Subject: Statins and other drugs for cholesterol / lipid (hypercholesterolemia/dyslipidemia/hyperlipidemia) control First version: 29-Apr-2004, last significant update: 1-Jan-2015. Statins (a/k/a "HMG-CoA Reductase Inhibitors") include... Third generation ("superstatins"): Crestor (rosuvastatin, nee visastatin, nee ZD4522), from Shionogi and AstraZeneca (2003). Available pill sizes are 5, 10, 20, & 40 mg. Usual starting dose is 10 mg qd. 5, 10, 20, and 40 mg pills are all priced at $2.25 ea. Half-life 20 hrs, Cmax @3-5 hrs. [partially metabolized by CYP 2C9, CYP 2C19] Articles: circa 8/2003: http://www.astrazeneca.com/pressrelease/590.aspx circa 4/2003: http://www.astrazeneca.com/pressrelease/485.aspx circa 2003: http://www.future-drugs.com/summery.asp?articleid=1052&submit=txt2 circa 2000: http://www.ims-global.com/insight/news_story/news_story_000316a.htm Contrary view: leftist Public Citizen website, worstpills.org, worries about safety: http://www.worstpills.org/public/crestor.cfm. However, just because they are leftist (stupid), that doesn't mean they are always wrong. Even smart people are sometimes wrong, and stupid people are sometimes right. This article http://www.eohsi.rutgers.edu/internal/classes/biochemical_toxicology/SM%20Huang%20D1.pdf indicates that Crestor is effective even in very tiny doses. On p. 26 it reports that 40 mg qd reduced LDL-C by 62%, 10 mg reduced LDL-C by 50%, 2.5 mg reduced LDL-C by 40% and even 1 mg reduced LDL-C by 33%. * The long half-life of Crestor means that it doesn't much matter what time of day it is taken. That's an advantage over some other statins, like simvastatin (Zocor), which should be taken in the evening. * Crestor no longer has patent protection in Canada or Brazil, but it still has patent protection in the USA until July 8, 2016. However, since it is effective in very small doses, cost-sensitive patients in the USA can divide the dose and still get most of the benefit at lower cost (and lower risk of side-effects). Livalo or Pitava (pitavastatin, NK-104, itavastatin, nisvastatin), from Kowa/Novartis. A 2011 study suggests that it is similar in effectiveness to Crestor (and to Lipitor at 5x the dose). However, a Japanese study comparing Livalo to Crestor in diabetic patients suggests that Crestor is slightly better. A 2013 study comparing Livalo to Lipitor found that Livalo was substantially more effective than Lipitor. First & second generation: Lipitor (atorvastatin), from Warner-Lambert and Pfizer/Parke Davis (1996). www.lipitor.com Prescribing information: http://www.lipitor.com/pi/ Plasma half-life 14 hrs, Cmax @1-2 hrs, but "the half-life of inhibitory activity for HMG-CoA reductase is 20-30 hours due to the contribution of active metabolites." http://www.pfizer.com/download/uspi_lipitor.pdf Available pill sizes are 10, 20, 40 & 80 mg. Most common dose is 10 mg qd. 10 mg pills are $2.10 each. 20 mg, 40 mg, and 80 mg pills are all $3.10 each. [metabolized via CYP 3A4, beware of +200% potentiation with grapefruit juice] A 2003 study found that Lipitor is more effective than Pravachol: http://www.seniorjournal.com/NEWS/Health/3-11-13lipitor.htm & http://www.rxlist.com/rxboard/lipitor.pl?read=3259 A 1998 Baylor study says Lipitor better than other 1st & 2nd generation statins: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9514454&dopt=Abstract Prescribing information indicates 10 mg qd is almost as effective as higher dose: 40 mg => -50% LDL-C, 20 mg => -43% LDL-C, 10 mg => -39% LDL-C. Consistent with that, Dr. Harold Bays (in Lipids Online) wrote that each halving ("titration") of the dose of a statin reduces effectiveness only about 5-6% (the so-called "rule of 6"): http://www.lipidsonline.org/slides/slide01.cfm?q=rule+of+6 (or here) Zocor (simvastatin), from Merck (1991) - a synthetic, more potent variant of Mevacor. [metabolized via CYP 3A4, beware of +1500% potentiation with grapefruit juice] The patent on simvastatin expired in Europe in May 2003, and expired in the USA on 23 June 2006. At of late 2005, Zocor was about $2.35 / 10 mg pill, but was predicted to drop to about half that for generic simvastatin by the end of 2006. By late 2007 the price of generic simvastatin was under $0.10 / 10mg or 20mg pill (in quantity 90) at Sam's Club pharmacy, a 96% drop! (Strangely, it is about 16x that price at Walmart Pharmacy, even though Sam's Club and Walmart are the same company.) As of 9/1/2008, Sam's Club had removed simvastatin from their $4/mo prescription drug program, but qty 100 of 20mg simvastatin was only $10.44 at Costco pharmacy (vs. a whopping $481 for the same quantity of name-brand Zocor). Pravachol (pravastatin), from Bristol-Myers Squibb (1991); as Mevalotin, from Sankyo. [not metabolized via P450 (CYP) isoenzyme system] Available in 10mg, 20mg, 40mg & 80mg tablets. Pravachol might be less likely than Lipitor, Crestor & Zocor to cause adverse side-effects. The U.S. patent on Pravachol expired in April 2006, and generic pravastatin is available for $0.13/tablet (10, 20 or 40mg) at Sam's Club & Walmart pharmacies. Lescol (fluvastatin), from Novartis (nee Sandoz) (1994). http://www.centerwatch.com/patient/drugs/dru648.html [metabolized via CYP 2C9] Mevacor (lovastatin), from Merck (1987); and Altocor, an extended-release form of lovastatin, from Andrx. [metabolized via CYP 3A4, beware of +1500% potentiation with grapefruit juice] The patent has expired, and generic lovastatin is now available for $0.13/tablet (10 or 20mg) at Sam's Club & Walmart pharmacies. Baycol (a/k/a Baychol or Lipobay) (cerivastatin), from Bayer - withdrawn from market because (in combination with gemfibrozil) it caused rhabdomyolysis (muscle breakdown) leading to kidney damage, and at least 31 deaths (or 52, or more than 100, depending on who you believe). Articles: http://www.fda.gov/bbs/topics/ANSWERS/2001/ANS01095.html and http://www.fda.gov/cder/drug/infopage/baycol/ and http://www.injuryboard.com/view.cfm/Topic=797 Non-Statin drugs (can be used with statins): Zetia (ezetimibe), a/k/a Ezetrol, from Merck/Schering-Plough. "The first clinically approved cholesterol absorption inhibitor." 10 mg pills (the only size available) are about $2.35 each. See www.zetia.com and full prescribing information. Zetia is often prescribed for use in combination with a statin, such as Crestor, Lipitor, Pravachol or Zocor. (Vytorin is a combination of Zetia & Zocor.) Like statins, ezetimibe's effectiveness is only mildly dependent on dose. The standard 10 mg/day dose typically results in about an 18% reduction (improvement) in LDL cholesterol, about 4% increase (improvement) in HDL cholesterol, and about 3-6% decrease (improvement) in triglycerides. Halving it to 5 mg is only slightly less effective, typically reducing LDL-C by 15-16% instead of 18%, and even 0.25 mg/day (1/40th of the usual dose) typically reduces LDL-C by about 10%: http://www.lipidsonline.org/slides/slide01.cfm?q=ezetimibe+efficacy&dpg=1 (or here) However, a 2006 study of 720 patients failed to find that Zetia+simvastatin (Vytorin) reduced growth of arterial plaque by more than simvastatin alone; other studies are ongoing. Niacin (nicotinic acid, a/k/a vitamin B3), to lower triglycerides & increase HDL-C. Very inexpensive OTC, except for a pricey extended release prescription form called Niaspan. Beware, niacin is dangerous. The theraputic dose of niacin is similar to the toxic dose, and it should never be used for lipid improvement except under the close supervision of a physician. Doses of 1000 mg/day or more are generally needed for substantial lipid improvement, but abnormal liver function has been reported in patients taking daily doses as low as 500 mg/day. Studies indicate that extended- release forms of niacin may be more dangerous than regular niacin. A recent study indicate that niacin's benefits are very slight, and its adverse side-effects major. Niacin is also discussed in this article. WelChol (colesevelam HCl), from Sankyo/GelTex - nonsystemic/non-absorbed. Requires huge dose: six 625 mg solid tablets / day This article http://www.sankyopharma.com/headlines/index.cfm?article_ID=19 says: "WelChol works by binding to bile acids in the intestine and taking those bile acids with it as it leaves the body. The body responds naturally by drawing cholesterol from the bloodstream to replenish the supply." Torcetrapib (nee CP-529414) - http://www.medscape.com/viewarticle/471969 - discontinued. Torcetrapib was described as a "cholesteryl ester transferase protein (CETP) inhibitor" which greatly increases HDL-C ("good cholesterol") with little effect on LDL-C. It was in phase III clinical trials until December, 2006, when the trials were halted due to an observered increase in patient mortality. See 2004 article and 2006 FDA announcement. Pfizer had hoped to sell it in a combined pill with Lipitor. Dalcetrapib (a/k/a JTT-705, R1658 or RO4607381), from Japan Tobacco and Roche - discontinued. Raises HDL-C, apparently similar to Torcetrapib, but without the adverse side-effects. However, development was halted in 2012 due to "lack of clinically meaningful efficacy." Avasimibe (CI 1011), from Pfizer - discontinued. Implitapide (BAY 13-9952), from PPD/MRLI and Bayer - investigational. ApoA-1 Milano (a/k/a ETC-216, MDCO-216, apolipoprotein A-I complex, or "Super-HDL") - investigational. This drug seems promising ("Like Drano For the Arteries"), but is apparently difficult to manufacture. Many companies have worked on it, including Esperion, Pfizer, OctoPlus, SemBioSys Genetics, Tasly Pharmaceuticals, Cardigant Medical, and The Medicines Company. The most recent of them, The Medicines Company, announced the discontinuation of their work on this drug in November 2016, due to lack of efficacy in a high-quality double-blind study. http://www.healthandage.com/Home/gm=0!gc=39!gid2=2756 (or here) http://pharmexec.com/pharmexec/content/printContentPopup.jsp?id=109681 (or here) ETC-1002 (a/k/a Bempedoic Acid), from Esperion - investigational. Here's an article about it. Lorelco (Panavir) (probucol) - not available in the USA. Article: http://content.nejm.org/cgi/content/abstract/337/6/365 Lowers total cholesterol, but unfortunately also lowers HDL-C. AGI-1067, from AtheroGenics & AstraZeneca http://www.google.com/search?q=AGI-1067 Designed to reduce cardiac inflammation - investigational. Evolocumab (AMG-145), from Amgen - investigational. A monthly injectible non-statin medication which dramatically lowers LDL cholesterol. Combinations are a hot topic, but note that the combination of Baycol (cerivastatin) and Lopid (gemfibrozil) proved deadly: Vytorin (Zetia+Zocor) (ezetimibe+simvastatin), from Merck/Schering-Plough Approved by FDA on July 23, 2004. Articles: 3/8/2004 lycos story (or here), and 11/23/2003 press release, 7/28/2004 TheDoctorsLounge.net article (or here), 1/15/08 WebMD story about a disappointing study. See Zetia in the "Non-Statin" category, above. Advicor (nee Nicostatin) (niacin+lovastatin) www.advicor.com torcetrapib+atorvastatin (torcetrapib+Lipitor), from Pfizer - investigational Articles: http://www.medscape.com/viewarticle/473217 and http://content.nejm.org/cgi/content/short/350/15/1505 Benicar+Pravachol (olmesartan+pravastatin) (CS-866MB) - investigational Norvasc+Lipitor (amlodipine+atorvastatin) - investigational JTT-705+pravastatin - investigational The FDA's "Advice on Statin Risks" is essential reading: http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm293330.htm Here's an excellent lecture (slides and notes) by Dr. Harold Bays, in Lipids Online, on the subject of combination lipid-altering drug therapies: http://www.lipidsonline.org//slides/talk_cme_activity.cfm?tk=33&shownotes=1 (or here) Some earlier (non-statin) cholesterol-lowering drugs are less effective than statins or Zetia (ezetimibe). They include: Lopid (gemfibrozil), from Warner Lambert - most common "fibrate" Other fibrates include Tricor (fenofibrate), and Bezalip (bezafibrate) Questran (cholestylramine), from Bristol Myers Here's a good web site about statins: www.statinanswers.com The most comprehensive study of statin side-effects was by UCSD in 2008: Article and paper. It suggests that CoQ10 supplementation might be helpful for patients taking statins. General safety concerns about statins: "The primary safety concern with statins has involved an uncommon condition called myopathy, which can cause muscle damage and in some cases, muscle and joint pain. The risk for myopathy is highest at higher doses and in older people, those who are small or frail, people who abuse alcohol, and those who are hypothyroid. There is also a higher risk if statins are used before surgery, and if people are taking multiple medications. ... In the past, there have been a few reports of a specific myopathy called rhabdomyolysis that can lead to kidney failure. Of note, fatal events from rhabdomyolysis occurred in less than 1 out of a million prescriptions and nearly always with the statin cerivastatin (Baycol), particularly at high doses and in combination with fibrates. ... Patients should tell their physicians about any unusual muscle discomfort or weakness and if their urine becomes brown-colored. ... Statins also can effect the liver, particularly at higher doses, so periodic liver function tests should be administered. Statins should not be taken by anyone with liver problems or by women during pregnancy or breast-feeding." -quoted from this very comprehensive article: http://www.well-connected.com/report.cgi/000023_9.htm Here are several somewhat conflicting articles about the effects of cholesterol and statins on the brain (both positive and negative): http://www.ucdmc.ucdavis.edu/ucdhs/health/a-z/23Cholesterol/doc23braineffect.html http://www.xagena.it/news/medicinenews_net_news/e29b722e35040b88678e25a1ec032a21.html http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15329062 http://in.reuters.com/article/health/idINTRE5076T120090108 There are also reports of two different adverse neurological symptoms which are (occasionally) associated with statins: vivid or abnormal dreams, and memory loss. It is unclear whether these two symptoms are correlated. Abnormal or vivid dreams have been associated with Lipitor and perhaps other statins, in a small percentage of patients. Of greater concern are reports of statin-associated memory loss among patients taking Lipitor, and occasionally patients taking Zocor or Crestor. The problem seems to be rare. This article www.medscape.com/viewarticle/458867_4 says that the problem appears to be less common with Pravachol than with either Lipitor or Zocor. An interesting article about the market battle between these products: http://www-personal.umich.edu/~afuah/cases/case11.html An interesting C&E News article about the generic drug industry: http://pubs.acs.org/cen/coverstory/8038/8038biogenerics.html A.D.A.M.'s quite comprehensive information about Cholesterol and other Lipids: http://www.well-connected.com/report.cgi/fr000023.html MedicineNet's quite comprehensive article about Cholesterol and related topics: http://www.medicinenet.com/cholesterol/article.htm But what about Dr. Russell Blaylock (who says statins are bad)?: http://www.burtonsys.com/blaylock_v_statins.html
Here's a web page similar to this one, but about bisphosphonates (drugs for osteoporosis / bone recalcification): http://www.burtonsys.com/osteoporosis.html Here's a web page similar to this one, but about Prilosec and similar drugs for treatment of GIRD: http://www.burtonsys.com/omeprazole.html
This page is uncopyrighted.