low-risk individuals (with <10% risk of a major vascular event occurring within 5 years) statins cause a 20%-22% relative reduction in major cardiovascular events (heart attack, stroke, coronary revascularization, and coronary death) for every 1 mmol/L reduction in LDL without any significant side effects or risks.

While all statin medications are considered equally effective from a clinical standpoint, rosuvastatin is considered the most potent; doses of 10 to 40mg rosuvastatin per day were found in clinical studies to result in a 45.8% to 54.6% decreases in LDL cholesterol levels, which is about three-fold more potent than atorvastatin's effects on LDL cholesterol. However, the results of the SATURN trial concluded that despite this difference in potency, there was no difference in their effect on the progression of coronary atherosclerosis.

Rosuvastatin is also a unique member of the class of statins due to its high hydrophilicity which increases hepatic uptake at the site of action, low bioavailability, and minimal metabolism via the Cytochrome P450 system. This last point results in less risk of drug-drug interactions compared to atorvastatin, lovastatin, and simvastatin, which are all extensively metabolized by Cytochrome P450 (CYP) 3A4, an enzyme involved in the metabolism of many commonly used drugs. Drugs such as ciclosporin, gemfibrozil, and some antiretrovirals are more likely to interact with this statin through antagonism of OATP1B1 organic anion transporter protein 1B1-mediated hepatic uptake of rosuvastatin.

Indication

The FDA monograph states that rosuvastatin is indicated as an adjunct to diet in the treatment of triglyceridemia, Primary Dysbetalipoproteinemia (Type III Hyperlipoproteinemia), and Homozygous Familial Hypercholesterolemia.

The Health Canada monograph for rosuvastatin further specifies that rosuvastatin is indicated for the reduction of elevated total cholesterol (Total-C), LDL-C, ApoB, the Total-C/HDL-C ratio and triglycerides (TG) and for increasing HDL-C in hyperlipidemic and dyslipidemic conditions when response to diet and exercise alone has been inadequate. It is also indicated for the prevention of major cardiovascular events (including risk of myocardial infarction, nonfatal stroke, and coronary artery revascularization) in adult patients without documented history of cardiovascular or cerebrovascular events, but with at least two conventional risk factors for cardiovascular disease.

Prescribing of statin medications is considered standard practice following any cardiovascular events and for people with a moderate to high risk of development of CVD. Statin-indicated conditions include diabetes mellitus, clinical atherosclerosis (including myocardial infarction, acute coronary syndromes, stable angina, documented coronary artery disease, stroke, trans ischemic attack (TIA), documented carotid disease, peripheral artery disease, and claudication), abdominal aortic aneurysm, chronic kidney disease, and severely elevated LDL-C levels.

Associated Conditions
Atherosclerosis, Atherosclerotic Cardiovascular Diseases, Cardiovascular Disease (CVD), Cardiovascular Events, Dysbetalipoproteinemia, Heterozygous Familial Hypercholesterolemia (HeFH), High Cholesterol, Homozygous Familial Hypercholesterolaemia (HoFH), Hypertension, Hypertension, Essential Hypertension, Hypertriglyceridemias, Major Adverse Cardiovascular Events, Mixed Dyslipidemias, Postoperative Thromboembolism, Primary Hypercholesterolemia, Primary Hyperlipidemia
Associated Therapies
Lipid-Lowering Therapy, Primary Prevention of Cardiovascular Diseases

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First Posted Date
2019-12-26
Last Posted Date
2022-05-25
Lead Sponsor
Actelion
Target Recruit Count
47
Registration Number
NCT04211272
Locations
🇧🇪

Clinical Pharmacology Unit, Merksem, Belgium

PsA T2T Statin Trial on Carotid and Coronary Atherosclerosis

First Posted Date
2019-11-26
Last Posted Date
2023-09-06
Lead Sponsor
Chinese University of Hong Kong
Registration Number
NCT04176978
Locations
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Department of Medicine and Therapeutics, Hong Kong, Hong Kong

A Study to Assess the Drug-drug Interaction of BMS-963272 and Rosuvastatin

Phase 1
Completed
Conditions
Interventions
First Posted Date
2019-10-11
Last Posted Date
2020-03-10
Lead Sponsor
Bristol-Myers Squibb
Target Recruit Count
28
Registration Number
NCT04124003
Locations
🇺🇸

PRA Health Sciences - Salt Lake, Salt Lake City, Utah, United States

A Study in Healthy Men to Test the Influence of BI 1358894 on the Amount of the Medicines Rosuvastatin and Dabigatran in the Blood

First Posted Date
2019-09-23
Last Posted Date
2020-01-13
Lead Sponsor
Boehringer Ingelheim
Target Recruit Count
26
Registration Number
NCT04099732
Locations
🇩🇪

Humanpharmakologisches Zentrum Biberach, Biberach, Germany

Investigation of the Gut Microbiome and Statin Response

Phase 4
Active, not recruiting
Conditions
Interventions
First Posted Date
2019-09-20
Last Posted Date
2024-07-24
Lead Sponsor
Sony Tuteja
Target Recruit Count
62
Registration Number
NCT04098003
Locations
🇺🇸

University of Pennsylvania, Philadelphia, Pennsylvania, United States

A Study of PF-06651600 Effect on Rosuvastatin Pharmacokinetics in Healthy Participants

Phase 1
Completed
Conditions
Interventions
First Posted Date
2019-09-17
Last Posted Date
2020-02-06
Lead Sponsor
Pfizer
Target Recruit Count
12
Registration Number
NCT04092595
Locations
🇧🇪

Brussels Clinical Research Unit, Brussels, Bruxelles-capitale, Région DE, Belgium

A Clinical Drug-Drug Interaction (DDI) Study With Omaveloxolone

First Posted Date
2019-07-05
Last Posted Date
2024-02-02
Lead Sponsor
Reata, a wholly owned subsidiary of Biogen
Target Recruit Count
61
Registration Number
NCT04008186
Locations
🇺🇸

Covance Clinical Research Unit (CRU) Inc., Dallas, Texas, United States

A Drug Interaction Study of KW-6356 With Midazolam, Caffeine, or Rosuvastatin

First Posted Date
2019-06-03
Last Posted Date
2019-11-29
Lead Sponsor
Kyowa Kirin Co., Ltd.
Target Recruit Count
50
Registration Number
NCT03970798
Locations
🇯🇵

Fukuoka Mirai Hospital Clinical Research Center, Fukuoka, Japan

Drug-Drug Interaction Study of Rucaparib, Rosuvastatin and Oral Contraceptives

First Posted Date
2019-05-17
Last Posted Date
2023-06-08
Lead Sponsor
pharmaand GmbH
Target Recruit Count
36
Registration Number
NCT03954366
Locations
🇵🇱

Zdrowie Kobiety Centrum Leczniczo-Rehabilitacyjne i Medycyny Pracy ATTIS Sp. z o.o., Zakład Onkologii Kobiecej, Warszawa, Poland

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Summit Clinical Research s.r.o., Bratislava, Slovakia

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PRA Magyarország Fázis I-es Klinikai Farmakológiai Vizsgálóhely FMC Dialízis Központ, II. em., Budapest, Hungary

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