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

An Efficacy and Safety Study of Alirocumab in Children and Adolescents With Heterozygous Familial Hypercholesterolemia

First Posted Date
2018-04-27
Last Posted Date
2023-05-06
Lead Sponsor
Sanofi
Target Recruit Count
153
Registration Number
NCT03510884
Locations
🇪🇸

Investigational Site Number :7240003, Pamplona, Navarra, Spain

🇵🇱

Investigational Site Number :6160002, Gdansk, Pomorskie, Poland

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Investigational Site Number :4840007, Oaxaca, Mexico

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An Efficacy and Safety Study of Alirocumab in Children and Adolescents With Homozygous Familial Hypercholesterolemia

First Posted Date
2018-04-27
Last Posted Date
2020-12-29
Lead Sponsor
Sanofi
Target Recruit Count
18
Registration Number
NCT03510715
Locations
🇩🇰

Investigational Site Number 2080001, Viborg, Denmark

🇪🇸

Investigational Site Number 7240001, A Coruna, Spain

🇸🇮

Investigational Site Number 7050001, Ljubljana, Slovenia

and more 7 locations

Phase IV Study to Evaluate the Effects of Statin Monotherapy or Statin / Ezetimibe Combination Therapy on Hepatic Steatosis in Patients With Hyperlipidemia and Nonalcoholic Fatty Liver Disease

First Posted Date
2018-02-15
Last Posted Date
2021-07-09
Lead Sponsor
Yonsei University
Target Recruit Count
64
Registration Number
NCT03434613
Locations
🇰🇷

Yonsei University College of Medicine, Department of Internal Medicine, Division of Endocrinology, Severance Hospital, Diabetes center, Seoul, Korea, Republic of

Safety and Efficacy of Statins for Chinese Patients With Dyslipidemia

First Posted Date
2018-02-01
Last Posted Date
2018-02-01
Lead Sponsor
Fudan University
Target Recruit Count
10000
Registration Number
NCT03418974
Locations
🇨🇳

School of Public Health, Fudan University, Shanghai, Shanghai, China

🇨🇳

Heart Center of Peking University People's Hospital, Beijing, Beijing, China

Usability Study of the Commercial Auto-injector Device and the New Auto-injector Device (SYDNEY) in Patients With High or Very High CV Risk With Hypercholesterolemia Not Adequately Controlled With Their Lipid-Modifying Therapy

First Posted Date
2018-01-30
Last Posted Date
2019-09-09
Lead Sponsor
Sanofi
Target Recruit Count
69
Registration Number
NCT03415178
Locations
🇺🇸

Investigational Site Number 8400022, Summerville, South Carolina, United States

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Investigational Site Number 8400017, Jacksonville, Florida, United States

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Investigational Site Number 8400013, Ponte Vedra, Florida, United States

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Safety, Tolerability and PK of PXL770 in Healthy Male Subjects

First Posted Date
2018-01-10
Last Posted Date
2018-08-24
Lead Sponsor
Poxel SA
Target Recruit Count
60
Registration Number
NCT03395470
Locations
🇬🇧

Hammersmith Medicines Research (HMR), London, United Kingdom

Clinical Study to Investigate the Effect of Macitentan on the Concentrations of Rosuvastatin in the Blood of Healthy Male Subjects

Phase 1
Completed
Conditions
Interventions
First Posted Date
2017-12-02
Last Posted Date
2017-12-20
Lead Sponsor
Actelion
Target Recruit Count
20
Registration Number
NCT03359291
Locations
🇩🇪

CRS Clinical Research Services Mannheim, Mannheim, Germany

A Study in Healthy Male Subjects to Investigate Whether Administration of ACT-541468 Can Affect the Fate in the Body (Amount and Time of Presence in the Blood) of Rosuvastatin

Phase 1
Completed
Conditions
Interventions
First Posted Date
2017-11-13
Last Posted Date
2017-12-11
Lead Sponsor
Idorsia Pharmaceuticals Ltd.
Target Recruit Count
20
Registration Number
NCT03339752
Locations
🇨🇿

Cepha s.r.o., Pilsen, Czechia

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