The largest manufacturer of the generic version of Lipitor has been forced to halt production after glass particles were found in certain batches of tablets.

The US FDA announced that Ranbaxy Pharmaceuticals had ceased production of atorvastatin after fragments the size of sand contaminated the popular generic.

Ranbaxy, a subsidiary of Daiichi Sankyo, said “the probability of an adverse event due to consumption of this product is unlikely but cannot be ruled out.”

More than 40 batches of the generic have now been recalled, although the FDA said it had not received any reports of patients being harmed by the contamination.

The New Jersey-based company (part of India-based Ranbaxy Laboratories) declined to reveal where the contaminated drugs were manufactured or why the problem occurred. However, the FDA said that the company has now stopped making the pill’s active ingredient – which is made in India – until an investigation has been completed.

It is not the first time that the quality of Ranbaxy’s products has come under scrutiny. The company has been working under a US court-ordered consent decree after a number of manufacturing issues were found at sites in America and in India. The decree prevents Ranbaxy from producing any more medication at these sites until it meets US standards.

Ranbaxy became one of the first generic manufacturers of the cholesterol lowering Lipitor when the blockbuster drug lost patent protection in November 2011. It now holds a market share of approximately 43%, according to IMS Health data.

Different statins vary in their potential to cause diabetes as a side-effect in certain patients, new research has shown.

Evidence presented at the World Congress on Prevention of Diabetes and its Complications (WCPD) in Madrid suggests that pitavastatin and pravastatin may pose less risk than other statins.

The Congress also noted that concern over diabetes risk has affected worldwide prescribing of statins in general.

Despite being the most-prescribed type of drug, statins – which have been shown to reduce blood cholesterol levels and this risk of cardiovascular events – have a range of medically significant side-effects.

Most notably, a meta-analysis of 13 trials with 91,000 participants has found that statin use is associated with 9% increase in risk of new-onset diabetes.

More recent studies suggest this effect varies strongly between drugs in the statin class, with atorvastatin increasing long-range blood glucose in intensive doses but with pitavastatin and pravastatin having no such impact.

The new J-PREDICT trial in Japan, due to conclude in 2015, is testing the effect of pitavastatin on risk of diabetes in 1,200 people with ‘pre-diabetes’ (impaired glucose tolerance).

Pitavastatin, the lead product of Japanese company Kowa, will be marketed (as Livazo) by Recordati in Europe, where it received MHRA approval in 2010.

Prof. Kausik Ray, Professor of Cardiovascular Disease Prevention at St George’s, University of London, said: “These insights demonstrate how the medical community is taking the diabetogenic risk of statins seriously and highlight the need for further research and guidance in how to treat patients with high cholesterol who are at risk of developing diabetes.”

Nearly half a billion pounds will be cut from the NHS drugs budget as part of the QIPP savings agenda, according to a new DH report.

Forecasts included in The Quarter, a report which reviews NHS QIPP targets, predict that up to £477m will be saved from the prescribing budget by April 2013.

Savings will be generated by a number of treatments losing patent protection in 2011/12 allowing the NHS to purchase cheaper generic alternatives.

AstraZeneca’s Seroquel (quetiapine) and Pfizer/Eisai’s Aricept (donepezil) are two products used throughout the NHS which recently lost patent protection. Pfizer’s Lipitor (atorvastatin), one of the biggest components of NHS drugs expenditure, came off-patent in May and will also contribute to the savings.

The report shows that the NHS saved £1.2bn in the first quarter of the financial year and is on track to meet its £5bn savings target this year. Cutbacks on drugs spend are predicted to be the second biggest saving behind efficiencies coming from acute services.

The expected £477m savings is down on the £700m saved on the medicines bill the year before – when the NHS made £5.8bn of savings through the QIPP agenda.

Teva has cancelled its plans to join the already crowded market for atorvastatin, the generic version of Pfizer’s fading blockbuster Lipitor.

The global generics leader will collaborate with Indian companies Ranbaxy and Dr. Reddy’s to promote the cholesterol-lowering drug in the US market, without offering its own version.

The decision, according to Teva, came down to two factors: increasing competition and limited manufacturing capability.

Since Lipitor’s patent expiry in November 2011 (US) and May 2012 (EU), eight companies (including Pfizer) have launched generic versions of atorvastatin.

In addition, the drug was likely to dominate Teva’s manufacturing facilities for active ingredients and pill formulations.

Pfizer has stopped marketing Lipitor where its patent has expired, meaning that the brand’s $13bn annual revenue is up for grabs.

Teva Americas CEO William Marth said: “It’s a tough decision, a hard decision not to launch at this time. That doesn’t mean that sometime in the future we may not launch atorvastatin.”

Referring to the challenge of manufacturing the world’s most widely prescribed drug, he added that the reason for the decision was “when we looked at our product, we only had it in the 30-tablet bottle”.

Ranbaxy has earned $600m from atorvastatin in the US under the company’s 180-day exclusivity period (now expired) as the first generic supplier. Half of that went to Teva by agreement.

A generic formulation of Pfizer’s blockbuster Lipitor (atorvastatin) has been launched in the UK on the first day of its patent expiry.

Indian pharmaceutical company Ind-Swift, in collaboration with its marketing partner Wockhardt UK, wasted no time in releasing the drug to gain market share.

Sirjiwan Singh, Wockhardt UK Managing Director, said the generic’s prompt launch was down to the partnership between the two companies.

“With increase in demand for cost effective drug for cardiovascular diseases, this generic launch is an excellent example of collaboration efforts of the two companies in leveraging on mutual strengths and competencies,” he said.

Lipitor, used for the treatment of high cholesterol and the prevention of heart attack, is the best selling drug in pharmaceutical history.

Pfizer recently admitted defeat in its fight against generic competition against the drug when it decided to cease marketing the product in the US. However, it is still expected to promote Lipitor in emerging markets, where increased demand may still generate billion dollar sales.

Pfizer has dropped attempts to market its cholesterol-lowering drug Lipitor (atorvastatin) in the US, nearly five months after its patent expiry.

The company said its post-expiry marketing campaign had been successful, but generic erosion of the Lipitor brand would soon escalate.

The decision is a milestone in the history of the world’s best-selling drug, used to help prevent cardiovascular events in high-risk patient groups.

Pfizer has ceased negotiating new contracts to sell Lipitor to health providers in the US or promoting it through sales representatives or advertising.

Following its US patent expiry on 30 November 2011, Pfizer invested $87m in sustaining the brand through doctor marketing, advertisements and price rebates. The strategy succeeded in retaining 33% of market share, bringing in $383m in the first quarter of 2012.

However, the second wave of generic atorvastatin following Lipitor’s patent expiry in the EU in May has prompted Pfizer to give up on the brand that at one time accounted for a quarter of its revenue.

The company will continue to promote the drug in emerging markets, including China, where it could still earn billions of dollars.

Teva UK has launched a generic atorvastatin tablet on the day after the expiry of UK patent protection on Pfizer’s cholesterol-lowering drug Lipitor.

According to the British Generic Manufacturers Association (BGMA), buying generic alternatives to Lipitor could save the NHS up to £350m per year.

Pfizer could lose 85% of its UK revenue from Lipitor by the end of this year.

Atorvastatin is the most widely prescribed statin, used in millions of patients worldwide to help prevent cardiovascular disease.

Kim Innes, Commercial Director at Teva, commented: “Millions of prescriptions are written each year in the UK for atorvastatin, and the availability of the generic will save the NHS millions of pounds each year.”

“The expiration of Pfizer’s patent exclusivity on Lipitor is hugely significant for the NHS and a demonstration of the valuable role generic drugs play in patient care in the UK,” said Warwick Smith, Director General of the BGMA.

Responding to recent claims that generics harm innovation, he argued: “It is generic competition that sustains innovation. Without competition from generic products, originators could continue to make their money out of established products and the patent system would simply not work effectively.”

Ranbaxy has launched its generic version of Pfizer’s Lipitor in four major EU markets with temporary exclusivity.

The Indian company’s generic atorvastatin has been launched in Germany, Italy, Sweden and the Netherlands ahead of its EU patent expiry in May.

The launch follows a 2008 agreement with Pfizer that Ranbaxy could launch its generic atorvastatin exclusively while Lipitor was still protected, in return for dropping a patent challenge.

Ranbaxy launched its generic version of the cholesterol-lowering drug in the US in November 2011, with a 180-day exclusivity period that is now ending. The generic caused fourth-quarter US sales of Lipitor to fall by 42% relative to the same quarter in 2010.

The market for statins remains highly lucrative despite concerns over their potential side-effects, including an increased risk of type 2 diabetes. Lipitor is the highest-selling drug in Italy, with annual sales of $377m.

Ranbaxy will sell its generic atorvastatin in Germany through its subsidiary Basics GmbH, with marketing assistance from Daiichi Sankyo.

From the end of May, other companies will be able to launch generic versions of Lipitor in the EU.

The FDA has requested label changes for Lipitor and other statins to warn of an increased risk of diabetes and cognitive effects.

Pfizer’s Lipitor (atorvastatin), AstraZeneca’s Crestor (rosuvastatin) and Merck’s Zocor (simvastatin) are among the ‘blockbuster’ drugs to carry new warnings.

Statins, which lower blood cholesterol levels, are widely prescribed to help prevent cardiovascular events, but concern over their possible side-effects has been rising for years.

The new label changes were prompted by studies showing that patients treated with statins may be at a slightly higher risk of developing type 2 diabetes and/or cognitive symptoms including mild confusion and memory loss.

According to the FDA, the reported cognitive effects in some patients have been successfully reversed by discontinuing statin use.

The new statin labels have also removed the warning that liver enzyme levels in patients taking the drugs should be routinely monitored, as later evidence has shown this to be a rare and unpredictable side-effect.

The indications now recommend liver enzyme tests before starting statin therapy, with follow-up tests only if there is evidence of liver damage.

“The value of statins in preventing heart disease has been clearly established,” said Dr Amy Egan, Deputy Director for Safety in the FDA’s Division of Metabolism and Endocrinology Products. “Their benefit is indisputable, but they need to be taken with care and knowledge of their side effects.”

AstraZeneca’s drug Crestor (rosuvastatin) is no more effective than rival Lipitor (atorvastatin) in reducing arterial plaques and cholesterol levels, according to a major head-to-head trial funded by AZ.

The SATURN trial confirms the value of using high doses of either drug to prevent strokes and heart attacks.

However, their demonstrated equivalence means that Crestor (whose patent will expire in 2016) may struggle to compete with the cheaper generic version of Lipitor about to be launched by Ranbaxy.

The SATURN (Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin Versus Atorvastatin) trial tested 1,385 participants in 215 centres over 24 months – the largest such trial ever undertaken.

It confirmed that high doses of Crestor (40mg) and Lipitor (80 mg) successfully reduced levels of arterial plaque – and the frequency of stroke, heart attack and need for angioplasty was reduced by half relative to previous trials with lower doses.

Trial outcomes such as increase in ‘good’ (HLD) cholesterol, reduction in ‘bad’ (LDL) cholesterol and reduction in plaque showed Crestor performing slightly better than Lipitor, but not to a statistically significant degree.

Darwin Labarthe, Professor of Preventive Medicine at Northwestern University, commented: “The study provides no basis to infer differential clinical benefit between the two interventions.”

SATURN trial leader Dr. Stephen J. Nicholls said the trial made a strong case for the use of high statin doses: “Regression of plaque has been the holy grail of heart disease treatment, and in this trial more than two-thirds of the patients had regression.

“Doctors have been reluctant to use high doses of statins, but in this study the drugs were safe, well tolerated and had a profound impact on lipid levels, the amount of plaque in vessel walls and the number of cardiovascular events.”