Rosuvastatin

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Rosuvastatin (INN), marketed under the tradename Crestor , is a statin group member, used in combination with exercise, diet and weight loss to treat high cholesterol and related conditions , and to prevent cardiovascular disease. It was developed by Shionogi. In 2013, Crestor is the fourth best-selling drug in the United States, counting approximately. $ 5.2 billion in sales. The generic version is available in the United States by 2016.

Video Rosuvastatin

Medical use

The main use of rosuvastatin is for the treatment of dyslipidemia.

Effect on cholesterol level

The effects of rosuvastatin on LDL cholesterol are associated with doses. Higher doses are more efficacious in increasing the lipid profile of patients with hypercholesterolaemia than equivalent doses of milligrams of atorvastatin and equivalent doses of milligrams or higher than simvastatin and pravastatin.

Meta analysis showed that rosuvastatin was able to increase HDL cholesterol levels well, as did other statins. The 2014 Cochrane Review provides no good evidence for rosuvastatin to lower non-HDL levels linearly with doses. HDL increased by 7% with no recorded dose effects.

Maps Rosuvastatin

Side effects and contraindications

Side effects are rare. The following side effects should be reported to the prescribing physician if they continue or get worse:

• constipation
• heartburn
• hungover
• can not sleep
• depression
• joint pain
• cough
• memory loss or forgetfulness
• confusion

The following rare side effects are more serious. Like all statins, rosuvastatin can cause myopathy, rhabdomyolysis. Stop taking rosuvastatin and contact your doctor prescribing if any of these occur:

• muscle pain, tenderness, or weakness
• lack of energy
• fever
• chest pain
• jaundice: yellowing of the skin or eyes
• dark, or foamy urine
• pain in the upper right abdomen
• nausea
• extreme fatigue
• weakness
• unusual bleeding or bruising
• loss of appetite
• flu-like symptoms
• sore throat, chills, or other signs of infection

If there are any signs of an allergic reaction, contact an emergency medical service immediately:

• rash
• nest
• itch
• difficulty breathing or swallowing
• swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
• hoarse voice
• numbness or tingling of fingers or toes

Rosuvastatin has several contraindications, conditions that guarantees retention of treatment with rosuvastatin, including hypersensitivity to rosuvastatin or components of formulation, active liver disease, elevated serum transaminases, pregnancy, or lactation. Rosuvastatin should not be taken while pregnant because it can cause serious harm to the unborn baby. In the case of breastfeeding, it is not known whether rosuvastatin is passed through breast milk, but because of the potential to disrupt the baby's lipid metabolism, the patient should not breastfeed while using rosuvastatin.

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Drug interactions

The following drugs may have negative interactions with rosuvastatin and should be discussed with the prescribing physician:

• Coumarin anticoagulants ('blood thinners', such as warfarin) can affect the removal of rosuvastatin
• Ciclosporin, colchicine
• Drugs that can decrease the level or activity of endogenous steroid hormones, eg. cimetidine, ketoconazole, and spironolactone
• Additional drugs for high cholesterol such as clofibrate, fenofibrate, gemfibrozil, and niacin (when taken in modified-conversion doses of 1 g/day or more)
• Specific protease inhibitors including atazanavir (when using ritonavir), lopinavir/ritonavir, and simeprevir
• Alcohol intake should be reduced when using rosuvastatin to reduce the risk of developing liver damage
• Aluminum and magnesium hydroxide antacids should not be taken within two hours of taking rosuvastatin
• Co-administration of rosuvastatin with eluxadoline may increase the risk of rhabdomyolysis and myopathy

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Structure

Rosuvastatin has a structural similarity to most other synthetic statins, for example, atorvastatin, cerivastatin and pitavastatin, but unlike other statins, rosuvastatin contains sulfur (in sulfonyl functional groups).

Crestor is actually a calcium rosuvastatin salt, which is calcium rosuvastatin, in which calcium replaces hydrogen in the carboxylic acid group to the right of the skeletal formula at the top right of this page.

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Action mechanism

Rosuvastatin is a competitive inhibitor of the enzyme HMG-CoA reductase, having a working mechanism similar to other statins.

The beneficial effects of putative rosuvastatin therapy on chronic heart failure can be negated by increased markers of collagen remodeling as well as decreased Q = 10/sub> coenzyme plasma levels in patients with chronic heart failure.

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Pharmacodynamics

In Cochrane's systematic review, the dosage of associated doses of rosuvastatin in blood lipids was determined. During the dose range of 1 to 80 mg/day total cholesterol decreased by 22.1% to 44.8%, LDL cholesterol by 31.2% to 61.2%, non-HDL cholesterol by 28.9% to 56.7% and triglycerides by 14.4% to 26.6%.

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Pharmacokinetics

The absolute bioavailability of rosuvastatin is about 20% and C _max is achieved in 3 to 5 hours; administration with food does not affect AUC according to the original sponsor proposed clinical studies and product labeling. However, subsequent clinical studies showed a sharp decline in rosuvastatin exposure when administered with food. This is a protein bound to 88%, especially for albumin. The fraction absorbed by rosuvastatin is often misquoted in the literature as about 0.5 (50%) because the calculated extraction calculation ratio in the original submission packet is then corrected by the FDA reviewer. It is likely that closer to 0.25 (25%) of the given dose is absorbed.

Rosuvastatin is metabolized mainly by CYP2C9 and is not extensively metabolized; about 10% is recovered as metabolite N -desmethyl rosuvastatin. It is excreted in the stool (90%) mainly and the elimination half-life of about 19 hours.

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Society and culture

Indications and settings

Rosuvastatin is approved in the United States for the treatment of high LDL cholesterol (dyslipidemia), total cholesterol (hypercholesterolemia), and/or triglycerides (hypertriglyceridemia). In February 2010, rosuvastatin was approved by the FDA for the primary prevention of cardiovascular events.

In 2004, rosuvastatin was approved in 154 countries and launched in 56. Approval in the United States by the FDA was conducted on August 12, 2003.

JUPITER (2008) trial results suggest rosuvastatin may reduce the relative risk of heart attack and stroke in patients without hyperlipidemia, but with elevated levels of highly sensitive C-reactive protein. This can greatly impact on medical practice by putting many patients on prophylactic statins that otherwise would not be treated. As a result of this clinical trial, the FDA approved rosuvastatin for the primary prevention of cardiovascular events.

The AURORA trial randomized 2776 patients undergoing hemodialysis due to kidney damage to receive rosuvastatin or placebo. Randomized, double-blind (2005 to 2009) studies found no differences in the two groups at the primary end point, a combination of cardiovascular mortality, nonfatal myocardial infarction, or nonfatal stroke. The study found no difference in all-cause mortality among these populations at an average follow-up of 3.8 years.

FDA Advisor for East Asian patients

According to the FDA, the risk of myopathy during rosuvastatin therapy may increase in Asia:

Because Asians seem to process drugs differently, half the standard doses may have the same cholesterol-lowering benefits in these patients, although full doses may increase the risk of side effects, a study by drugmaker AstraZeneca showed.

Therefore, doctors should start an Asian-American or East Asian patient at the lowest dose level.

Patent protection and generic version

The main patent protecting rosuvastatin (RE37,314 - due to expire in 2016) is challenged as an improper reissue of previous patents. This challenge was rejected in 2010, confirming protection until 2016.

In April 2016, the FDA approved the first generic rosuvastatin version (from Watson Pharmaceuticals Inc.).

In July 2016 Mylan got approval for his generic rosuvastatin calcium.

Marketing

The drug was billed as a "super-statin" during its clinical development; His claim is that it offers high potential and increases cholesterol reduction compared to competitors in the class. The main competitors for rosuvastatin are atorvastatin (Lipitor) and simvastatin (Zocor). However, one can also combine ezetimibe with simvastatin or atorvastatin and other agents by itself, for a somewhat similar response rate. In 2006 some published information to compare the results of rosuvastatin, atorvastatin, and ezetimibe/simvastatin was available, but many relevant studies are still in process.

First launched in 2003, sales of rosuvastatin were $ 129 million and $ 908 million in 2003 and 2004, respectively, with a total patient care population of over 4 million by the end of 2004. The typical cost per patient to NHS UK is Ã, Â £ 18.03 - 26.02/month (compared with Ã, Â £ 0.85 to 1.37/month for simvastatin).

Debates and criticism

In October 2003, a few months after its introduction in Europe, Richard Horton, editor of the medical journal The Lancet, criticized the way the Crestor was introduced. "AstraZeneca's tactic of marketing cholesterol-lowering drugs, rosuvastatin, raises troubling questions about how medicines enter clinical practice and what measures exist to protect patients from inadequately researched drugs," according to the editorial. The Lancet's editorial position is that the data for Crestor superiority is too dependent on extrapolation of lipid profile data (end-point replacement) and too little on harsh clinical endpoints, available for other statins. which has been in the market longer. Manufacturers respond by stating that some drugs have been tested successfully in many patients. In a correspondence published in The Lancet, AstraZeneca CEO Sir Tom McKillop called the editorial "flawed and wrong" and criticized the journal for making "outrageous criticisms of seriously studied drugs."

In 2004, public interest organizations Public Citizen filed Citizens Petition with the FDA, requesting that Crestor be withdrawn from the US market. On March 11, 2005, the FDA issued a letter to Sidney M. Wolfe, MD of Public Citizen who rejected the request and provided a detailed analysis of the findings that showed no basis for concern about rosuvastatin compared with other approved statins for marketing in the United States.

Myopathy

Like all statins, there are concerns of rhabdomyolysis, undesirable side effects. The FDA has shown that "it does not appear that the risk of [rhabdomyolysis] is greater with Crestor compared to other marketed statins", but has mandated that warnings about these adverse effects, as well as warnings of renal toxicity, are added to product labels.

Diabetes mellitus

Statins increase the risk of diabetes, consistent with an FDA review of the JUPITER trial, which reported a 27% increase in diabetes mellitus reported by researchers in patients treated with rosuvastatin compared with patients treated with placebo.

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References

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References

• "Annual Report and Form 20-F, Information 2004" (PDF) . AstraZeneca PLC. 2005. Archived from the original (PDF) in 2007-02-02. Ã,
• "Annual Report and Form 20-F, 2003" (PDF) . AstraZeneca PLC. 2004. Archived from the original (PDF) in 2004-07-28 . Obtained 2005-03-20 .
• "Preset Highlighting Information" (PDF) . AstraZeneca PLC. 2008 . Retrieved 2009-03-11 .
McTaggart F, Buckett L, Davidson R, Holdgate G, McCormick A, Schneck D, Smith G, Warwick M (2001). "Preclinical and clinical pharmacology of Rosuvastatin, a new 3-hydroxy-3-methylglutaryl A reductase inhibitor coenzyme. Am J Cardiol . 87 (5A): 28B-32B. doi: 10.1016/S0002-9149 (01) 01454-0. PMID 11256847.

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External links

• "Information Rosuvastatin (Crestor)". eMedicineHealth. Ã,
• Rosuvastatin, Drug Information Portal National US Library
• Crestor Official Website

Source of the article : Wikipedia