How did Lipitor become the world’s best-selling prescription drug. What role did marketing play in its success. Why was the Jarvik advertising campaign controversial. What lessons can be learned from Lipitor’s dominance in the pharmaceutical market.

The Rise of Lipitor: From “Me-Too” Drug to Market Leader

Lipitor (atorvastatin), developed by Pfizer, entered the pharmaceutical market in January 1997 as the fifth statin drug to be approved by the U.S. Food and Drug Administration (FDA). Despite joining an already crowded field of cholesterol-lowering medications, Lipitor quickly rose to prominence, becoming the world’s best-selling prescription drug for over a decade. This remarkable success story raises several intriguing questions about the pharmaceutical industry, marketing strategies, and the complex interplay between medical efficacy and public perception.

What set Lipitor apart from other statins?

Lipitor distinguished itself through claims of superior cholesterol-lowering ability. This, combined with an aggressive marketing campaign, propelled it to the forefront of the statin market. Even as other statin drugs became available in generic forms at significantly lower prices, Lipitor maintained its dominance. The drug’s success was not just a matter of timing or luck; it was the result of a carefully crafted strategy that emphasized its unique benefits and positioned it as the gold standard in cholesterol management.

The Jarvik Campaign: Marketing Authenticity and Uniqueness

In 2006, Pfizer launched a high-profile advertising campaign featuring Dr. Robert Jarvik, the inventor of the Jarvik artificial heart. This campaign coincided with the market entry of generic simvastatin and was designed to convince consumers and physicians that Lipitor was irreplaceable.

How did the Jarvik campaign attempt to differentiate Lipitor?

The campaign’s central message was encapsulated in Dr. Jarvik’s statement: “For me, there is no substitute.” This powerful assertion aimed to instill brand loyalty and discourage the use of generic alternatives. The advertisements portrayed Jarvik as a credible medical authority, emphasizing the authenticity of both the spokesperson and the product. By featuring a “real” doctor rather than an actor, Pfizer sought to lend an air of medical legitimacy to its marketing efforts.

Clinical Efficacy and Market Dominance

Pfizer’s claims of Lipitor’s superiority were not based solely on marketing rhetoric. The company had invested heavily in clinical trials to demonstrate the drug’s efficacy across a range of cardiovascular conditions.

What evidence supported Lipitor’s claims of superiority?

By the time of the Jarvik campaign, Pfizer could point to over 400 trials involving more than 80,000 patients. These studies allowed Lipitor to make unique claims about its clinical efficacy. For instance, in 2007, Lipitor became the first cholesterol-reducing drug approved by the FDA to lower the risk of hospitalization in patients with heart failure. Additionally, comparative studies like the PROVE-IT trial demonstrated better cardiovascular outcomes for patients treated with high-dose Lipitor compared to conventional doses of pravastatin following myocardial infarction.

The Backfire: Controversy and Criticism

Despite its initial success, the Jarvik campaign soon became a lightning rod for criticism in an environment increasingly skeptical of direct-to-consumer (DTC) pharmaceutical advertising.

Why did the Jarvik campaign face ethical scrutiny?

Bioethicists and industry critics raised concerns about the ethical implications of a physician acting as a celebrity sponsor for pharmaceutical promotion. Katie Watson, a bioethicist at Northwestern University, argued that it was an ethical lapse for someone who appeared to be a practicing physician to accept funds to promote a prescription drug. This criticism highlighted the complex ethical considerations surrounding the intersection of medical authority and commercial interests in pharmaceutical marketing.

Scrutiny of Jarvik’s Credentials and Background

As the controversy surrounding the Lipitor campaign grew, increased attention was paid to Dr. Jarvik’s background and qualifications.

What aspects of Jarvik’s background came under scrutiny?

Public records revealed that Jarvik had faced academic challenges, including poor grades as an undergraduate at Syracuse University and difficulties gaining admission to medical school. He ultimately received his MD from an offshore medical school after being rejected from U.S. programs. These revelations raised questions about the authenticity of Jarvik’s portrayal as a medical authority in the Lipitor advertisements and fueled further debate about the ethics of pharmaceutical marketing practices.

The Impact of Marketing on Pharmaceutical Success

The Lipitor case study provides valuable insights into the role of marketing in the pharmaceutical industry and its influence on prescribing practices and patient preferences.

How did marketing contribute to Lipitor’s success?

Lipitor’s journey from a “me-too” drug to the world’s best-selling prescription medication demonstrates the power of strategic marketing in the pharmaceutical sector. By emphasizing its unique benefits, leveraging celebrity endorsements, and investing heavily in clinical trials, Pfizer was able to differentiate Lipitor in a crowded market. This approach allowed the company to maintain high prices and market share even as generic alternatives became available.

Lessons from Lipitor: Balancing Innovation, Marketing, and Ethics

The Lipitor story offers important lessons for the pharmaceutical industry, healthcare providers, and policymakers about the complex interplay between drug efficacy, marketing strategies, and ethical considerations in healthcare.

What can be learned from Lipitor’s market dominance?

Lipitor’s success highlights the importance of both clinical efficacy and effective marketing in the pharmaceutical industry. However, it also underscores the need for careful scrutiny of marketing practices, particularly when they involve medical professionals. The controversy surrounding the Jarvik campaign demonstrates the potential risks of blurring the lines between medical authority and commercial interests.

How can the pharmaceutical industry balance innovation with ethical marketing?

The Lipitor case suggests that pharmaceutical companies must strike a delicate balance between promoting their products and maintaining ethical standards. This may involve more transparent marketing practices, clearer disclosure of potential conflicts of interest, and a greater emphasis on communicating scientific evidence rather than relying on celebrity endorsements. Additionally, regulatory bodies may need to re-evaluate guidelines for direct-to-consumer advertising to ensure that patients receive accurate and unbiased information about their treatment options.

The Future of Pharmaceutical Marketing in a Post-Lipitor World

As Lipitor faced the end of its patent exclusivity in 2011, the pharmaceutical industry was forced to reconsider its strategies for developing and marketing new drugs.

How might the Lipitor experience influence future drug development and marketing?

The Lipitor saga may encourage pharmaceutical companies to focus more on developing truly innovative drugs that offer significant advantages over existing treatments, rather than relying heavily on marketing to differentiate “me-too” products. There may also be a shift towards more evidence-based marketing approaches that emphasize clinical trial results and real-world outcomes data over celebrity endorsements or emotional appeals.

Furthermore, the industry may need to adapt to increasing scrutiny from regulators, healthcare providers, and consumers regarding marketing practices. This could lead to more collaborative approaches between pharmaceutical companies, healthcare providers, and patient advocacy groups to ensure that marketing messages are accurate, balanced, and serve the best interests of patients.

What role will generic competition play in shaping future pharmaceutical strategies?

The entry of generic competitors to Lipitor highlighted the challenges faced by brand-name drug manufacturers in maintaining market share and profitability after patent expiration. This experience may drive pharmaceutical companies to invest more heavily in developing drugs for rare diseases or complex conditions where generic competition is less likely to emerge quickly. Additionally, companies may focus on developing combination therapies or novel drug delivery systems that are more difficult to replicate generically.

The Lipitor story also underscores the importance of lifecycle management strategies for pharmaceutical products. Companies may increasingly explore ways to extend the commercial viability of their drugs through new formulations, additional indications, or value-added services that complement the core medication.

Ethical Considerations in Physician-Endorsed Pharmaceutical Advertising

The controversy surrounding Dr. Jarvik’s role in the Lipitor campaign raises important questions about the ethical implications of physicians participating in pharmaceutical advertising.

What ethical guidelines should govern physician involvement in drug promotion?

The Lipitor case highlights the need for clearer ethical guidelines regarding physician participation in pharmaceutical advertising. Professional medical organizations may need to develop more specific standards for such involvement, addressing issues such as:

• Disclosure of financial relationships between physicians and pharmaceutical companies
• Restrictions on physicians promoting specific products rather than providing general health information
• Requirements for physicians to have relevant expertise in the therapeutic area being promoted
• Guidelines for ensuring that promotional claims are consistent with scientific evidence and professional medical advice

How can the medical community maintain public trust while engaging with the pharmaceutical industry?

Maintaining public trust is crucial for both the medical community and the pharmaceutical industry. To address concerns raised by cases like the Lipitor campaign, several approaches could be considered:

1. Increased transparency: Physicians and medical institutions should be transparent about their relationships with pharmaceutical companies, including any financial compensation received for promotional activities.
2. Education and awareness: Medical schools and professional organizations could provide more comprehensive training on ethical interactions with the pharmaceutical industry.
3. Collaborative research: Encouraging more independent, collaborative research between academia and industry could help ensure that drug efficacy claims are based on robust scientific evidence rather than marketing imperatives.
4. Patient-centered approach: Emphasizing patient education and shared decision-making in promotional materials could help shift the focus from product promotion to informed healthcare choices.

By addressing these ethical considerations, the medical community and pharmaceutical industry can work towards maintaining public trust while still fostering innovation and advancing healthcare.

The Role of Regulatory Bodies in Pharmaceutical Advertising

The Lipitor case study raises questions about the adequacy of existing regulatory frameworks for pharmaceutical advertising, particularly in the realm of direct-to-consumer (DTC) marketing.

How might regulatory bodies adapt to address the challenges highlighted by the Lipitor campaign?

Regulatory agencies such as the FDA may need to reassess their approach to overseeing pharmaceutical advertising in light of the issues raised by the Lipitor campaign. Potential areas for regulatory reform could include:

• Stricter guidelines for the use of medical professionals in pharmaceutical advertisements
• Enhanced requirements for the presentation of risk information and potential side effects in DTC advertising
• More rigorous review processes for advertising claims, particularly those related to comparative efficacy or uniqueness
• Increased monitoring of social media and digital marketing strategies employed by pharmaceutical companies
• Development of clearer standards for the use of patient testimonials and celebrity endorsements in drug promotion

What role should post-marketing surveillance play in validating advertising claims?

The Lipitor experience underscores the importance of ongoing evaluation of drug safety and efficacy beyond initial clinical trials. Regulatory bodies might consider:

1. Requiring pharmaceutical companies to conduct more extensive post-marketing studies to validate advertising claims
2. Implementing systems for real-time monitoring of adverse events and treatment outcomes to inform ongoing assessment of drug benefits and risks
3. Establishing mechanisms for rapid communication of new safety or efficacy information to healthcare providers and the public
4. Developing frameworks for reassessing and potentially modifying approved indications or marketing claims based on post-marketing data

By strengthening post-marketing surveillance and linking it more closely to advertising oversight, regulatory bodies can help ensure that promotional claims remain aligned with the most current evidence on drug safety and efficacy.

The Impact of Lipitor on Patient Perceptions and Healthcare Decisions

The widespread marketing of Lipitor and the subsequent controversy surrounding its promotion had significant implications for patient perceptions of cholesterol management and their healthcare decision-making processes.

How did Lipitor’s marketing influence patient expectations about cholesterol treatment?

The aggressive marketing of Lipitor, particularly the emphasis on its uniqueness and superiority, may have shaped patient expectations about cholesterol treatment in several ways:

• Creating a preference for brand-name medications over generic alternatives
• Establishing Lipitor as the “gold standard” for cholesterol management, potentially making patients reluctant to try other treatments
• Raising expectations about the degree of cholesterol reduction that should be achieved through medication
• Potentially overshadowing the importance of lifestyle modifications in managing cardiovascular health

What lessons can be drawn about patient education and shared decision-making in the context of heavily marketed medications?

The Lipitor case highlights the need for improved patient education and shared decision-making processes in the face of pervasive pharmaceutical marketing. Healthcare providers and policymakers might consider:

1. Developing more comprehensive patient education materials that provide balanced information about all available treatment options, including generics and lifestyle interventions
2. Implementing decision support tools that help patients weigh the potential benefits, risks, and costs of different cholesterol management strategies
3. Encouraging more open dialogues between patients and healthcare providers about the influence of pharmaceutical marketing on treatment preferences
4. Promoting health literacy initiatives to empower patients to critically evaluate health-related advertising and make informed decisions

By addressing these aspects of patient engagement and education, the healthcare system can work towards ensuring that treatment decisions are based on individual patient needs and preferences rather than marketing influence alone.

The Legacy of Lipitor in the Pharmaceutical Industry

As one of the most commercially successful drugs in history, Lipitor has left a lasting impact on the pharmaceutical industry, influencing everything from drug development strategies to marketing practices.

How has Lipitor’s success shaped pharmaceutical research and development priorities?

The unprecedented success of Lipitor has likely influenced pharmaceutical R&D in several ways:

• Encouraging the pursuit of “blockbuster” drugs that can achieve high sales volumes and long-term market dominance
• Highlighting the potential of incremental innovations in crowded therapeutic areas
• Demonstrating the value of extensive clinical trial programs to support broad indications and marketing claims
• Emphasizing the importance of differentiating new products from existing therapies, even when entering established markets

What lessons does Lipitor offer for the future of drug pricing and market access?

The Lipitor experience provides several insights into drug pricing and market access strategies:

1. The power of perceived uniqueness in justifying premium pricing, even in the face of lower-cost alternatives
2. The importance of robust clinical evidence in supporting value propositions to payers and healthcare providers
3. The potential for effective marketing to maintain market share and pricing power even as patents expire
4. The need for pharmaceutical companies to develop more sophisticated lifecycle management strategies to address generic competition

As the industry continues to evolve, these lessons from Lipitor’s journey will likely inform strategies for developing, pricing, and marketing new medications in an increasingly competitive and cost-conscious healthcare environment.

“For Me There Is No Substitute”: Authenticity, Uniqueness, and the Lessons of Lipitor | Journal of Ethics

Analysts of the pharmaceutical industry have questioned what will happen in 2011 when Lipitor—Pfizer’s sales leader for more than a decade and the world’s best-selling prescription drug, ever—loses its patent exclusivity and faces generic competition [1]. When it was first approved for marketing by the U.S. Food and Drug Administration (FDA) in January 1997, Lipitor (atorvastatin) was a “me-too” drug, the fifth entry into the therapeutic class of HMG-CoA-reductase inhibitors, or statins. Entering this already-crowded field alongside Merck’s Mevacor (lovastatin) and Zocor (simvastatin), Novartis’ Lescol (fluvastatin) and Bristol-Myers Squibb’s Pravachol (pravastatin), Lipitor stood out for its claims of superior cholesterol-lowering ability, which—along with a massive marketing campaign—led to its swift and lasting dominance of the statin market, even as other agents became available in generic forms at far lower prices. Indeed, for most of the past decade, Pfizer’s promotion of Lipitor has centered on convincing consumers (and their physicians) that no generic could compare to Lipitor.

The phrase “I take Lipitor instead of a generic” was embedded in the public consciousness through an advertising campaign that featured Robert Jarvik, the medical investigator-cum-entrepreneur credited with the invention of the Jarvik artificial heart. The Jarvik Lipitor campaign, first aired in early 2006, coincided with the market entry of generic simvastatin. Many readers will remember images of his silver-haired visage on bus-stops and billboards, and video sequences of a calm, confident Dr. Jarvik rowing across a mountain lake while discussing the central role of Lipitor in the maintenance of his own cardiovascular vigor. These advertisements taught patients to be wary of pharmacists, insurers, or physicians who might try to substitute a generic statin for Lipitor. “For me,” Dr. Jarvik voiced, looking straight into the camera, “there is no substitute. ”

The campaign revolved around authenticity and the perils of imitation. Dr. Jarvik, as many would soon point out, was not an actor playing a doctor, but a “real” doctor—the first well-known case of a physician serving as a celebrity sponsor for pharmaceutical promotion. By analogy, Lipitor was the authentic center of cholesterol therapy—the market leader and strongest statin available (until the launch of Astra-Zeneca’s Crestor [rosuvastatin] and now Kowa’s Livalo [pitavastatin]). While the forces of cost containment might attempt to foist cheap generic “substitutes” upon patients and prescribers, the ads seemed to imply, none of these could boast the same results as Lipitor.

These claims of superior efficacy were based partly on pharmacological principles of potency—milligram per milligram, Lipitor reduced the biomarker of low-density lipoprotein (LDL)-cholesterol more than any generic statin, an abstract concept cleverly rendered graphic in the form of the curve traced by Jarvik’s boat. Beyond biomarkers, by the time of the Jarvik ad campaign Pfizer could point to more than 400 trials of Lipitor, involving over 80,000 patients, which allowed for claims of clinical efficacy simply not studied in other statins. For example, one year into the Jarvik campaign, Lipitor became the first cholesterol-reducing drug approved by the FDA to lower the risk of hospitalization in patients with heart failure [2]. In other, select cases, Lipitor had been compared to the now-generically available statins in, for example, the PROVE-IT trial, which revealed better cardiovascular outcomes for patients treated with Lipitor at high doses than for those treated with pravastatin at conventional doses following myocardial infarction [3]. The implication was clear: what other drug could claim to be the same as Lipitor?

Pfizer’s narrative of authenticity would soon backfire. In a popular and political environment increasingly skeptical of direct-to-consumer (DTC) pharmaceutical advertising, this broadly visible campaign was a lighting rod for criticism. Katie Watson, a bioethicist at Northwestern University, claimed that it was an ethical lapse for someone who appeared to be a practicing physician—who had direct responsibilities to patients—to accept funds to promote a prescription pharmaceutical [4]. As Jarvik became a topic of conversation for pharmaceutical industry bloggers both sympathetic to and critical of DTC advertising, publicly available sources of information were scoured to flesh out the story of this controversial spokesperson.

Jarvik had received poor grades as an undergraduate at Syracuse University. He had difficulty getting into medical school and had ultimately received his MD from an offshore medical school, after having been rejected for admission by American schools. Then came the most surprising detail: not only had Jarvik attended a suspect school—he was not a cardiologist [5]. Not only was he not a cardiologist, he was not currently licensed to practice medicine. Not only was he not currently licensed, but he had never had a license to prescribe drugs in the United States. Indeed, through the work of a loose collective of bloggers, it soon became apparent that Robert Jarvik—though an accomplished researcher who had received a full undergraduate medical education—had never completed a residency or internship and had no clinical experience in internal medicine beyond the few months afforded by his undergraduate clerkships. As the story grew, competitors in the field of cardiovascular engineering came forward and announced that Jarvik had falsely claimed credit for inventing the artificial heart, arguing that the concept and technique had predated his own work.

These critiques of Jarvik as professional were soon joined by critiques of Jarvik as patient. By mid-2006, a middle-aged rower in Seattle named Dennis Williams, whose receding silver hairline bore close similarity to Jarvik’s own, announced that he had served as a body double for Jarvik’s solo-rowing craft during a 3-day commercial shoot at Lake Crescent, Washington [6]. Jarvik, who had rowed when younger but had not been an active rower for several years, was filmed with oars in hand on a rowing platform by the side of the lake, and the frames had been superimposed to give the appearance that Jarvik himself was navigating the mountain waters. A subsequent admission by Jarvik that his own use of Lipitor did not begin until after he had been hired as a Pfizer spokesperson rendered the implied depiction of Lipitor as responsible for Jarvik’s cardiovascular health still more troubling [7].

Jarvik’s authenticity as both physician and patient spokesperson was visibly frayed. Taken claim by claim, the Jarvik Lipitor advertisements contained no outright lies, but constituted an assemblage of partial truths that, taken together, gave viewers the wrong impression. For a marketing campaign based on the importance of authenticity, these revelations of dissimulation were intensely damaging. The rowing ad was replaced by an ad showing a person unequivocally identifiable as Jarvik jogging with his son. But substituting one form of cardiovascular performance (jogging) for another (rowing) was not sufficient to quell the growing unrest over the campaign. By late 2007, it had been taken up by Congressman John Dingell’s (D-MI) Committee on Energy and Commerce as a signature example of duplicity in DTC marketing. Pfizer received letters of investigation and a subpoena in January of 2008, and a Pfizer executive appeared in congressional hearings to testify about the campaign in May of 2008 [8]. Concerns about Jarvik’s authenticity as clinician, prescriber, patient, and athlete seemed to threaten Lipitor’s authenticity as a singular form of therapy. The portrayal of Jarvik as spokesperson and the positioning of Lipitor as superior to generic statins were explicitly linked in the congressional cross-examination of Pfizer’s representative. If, for Jarvik, there clearly was a substitute (Dennis Williams), then quite possibly there was a substitute for Lipitor as well (generic simvastatin).

By the time of the congressional hearings, Pfizer had already announced the termination of the Jarvik ads. The executive responsible for marketing Lipitor, James Sage, apologized and said that, while Pfizer regretted that “the way in which we presented Dr. Jarvik in these ads has, unfortunately, led to mis-impressions and distractions” [9], Pfizer and Jarvik could nonetheless maintain that every individual statement made in these advertisements was based in a defensible claim. Real physicians and patients were left to wonder how much of Lipitor’s reputation was likewise based on a string of facts each of which may have been technically correct, but which taken together may have created an impression that was misleading. After the Congressional hearings, the matter was soon forgotten: no fines or penalties were issued, no aspect of DTC advertising regulations was changed, and Pfizer moved on to another, less controversial Lipitor campaign involving “everyman” patients in place of experts.

The artful negotiation of similarity and difference continues, however, to be central to Lipitor’s marketing success as the company girds for the imminent appearance of generic atorvastatin products. This is perhaps most explicit in the current Lipitor campaign, which claims with deliberate (and, for now, easy to defend) tautology that “only Lipitor is Lipitor” [10]. Absent Jarvik, the underlying promotional message of inimitableness is still in place. Also in place is a delicate fabric of implication in which individually verifiable claims are woven together to suggest a broader untruth: that for most patients Lipitor is a drug incommensurate with all other statins.

Although Lipitor is more potent than generically available statins, the utility of taking a more potent drug at a higher price —when equivalent LDL-lowering capacity for most patients can simply be found at a higher dosage of the generic—remains irrelevant for most statin consumers other than those with stubbornly high initial LDL levels, or patients who require extreme lipid lowering. While clinical trials support claims of Lipitor’s superior efficacy in preventing coronary events in specific sub-populations (i.e., those who have just had a myocardial infarction or been diagnosed with heart failure), these populations do not represent the lion’s share of Lipitor consumers, many of whom take it at low doses, at which it is basically interchangeable with other statins.

For the majority of Lipitor consumers—who take Lipitor for primary prevention—there is no clear evidence that the higher potency of this statin translates into more favorable outcomes. There is, however, evidence that patients who take brand-name drugs are significantly less likely to be consistently adherent with their treatment regimens than those who take generic drugs [11], and high cost is a clear predictor of poorer adherence—a very real cause of adverse clinical outcomes. Moreover, while it is true in late 2010 that there is no generic equivalent of Lipitor, this will no longer be true in 6 months. The concept that “only Lipitor is Lipitor” seems intended to last long after atorvastatin is generically available.

Conclusion

As pharmaceutical scandals go, the Jarvik/Lipitor story was a minor affair. But the importance of scandals lies not so much in the extraordinary circumstances that give rise to their publicity, but in the vantage they provide on the political, economic, and moral structures governing ordinary activity. For decades the substitution of brand-name drugs with chemically equivalent generic versions—which provide vital cost savings for the increasingly unaffordable American health system—has been undercut by the marketing efforts of brand-name pharmaceutical manufacturers.

Although suspicion of therapeutic equivalence is occasionally grounded by specific demonstrations of well-demarcated, clinically important differences between putative equivalents (as in the case of high-dose Lipitor’s superiority over moderate-dose pravastatin in post-MI patients), the history of generic drugs is a chronicle of the repeated magnification of small and specific differences into widespread popular and professional skepticism of generic drugs as a category [12]. Indeed, only in recent years has a consensus emerged that generic drugs—at least within the field of cardiovascular medicine—can be equivalent and cost-effective replacements for brand-name versions [13]. Within other fields of medicine, such as neurology, antigeneric sentiment continues apace and has led to efforts in recent years to undo state laws governing generic substitution [14]. As the economic crisis of American health care continues to intensify, the need to reconcile our aversion to substitution in medicine has only become more urgent.

For the practicing physician, the ethics of therapeutic substitution must navigate between two comparable potential harms. On the one hand, to substitute a drug that is therapeutically different—under the pretext of assumed similarity—risks harming the patient through adverse effects, allergic responses, or decreased efficacy. On the other hand, to prescribe an expensive, brand-name drug when an inexpensive generic form is therapeutically equivalent is to cause another form of harm to the individual patient’s chances for long-term therapeutic adherence—not to mention his or her pocketbook.

More perilous still is the paucity of data available to distinguish between these two risks. Indeed, the continued promotion of Lipitor’s singularity in the face of impending generic competition reminds us how heavily our system for generating, circulating, and acting on medical knowledge relies upon industry-funded and industry-promoted studies meant to differentiate products rather than to provide meaningful clinical comparisons of therapies. Recent enhanced federal support for the field of comparative effectiveness research and the founding of a new Patient-Centered Outcomes Research Institute under the Patient Protection and Affordable Care Act of 2010 offer some promise for patching up these gaps in our collective knowledge base. For the present, however, resolving the everyday yet urgent problems of therapeutic equivalence—or knowing when a medicine is good enough—remains elusive for real and imitation doctors alike.

References

1. Douthat N. Pfizer learns to live with leaner Lipitor cash cow. Forbes. April 7, 2010. http://blogs.forbes.com/greatspeculations/2010/04/07/pfizer-learns-live-with-leaner-lipitor-cash-cow/. Accessed September 10, 2010.

2. Khush KK, Waters DD, Bittner V, et al.
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3. Cannon CP, Braunwald E, McCabe CH, et al.
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4. Watson K. Dr. Jarvik’s Lipitor endorsement. NPR. http://www.npr.org/templates/story/story.php?storyId=5519081. Accessed September 10, 2010.

5. Bazell R. Is this celebrity doctor’s TV ad right for you? MSNBC.com. March 1, 2007. http://www.msnbc.msn.com/id/23338842/. Accessed September 22, 2010.

6. Williams D. Lights…camera…attention…row! (or my brief career as a drug pusher). Lake Washington Rowing Club Newsletter. April 2006. www.lakewashingtonrowing.com/newsletters/april2006.pdf. Accessed September 10, 2010.

7. Statement of Bart Stupak. Direct-to-consumer advertising: Marketing, education, or deception? Hearing before the Subcommittee on Oversight and Investigations of the Committee on Energy and Commerce, House of Representatives. Washington, DC: US Government Printing Office, 2008; 1-3. http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=110_house_hearings&docid=f:54104.wais. Accessed September 10, 2010.

8. Saul S. Pfizer to end Lipitor campaign by Jarvik.  New York Times. Feb 25, 2008. http://www.nytimes.com/2008/02/25/business/25cnd-pfizer.html?hp. Accessed September 10, 2010.

9. Statement of James Sage. Direct-to-consumer advertising: Marketing, education, or deception? Hearing before the Subcommittee on Oversight and Investigations of the Committee on Energy and Commerce, House of Representatives. Washington, DC: US Government Printing Office, 2008; 104. http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=110_house_hearings&docid=f:54104.wais. Accessed September 10, 2010.

10. Comer B. Statins: making new friends. Medical Marketing and Media. http://www.mmm-online.com/statins-making-new-friends/article/127959/. Accessed September 10, 2010.

11. Shrank WH, Hoang T, Ettner SL, et al.
    The implications of choice: prescribing generic or preferred formulary medications improves adherence for chronic medications.

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12. Greene JA. What’s in a name? Generics and the persistence of the branded drug in American medicine. J Hist Med Allied Sci. In press.

13. Kesselheim AS, Misono AS, Lee JL, et al.
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14. Cassell DK. Should generic substitution of antiepileptic drugs be restricted? Drug Topics. August 6, 2007.http://drugtopics.modernmedicine.com/drugtopics/article/articleDetail.jsp?id=443131&sk=&date=&pageID=3. Accessed September 10, 2010.

Citation

Virtual Mentor. 2010;12(10):818-823.

DOI

10.1001/virtualmentor.2010.12.10.msoc2-1010.

The viewpoints expressed in this article are those of the author(s) and do not necessarily reflect the views and policies of the AMA.

Author Information

• Jeremy A. Greene, MD, PhD is an assistant professor in the Department of the History of Science of Harvard University, instructor in the Division of Pharmacoepidemiology and Pharmacoeconomics of Harvard Medical School, and associate physician in the Department of Medicine of Brigham & Women’s Hospital in Boston. His research interests focus on the history of the pharmaceutical industry and its interactions with medical research, clinical practice, and public health, and his first book, Prescribing by Numbers: Drugs and the Definition of Disease, traces the development of chronic disease categories as markets for risk-reducing pharmaceuticals.

From old behemoth Lipitor to new king Humira: Best-selling U.S. drugs over 25 years

Take a look at 25 years’ worth of drug sales, and some familiar names pop up: the megablockbuster cholesterol drug Lipitor, for one. But you’ll also find some drugs that aren’t the mass-market successes Lipitor was. Amgen’s staple anemia treatment Epogen, for one.

Beyond the drugs themselves, we gleaned some tried-and-true advice for drugs looking to make the top 10 two and a half decades from now. Launch timing, medical need, scientific improvement and marketing efforts all factor into a drug’s success.

With data provided by IQVIA, we ranked the 10 best-selling drugs in the U.S. by the revenue they accumulated from 1992 to 2017. In addition to Lipitor and Epogen, they include the stalwart blood thinner Plavix—long a cash cow for Bristol-Myers Squibb and Sanofi and still a big seller as a generic. And a trio of immunology mainstays are led by their king, Humira, which is predicted to become the first drug ever to pass $20 billion in annual sales.

1. Lipitor
U.S. sales 1992-2017: $94.67 billion
Company: Pfizer
Indications: Treat high cholesterol and reduce the risk of heart disease

Pfizer’s cholesterol-lowering drug Lipitor is by far the best-selling drug of all time. But it wasn’t a sure thing in the megablockbuster races. Originally developed by Warner-Lambert—bought by Pfizer in 2000 for a whopping $90 billion—and approved by the FDA in late 1996, Lipitor wasn’t even the first statin on the market.

But in a historic trial run by trailblazer Merck & Co., statins showed they could not only lower cholesterol but also lower heart attack incidents. Pfizer then padded its Lipitor case with some massive clinical studies proving its own worth. Meanwhile, increased public awareness of the potential link between bad cholesterol and the risks of heart disease, plus Pfizer’s marketing clout and the FDA’s relaxation of consumer advertising rules in 1997, together boosted Lipitor to the throne. Though sales declined dramatically after its patent expired in late 2011, even today, Lipitor is still a force to be reckoned with, with 2017 sales of $1.92 billion.

2. Humira
U.S. sales 1992-2017: $75.72 billion
Company: AbbVie
Indications: Inflammatory diseases

Humira, first approved as a rheumatoid arthritis treatment, is the heir apparent, thanks to astronomical growth of its own and Lipitor sales declining post-patent cliff. On the last day of 2002, the anti-inflammatory therapy became the first fully human monoclonal antibody to reach the market. At that time, two TNF-alpha inhibitors, Enbrel and Remicade, had already been sold for more than four years.

But Humira’s convenience in administration—as a self-injection rather than IV—and AbbVie’s (then Abbott Laboratories) quick work at adding indications in other inflammatory diseases such as psoriatic arthritis, Crohn’s disease and juvenile idiopathic arthritis, helped it surpass the other two. Price hikes have also played a part in keeping Humira at the top. Just over the past five years, its price has more than doubled, according to Wells Fargo analyst David Maris. Thanks to a patent settlement, AbbVie will continue to rake in megablockbuster sales from Humira in the U.S. until 2023.

3. Nexium
U.S. sales 1992-2017: $72.45 billion
Company: AstraZeneca
Indications: Stomach acid reflux, peptic and duodenal ulcers

Nexium, known as “the purple pill,” was AstraZeneca’s follow-up to its first reflux remedy, Prilosec (omeprazole). Approved in the U.S. in 2001, Nexium showed in clinical trials that it was better at treating gastroesophageal reflux disease, with higher healing rates compared to omeprazole. But some other studies didn’t find much difference among proton pump inhibitors, the class that includes both Nexium and Prilosec.

Because of the similarity in the two drugs, AZ was criticized for pushing for the new, more expensive Nexium. The drug was previously also at the center of a pay-for-delay lawsuit, where AZ allegedly paid Ranbaxy Laboratories to abandon its patent challenge. But Nexium kept on bringing in cash: Before Teva’s generic version and Pfizer’s OTC version hit in 2015, Nexium was returning around $3 billion in annual sales.

4. Advair
U.S. sales 1992-2017: $69.08 billion
Company: GlaxoSmithKline
Indications: Asthma and COPD

GlaxoSmithKline’s Advair, a combination of fluticasone and salmeterol, is meant to treat asthma and COPD, two chronic respiratory diseases with high prevalence in the U.S. Delays in generic competition due to the hard-to-copy Diskus inhaler technology are a key reason why it still racked up £3.48 billion in 2016 sales.

Though it lost patent protection back in 2010, Teva only launched AirDuo RespiClick and its authorized generic last April. They come at a huge discount to Advair but aren’t readily substitutable for the GSK behemoth at the pharmacy. A long list of generic drugmakers, including Novartis’ Sandoz, Hikma and Mylan, are still struggling to get their versions past the FDA. Mylan said in early May that it’s expecting a generic approval in 2018.

5. Enbrel
U.S. sales 1992-2017: $67.78 billion
Company: Amgen
Indications: Autoimmune diseases

Enbrel was the first TNF-alpha inhibitor, approved by the FDA in 1998 to treat rheumatoid arthritis and later expanded into other autoimmune diseases. Like latecomer Humira, Enbrel also comes with a big price tag. Even though it doesn’t boast as many FDA-approved indications as Humira, it’s still among doctors’ favorites. In 2017, the drug racked up $5.21 billion in U.S. sales, and Amgen has been able to stall the launch of a biosim from Sandoz with a patent suit.

6. Epogen
U.S. sales until 1992-2017: $55.63 billion
Companies: Amgen
Indication: Anemia

Approved in 1989, Epogen soon moved to dominate the kidney disease-related anemia market. With orphan drug status, it enjoyed a long exclusivity period, and it has contributed billions of dollars year after year to Amgen and Johnson & Johnson, which sells the drug under the Procrit brand (sales not included here). It could have faced direct competition from Roche’s Mircera as early as 2007, but an injunction prevented the Swiss drugmaker’s competitor from launching in the U.S. until 2014. Even after Medicare instituted new rules for use of anemia drugs in some patients, Epogen prevailed; for 2017, Epoetin alfa brought in $1.77 billion in U.S. sales. And it’s set for more despite expired patents. Efforts to bring biosimilars to the U.S. market have suffered several setbacks.

7. Remicade
U.S. sales 1992-2017: $54.67 billion
Company: Johnson & Johnson
Indications: Autoimmune diseases

Remicade emerged almost at the same time as Enbrel, but it was first approved as a treatment for Crohn’s disease, only later expanding into other inflammatory diseases such as rheumatoid arthritis and psoriatic arthritis. The requirement for intravenous infusion—which means inconvenience for patients and the additional cost of outpatient administration—marked a key disadvantage for Remicade against its TNF counterparts. Pfizer launched a biosim version in the U.S. back in 2016, but it hasn’t been able to steal much share from J&J, thanks to the branded drugmaker’s aggressive deals with payers.

8. Abilify
U.S. sales 1992-2017: $51.34 billion
Companies: Otsuka/Bristol-Myers Squibb
Indications: Schizophrenia, bipolar disorder, and other CNS indications.

Discovered by scientists at Otsuka, Abilify was greenlighted by the FDA in 2002 to treat acute episodes of schizophrenia and as a maintenance therapy in the same group of patients. More indications followed; the drug racked up approvals for bipolar disorder, add-on treatment of major depression, and autism. The antipsychotic later acquired a long-lasting sister called Abilify Maintena, an injectable that freed patients from daily pill-taking. The drug caught the industry’s attention last November when Otsuka won an FDA approval for Abilify MyCite, a digital version of the drug that has a sensor that digitally tracks patients’ dosing.

9. Neulasta
U.S. sales 1992-2017: $47.40 billion
Company: Amgen
Indication: Boost white blood cells in patients undergoing chemotherapy

Approved in the U.S. in 2001, Neulasta is designed to help chemotherapy patients fight infection by boosting their white blood cell counts. Each year, about 650,000 cancer patients undergo chemotherapy in an outpatient setting in the U.S., according to the CDC. To help patients self-manage injections, Amgen rolled out the Neulasta Onpro kit in 2014. In 2017, Neulasta returned $4.53 billion in sales, and about 87% of that came from the U.S.

Though Neulasta’s shorter-acting predecessor Neupogen now faces biosimilar competition from Sandoz’s Zarxio, Neulasta doesn’t yet have a rival. Would-be biosim makers fell short with their FDA applications last year. But 2018 could well change that. Mylan says it’s on track for a Neulasta copy this year; the FDA is set to decide by June.

10. Plavix
U.S. sales 1992-2017: $46.48 billion
Companies: Sanofi/Bristol-Myers Squibb
Indication: Prevent heart attack and stroke

Plavix was approved in 1998 and became the standard-of-care blood thinner, earning a place on the WHO’s list of essential medicines. Plavix and Lipitor were the mainstays of the drug industry in the 1990s, so when Plavix’s patent expired in 2012—about half a year after Lipitor’s—it marked a major shift away from the mass-market megablockbuster era. With an influx of multiple generics from the get-go, Bristol-Myers Squibb and Sanofi were hit hard, as Plavix’s $7.1 billion in 2011 sales accounted for a third of BMS’ revenue for the year. But its legacy remains. Even today, new drugs like AZ’s Brilinta still use it as a comparator to demonstrate their products’ safety and efficacy.

Atorvastatin. Cholesterol drugs, atorvastatin side effects.

About atorvastatin

Lipids, or fats, are easily stored in your body and serve as a source of energy. Cholesterol is a type of lipid that is made in your liver from the fatty foods that you eat. When the concentration of cholesterol in your blood is too high, it is called hypercholesterolaemia. Although a high level of cholesterol will not make you feel ill, it can cause a problem if left untreated.

People with hypercholesterolaemia can develop small fatty patches called atheroma. These patches develop when excess fat is deposited on to the walls of blood vessels. Over time, these patches can make a blood vessel narrower and this is called atherosclerosis (sometimes referred to as ‘hardening of the arteries’). The narrowing reduces the blood flow through the artery and increases the risk of a number of heart and blood vessel diseases, such as heart attack and stroke.

Atorvastatin belongs to a group of medicines known as statins (or HMG-CoA reductase inhibitors). It reduces the amount of cholesterol made by your body. It does this by blocking the action of a certain enzyme which is needed to make cholesterol. This lowers your risk of heart and blood vessel disease. Atorvastatin can also reduce the risk of heart disease in people who have an increased risk of it, even if their cholesterol levels are normal.

Before taking atorvastatin

Some medicines are not suitable for people with certain conditions, and sometimes a medicine may only be used if extra care is taken. For these reasons, before you start taking atorvastatin it is important that your doctor knows:

• If you are pregnant, trying for a baby or breastfeeding.
• If you have any problems with the way your liver works, or if you have ever had a disease which has affected your liver.
• If you have a problem with unexplained muscle aches or pains.
• If you regularly drink large amounts of alcohol.
• If you have an underactive thyroid gland.
• If you have previously had a stroke caused by bleeding into your brain.
• If you have ever had an allergic reaction to a medicine.
• If you are taking any other medicines. This includes any medicines you are taking which are available to buy without a prescription, as well as herbal and complementary medicines.

How to take atorvastatin

• Before you start the treatment, read the manufacturer’s printed information leaflet from inside the pack. It will give you more information about atorvastatin and will provide you with a full list of the side-effects which you may experience from taking it.
• Take atorvastatin once each day. There are several strengths of tablet available, so your doctor will tell you which strength is right for you.
• You can generally take atorvastatin at a time of day to suit you, but it is best to take your doses at the same time of day each day. You can take the tablets either before or after food.
• If you have been given atorvastatin chewable tablets, you can chew the tablets to help you swallow, or you can swallow them whole with a drink of water.
• If you forget to take a dose, take it as soon as you remember. If you do not remember until the following day, skip the missed dose. Do not take two doses together to make up for a forgotten dose.

Getting the most from your treatment

• Try to keep your regular appointments with your doctor. This is so that your doctor can check on your progress. You will need to have blood tests from time to time. These are to measure your cholesterol level and also to check that your liver has not been affected by taking atorvastatin.
• Your doctor will give you advice about eating a healthy diet, cutting down on the amount of alcohol you normally drink, reducing the amount of salt in your diet, stopping smoking, and taking regular exercise. Following this advice will also help you to reduce your risk of developing heart and blood vessel disease.
• Do not drink more than one or two small glasses of grapefruit juice a day. This is because a chemical in grapefruit juice can increase the amount of atorvastatin in your bloodstream, which can make side-effects more likely.
• Women taking atorvastatin must avoid getting pregnant. Make sure you have discussed with your doctor which types of contraception are suitable for you and your partner.
• Treatment with atorvastatin is usually long-term unless you experience an adverse effect. Continue to take the tablets unless you are advised otherwise by your doctor.

Can atorvastatin cause problems?

Along with their useful effects, most medicines can cause unwanted side-effects although not everyone experiences them. The table below contains some of the most common ones associated with atorvastatin, although these tend to be mild. You will find a full list in the manufacturer’s information leaflet supplied with your medicine. Unwanted effects often improve as your body adjusts to the new medicine, but speak with your doctor or pharmacist if any of the following continue or become troublesome.

Important: atorvastatin has been associated with more serious side-effects in a very few people. Although these occur only rarely, it is important that you tell your doctor straightaway if you experience any of the following symptoms:

• If you develop any muscle cramps or pains, particularly if they are in your legs and you also feel unwell or have a high temperature (fever).
• If you feel short of breath or develop an unexplained cough. This is because (in very rare cases), atorvastatin may cause a disease called interstitial lung disease.
• If you develop any allergic-type reactions, such as swelling around your mouth or face, or a skin rash.

If you experience any other symptoms which you think may be due to the tablets, speak with your doctor or pharmacist for further advice.

How to store atorvastatin

• Keep all medicines out of the reach and sight of children.
• Store in a cool, dry place, away from direct heat and light. 

Important information about all medicines

Atorvastatin to Prevent Avascular Necrosis of Bone in Steroid Treated Exacerbated Systemic Lupus Erythematosus – Full Text View

Brief Summary:

This study uses the cholesterol lowering drug atorvastatin, also known as lipitor, to show reduction of avascular necrosis in steroid treated lupus patients. Avascular necrosis is a disease resulting from the loss of blood supply to the bones which can cause the bone to collapse. The collapse of bone may require a surgical replacement of the joint and can be disabling for life. Avascular necrosis is presently not preventable but research has shown that lipid lowering drugs such as lipitor can reduce or prevent avascular necrosis in animals. We therefore hypothesize that lipitor will reduce the incidence of avascular necrosis in lupus patients taking high dose steroids.

If you have started on prednisone 30mg or greater and expect to be on it for greater than two weeks you may be a candidate for the study. Also, you would need to be enrolled in the study within three days of starting prednisone. If you are eligible you will receive lipitor 40mg per day or pills which look exactly like lipitor but do not contain any medication (called placebo). During the time of the study, you will not know if you are taking lipitor or the placebo. The period of time that you will receive lipitor or placebo is 9 months and you must be willing to return for 5 follow up visits during this time which include blood tests, physical exams and 3 MRI studies of the hips, knees and ankles.

Lipitor (atorvastatin calcium) | CenterWatch

General Information

Lipitor (atorvastatin calcium) is a synthetic lipid-lowering agent. It is an inhibitor of the enzyme HMG-CoA reductase. By blocking or inhibiting the action of HMG-CoA reductase, a link is broken in the chain of reactions that produces cholesterol. When less cholesterol is produced, the liver takes up more cholesterol from the bloodstream, which results in lower levels of cholesterol circulating in the blood.

Lipitor is specifically indicated for the prevention of cardiovascular disease, including myocardial infarction and stroke, and for primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia.

Lipitor is supplied as a tablet for oral administration. The recommended initial dose of Lipitor is 10 or 20 mg once daily. Patients who require a large reduction in LDL-C (more than 45%) may be started at 40 mg once daily. The dosage range of Lipitor is 10 to 80 mg once daily, based on patient characteristics such as goal of therapy and response.

Clinical Results

FDA Approval

The FDA approval of Lipitor for the prevention of cardiovascular disease was based on four clinical trials.
ASCOT
The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) was a double-blind, placebo-controlled study evaluating the effect of Lipitor on fatal and non-fatal coronary heart disease. The trial enrolled 10,305 hypertensive subjects 40 to 80 years of age without a previous myocardial infarction and with TC levels ≤251 mg/dL (6.5 mmol/L) and with certain cardiovascular risk factors. The subjects received anti-hypertensive therapy and allocated to either Lipitor 10 mg daily or placebo, according to their baseline characteristics. Lipitor significantly reduced the rate of coronary events, both fatal coronary heart disease (46 events in the placebo group vs. 40 events in the Lipitor group) and non-fatal MI (108 events in the placebo group vs. 60 events in the Lipitor group), with a relative risk reduction of 36% (based on incidences of 1.9% for Lipitor vs. 3.0% for placebo) (p=0.0005). Lipitor also significantly decreased the relative risk for revascularization procedures by 42%. Although the reduction of fatal and non-fatal strokes did not reach a pre-defined significance level (p=0.01), a favorable trend was observed with a 26% relative risk reduction (incidences of 1.7% for Lipitor and 2.3% for placebo).
CARDS
The Collaborative Atorvastatin Diabetes Study (CARDS) was a multicenter, placebo-controlled, double-blind study evaluating the effect of Lipitor on cardiovascular disease (CVD) endpoints. The trial enrolled 2,838 subjects, ages 40 to 75, with type II diabetes, without prior history of cardiovascular disease and with LDL ≤160 mg/dL and TG ≤600 mg/dL. In addition to diabetes, subjects had 1 or more risk factors. The subjects were randomly allocated to either Lipitor 10 mg daily or placebo and were followed for a median duration of 3.9 years. The primary endpoint was the occurrence of any of the major cardiovascular events: myocardial infarction, acute CHD death, unstable angina, coronary revascularization, or stroke. Lipitor significantly reduced the rate of major cardiovascular events (83 events in the Lipitor group vs. 127 events in the placebo group) with a relative risk reduction of 37% (p=0.001). Lipitor significantly reduced the risk of stroke by 48% (21 events in the Lipitor group vs. 39 events in the placebo group; p=0.016) and reduced the risk of MI by 42% (38 events in the Lipitor group vs. 64 events in the placebo group; p=0.007). There was no significant difference between the treatment groups for angina, revascularization procedures, and acute CHD death.
TNT
The Treating to New Targets (TNT) study evaluated the effect of Lipitor 80 mg/day vs. Lipitor 10 mg/day on the reduction in cardiovascular events. The trial enrolled 10,001 subjects with clinically evident coronary heart disease who had achieved a target LDL-C level <130 mg/dL after completing an 8-week, open-label, run-in period with Lipitor 10 mg/day. The subjects received either 10 mg/day or 80 mg/day of Lipitor and followed for a median duration of 4.9 years. The primary endpoint was the time-to-first occurrence of any of the following major cardiovascular events (MCVE): death due to CHD, non-fatal myocardial infarction, resuscitated cardiac arrest, and fatal and non-fatal stroke. Treatment with Lipitor 80 mg/day significantly reduced the rate of MCVE (434 events in the 80 mg/day group vs. 548 events in the 10 mg/day group) with a relative risk reduction of 22% (p=0.0002). Of the events that comprised the primary efficacy endpoint, treatment with Lipitor 80 mg/day significantly reduced the rate of non-fatal, non-procedure related MI and fatal and non-fatal stroke, but not CHD death or resuscitated cardiac arrest.
IDEAL
The Incremental Decrease in Endpoints Through Aggressive Lipid Lowering (IDEAL) study evaluated Lipitor 80 mg/day compared to simvastatin 20 to 40 mg/day in 8,888 subjects up to 80 years of age with a history of CHD to assess whether reduction in CV risk could be achieved. The subjects subjects were followed for a median duration of 4.8 years. There was no significant difference between the treatment groups for the primary endpoint, the rate of first major coronary event (fatal CHD, non-fatal MI, and resuscitated cardiac arrest): 411 (9.3%) in the Lipitor 80 mg/day group vs. 463 (10.4%) in the simvastatin 20 to 40 mg/day group (p=0.07). There were no significant differences between the treatment groups for all-cause mortality: 366 (8.2%) in the Lipitor 80 mg/day group vs. 374 (8.4%) in the simvastatin 20 to 40 mg/day group.

The FDA approval of Lipitor for hyperlipidemia (Heterozygous Familial and Nonfamilial) and mixed dyslipidemia (Fredrickson Types IIa and IIb) was based on a variety of clincal tials. In two multicenter, placebo-controlled, dose-response studies Lipitorwas given as a single dose over six weeks. Lipitor significantly reduced total-C, LDL-C, apo B, and TG. Twenty four (24) controlled trials enrolled subjects with Fredrickson Types IIa and IIb hyperlipoproteinemia. The median (25th and 75th percentile) percent changes from baseline in HDL-C for Lipitor 10, 20, 40, and 80 mg were 6.4 (-1.4, 14), 8.7 (0, 17), 7.8 (0, 16), and 5.1 (-2.7, 15), respectively. Analysis of the pooled data also demonstrated consistent and significant decreases in total-C, LDL-C, TG, total-C/HDL-C, and LDL-C/HDL-C.

The FDA approval of Lipitor for Hypertriglyceridemia (Fredrickson Type IV) and Dysbetalipoproteinemia (Fredrickson Type III) were also positive.

The FDA approval of Lipitor for Homozygous Familial Hypercholesterolemia was based on a trial in 29 subjects ages 6 to 37 years with homozygous FH received maximum daily doses of 20 to 80 mg of Lipitor. The mean LDL-C reduction in this study was 18%. Twenty-five subjects with a reduction in LDL-C had a mean response of 20%; the remaining four subjects had 7% to 24% increases in LDL-C. Five of the 29 subjects had absent LDL-receptor function. Of these, 2 subjects also had a portacaval shunt and had no significant reduction in LDL-C. The remaining 3 receptor-negative subjects had a mean LDL-C reduction of 22%.

The FDA approval of Lipitor for Heterozygous Familial Hypercholesterolemia in pediatrics was based on a double-blind, placebo-controlled study, which was followed by an open-label phase. The study enrolled 187 boys and postmenarchal girls 10-17 years of age. with heterozygous FH or severe hypercholesterolemia. The subejcts were randomized to Lipitor or placebo for 26 weeks and then all received Lipitor for 26 weeks. The mean baseline LDL-C value was 218.6 mg/dL in the Lipitor arm compared to 230.0 mg/dL in the placebo arm. The dosage of Lipitor (once daily) was 10 mg for the first four weeks and uptitrated to 20 mg if the LDL-C level was > 130 mg/dL. Lipitor significantly decreased plasma levels of LDL-C. The mean achieved LDL-C value was 130.7 mg/dL in the Lipitor group compared to 228.5 mg/dL in the placebo group during the 26-week double-blind phase.

Side Effects

Adverse reactions associated with the use of Lipitor may include, but are not limited to, the following:

• nasopharyngitis
• arthralgia
• diarrhea
• pain in extremity
• urinary tract infection

Mechanism of Action

Lipitor (atorvastatin calcium) is a synthetic lipid-lowering agent. It is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. This enzyme catalyzes the conversion of HMG-CoA to mevalonate, an early and rate-limiting step in cholesterol biosynthesis. By blocking or inhibiting the action of HMG-CoA reductase, a link is broken in the chain of reactions that produces cholesterol. When less cholesterol is produced, the liver takes up more cholesterol from the bloodstream, which results in lower levels of cholesterol circulating in the blood.

Additional Information

For additional information regarding Lipitor or cardiovascular disease, hyperlipidemia and dyslipidemia, please visit the Lipitor web page.

Lipitor | European Medicines Agency

The CHMP, in the light of the data submitted and the scientific discussion within the Committee, was of the opinion that the SmPCs, labelling and package leaflets should be harmonised across the EU.

The areas harmonised include:

4.1 Therapeutic indications

The CHMP harmonised the wording for lowering blood lipids as follows:

‘Lipitor is indicated as an adjunct to diet for reduction of elevated total cholesterol (total-C), LDL-cholesterol (LDL-C), apolipoprotein B, and triglycerides in patients with primary hypercholesterolaemia including familial hypercholesterolaemia (heterozygous variant) or combined (mixed) hyperlipidaemia (corresponding to Types IIa and IIb of the Fredrickson classification) when response to diet and other nonpharmacological measures is inadequate.

Lipitor is also indicated to reduce total-C and LDL-C in patients with homozygous familial hypercholesterolaemia as an adjunct to other lipid-lowering treatments (e.g. LDL apheresis) or if such treatments are unavailable.’

The CHMP agreed on the following wording for the prevention of cardiovascular events:

‘Prevention of cardiovascular events in patients estimated to have a high risk for a first cardiovascular event, as an adjunct to correction of other risk factors’.

4.2 Posology and method of administration

The usual starting dose is 10 mg once a day. Adjustment of dose should be made at intervals of four weeks or more. The maximum dose is 80 mg once a day.

4.3 Contra-indications

The CHMP agreed that Lipitor should not be used in patients who are hypersensitive (allergic) to atorvastatin or to any of the ingredients of the medicine. It must not be used in patients with active liver disease or unexplained persistent elevations of serum transaminases (proteins in the blood) exceeding three times the upper limit of normal. It must also not be used during pregnancy, while breast-feeding and in women of child-bearing potential not using appropriate contraception.

Other changes

The CHMP also harmonised wording for other sections of the SmPC including sections on special warnings, interaction with other medicinal products, precautions for use, pregnancy and lactation, and adverse effects.

The amended information to doctors and patients is available in Annex III.

The European Commission issued a decision on 13 December 2010.

Researchers Awarded Grant to Study Use of Lipitor in Patients With Lynch Syndrome | Fox Chase Cancer Center

PHILADELPHIA (March 3, 2021)—Margie L. Clapper, PhD, co-leader of Fox Chase Cancer Center’s Cancer Prevention and Control Program, has been awarded a grant by the Prevent Cancer Foundation to investigate the use of atorvastatin, also known by the brand name Lipitor, to prevent cancer in patients with Lynch syndrome. Clapper will be working with Michael J. Hall, MD, MS, co-leader of Fox Chase’s Cancer Prevention and Control Program, on the project. 

Lynch syndrome is an inherited disorder that increases a patients’ risk of multiple types of cancer. Colorectal cancer is one of the most common in patients with this syndrome, with a lifetime risk of up to 80% in those with the genetic mutation.

“Many of these folks have lived through years of seeing parents and siblings develop one and sometimes many cancers, and this is terrifying,” said Hall. “If a once-a-day common medication like atorvastatin can help lower risk by even 20% or 30%, that’s well worth it for most of these folks.”

Currently the only cancer prevention regimen available to Lynch syndrome patients involves taking high doses of aspirin on a daily basis. However, as research has shown, aspirin, particularly when high doses are taken over a long period of time, can cause gastrointestinal bleeding and other high-risk side effects. Clapper and Hall believe atorvastatin can be a safer option.

Their study began with animal-based colon cancer research in Clapper’s lab. There they found that if, through colonoscopies, they first identified which mice had already developed polyps (i.e., precancerous growths), the researchers could tailor treatment to be more effective.

Dr. Margie Clapper

Dr. Michael Hall

In animals that were polyp-free, atorvastatin showed a chemopreventive, antitumor effect. If the animal had a polyp, atorvastatin was only effective when combined with a nonsteroidal anti-inflammatory agent.

To advance this research and see whether atorvastatin with or without aspirin could help to prevent colon cancer in humans, Clapper has joined forces with Hall, who treats a large Lynch syndrome population.

“The beauty of this research is that it’s translational,” said Clapper. “You actually go from the bench to the bedside.”

The Lynch syndrome population is ideal for this study, because the researchers need individuals who are high-risk but have not yet developed polyps or tumors. Patients who elect to participate in the study are stratified based on the results of their routine colonoscopy. If they don’t have any abnormal growths, they are given atorvastatin for six weeks. If they are found to have a polyp or cancer, they are given a combination of atorvastatin and aspirin for the same length of time.

After six weeks, investigators will take colon biopsies to check for biomarkers, which are indicators in the tissues that the therapy is having an antitumor effect.

This study, “Impact of Atorvastatin With or Without Aspirin on Colorectal Biomarkers in Patients with Lynch Syndrome: A Pilot Study,” is currently in progress, with nearly 60% of the target population already enrolled. Funds will be used to assess the effectiveness of the drugs in colon tissue samples.

The resulting data are expected to accelerate the early stage development of a novel preventive option for patients who face a very high lifetime risk of colorectal cancer. The study’s goal is closely aligned with the Prevent Cancer Foundation’s vision to “Stop Cancer Before It Starts” using primary and secondary prevention strategies.

For more information about Fox Chase’s clinical trials, please call 215-214-1515 or visit the clinical trials section of our website.

Pharmacy & Personal Care :: Pharmacy products :: Blood pressure :: Lipitor, 10 mg, 30 tablets

Active ingredient, group

Atorvastatin, Lipid-lowering agent – HMG-CoA reductase inhibitor

Dosage form

Film-coated tablets

Indications for use

Primary hypercholesterolemia (heterozygous familial and nonfamilial hypercholesterolemia, according to Frederickson type IIa), combined (mixed) hyperlipidemia (according to Frederickson types IIb and III), dysbetalipoproteinemia (according to Frederickson’s type III) (in addition to familial hyperlipidemia Frederickson type IV) resistant to dietary therapies.

Homozygous hereditary hypercholesterolemia (as an adjunct to hypolipidemic therapy, including autohemotransfusion of blood purified from LDL).

Also, indications for treatment are CVS diseases against the background of dyslipidemia, secondary prevention in order to reduce the total risk of death, myocardial infarction and re-hospitalization for angina pectoris.

Contraindications

Hypersensitivity to drug components, active liver diseases (incl.including active chronic hepatitis, chronic alcoholic hepatitis), increased activity of “hepatic” transaminases (more than 3 times) of unknown origin, liver failure (severity A and B on the Child-Pugh scale), pregnancy, lactation period.

Carefully. Severe electrolyte imbalance, endocrine and metabolic disorders, alcoholism, history of liver disease, arterial hypotension, severe acute infections, uncontrolled convulsions, major surgical interventions, trauma, childhood (efficacy and safety of use have not been established).

How to use: dosage and course of treatment

Inside, take at any time of the day, regardless of the meal. The initial dose is 10 mg once a day. The dose should be changed at intervals of at least 4 weeks. The maximum daily dose is 80 mg in 1 dose.

For primary hypercholesterolemia and combined (mixed) hyperlipidemia, 10 mg is prescribed once a day. The effect of treatment appears within 2 weeks, the maximum effect is observed within 4 weeks.

In case of homozygous familial hypercholesterolemia, 80 mg is prescribed once a day (decrease in LDL content by 18-45%).

Before starting therapy, the patient must be assigned a standard cholesterol-lowering diet, which he must follow during treatment.

Pharmacological action

Lipid-lowering agent from the statin group. Selective competitive inhibitor of HMG-CoA reductase, an enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonic acid, which is a precursor of sterols, including cholesterol.

TG and cholesterol in the liver are included in VLDL, enter the plasma and are transported to peripheral tissues.LDL is formed from VLDL through interaction with LDL receptors.

Taking the drug reduces plasma cholesterol and lipoprotein levels by inhibiting HMG-CoA reductase, cholesterol synthesis in the liver and increasing the number of “hepatic” LDL receptors on the cell surface, which leads to increased uptake and catabolism of LDL.

Reduces the formation of LDL, causes a pronounced and persistent increase in the activity of LDL receptors. Reduces the level of LDL in patients with homozygous familial hypercholesterolemia, which usually does not respond to lipid-lowering drugs.

Reduces the level of total cholesterol by 30-46%, LDL – by 41-61%, apolipoprotein B – by 34-50% and TG – by 14-33%; causes an increase in HDL cholesterol (high density lipoprotein) and apolipoprotein A.

Taking the drug Lipitor dose-dependently reduces the level of LDL in patients with homozygous hereditary hypercholesterolemia, resistant to therapy with other lipid-lowering drugs.

Treatment with Lipitor significantly reduces the risk of ischemic complications (incl.including the development of death from myocardial infarction) by 16%, the risk of re-hospitalization for angina pectoris, accompanied by signs of myocardial ischemia, by 26%.

Atorvastatin has no carcinogenic or mutagenic effects.

Side effects

From the nervous system: more often 2% – insomnia, dizziness; less often 2% – headache, asthenia, malaise, drowsiness, unusual dreams, amnesia, paresthesia, peripheral neuropathy, amnesia, emotional lability, ataxia, facial paralysis, hyperkinesis, depression, hyperesthesia, loss of consciousness.

From the senses: less often 2% – amblyopia, ringing in the ears, dryness of the conjunctiva, impaired accommodation, hemorrhage in the eyes, deafness, glaucoma, parosmia, loss of taste, taste perversion.

From the digestive system: more often 2% – nausea; less often 2% – heartburn, constipation or diarrhea, flatulence, gastralgia, abdominal pain, anorexia, decreased or increased appetite, dry mouth, belching, dysphagia, vomiting, stomatitis, esophagitis, glossitis, erosive and ulcerative lesions of the oral mucosa, gastroenteritis, hepatitis, biliary colic, cheilitis, duodenal ulcer, pancreatitis, cholestatic jaundice, liver dysfunction, rectal bleeding, melena, bleeding gums, tenesmus.

From the respiratory system: more often 2% – bronchitis, rhinitis; less often 2% – pneumonia, dyspnea, bronchial asthma, epistaxis.

From the CVS: more often 2% – chest pain; less often 2% – palpitations, vasodilation, migraine, postural hypotension, increased blood pressure, phlebitis, arrhythmia, angina pectoris.

From the hematopoietic system: less often 2% – anemia, lymphadenopathy, thrombocytopenia.

From the musculoskeletal system: more often 2% – arthritis; less often 2% – leg muscle cramps, bursitis, tendosynovitis, myositis, myopathy, arthralgia, myalgia, rhabdomyolysis, torticollis, muscle hypertonia, joint contractures.

From the genitourinary system: more often 2% – urogenital infections, peripheral edema; less often 2% – dysuria (including pollakiuria, nocturia, urinary incontinence or urinary retention, urgency to urinate), nephritis, hematuria, vaginal bleeding, nephrourolithiasis, metrorrhagia, epididymitis, decreased libido, impotence, impaired ejaculation.

On the part of the skin: more often 2% – alopecia, xeroderma, increased sweating, eczema, seborrhea, ecchymosis, petechiae.

Allergic reactions to the components of the drug: less often 2% – pruritus, skin rash, contact dermatitis, rarely – urticaria, angioedema, facial edema, photosensitivity, anaphylaxis, exudative erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome).

Laboratory indicators: less often 2% – hyperglycemia, hypoglycemia, increased serum CPK, albuminuria.

Others: less often 2% – weight gain, gynecomastia, mastodynia, exacerbation of gout.

Overdose.

Treatment of overdose: there is no specific antidote, symptomatic therapy is performed. Hemodialysis is ineffective.

Special instructions

Treatment can cause an increase in serum CPK, which should be taken into account in the differential diagnosis of chest pain.

It is necessary to regularly monitor liver function indicators before starting treatment, 6 and 12 weeks after starting the drug or after increasing the dose, and also periodically during the entire period of use (until the condition of patients whose transaminase levels exceed normal) is completely normalized.An increase in the parameters of “hepatic” transaminases is observed mainly in the first 3 months of using the drug.

It is recommended to discontinue the drug or reduce the dose if the AST and ALT parameters increase more than 3 times. The use of the drug should be temporarily discontinued with the development of clinical symptoms suggesting the presence of acute myopathy, or in the presence of factors predisposing to the development of acute renal failure against the background of rhabdomyolysis (severe infections, hypotension, traumatic surgery, trauma, metabolic, endocrine or severe electrolyte disturbances).Patients should be warned to see a doctor immediately if they develop unexplained muscle pain or weakness, especially if accompanied by malaise or fever.

Women of reproductive age should use reliable methods of contraception.

In children, the experience of using at a dose of 80 mg / day is limited. Controlled studies in children have not been conducted, however, adverse reactions when using the drug in 8 children over 9 years of age with familial homozygous hypercholesterolemia at a dose of up to 80 mg / day for 1 year were not detected.

Application during pregnancy and lactation

The drug is contraindicated in pregnancy and lactation.

Interaction

With the simultaneous administration of cyclosporine, fibrates, erythromycin, clarithromycin, immunosuppressive, antifungal drugs (related to azoles) and nicotinamide with atorvastatin, the concentration of atorvastatin in plasma (and the risk of myopathy) increases.

Antacids reduce the concentration by 35% (the effect on LDL cholesterol does not change).

The simultaneous use of atorvastatin with protease inhibitors, known as inhibitors of cytochrome CYP3A4, is accompanied by an increase in plasma concentration of the drug.

When using digoxin in combination with atorvastatin at a dose of 80 mg / day, the concentration of digoxin increases by about 20%.

Increases the concentration by 20% (when prescribed with the drug at a dose of 80 mg / day) of oral contraceptives containing norethindrone and ethinyl estradiol.

The lipid-lowering effect of the combination with colestipol is superior to that for each drug separately.

Storage conditions

Store in a place protected from children at temperatures up to 25 ° C.

Expiry date

2 years.

Terms of dispensing from pharmacies

By prescription.

Pharmacists are looking for a recipe for their own survival

Recently, amid the massive expiration of exclusive patents for popular drugs, large pharmaceutical corporations have recorded a decline in profits. To get out of a difficult situation, the management of corporations, whose own research and development takes a lot of money and time, are forced to take urgent measures – to buy competitors with new patents and the formation of partnerships with independent research companies.

Profits storage period expires

At the beginning of June, the International Society for Pharmaceutical Engineering will host a conference in Tampa, USA, at which market participants will discuss the situation in the global pharmaceutical market. In 2011-2012, patents for a number of popular drugs that have brought billions of dollars to their companies have expired or are about to expire (see table). After that, smaller companies can start producing analogs, often much cheaper.

Some corporations have already begun to feel the consequences of these events. On May 1, the American Pfizer announced that its first-quarter net profit fell 19% compared to the first quarter of last year, to $ 1.8 billion. lipitor, which lowers blood cholesterol levels. In the US alone, its sales fell 42% in the first three months, dropping Pfizer’s total US sales by 15%.A week earlier, on April 26, the head of one of the largest corporations AstraZeneca, David Brynnan, was forced to resign after the company reported a fall in the first quarter of net profit by 45% (to $ 1.6 billion) and revenue by 11% ( up to $ 7.8 billion). The reasons are the same as those of Pfizer – in March the patent for the drug Seroquel, intended for the treatment of acute psychosis and schizophrenia, expired. Reports of falling profits and the resignation of the CEO of AstraZeneca led to the company’s shares on the LSE falling 5.6%.Investors considered that the company was not sufficiently prepared for the imminent expiration of patents for two more drugs – Nexium (treatment of gastric ulcer, the first patent expires in 2014) and Crestor (lowering cholesterol, the first patent expires in 2016).

The results of manufacturers of generics (cheaper analogues), on the contrary, are growing. Last week, May 9, the largest of them, Israel’s Teva, reported that in the first quarter its net profit increased by 13%, to $ 860 million, and revenues increased by 25%, to $ 5.1 billion.The positive performance was largely driven by strong sales growth in the US, up 46%, where Teva recently began selling generics of recently patent expired drugs Pfizer’s Lipitor and Eli Lilly’s Zyprexa (schizophrenia treatment). “In the next couple of years, due to expiring patents, total sales of patented drugs could be reduced by $ 200 billion. Pharmaceutical companies need to develop a new, more differentiated strategy,” said Wagadhar Roit, an analyst at GBI Research.

Buy a competitor before it’s too late

One of the ways to adapt to the new conditions was the takeover of competitors who have long-term patents for popular drugs. Recently, pharmaceutical companies have been one of the most active participants in the M&A market. Even during the financial crisis of 2008-2010, when the activity on the global M&A market was close to zero, pharmaceutical companies made large deals. For example, in the first quarter of 2009, almost a quarter of the global M&A market volume was provided by two acquisitions in the pharmaceutical market.In late January 2009, Pfizer announced it had reached an agreement to acquire its competitor, Wyeth, for $ 68 billion, and in early March 2009, the American Merck & Co announced that it had reached an agreement to purchase its competitor Schering-Plow Corp. for $ 41.1 billion

M&A in the pharmaceutical market continues to this day. On April 23, AstraZeneca agreed to purchase Ardea, an American biotechnology company that specializes in the development of new drugs for the treatment of cancer and blood diseases, for $ 1.3 billion.Since the beginning of the year, the world’s largest independent biotechnology company, the American Amgen, announced the purchase of two promising companies: in January, the American Micromet, which develops drugs for the treatment of blood cancer, was bought for $ 1.2 billion; On April 10, the purchase of a private American company KAI Pharmaceuticals (drugs for the treatment of diseases of the endocrine system) was announced. Last week, May 10, Britain’s GlaxoSmithKline (GSK) launched a hostile takeover of the American Human Genome Sciences, which specializes in the development of new drugs for the treatment of cancer, hepatitis C and diseases of the immune system.The management of this company in April did not agree to GSK’s offer to purchase, considering the price of $ 2.6 billion too low. GSK will now make an offer to sell Human Genome Sciences shares directly to its shareholders at an 80% premium to the April price.

New drugs without high costs

Corporations that are too expensive to research on their own have recently increasingly begun to use third-party assistance to develop new products. According to GBI Research, the share of outsourcing in the volume of research costs in pharmaceuticals in 2011 was 26.5%, and by 2018 it will reach 37.1%.The total revenue of Contract Research Organizations (CRO), to which pharmaceutical companies outsource R&D, is estimated at $ 24.1 billion in 2011.

Among the latest important deals, GBI Research analyst Vagadhar Roit notes several agreements at once. In February of this year, Charles River Laboratories International, a major international research company, entered into an agreement with EMD Millipore (part of German Merck) to jointly work on a new TrueSpike technology (which can be used to produce more effective antiviral drugs and reduce side effects).Last April there was research Quintiles Translational Corp. and Samsung Electronics form the biopharmaceutical company Samsung Biologics. In general, over the past two years, pharmaceutical companies have announced 20 similar deals with contract research organizations (see table).

Experts note that among developing countries, India and China are the obvious leaders in pharmaceutical R&D outsourcing (see “The question of price”). But, according to Mr. Roit, other developing countries such as Argentina, Poland, Brazil and Russia are increasingly viewed by large pharmaceutical companies as possible targets for outsourcing projects.

We have

In Russia, generics now dominate: according to the marketing agency Cegedim Strategic Data (CSD), it is about 90%. “At the same time, the portfolio of most Russian factories is made up of generics targeted at the mass consumer, for example, Drotaverin or Enalapril,” says CSD Director David Melik-Guseinov. According to him, the development of the industry in Russia began only in the 1990s and it was impossible to create a breakthrough R&D cluster in such a short time.This is probably due to the fact that the state-owned Rusnano prefers to invest in the creation of innovative drugs not in Russia, but in the West. So, in March, she and the US fund Domain Associates agreed to invest $ 760 million on parity in at least 20 US drug development companies that are in the late stages of clinical trials or in the registration process. Earlier, Rusnano also invested in American companies Cleveland BioLabs, Selecta Biosciences and BIND Biosciences – in all cases, the state company received shares in the developers’ capital not exceeding the controlling shares in exchange for investments.

Own Russian developments, which account for the remaining 10% of domestic drugs, sometimes have an ambiguous reputation. An example is the antiviral drug Arbidol, which has been produced since 1992 (now produced by Pharmstandard). Its effectiveness in the prevention of influenza and SARS has been questioned by the World Health Organization. The United States refused to register the drug as a drug.

Not all Russian generic manufacturers will be able to skim the cream off popular drugs that are about to expire.Most of them today are unable to quickly start production of first-tier generics – those that are released immediately after the expiration of patents. Of the Russian companies, only Pharmstandard and Biocad, whose laboratory complexes can quickly reproduce a molecule identical to the original, can do this, Mr. Melik-Guseinov believes. “For first-tier generics, the margin is comparable to the original drugs, while the fifth or sixth generics are no longer needed,” he notes.

Evgeniy Khvostik, Oleg Trutnev

LIPITOR: instructions, reviews, analogs, price in pharmacies

Lipitor is a means that blocks the production of cholesterol in the body. The drug is used in conjunction with a specific diet to lower cholesterol and fat (triglycerides) levels in the blood.

Pharmacological properties

Lipitor (Lipitor) is used in conjunction with a certain diet to lower cholesterol and fat (triglycerides) levels in the blood.This remedy is usually used when drug-based cholesterol-lowering treatments (eg, dietary changes, weight loss, if overweight) have not been successful enough. Lowering your cholesterol levels can help prevent a heart attack. Lipitor is used in adults and children (10 years and older). Young girls must have had their first menstrual period before starting this drug. This medication belongs to an enzyme blocker, also known as statin.

Lipid-lowering agent from the statin group. Selective competitive inhibitor of HMG-CoA reductase, an enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonic acid, which is a precursor of sterols, including cholesterol.

TG and cholesterol in the liver are included in VLDL, enter the plasma and are transported to peripheral tissues. LDL is formed from VLDL through interaction with LDL receptors.

Taking the drug reduces plasma cholesterol and lipoprotein levels by inhibiting HMG-CoA reductase, cholesterol synthesis in the liver and increasing the number of “hepatic” LDL receptors on the cell surface, which leads to increased uptake and catabolism of LDL.

Reduces the formation of LDL, causes a pronounced and persistent increase in the activity of LDL receptors. Reduces the level of LDL in patients with homozygous familial hypercholesterolemia, which usually does not respond to lipid-lowering drugs.

Reduces the level of total cholesterol by 30-46%, LDL – by 41-61%, apolipoprotein B – by 34-50% and TG – by 14-33%; causes an increase in the level of HDL cholesterol (high density lipoproteins) and apolipoprotein A.

lipid-lowering drugs.

Treatment with Lipitor significantly reduces the risk of ischemic complications (including the development of death from myocardial infarction) by 16%, the risk of re-hospitalization for angina pectoris, accompanied by signs of myocardial ischemia, by 26%.

Atorvastatin has no carcinogenic or mutagenic effects.

Mechanism of action

Lipitor reduces the levels of cholesterol and lipoproteins in the blood plasma while suppressing the activity of HMG-CoA reductase, cholesterol synthesis in the liver and an increase in the number of hepatic LDL receptors on the cell surface, which leads to increased uptake and catabolism of LDL.

The drug leads to a reduced formation of LDL, to a pronounced and persistent increase in the activity of LDL receptors. Reduces the level of LDL in patients with homozygous familial hypercholesterolemia, resistant to treatment with other lipid-lowering drugs.

Efficacy

According to the results of clinical studies, Lipitor significantly reduces the risk of ischemic complications (including death from myocardial infarction), the risk of re-hospitalization due to angina pectoris, accompanied by signs of myocardial ischemia.

Indications for use

• heterozygous familial and nonfamilial (primary) hypercholesterolemia, according to Frederickson’s type IIa), combined hyperlipidemia (according to Frederickson’s types IIb and III), dysbetalipoproteinemia (according to Frederickson’s), dysbetalipoproteinemia (according to Frederickson’s) type III) (according to Frederickson type IV), which does not lend itself to correction with diet.
• homozygous hereditary hypercholesterolemia (in addition to lipid-lowering therapy, including autohemotransfusion of blood purified from LDL).
• cardiovascular diseases associated with dyslipidemia
• secondary prevention to reduce the overall risk of death, myocardial infarction and re-hospitalization due to angina pectoris.

Method of administration

The dose is set individually, depending on the initial cholesterol level.

The drug is taken orally, regardless of food intake. The initial dose of Lipitor is 10 mg once a day. The maximum daily dose is 80 mg once a day.

The effect appears within 2 weeks, and the maximum effect within 4 weeks.

Contraindications

• High sensitivity to the drug;
• liver diseases with severe dysfunction;
• pregnancy, lactation period.

Side effect

From the nervous system: more often 2% – insomnia, dizziness; less often 2% – headache, asthenia, malaise, drowsiness, unusual dreams, amnesia, paresthesia, peripheral neuropathy, amnesia, emotional lability, ataxia, facial paralysis, hyperkinesis, depression, hyperesthesia, loss of consciousness.

On the part of the senses: less often 2% – amblyopia, ringing in the ears, dry conjunctiva, impaired accommodation, hemorrhage in the eyes, deafness, glaucoma, parosmia, loss of taste, taste perversion.

From the digestive system: more often 2% – nausea; less often 2% – heartburn, constipation or diarrhea, flatulence, gastralgia, abdominal pain, anorexia, decreased or increased appetite, dry mouth, belching, dysphagia, vomiting, stomatitis, esophagitis, glossitis, erosive and ulcerative lesions of the oral mucosa, gastroenteritis, hepatitis, biliary colic, cheilitis, duodenal ulcer, pancreatitis, cholestatic jaundice, liver dysfunction, rectal bleeding, melena, bleeding gums, tenesmus.

From the respiratory system: more often 2% – bronchitis, rhinitis; less often 2% – pneumonia, dyspnea, bronchial asthma, epistaxis.

From the CVS: more often 2% – chest pain; less often 2% – palpitations, vasodilation, migraine, postural hypotension, increased blood pressure, phlebitis, arrhythmia, angina pectoris.

From the side of the hematopoietic system: less often 2% – anemia, lymphadenopathy, thrombocytopenia.

From the musculoskeletal system: more often 2% – arthritis; less often 2% – leg muscle cramps, bursitis, tendosynovitis, myositis, myopathy, arthralgia, myalgia, rhabdomyolysis, torticollis, muscle hypertonia, joint contractures.

From the genitourinary system: more often 2% – urogenital infections, peripheral edema; less often 2% – dysuria (including pollakiuria, nocturia, urinary incontinence or urinary retention, urgency to urinate), nephritis, hematuria, vaginal bleeding, nephrourolithiasis, metrorrhagia, epididymitis, decreased libido, impotence, impaired ejaculation.

On the part of the skin: more often 2% – alopecia, xeroderma, increased sweating, eczema, seborrhea, ecchymosis, petechiae.

Allergic reactions to the components of the drug: less often 2% – itching, skin rash, contact dermatitis, rarely – urticaria, angioedema, facial edema, photosensitivity, anaphylaxis, exudative erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome).

Laboratory indicators: less often 2% – hyperglycemia, hypoglycemia, increased serum CPK, albuminuria.

Others: less often 2% – weight gain, gynecomastia, mastodynia, exacerbation of gout.

Seek immediate medical attention if you develop these muscle problems (especially fever or unusual tiredness).

If you experience any unusual but serious side effects of Lipitor such as heaviness of the stomach / abdominal pain, nausea, yellowing of the eyes and skin, dark urine, severe fatigue, changes in the amount of urine, then inform your doctor right away.

Seek medical attention if you experience a serious allergic reaction.Symptoms of serious allergic reactions are: severe dizziness, hives, itching, swelling, trouble breathing.

Application during pregnancy and lactation

The drug is contraindicated during pregnancy and lactation.

Interaction with other drugs

With the simultaneous administration of cyclosporin, fibrates, erythromycin, clarithromycin, immunosuppressive, antifungal drugs (related to azoles) and nicotinamide with atorvastatin, the plasma concentration of atorvastatin (and the risk of myopathy) increases (and the risk of myopathy.

Antacids reduce the concentration by 35% (the effect on LDL cholesterol does not change).

The simultaneous use of atorvastatin with protease inhibitors, known as inhibitors of cytochrome CYP3A4, is accompanied by an increase in the concentration of the drug in plasma.

When using digoxin in combination with atorvastatin at a dose of 80 mg / day, the concentration of digoxin increases by about 20%.

Increases the concentration by 20% (when prescribed with the drug at a dose of 80 mg / day) of oral contraceptives containing norethindrone and ethinyl estradiol.

The hypolipidemic effect of the combination with colestipol is superior to that for each drug separately.

Overdose

Treatment of overdose: there is no specific antidote, symptomatic therapy is performed. Hemodialysis is ineffective.

Storage conditions

Store at a temperature not exceeding 25 ° C, protected from moisture and light. Keep out of the reach of children.

Shelf life 2 years.

Prescription conditions.

Composition

The active ingredient is Atorvastatin.

Additionally

Treatment may cause an increase in serum CPK, which should be taken into account in the differential diagnosis of chest pain.

It is necessary to regularly monitor liver function indicators before starting treatment, 6 and 12 weeks after starting the drug or after increasing the dose, and also periodically during the entire period of use (until the condition of patients with transaminase levels exceeds normal) is completely normalized.An increase in the parameters of “hepatic” transaminases is observed mainly in the first 3 months of using the drug.

It is recommended to discontinue the drug or reduce the dose if the AST and ALT parameters increase more than 3 times. The use of the drug should be temporarily discontinued with the development of clinical symptoms suggesting the presence of acute myopathy, or in the presence of factors predisposing to the development of acute renal failure against the background of rhabdomyolysis (severe infections, hypotension, traumatic surgery, trauma, metabolic, endocrine or severe electrolyte disturbances).Patients should be warned to see a doctor immediately if they develop unexplained muscle pain or weakness, especially if accompanied by malaise or fever.

Women of reproductive age should use reliable methods of contraception.

In children, the experience of using at a dose of 80 mg / day is limited. Controlled studies in children have not been conducted, however, adverse reactions when using the drug in 8 children over 9 years of age with familial homozygous hypercholesterolemia at a dose of up to 80 mg / day for 1 year were not detected.

Pharmaceutical Myths by Marcia Angell

Pharmaceutical companies want to convince us that the explosion in prescription drug prices is driven by the need to cover research and development (R&D) costs. This statement implies that they spend most of their money on R&D, and that after paying for this work, they have only a modest profit. They say that price control would ruin R&D and stifle innovation.But in reality, everything is completely different.

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In fact, large pharmaceutical companies spend relatively little on R&D – significantly less than on marketing and administrative needs, and even less than they have left in profit.For example, in 2002, the top ten pharmaceutical companies in America had combined sales of $ 217 billion. According to their own statistics, they spent 14% of their sales on R&D. But their costs for marketing and administration amounted to a huge amount, more than 2 times higher than the cost of research and development – 31%. And 17% remained with them in the form of profit.

Most pharmaceutical companies report total marketing and administration spending in their annual reports, but one reported that 85% of that amount was spent on marketing.If we assume that for other large companies the ratio is about the same – and there is reason for such an assumption – then it turns out that they spent almost twice as much on marketing alone as on research and development.

In public statements, the industry denies this, citing marketing to only four specific activities – sales visits to doctors, the cost of free samples, direct-to-consumer advertisements, and advertisements in medical journals.But in fact, the money allocated for marketing is not only spent on this, and the most important item is “educating” doctors (in which they are taught to prescribe more drugs).

What about profits? For many years now, pharmaceutical companies have far higher profits than any other industry — and that’s after deducting R&D and other costs. Compare the 17% profit margin for America’s top ten pharmaceutical companies in 2002 with just 3.1% profit margin across all US industries reported in the Fortune 500 for the same year.In 2003, for the first time ever, the industry moved from first to third in terms of profitability, but earnings were still well above average.

The recent claim that pharmaceutical companies spend an average of $ 802 million to bring each new drug to market is based on classified, classified data and is an incredible exaggeration. But, no matter how much these companies spend on R&D, they are unlikely to be able to argue that high prices are necessary to cover this cost item if both profit margins and marketing costs exceed it.High prices are not needed for this, but to cover their huge marketing costs and maintain profits at fabulously high levels. Prices have dropped somewhat now, but pharmaceutical companies are compensating by persuading more people to take more drugs for dubious or artificially exaggerated reasons, thereby increasing sales.

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The big question is not how much pharmaceutical companies spend on R&D, but whether the drugs they sell us are worth the money we pay for them.It is noteworthy that only a small part of drugs can be called new in any meaningful sense of the word.

For six years, from 1998 to 2003, of the 487 drugs on the market, a whopping 78%, according to the US Food and Drug Administration classification, hardly exceeded the drugs already on the market. Moreover, 68% did not even represent new chemical compounds – they were just old drugs in new forms or combinations.

In other words, the bulk of the industry’s production is not made up of important new drugs, but minor variations on drugs already on the market – what are called imitations or clone drugs. For example, the world’s largest-selling drug, Pfizer’s Lipitor, is the fourth of six cholesterol-lowering drugs of the same type. Currently, there are entire families of such clone drugs, and there is hardly any reason to believe that in comparable doses one is at least any better than the other.

Far from being a free enterprise model, the pharmaceutical industry is completely dependent on government-funded research and government-granted monopolies in the form of patents and exclusive marketing rights. The few truly new drugs are usually the result of budget-funded research in government or university laboratories. Even in the class of related clone drugs, the progenitor is usually a drug derived from publicly funded work.

For example, the first Lipitor analogue, Mevacor, entered the market in 1987 and its development was based mainly on university research. Most of the best-selling drugs today have precursors dating back to the 1980s or even earlier.

The basic idea is that, despite their claims to this effect, pharmaceutical companies are becoming less and less innovative.They simply reshuffle the same old drugs, get new patents and exclusive rights, and rely on their marketing power to convince doctors and patients that they are doing medical miracles.

In every developed country, prescription drugs are regulated in some way. Even in the United States, fees for doctors and hospital care are regulated by Medicare. So we shouldn’t worry about strangling R&D for new drugs.Pharmaceutical companies are doing much less in this direction than they claim, and what they are doing is quite affordable for them.

Scientists have explained what time it is better to drink drugs – Rossiyskaya Gazeta

Biorhythms of the body affect the effectiveness of drugs. This is why different medications are best taken at specific times of the day. The results of a study by a group of scientists from the University of Pennsylvania were published in the National Academy of Sciences.

Researchers monitored how the internal organs of animals work throughout the day. Every two hours, they analyzed the functioning of the cells of the kidneys, adrenal glands, lungs, aorta, brainstem, cerebellum, hypothalamus, heart, muscle tissue, and also monitored the state of DNA. It turned out that the greatest changes in cell activity occur at the time before sunrise and sunset.

The scheme of gene activity in different organs is different, so the peaks of cell activity do not always coincide.The most pronounced daily dynamics in the work of liver cells, the smallest scatter, according to research results, showed cells of the hypothalamus.

Scientists believe that studying the effect of biorhythms will help develop more effective treatment regimens for various diseases. Doctors have known for a long time that most cardiovascular accidents occur at night and in the early morning. In addition, it is known, for example, that statins, which are actively used for the prevention and treatment of cardiovascular diseases, are best taken in the evening.Now the nature of this phenomenon has become clear. The fact is that the liver produces the maximum amount of cholesterol at night, so drugs that lower its level work more effectively if taken in the evening, after dinner.

“I hope we can use this information to develop better treatments with existing drugs. And this is very impressive because it does not require additional costs,” – quoted by the BBC one of the participants in the study, Dr. John Hogenetsch.

Professor Andrew Loudon of the University of Manchester, in turn, said that this is a “very important” study. Treatment with any drug is a compromise of a positive result and possible side effects, such as liver damage, the scientist explained. According to him, pharmaceutical companies are constantly working on the creation of long-acting dosage forms so that one tablet can be used a day, but this is an additional risk for the body. Therefore, it is important to create “targeted” drugs that will be removed from the body faster, but due to the exact time of administration, will remain effective and have a minimal risk of side effects, the professor said.

90,000 Pharmacists looking for a prescription – Retail & Retail News

own survival

The industry is undergoing global structural changes

Recently, amid the massive expiration of exclusive patents for popular drugs, large pharmaceutical corporations have recorded a decline in profits. To get out of a difficult situation, the management of corporations, whose own research and development takes a lot of money and time, are forced to take urgent measures – to buy competitors with new patents and the formation of partnerships with independent research companies.

Profit retention period expires

At the beginning of June, the International Society for Pharmaceutical Engineering will host a conference in Tampa, USA, at which market participants will discuss the situation in the global pharmaceutical market. In 2011-2012, patents for a number of popular drugs that have brought billions of dollars to their companies expired or are about to expire (see table). After that, smaller companies can start producing analogs, often much cheaper.

Some corporations have already begun to feel the consequences of these events. On May 1, the American Pfizer announced that its first-quarter net profit fell 19% compared to the first quarter of last year, to $ 1.8 billion. lipitor, which lowers blood cholesterol levels. In the US alone, its sales fell 42% in the first three months, dropping Pfizer’s total US sales by 15%.A week earlier, on April 26, the head of one of the largest corporations AstraZeneca, David Brynnan, was forced to resign after the company reported a fall in the first quarter of net profit by 45% (to $ 1.6 billion) and revenue by 11% ( up to $ 7.8 billion). The reasons are the same as those of Pfizer – in March the patent for the drug Seroquel, intended for the treatment of acute psychosis and schizophrenia, expired. Reports of falling profits and the resignation of the CEO of AstraZeneca led to the company’s shares on the LSE falling 5.6%.Investors considered that the company was not sufficiently prepared for the imminent expiration of patents for two more drugs – Nexium (treatment of gastric ulcer, the first patent expires in 2014) and Crestor (lowering cholesterol, the first patent expires in 2016).

The results of manufacturers of generics (cheaper analogues), on the contrary, are growing. Last week, May 9, the largest of them, Israel’s Teva, reported that in the first quarter its net profit increased by 13%, to $ 860 million, and revenues increased by 25%, to $ 5.1 billion.The positive performance was largely driven by strong sales growth in the US, up 46%, where Teva recently began selling generics of recently patent expired drugs Pfizer’s Lipitor and Eli Lilly’s Zyprexa (schizophrenia treatment). “In the next couple of years, due to expiring patents, total sales of patented drugs could be reduced by $ 200 billion. Pharmaceutical companies need to develop a new, more differentiated strategy,” said Wagadhar Roit, an analyst at GBI Research.

Buy a competitor before it’s too late

One of the ways to adapt to the new conditions was the takeover of competitors who have long-term patents for popular drugs. Recently, pharmaceutical companies have been one of the most active participants in the M&A market. Even during the financial crisis of 2008–2010, when activity in the global M&A market was close to zero, pharmaceutical companies were making large deals. For example, in the first quarter of 2009, almost a quarter of the global M&A market volume was provided by two acquisitions in the pharmaceutical market.At the end of January 2009, Pfizer announced that it had reached an agreement to acquire its competitor, Wyeth, for $ 68 billion, and in early March 2009, the American Merck & Co announced that it had reached an agreement to purchase its competitor Schering-Plow Corp. for $ 41.1 billion

M&A in the pharmaceutical market continues to this day. On April 23, AstraZeneca agreed to purchase Ardea, an American biotechnology company that specializes in the development of new drugs for the treatment of cancer and blood diseases, for $ 1.3 billion.Since the beginning of the year, the world’s largest independent biotechnology company, the American Amgen, announced the purchase of two promising companies: in January, the American Micromet, which develops drugs for the treatment of blood cancer, was bought for $ 1.2 billion; On April 10, the purchase of a private American company KAI Pharmaceuticals (drugs for the treatment of diseases of the endocrine system) was announced. Last week, May 10, Britain’s GlaxoSmithKline (GSK) launched a hostile takeover of the American Human Genome Sciences, which specializes in the development of new drugs for the treatment of cancer, hepatitis C and diseases of the immune system.The management of this company in April did not agree to GSK’s offer to purchase, considering the price of $ 2.6 billion too low. GSK will now make an offer to sell Human Genome Sciences shares directly to its shareholders at an 80% premium to the April price.

New drugs without high costs

Corporations that are too expensive to research on their own have recently increasingly begun to use third-party assistance to develop new products. According to GBI Research, the share of outsourcing in the volume of research costs in pharmaceuticals in 2011 was 26.5%, and by 2018 it will reach 37.1%.The total revenue of Contract Research Organizations (CRO), to which pharmaceutical companies outsource R&D, is estimated at $ 24.1 billion in 2011.

Among the latest important deals, GBI Research analyst Vagadhar Roit notes several agreements at once. In February of this year, Charles River Laboratories International, a major international research company, entered into an agreement with EMD Millipore (part of German Merck) to jointly work on a new TrueSpike technology (which can be used to produce more effective antiviral drugs and reduce side effects).Last April there was research Quintiles Translational Corp. and Samsung Electronics form the biopharmaceutical company Samsung Biologics. In general, over the past two years, pharmaceutical companies have announced 20 similar deals with contract research organizations (see table).

Experts note that among developing countries, India and China are the obvious leaders in pharmaceutical R&D outsourcing (see “The question of price”). But, according to Mr. Roit, other developing countries such as Argentina, Poland, Brazil and Russia are increasingly viewed by large pharmaceutical companies as possible targets for outsourcing projects.

We have

In Russia, generics now dominate: according to the marketing agency Cegedim Strategic Data (CSD), it is about 90%. “At the same time, the portfolio of most Russian factories is made up of generics targeted at the mass consumer, for example, Drotaverin or Enalapril,” notes CSD Director David Melik-Guseinov. According to him, the development of the industry in Russia began only in the 1990s and it was impossible to create a breakthrough R&D cluster in such a short time.This is probably due to the fact that the state-owned Rusnano prefers to invest in the creation of innovative drugs not in Russia, but in the West. So, in March, she and the US fund Domain Associates agreed to invest $ 760 million on parity in at least 20 US drug development companies that are in the late stages of clinical trials or in the registration process. Earlier, Rusnano also invested in American companies Cleveland BioLabs, Selecta Biosciences and BIND Biosciences – in all cases, the state company received, in exchange for investments, shares in the developers’ capital that did not exceed the controlling ones.

Own Russian developments, which account for the remaining 10% of domestic drugs, sometimes have an ambiguous reputation. An example is the antiviral drug Arbidol, which has been produced since 1992 (now produced by Pharmstandard). Its effectiveness in the prevention of influenza and SARS has been questioned by the World Health Organization. The United States refused to register the drug as a drug.

Not all Russian generic manufacturers will be able to skim the cream off popular drugs that are about to expire.Most of them today are unable to quickly start production of first-tier generics – those that are released immediately after the expiration of patents. Of the Russian companies, only Pharmstandard and Biocad, whose laboratory complexes can quickly reproduce a molecule identical to the original, can do this, says Mr. Melik-Guseinov. “For first-tier generics, the margin is comparable to the original drugs, while the fifth or sixth generics are no longer needed,” he notes.

Evgeniy Khvostik, Oleg Trutnev, Publishing House Kommersant

90,000 US pharmaceutical titanium Pfizer is in talks to acquire another major US drug manufacturer, Wyeth

US pharmaceutical titanium Pfizer is in talks to acquire another major US drug maker, Wyeth. This deal could spawn a giant holding with revenues of $ 75 billion. The merger will allow them to significantly reduce spending on research and development and other expenses, which is important in times of crisis.

Pharmaceutical giant Pfizer Inc is in talks to buy its competitor in the drug market Wyeth for more than $ 60 billion, writes The Wall Street Journal, citing informed sources. The corporations themselves do not comment on the negotiations.

If the deal is concluded between the two leaders of the global pharmaceutical industry, a corporation will emerge with total revenues of $ 75 billion. The synergistic effect of the merger could translate into cost savings of billions of dollars through the combination of back offices, research groups, as well as development, sales and production operations …

The difficult situation of the US pharmaceutical industry pushed the companies to merge, even though the financial crisis actually bypassed it. Like many drug manufacturers, Pfizer and Wyeth will soon expire on patents for their most profitable products – the cholesterol-lowering Lipitor and the well-known Viagra from Pfizer, and the Prevnar vaccine, which is designed to immunize children against pneumococcal disease ( sepsis, meningitis, pneumonia), which is produced by Wyeth.Also, the two pharmaceutical holdings are increasingly feeling competition from manufacturers of generics, that is, drugs that are bioequivalent to the registered patented drug in terms of pharmacokinetic and pharmacodynamic properties, but sold at a lower price. Also, medical product manufacturers face stricter regulatory procedures in the United States and other countries, which also has a negative effect on their operations.

These challenges are forcing the investment community to respond to demands to accelerate sector consolidation.Over the years, companies have refused to merge, expecting that new developments will help them maintain their independence. But now many analysts say that industry consolidation has become inevitable.

Combining the two companies will not be able to solve the problem of creating new drugs in the short term, but it will allow them to significantly reduce spending on research and development, which on average in the industry is 20% of all sales. Larger corporations also have advantages in buying biotech companies, which will increase their competitiveness in the marketplace.However, this effect is also expected in the long term.

Despite the financial crisis, the value of the two companies did not drop much. While Pfizer shares dropped 23%, Wyeth lost only 7.5%. During the same period, the S&P 500 fell 37%. On news of Pfizer Inc’s possible purchase of its competitor, Wyeth shares rose significantly in value. Wyeth’s capitalization is currently $ 52 billion, and in combination with a premium to the market, the deal could amount to $ 60 billion.Pfizer will likely use both cash and equity to acquire its competitor. However, the terms of the purchase have not yet been worked out, notes The Wall Street Journal.

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