Aspirine : Protéger les victimes d'infarctus

Depuis une vingtaine d'années, plusieurs études se sont succédées, indiquant les vertus préventives de ce médicament face aux maladies cardiovasculaires. L'aspirine inhibe, en effet, l'agrégation des plaquettes, donc la formation de caillots sanguins à l'intérieur des vaisseaux. Une dose aussi faible que 80 mg par jour pendant une semaine (alors que les comprimés pour adulte varient habituellement entre 300 mg et 1 g) suffit à réduire de 90 % la libération de substances agrégantes par les plaquettes et à allonger le temps de saignement. A cette action antiagrégante s'ajoute un effet anti-inflammatoire bénéfique pour la paroi vasculaire.

Des essais thérapeutiques ont montré que la prise régulière de 

Pharmaceutical mergers: Merck's manoeuvres

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THE language was reminiscent of a happier time before the credit crunch and brewing economic devastation closed the book on most such mergers. Merck’s boss, Dick Clark, called the agreed deal to acquire Schering-Plough, which was announced on Monday March 9th, a “transformational event”. He then expounded on the “strategic sense and…exceptional promise” on offer. Fred Hassan, boss of the rival American pharmaceutical giant, perhaps mindful of appearing triumphalist as the world wobbles, chipped in with a more sober vision of a “leading company” that will be “well positioned”.

Perhaps Mr Clark could be forgiven his exuberance. The deal is a (mostly) bright spot amid a global corporate landscape of bankruptcy and retrenchment. Merck will pay $41 billion for Schering-Plough, with the total made up partly of shares, $9.8 billion from cash reserves and another $8.5 billion prised from the clutches of a bank, JPMorgan. Although credit has dried up almost everywhere else, drug companies, with their cash reserves and healthy revenues, can still call on the banks. Last month Pfizer, another American drug company, was able to count on bank loans to assist in its $68 billion acquisition of Wyeth.

Big drug firms are also keen to consolidate as a way of heading off gathering problems. On Friday Switzerland’s Roche raised its offer for the 44% of Genentech, an American biotech firm, that it does not already own. Sanofi-Aventis of France is also said to be on the acquisition trail. Buying rivals is one way for drug companies to boost anaemic product pipelines, under assault from expiring patents on blockbuster medicines and generic competitors. Merck's asthma medicine, which gives it a sixth of its revenues, loses patent protection in the next few years. In one swoop Merck will double—to 18—the number of drugs it has in the later stages of development.

Drug companies are also gearing up for a reform of American healthcare. Precisely what will transpire is unclear, but it seems likely that government health schemes will demand bigger discounts from drug suppliers. Added to this is the worry that cash-strapped American consumers (the biggest single market for drugmakers) who lack insurance or who face high bills before insurance kicks in, are cutting back on spending. However Schering-Plough derives 70% of its revenues outside of America, which should spread risk. The deal will also give Merck greater access to foreign drug markets: half of the new firm’s revenues will come from beyond America’s shores.

The deal should afford the opportunity to cut costs. Mr Clark said that 15% of the combined firm’s 106,000 employees would lose their jobs. In addition to existing rounds of cost-cutting by both firms, Merck expects to make another $3.5 billion in annual savings after 2011. One difficulty for Merck is that the deal might jeopardise Schering-Plough’s co-marketing agreement with Johnson & Johnson for Remicade, a money-spinning anti-inflammatory drug. But Mr Clark is confident the structure of the deal should guard against this.

The deal goes some way to answering critics who complained that Merck was not acting as vigorously as competitors in buying rivals and moving into new markets. The challenge for Mr Clark, who will become boss of the new company, is to show that, despite a lack of experience, he can see through the big deal smoothly. Mr Clark has done a fine job of steering the firm out of the crisis caused by the safety scandal surrounding Vioxx, its blockbuster painkiller. But Merck, unlike many of its peers, has never before attempted a mega-merger of this sort: the company has preferred to grow by developing new products in it own laboratories. Mr Hassan is getting out because he fears that the macroeconomic conditions are growing more difficult for drug firms. Mr Clark must hope that the deal will help Merck to weather the storm.

Cancer drugs: Big Pharma's gripes about the FDA

TALK to anyone in the pharmaceutical industry—a private-equity investor, a drug executive, a scientist—and within three minutes Mr Pharma will start griping about the Food and Drug Administration (FDA). The agency is incredibly powerful. Its judgment of a drug's safety and efficacy is the single biggest “X Factor” in America’s enormous pharmaceutical market. In recent years, Mr Pharma will complain, the FDA’s approval process has become slower, its decisions more erratic. A few expletives will follow.

This tension was on dramatic display this week in Washington, DC. The FDA held a two-day hearing on Avastin, a cancer drug that last year generated more than $7 billion in global sales for Genentech, a biotech firm in California, and its parent company, Roche. Avastin treats a variety of cancers, including those of the lung and kidney. In 2008 the FDA gave accelerated approval for Avastin to be used in breast cancer patients. Final approval would depend on further studies that proved Avastin’s beneficial effect.

But the glowing studies never materialised. What is more, some patients experienced severe side-effects, such as haemorrhages and holes in their gastrointestinal tracts. Last year an FDA panel decided that Avastin’s risks to breast cancer patients outweighed its benefits. Uproar followed. Genentech challenged the FDA on its decision, a remarkable move. Even more surprising, the FDA agreed to hold this week’s hearings.

But the panel upheld the earlier decision. Patients will still be able to obtain Avastin, as the drug is approved for other uses. However it is less clear that insurers will continue to cover the drug, which costs about $88,000 a year. Genentech is appealing to Margaret Hamburg, the FDA’s commissioner, who will make a final decision.

The FDA has its flaws. Big Pharma’s complaints about the agency are often justified. But in its evaluation of Avastin, the FDA has served a legitimate role. However Avastin is only the first chapter in a larger fight. The debate over oncology drugs is one of the thorniest in American health care. Americans’ spending on cancer may rise from $125 billion last year to up to $207 billion by 2020, according to Medco, a pharmacy-benefit manger. Some of the new cancer drugs hold immense promise, but others have limited efficacy and are exorbitant.

Nevertheless, a rational debate is elusive. The FDA does not consider drugs’ costs (beware talk of “rationing”). Cancer arouses intense emotion. Patients and their doctors desperately try treatments that have little chance of working. At the Avastin hearing, one patient sobbed and others booed the panelists. Regulators and politicians have a tough job. They must protect patients’ safety, encourage innovation and—soon—have a serious conversation about how much society should pay for a small extension of life. The fight over Avastin has been bitter. Much more is to come.

Justices Back Drug Industry on Overtime

WASHINGTON (AP) — The Supreme Court has ruled that sales representatives for pharmaceutical companies do not qualify for overtime pay under federal law, a big victory for the drug industry.

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In a 5-4 decision Monday, the court's conservative majority concluded that the roughly 90,000 people who try to persuade doctors to prescribe certain drugs to their patients are not covered by the federal law governing overtime pay.

Two salesmen who once worked for drug maker GlaxoSmithKline filed a class-action lawsuit claiming that they were not paid for the 10 to 20 hours they worked each week on average outside the normal business day. Their jobs required them to meet with doctors in their offices, but also to attend conventions, dinners, even golf outings.

Many sales jobs are exempt from overtime pay under the Fair Labor Standards Act. But unlike typical salespeople who often work on commission, pharmaceutical sales representatives cannot seal a deal with doctors. Federal law, in fact, forbids any binding agreement by a doctor to prescribe a specific drug.

Justice Samuel Alito, writing for the majority, said that the drug sales reps' "end goal was not merely to make physicians aware of the medically appropriate uses of a particular drug. Rather, it was to convince physicians actually to prescribe the drug in appropriate cases."

Chief Justice John Roberts and Justices Anthony Kennedy, Antonin Scalia and Clarence Thomas joined with Alito.

In dissent, Justice Stephen Breyer said the sales reps do not consummate sales and so should be allowed to claim overtime. Breyer referred to the employees not as salesmen, but as "detailers," as they are known in the industry. "The detailer's work, in my view, is more naturally characterized as involving 'promotional activities designed to stimulate sales...made by someone else,'" Breyer said, quoting from federal regulations.

Justices Ruth Bader Ginsburg, Elena Kagan and Sonia Sotomayor signed Breyer's dissent.

The Obama administration backed the sales reps and argued that they do not make sales, as the law requires for a job to be exempt from overtime.

The case is Christopher v. SmithKline Beecham Corp., 11-204.

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medicament - (medicine) something that treats or prevents or alleviates the symptoms of disease

medication, medicinal drug, medicine

acyclovir, Zovirax - an oral antiviral drug (trade name Zovirax) used to treat genital herpes; does not cure the disease but relieves the symptoms

alendronate, Fosamax - a tablet (trade name Fosamax) prescribed to prevent or treat osteoporosis in women after menopause

allopurinol, Zyloprim - a drug (trade name Zyloprim) used to treat gout and other conditions in which there is an excessive buildup of uric acid

amrinone, Inocor - a drug (trade name Inocor) used intravenously in heart failure; increases strength of contraction of myocardium

analgesic, anodyne, pain pill, painkiller - a medicine used to relieve pain

angiogenesis inhibitor - a drug that is designed to prevent the growth of blood vessels that nourish tumors

antiarrhythmic, antiarrhythmic drug, antiarrhythmic medication - a drug used to treat an abnormal heart rhythm

antibacterial, antibacterial drug, bactericide - any drug that destroys bacteria or inhibits their growth

anticholinergic, anticholinergic drug - a substance that opposes or blocks the action of acetylcholine

anticholinesterase - a medicine that inhibits cholinesterase by combining with it and so has a cholinergic effect

anticoagulant, anticoagulant medication, decoagulant - medicine that prevents or retards the clotting of blood

anticonvulsant, anticonvulsant drug, antiepileptic, antiepileptic drug - a drug used to treat or prevent convulsions (as in epilepsy)

antidepressant, antidepressant drug - any of a class of drugs used to treat depression; often have undesirable side effects

antidiabetic, antidiabetic drug - a drug used to treat diabetes mellitus

antidiarrheal, antidiarrheal drug - a drug used to control or stop diarrhea

antidiuretic, antidiuretic drug - a drug that limits the formation of urine

antiemetic, antiemetic drug - a drug that prevents or alleviates nausea and vomiting

antihistamine - a medicine used to treat allergies and hypersensitive reactions and colds; works by counteracting the effects of histamine on a receptor site

antihypertensive, antihypertensive drug - a drug that reduces high blood pressure

anti-inflammatory, anti-inflammatory drug - a medicine intended to reduce inflammation

antiprotozoal, antiprotozoal drug - a medicinal drug used to fight diseases (like malaria) that are caused by protozoa

antipyretic, febrifuge - any medicine that lowers body temperature to prevent or alleviate fever

antiseptic - a substance that destroys micro-organisms that carry disease without harming body tissues

antispasmodic, antispasmodic agent, spasmolytic - a drug used to relieve or prevent spasms (especially of the smooth muscles)

antitussive - any medicine used to suppress or relieve coughing

antiviral, antiviral agent, antiviral drug - any drug that destroys viruses

APC - a drug combination found in some over-the-counter headache remedies (aspirin and phenacetin and caffeine)

astringent, astringent drug, styptic - a drug that causes contraction of body tissues and canals

atomic cocktail - an oral dose of radioactive substance used in treatment and diagnosis of cancer

azathioprine, Imuran - an immunosuppressive drug (trade name Imuran) used to prevent rejection of a transplanted organ

blocking agent, blocker - a class of drugs that inhibit (block) some biological process

bronchodilator - a drug that relaxes and dilates the bronchial passageways and improves the passages of air into the lungs

calcium blocker, calcium-channel blocker - any of a class of drugs that block the flow of the electrolyte calcium (either in nerve cell conduction or smooth muscle contraction of the heart); has been used in the treatment of angina or arrhythmia or hypertension or migraine

carminative - medication that prevents the formation of gas in the alimentary tract or eases its passing

published

Practical guidance on implementation of pharmacovigilance legislation published

The European Medicines Agency has published a set of questions and answersconcerning the initial phases of the operation of the pharmacovigilance legislation.

The document, published today, clarifies some practical considerations that pharmaceutical companies will need to take into account before and after the legislation starts to apply in July this year. It includes the agreed position of the European Union (EU) regulatory network, following discussions between the Agency, national regulatory authorities and the European Commission services.

The document includes answers to frequently asked questions on the following topics:

• Good pharmacovigilance practice guidelines;
• Pharmacovigilance system master files and summary of the pharmacovigilance system;
• Risk management plans;
• Post-authorisation safety studies;
• Periodic safety update reports and EU reference date list;
• Literature monitoring;
• Product information and the black symbol;
• Adverse-drug-reaction reporting and signal management;
• Renewals.

The Agency will update the question-and-answer document on a regular basis with questions received at qanda-pv-legislation@ema.europa.eu. The Agency cannot reply directly to questions submitted to this address.

The Agency encourages company employees to read this document in conjunction with the questions and answers on transitional arrangements published by the European Commission in February 2012. 

International Clinical Trials Day: 20 May 2012

The European Medicines Agency supports International Clinical Trials Day, which is taking place on Sunday 20 May 2012.

International Clinical Trials Day aims to enhance communication and coordination of clinical trials between countries, resulting in better clinical research that is relevant to the needs of patients everywhere. It is celebrated every year on or around 20 May, commemorating the day thatJames Lind started his famous trial comparing treatments for scurvy on 20 May 1747.

The majority of the Agency's scientific work is centred on the review, coordination and supervision of clinical trials:

• its scientific evaluation work involves the review of clinical-trial data that are included in the application information from a pharmaceutical company when seeking marketing authorisation;
• it provides scientific advice on the design of clinical trials conducted as part of medicine development and decisions on clinical-trial design as part of paediatric investigation plans (PIPs);
• it provides scientific guidance on the design and conduct of clinical trials in specific therapeutic areas;
• it has a central role in ensuring application of good clinical practice (GCP) at a European Union (EU) level. GCP is the international ethical and scientific quality standard for designing, recording and reporting clinical trials that involve the participation of human subjects.

The Agency hosts the EU clinical trials register on behalf of EU Member States. This website contains information on interventional clinical trials of medicines, allowing users to view descriptions of clinical trials being conducted in the EU, as well as Iceland, Liechtenstein or Norway, and descriptions of trials forming part of a PIP including those where the investigator sites are outside the EU.

The Agency is also responsible for the development, maintenance and coordination of the EudraCT database, an application used by national medicine regulatory authorities to enter clinical trial data from clinical trial sponsors.

The Agency expects clinical trials carried out in countries outside the EU submitted in marketing-authorisation applications to EU regulatory authorities to meet the same ethical principles and standards as those performed within the EU. In response to this challenge, the Agency recently published a reflection paper offering practical guidance on how clinical trials outside the EU should be conducted, when data from these trials is included in marketing-authorisation applications submitted in the EU.

The paper puts forward concrete steps for international cooperation in the regulation of clinical trials, with a specific emphasis on capacity-building initiatives for a common approach to oversight of trials.

It also clarifies and determines the practical steps by which EU regulators will gain assurance that ethical and GCP standards are applied to clinical trials for human medicines, both during the development and during the marketing-authorisation-application phase. It also promotes greater transparency regarding the evaluation of these matters during the marketing-authorisation phase.

medicines

European Medicines Agency launches new e-learning course for Article 57(2) requirements on submission of information on medicines

The European Medicines Agency has launched an e-learning course for marketing-authorisation holders to support compliance with Article 57(2) on the submission of information on medicines, one of the key measures of the new pharmacovigilance legislation. 

The course is comprised of six modules which cover: 

• an introduction to the Eudravigilance system;
• the regulatory background;
• the architecture of the Extended EudraVigilance Medicinal Product Dictionary (XEVMPD);
• submission of the XEVPRM with practical examples;
• the XEVMPD data entry tool also known as EVWEB. 

The modules are cost-free to access and can be streamed live from today or can be downloaded from early next week. On completion of the e-learning course, participants are able to take a knowledge evaluation test.

At least one user from each marketing-authorisation holder should be trained to understand how to submit medicinal product data to the Agency and to ensure quality of medicinal product data submitted to the XEVMPD. A notification of successful completion of the XEVMPD knowledge evaluation provided by the Agency will be required for one user before the electronic submission process can be initiated by a marketing-authorisation holder as per Article 57(2) of Regulation (EU) No 1235/2010.

The e-learning course complements existing training initiatives including classroom training and guidance material available on the Agency's website. 

World Hypertension Day: 17 May 2012

The European Medicines Agency supports World Hypertension Day, which is taking place on Thursday 17 May 2012.

World Hypertension Day is held every year on 17 May to highlight the preventable stroke, heart and kidney diseases caused by high blood pressure and to communicate information on prevention, detection and treatment to the public. In 2012, the theme is 'healthy lifestyle, healthy blood pressure.'

The Day was started by the World Hypertension League, a federation of leagues, societies, and other national bodies devoted to the promotion of the detection, control and prevention of high blood pressure.

Long-term high blood pressure can damage the arteries and vital organs throughout the body, leading to heart disease, stroke, kidney disease and diabetes. Globally, around 7 million people die every year because of high blood pressure, making it the biggest single risk factor for death worldwide.

The European Commission has authorised a number of medicines for the treatment of high blood pressure on the recommendation of the Agency's Committee for Medicinal Products for Human Use (CHMP). The Agency also publishes guidelines for pharmaceutical companies, describing how they should design and carry out studies of medicines for the treatment of high blood pressure.

What are aliskiren-containing medicines?

Aliskiren-containing medicines are used to treat essential hypertension (high blood pressure) in adults. ‘Essential’ means that the hypertension has no obvious cause.

Aliskiren is a renin inhibitor. It blocks the activity of a human enzyme called renin, which is involved in the production of a substance called angiotensin I in the body. Angiotensin I is converted into the hormone angiotensin II, which is a powerful vasoconstrictor (a substance that narrows blood vessels). By blocking the production of angiotensin I, levels of both angiotensin I and angiotensin II fall. This causes vasodilation (widening of the blood vessels), so that the blood pressure drops.

Eight aliskiren-containing medicines have been authorised in the European Union (EU) since 2007: Rasilamlo, Rasilez, Rasilez HCT, Rasitrio, Riprazo, Riprazo HCT, Sprimeo and Sprimeo HCT. Some of these medicines (Rasilamlo, Rasilez HCT, Rasitrio, Riprazo HCT and Sprimeo HCT) are combinations of aliskiren with other antihypertensive medicines. Aliskiren-containing medicines are available as tablets and marketed in all European Union (EU) Member States, except Estonia, Latvia, Lithuania and Romania.

Chelsea 3rd worst winners ever

I just want to make it clear quickly, that I’m not being petty here; I’ve got over Chelsea winning the Champions League and this article is not intended to have a dig (I’ve done that more than enough already), merely to have a look at something, admittedly kind of pointless, that interests me.

It occurred to me last night that I really could not recall a team winning the Champions League whilst finishing as low as Chelsea did in their domestic league this season. The closest I could think of was Liverpool in 2005, who finished 5th. At the time this caused a big stir, as it was unclear if the European champions would be allowed to defend their crown the next season. Incredibly, there wasn’t a system in place to take into account that a team could finish outside the top four (or whatever the qualifying positions in their country) and still be good enough to go all the way and win the thing in the same season. This was not the case this season, as Spurs fans watched knowing their own Champions League future was in jeopardy.

But the Liverpool situation surprised me, and it therefore occurred to me that perhaps it has, indeed, been extremely rare for a team to become champions of Europe whilst being fairly average in their own league. I had a lot of time on my hands so I thought I’d have a scan through the proverbial history books (Wikipedia) and find out how Chelsea ranked as one of the ‘worst’ winners of the competition.

After going through the last twenty-one seasons, it started to get a bit tiring writing it all down, so I stopped at the final between Barcelona and Sampdoria in 1992, the last season it was called the European Cup. That year, Barcelona, who finished 1st in La Liga, beat Sampdoria, who finished 6th in Serie A. As well as Chelsea, they were the only team as well as Chelsea to finish as low as 6th domestically and make an appearance in the final. In the ‘Champions League era’ Chelsea are the lowest-placed finalists and winners.

As the pie chart shows, 1st in the league was overwhelmingly the most common position of teams making an appearance in the final. After that it’s pretty close. With winners of the competition, it’s basically the same…

So, perhaps unsurprisingly, teams doing well domestically tend to take their form into Europe. However, it’s less common that the final will feature two domestic champions contesting the title…

Most finals feature a 1st placed team against another lower placed side. The least common final features two teams who have failed to top their domestic leagues that season.

This season, 6th placed Chelsea beat 2nd placed Bayern Munich, continuing the trend in the Champions League era, of the lower-placed team beating the higher-placed one. Of 15 finals featuring sides in different positions in their league, 9 of them have been won by the lower-placed side.

So, while some people downplay the relevance of this competition as showing who is the best team in Europe, in recent history the teams making the final do tend to be up there with the best. Before this season, the last three finals were 1st vs 1st affairs, featuring Barcelona against Man Utd twice and Inter vs Bayern. In the only all-English final of 2008, it was 1st vs 2nd in the country battling it out to conquer the continent. In that sense, Chelsea’s win this season will probably go down as a relative one-off.

However, (without noting it all down) I was too tempted to go through every European Cup final to see any notable winners or finalists. It took me a while, as throughout history it seems the finals have involved mainly 1st and 2nd placed sides, but I found some big exceptions.

Forgive me if you know this, but I’m young and was not alive when this happened, but Aston Villa won the European Cup in 1982 whilst finishing an incredible 11th in the league! They overcame a 3rd placed Bayern Munich that year, while Bayern themselves won it in 1975 whilst finishing 10th in the Bundesliga; this being the lowest combined final, as they beat Leeds United, who finished 9th in England.

Those were the only two teams to finish lower than Chelsea and win it. There have been a few low runners-up, but surprisingly few – Sampdoria, as I already mentioned; an 11th placed Partizan Belgrade in 1966, a 9th placed AC Milan in 1958 and a 10th placed Stade de Reims in the first European Cup final in 1956, all three losing to Real Madrid, who finished 2nd, 1st and 1st, respectively.

A couple of other interesting facts I found along the way were: Nottingham Forest are the only team to have won the European Cup more times (twice) than their domestic title (once). Bayer Leverkusen, beaten by Real Madrid in 2002, are the only team ever to have appeared in the final despite never having won their domestic league.

Yes, it’s a knock-out tournament and it occasionally throws up some – perhaps undeserved – surprises, but, by and large, I’m impressed by the quality of the teams to have contested the finals. The big clubs have dominated hugely, and have done so while managing to dominate domestically as well.

Marouane Chamakh has been speaking to L’Equipe TV about the possible departures of key Arsenal duo Cesc Fabregas and Samir Nasri, which he believes will happen once manager Arsene Wenger indentifies some replacements.

Fabregas was widely tipped to leave the club last summer, but ended up staying, but now appears to be on his way back to boyhood club Barcelona.

Nasri, too, looks likely to seal a big-money move to Premier League rivals Manchester City, Chamakh revealed.

“I think both of them are likely leaving the club. It’s a difficult situation for the manager,” he explained.

“I don’t think it’s a matter of money for Fabregas or Samir, I think he (Wenger) is looking for their successors and he hasn’t found them. I think before letting them go he wants to find the players to replace them. That’s my opinion about the situation. The problem is the season starts this weekend, and it’s even more difficult for us.

“I think in the situation the club was in, they could have let only one leave. Especially Cesc – he wants to leave for several seasons because he’s born in Barcelona. But Samir is now in a situation where he has 1 year left on his contract, so if they don’t sell him this summer he will leave for free at the end of the season.

“Is the club ready to refuse a little bit more than €20m to keep a good player for 1 season? It’s strange – at a club like Arsenal – that he’s now with 1 year left on his contract, that the club couldn’t make him sign a new contract before.”