Atorvastatin

Structural formula
General
Non-proprietary name	Atorvastatin
other names	(3 R , 5 R ) -7- [2- (4-fluorophenyl) -5-isopropyl-3-phenyl-4- (phenylcarbamoyl) pyrrol-1-yl] -3,5-dihydroxyheptanoic acid ( IUPAC )
Molecular formula	C 33 H 35 FN 2 O 5
External identifiers / databases
CAS number 134523-00-5 134523-03-8 (calcium salt) EC number 806-698-0 ECHA InfoCard 100.125.464 PubChem 60823 ChemSpider 54810 DrugBank DB01076 Wikidata Q668093
Drug information
ATC code	C10 AA05
Drug class	Statins
Mechanism of action	HMG-CoA reductase - inhibitor
properties
Molar mass	558.65 g · mol -1
Melting point	159.2-160.7 ° C 158.3 ° C (calcium salt) 190.9 ° C (magnesium salt) 197.2 ° C (calcium salt)
solubility	almost insoluble in water (1.12 mg l −1 at 25 ° C)
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS labeling of hazardous substances no GHS pictograms H and P phrases H: no H-phrases P: no P-phrases
Toxicological data	> 5000 mg kg −1 ( LD 50 ,  rat ,  oral , calcium salt)
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Atorvastatin is a drug from the group of statins that is used to treat hypercholesterolemia . In German-speaking countries, it is sold under the names Sortis ^® and Atorvalan and in many other countries as Lipitor . It was first marketed by Warner-Lambert in 1997, but is now marketed by Pfizer . The active ingredient has been available as a generic in Germany for the first time since May 2012 . The drug was developed in 1985 by Bruce D. Roth .

Mechanism of action

Atorvastatin is a competitive HMG-CoA reductase inhibitor. The HMG-CoA reductase acts as a catalyst in the reduction of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) to mevalonate, which is a limiting step in hepatic cholesterol synthesis.

By lowering the cholesterol synthesis, the liver cells increase the number of LDL receptors on the cell surface, so that the LDL uptake into the liver cell increases and thus the LDL level in the blood is reduced.

Potency

Until the beginning of 2009, atorvastatin was considered to be the strongest statin on the German market in the doses used (10 to 20, rarely up to 80 mg per day) and is around two to three times as strong as simvastatin (10 mg atorvastatin corresponds to around 20–30 mg simvastatin ). Rosuvastatin , which has been available on the German market since January 2009, is stronger than atorvastatin . As of May 8, 2012, the strengths of 30 and 60 mg will also be offered by generic companies; these allow individual therapy settings for each patient so that the risk of possible side effects can be minimized.

Side effects

Atorvastatin can u. a. Disorders of the gastrointestinal tract (diarrhea, constipation, flatulence), fatigue, muscle pain and headache and joint pain. Serious, albeit rare, side effects include toxic myopathies , which can be fatal.

More recent studies show an increased risk of diabetes mellitus with statins, even if the risk-benefit ratio is apparently favorable.

Market importance / therapeutic advantages

World market

Sales of atorvastatin (Lipitor) in

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In 2008 atorvastatin had a market share of approx. 40–50% in the global statin market. In 2008 it generated sales of $ 12.4 billion for Pfizer. In 2011, atorvastatin was the # 1 top-selling drug in the world, with sales of $ 12.264 billion.

Germany

At the end of 2003, the market share on the German market was around 50%. At the beginning of 2004, a health reform came into force that specified a fixed amount for all statins. The Pfizer company decided not to adjust the prices for Sortis to the fixed amounts, so that since then, when prescribing Sortis ^®, a higher co-payment was incurred for the patients. The manufacturer justified this measure with economic reasons in an international context. As a result of this campaign, the market share of the Sortis packs prescribed by the statutory health insurance in Germany fell to less than 5 percent in 2005, according to the health insurance companies. The market share in private health insurance was over 50 percent in the same period. On May 7, 2012 the patent protection for atorvastatin expired; Since May 8, 2012, the active ingredient has been free for generic suppliers. Since, according to the study, more than 50% of patients who are already in therapy e.g. B. with simvastatin, have an insufficiently lowered LDL and total cholesterol level, atorvastatin is an alternative for health insurance patients with better effectiveness at a similar price.

Trade names

Monopreparations

Sortis (D, A, CH); Atoris (D) and other generics (D, A, CH)

Combination preparations

• with amlodipine : Caduet (A, CH) and generics
• with ramipril and acetylsalicylic acid : Sincronium (DE)
• with ezetimibe : Atozet , Tioblis

literature

• U. Gresser, BS Gathof: Review: Atorvastatin: Gold Standard For Prophylaxis Of Myocardial Ichemia And Stroke. Comparison Of The Clinical Benefit Of Statins On The Basis Of Randomized Controlled Endpoint Studies. Eur. J. Med. Res. (2004) 9: pp. 1-17.

Individual evidence

1. ↑ ^{a b} Entry on atorvastatin in the DrugBank of the University of Alberta .
2. ↑ ^{a b c} V. M. Sonje, L. Kumar, V. Puri, G. Kohli, AM Kaushal, AK Bansal: Effect of counterions on the properties of amorphous atorvastatin salts. In: Eur J Pharm Sci . 44 (2011) pp. 462-470, doi: 10.1016 / j.ejps.2011.08.023 .
3. ↑ ^{a b} Data sheet atorvastatin calcium salt trihydrate, ≥98% (HPLC) from Sigma-Aldrich , accessed on February 10, 2013 ( PDF ).
4. ↑ Entry on atorvastatin. In: Römpp Online . Georg Thieme Verlag, accessed on May 30, 2014.
5. ↑ Ifap Arzneimittelews: Basics GmbH brings the first generic atorvastatin preparation onto the market ( Memento of July 7, 2012 in the web archive archive.today ), accessed on March 2, 2012.
6. ↑ Richard Daikeler, idols Use, Sylke Waibel: diabetes. Evidence-based diagnosis and therapy. 10th edition. Kitteltaschenbuch, Sinsheim 2015, ISBN 978-3-00-050903-2 , p. 149.
7. ↑ P. Jones et al .: Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study). At J Cardiol. March 1, 1998; 81 (5): pp. 582-587; PMID 9514454 .
8. ↑ Anton FH Stalenhoef et al .: A Comparative study with rosuvastatin in subjects with metabolic syndrome: results of the COMETS study Eur Heart J . December 2005; 26 (24): pp. 2664–2672 full text (HTML) full text (PDF; 264 kB) , PMID 16143705 .
9. ↑ Ifap: As of May 8, 2012.
10. ↑ MedLine Plus drug information .
11. ↑ MedWatch report on IMNM: HMGCoA reductase inhibitor (statin) drugs- Risk of immune-mediated necrotizing myopathy (IMNM) Label Changes (October 2012)
12. ^ N. Sattar et al .: Statins and risk of incident diabetes: a collaborative meta-analysis of randomized statin trials . In: The Lancet . tape 375 , no. 9716 , 2010, p. 735-742 , doi : 10.1016 / S0140-6736 (09) 61965-6 .
13. ↑ ROUNDUP: Industry leader Pfizer attacks in the generics business ( Memento from June 4, 2009 in the Internet Archive ) , finanzen.net March 19, 2009.
14. ↑ Fabian Weber, Gottfried Sedelmeier: 200 top-selling drugs . In: News from chemistry . tape 61 , no. 5 , May 2013, p. 528-529 , doi : 10.1002 / nadc.201390162 .
15. ↑ B. Hibbeler: Statins: Sortis' market share is falling. In: Deutsches Ärzteblatt 2005, 102 (12): A-792 / B-668 / C-624 ( online version ).
16. ↑ Law et al. BMJ 2003; 326: p. 1423.
17. ↑ Red List Online, as of August 2009.
18. ↑ Swiss Medicines Compendium , as of August 2009.
19. ↑ AGES-PharmMed, as of August 2009.

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !