{
  "id": "atorvastatin",
  "title": "Atorvastatin",
  "lang": "en",
  "source_lang": "en",
  "summary": "Atorvastatin is a synthetic statin that lowers blood cholesterol by inhibiting HMG-CoA reductase; it is sold mainly as Lipitor.",
  "category": "health",
  "subcategory": "drugs",
  "type": "product",
  "aliases": [
    "Lipitor",
    "atorvastatin calcium",
    "CI-981 (development code)"
  ],
  "generated_at": "2026-10-15",
  "model": "pro/claude-haiku-5-5",
  "url": "https://aiwiki.page/en/atorvastatin/",
  "translations": {
    "zh-Hans": {
      "url": "https://aiwiki.page/zh/atorvastatin/",
      "json": "https://aiwiki.page/zh/atorvastatin.json"
    }
  },
  "sections": [
    {
      "heading": "",
      "text": "Atorvastatin is a synthetic lipid-lowering drug of the statin class, widely prescribed to reduce cholesterol levels and lower the risk of cardiovascular disease. It is best known under the brand name Lipitor. At the time of its patent expiry it was one of the best-selling drugs in pharmaceutical history, and it remains an important generic medicine."
    },
    {
      "heading": "Pharmacology and mechanism of action",
      "text": "Atorvastatin acts as a competitive inhibitor of HMG-CoA reductase. The enzyme converts HMG-CoA into mevalonate, an early, rate-limiting step in cholesterol biosynthesis. Because the drug competes with the natural substrate for the enzyme's active site, it slows cholesterol production, particularly in the liver.\n\nLower intracellular cholesterol in liver cells triggers a compensatory response: hepatocytes increase their number of LDL receptors, which draw LDL cholesterol out of the bloodstream. Labeling data cited in the literature put the reduction in LDL cholesterol at roughly 39 to 60 percent, depending on the dose. Atorvastatin also lowers triglycerides and raises HDL cholesterol to a modest degree.\n\nAnimal studies indicate that the drug's effect on the enzyme is more complex than simple inhibition. In treated rats, hepatic reductase protein levels rose far more than measured enzyme activity did, which researchers attributed to the feedback relief that statins typically cause. The drug's pharmacological profile is also shaped by metabolism. Atorvastatin is oxidized by the cytochrome P450 3A4 enzyme into ortho- and para-hydroxylated derivatives, which are themselves active. One frequently cited estimate holds that nearly 70 percent of the HMG-CoA reductase inhibition attributed to atorvastatin comes from these active metabolites."
    },
    {
      "heading": "Chemistry and discovery",
      "text": "Atorvastatin was first synthesized in August 1985 by the medicinal chemist Bruce Roth at Warner-Lambert, under the code CI 981. Management initially hesitated to advance the compound into clinical trials, because its structure resembled that of lovastatin, an existing Merck product. Early comparisons with simvastatin suggested that atorvastatin was more potent and had fewer side effects.\n\nThe marketed product is the calcium salt of a single enantiomer. Its design is often cited in medicinal chemistry as a case study in how structure relates to pharmacological properties. Atorvastatin was the fourth statin to reach the market, roughly a decade after the first.\n\nThe U.S. Food and Drug Administration approved Lipitor on December 17, 1996, for primary hypercholesterolemia and mixed dyslipidemia. Pfizer had the marketing capacity that Warner-Lambert lacked, and the two companies entered a co-marketing arrangement. Pfizer later acquired Warner-Lambert in 2000, bringing the atorvastatin rights into its portfolio."
    },
    {
      "heading": "Clinical use and evidence",
      "text": "Atorvastatin is indicated for lowering lipid levels and reducing the risk of cardiovascular events, including myocardial infarction and stroke. The FDA approval rested on four Phase III clinical trials. Among the most cited outcome studies is the ASCOT-LLA trial, which enrolled about 10,000 hypertensive patients with average cholesterol levels. In that trial, atorvastatin 10 mg reduced coronary heart disease events by 36 percent relative to placebo over roughly 3.3 years. Trials of this kind are central to the drug's clinical justification, although the magnitude of benefit varies with the population studied.\n\nResearch into atorvastatin has extended beyond cardiovascular disease. Preclinical work in lymphoma models has reported that inhibiting HMG-CoA reductase with the drug altered MYC-driven signaling and suppressed tumor development. These findings remain experimental and are not an established clinical use."
    },
    {
      "heading": "Adverse effects",
      "text": "The most important safety concern is skeletal muscle toxicity. Myopathy, which presents as muscle pain, tenderness, or weakness and typically shows elevated creatine kinase, has been reported frequently with atorvastatin. Muscle symptoms can appear even after more than six months of treatment. In severe cases, myopathy can progress to rhabdomyolysis, a syndrome in which muscle fibers break down and release their contents into the circulation, with the risk of kidney injury. Liver enzyme abnormalities and, less commonly, liver dysfunction have also been reported. Common non-serious effects in trials include constipation, diarrhea, fatigue, headache, joint pain, and urinary tract infection.\n\nSome clinical guidance notes that routine creatine kinase monitoring cannot guarantee that serious myopathy will be prevented, so the emphasis falls on recognizing risk factors and interacting drugs."
    },
    {
      "heading": "Drug interactions",
      "text": "Because atorvastatin is cleared largely through CYP3A4 and is handled by transporters such as OATP1B1 and P-glycoprotein, its plasma concentration is sensitive to co-administered drugs. Strong CYP3A4 inhibitors raise exposure and therefore the risk of myopathy, while CYP3A4 inducers such as rifampin and efavirenz lower it. Relevant drug interactions include:\n\n- Cyclosporine, for which atorvastatin is generally to be avoided.\n- Clarithromycin, itraconazole, and several HIV protease inhibitors, which call for a daily dose cap of 20 mg.\n- Nelfinavir and boceprevir, which call for a cap of 40 mg.\n- Gemfibrozil, a fibrate that raises myopathy risk.\n- Colchicine, which has been linked to myopathy and rhabdomyolysis when combined with atorvastatin.\n- Large amounts of grapefruit juice, which increase blood levels of the drug.\n\nPrescribing information generally advises suspending atorvastatin during short courses of strong CYP3A4 inhibitors where possible."
    },
    {
      "heading": "Commercial history and patents",
      "text": "Patent protection shaped the drug's commercial history. Under a co-marketing agreement, Pfizer's large sales force promoted Lipitor alongside Warner-Lambert's own team. Peak annual sales were reported at about 12.9 billion U.S. dollars in 2006, and lifetime revenue estimates vary widely, from over 125 billion to about 150 billion dollars. Sources also differ on the expiry dates of individual patents, including the compound patent, so exact timelines depend on which patent is considered.\n\nPfizer extended its exclusivity through litigation and a pediatric exclusivity extension, to November 30, 2011. Ranbaxy Laboratories then launched the first generic version under a 180-day exclusivity period in the United States, and multiple generics entered the market within months. Pfizer and Ranbaxy settled most of their worldwide patent litigation in 2010, which allowed earlier generic entry in several other countries. In Australia, courts upheld a Lipitor patent, delaying generic competition in that market. Even after patent expiry, atorvastatin has continued to generate substantial sales."
    },
    {
      "heading": "Limitations and ongoing discussion",
      "text": "Discussion about atorvastatin centers on the trade-off between cardiovascular benefit and muscle and liver toxicity, which depends on dose, age, comorbidities, and concomitant medications. Differences in individual response, the relevance of drug interactions in older or polypharmacy patients, and the uncertain extent of benefit in lower-risk groups remain active topics in clinical practice."
    }
  ],
  "links": [
    "cholesterol",
    "cardiovascular-disease",
    "pharmacology",
    "stroke",
    "clinical-trial"
  ],
  "sources": [
    {
      "title": "Atorvastatin: Uses, Interactions, Mechanism of Action",
      "url": "https://go.drugbank.com/drugs/DB01076"
    },
    {
      "title": "Atorvastatin action involves diminished recovery of hepatic HMG-CoA reductase activity - PubMed",
      "url": "https://pubmed.ncbi.nlm.nih.gov/9469588/"
    },
    {
      "title": "Atorvastatin - an overview",
      "url": "https://www.sciencedirect.com/topics/medicine-and-dentistry/atorvastatin"
    },
    {
      "title": "HMG CoA-reductase inhibitors",
      "url": "https://image-ppubs.uspto.gov/dirsearch-public/print/downloadPdf/7078430"
    },
    {
      "title": "Lipitor Patent Field and Generic Atorvastatin Timeline",
      "url": "https://healthrx.com/atorvastatin/patent-generic-timeline"
    },
    {
      "title": "Lipitor History and Development: How Atorvastatin Became the Best-Selling Drug in History",
      "url": "https://healthrx.com/atorvastatin/history-development"
    },
    {
      "title": "Lipitor",
      "url": "https://www.linkedin.com/pulse/lipitor-short-account-its-life-cycle-wallace-macindoe-phd-mba"
    },
    {
      "title": "Lipitor (Atorvastatin) - Treatment for High Cholesterol - Clinical Trials Arena",
      "url": "https://www.clinicaltrialsarena.com/projects/lipitor-atorvastatin-cholesterol-lowering-drug/"
    },
    {
      "title": "Pfizer Inc. and Ranbaxy Laboratories Settle Lipitor Patent Dispute; Generic Lipitor to be Launched Nov. 2011",
      "url": "https://www.biospace.com/pfizer-inc-and-ranbaxy-laboratories-settle-lipitor-patent-dispute-generic-lipitor-to-be-launched-nov-2011"
    },
    {
      "title": "Who holds the patent for Atorvastatin?",
      "url": "https://synapse.patsnap.com/article/who-holds-the-patent-for-atorvastatin"
    },
    {
      "title": "Generic Atorvastatin Hits the Market",
      "url": "https://www.forbes.com/sites/larryhusten/2011/11/30/generic-atorvastatin-hits-the-market/"
    },
    {
      "title": "classics in medicinal chemistry 1",
      "url": "https://medchemash.substack.com/p/classics-in-medicinal-chemistry-1"
    },
    {
      "title": "Atorvastatin Uses, Interactions & Side Effects",
      "url": "https://www.news-medical.net/health/Atorvastatin-Uses-Interactions-Side-Effects.aspx"
    },
    {
      "title": "Side Effects of Lipitor (atorvastatin) & Drug Interactions",
      "url": "https://www.medicinenet.com/side_effects_of_atorvastatin/side-effects.htm"
    },
    {
      "title": "STOP Heart Disease in Breast Cancer Survivors Trial",
      "url": "https://cdn.clinicaltrials.gov/large-docs/04/NCT02674204/Prot_SAP_000.pdf"
    },
    {
      "title": "Survival Benefits of Statins in Breast Cancer Patients",
      "url": "https://cdn.clinicaltrials.gov/large-docs/19/NCT03971019/Prot_SAP_ICF_001.pdf"
    },
    {
      "title": "Atorvastatin-Induced Necrotizing Myopathy and its Response to Combination Therapy",
      "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920241/"
    },
    {
      "title": "Inhibition of HMGcoA reductase by atorvastatin prevents and reverses MYC-induced lymphomagenesis",
      "url": "https://ashpublications.org/blood/article/110/7/2674/103656/Inhibition-of-HMGcoA-reductase-by-atorvastatin"
    }
  ],
  "license": "https://creativecommons.org/licenses/by/4.0/"
}