Drug Information Bulletin

Bengal Branch Tele fax: 033 24612776, E-mail: ipabengal.dic@gmail.com Web Site: http://www.ipabengal.org Contact: 09830136291

Drug Information Centre (DIC) Indian Pharmaceutical Association

Volume: 06

Number: 13
Content

8th July 2012

Pioglitazone: bladder cancer Domperidone maleate: ventricular arrhythmias and cardiac death Pyronaridine and artesunate: new anti-malarial approved Free medicines for all from October in India GlaxoSmithKline to pay $3B in settlement

Pioglitazone: bladder cancer Important safety information has been released concerning a potential risk of bladder cancer in patients treated with pioglitazone hydrochloride (Actos). Pioglitazone, an oral anti-diabetic drug, is authorized in Canada in patients with type 2 diabetes mellitus as an adjunct to decrease blood glucose levels not controlled by diet and exercise alone. It is also indicated in combination with a sulfonylurea or metformin when diet and exercise plus the single agent do not result in adequate glycaemic control. Findings from new studies reveal that there is a potential increased risk of bladder cancer in patients treated with pioglitazone-containing products. Pioglitazone is now contraindicated in patients with active bladder cancer, a history of bladder cancer or uninvestigated macroscopic haematuria. Any macroscopic haematuria should be investigated before starting pioglitazone therapy. Risk factors for bladder cancer should be assessed before initiating treatment with pioglitazone. Patients prescribed pioglitazone should be advised to seek medical attention if macroscopic haematuria or other

symptoms such as dysuria or urinary urgency develop during treatment, as these may be symptoms of bladder cancer. Reference: Communication from Takeda Canada, Inc. 16 April 2012 at http://www. hc-sc.gc.ca/dhp-mps/medeff/advisoriesavis/prof/_2012/actos_3_hpc-cps-eng.php Domperidone maleate: ventricular arrhythmias and cardiac death Canada Healthcare professionals have been informed that the gastrointestinal motility modifier, domperidone, should be initiated at the lowest possible dose in adults. Recent epidemiological studies have shown that the use of domperidone may be associated with an increased risk of serious ventricular arrhythmias or sudden cardiac death, particularly in patients taking daily doses greater than 30 mg, and in patients older than 60 years of age. Domperidone is indicated in adults for the symptomatic management of upper gastrointestinal motility disorders associated with chronic and subacute gastritis and diabetic gastroparesis. Domperidone is also indicated to prevent gastrointestinal symptoms associated with the use of dopamine agonist antiparkinson agents.

2 Caution should be exercised when using domperidone concomitantly with drugs that prolong the QT interval, in patients who have existing prolongation of cardiac conduction intervals, particularly QTc, and in patients with significant electrolyte disturbances or underlying cardiac disease such as congestive heart failure. Reference: Health Canada. Safety Advisory.2 March 2012 at http://www.hcc.gc.ca/dhpmps/medeff/advisoriesavis/prof/_2012/domperidone_hpc-cpseng.php Pyronaridine and artesunate: new anti-malarial approved European Union The European Medicines Agency (EMA) has recommended Pyramax, a fixed combination consisting of pyronaridine and artesunate for the treatment of acute, uncomplicated malaria infection caused by Plasmodium falciparum or by Plasmodium vivax in adults and children weighing 20 kg or more in areas of low transmission with evidence of artemisinin resistance. The scientific opinion for Pyramax was given under Article 58 of Regulation (EC) No 726/2004, which allows the Agencys Committee for Medicinal Products for Human Use (CHMP) to give a scientific opinion, in cooperation with the World Health Organization (WHO), on medicines for human use intended exclusively for markets outside the European Union (EU). Applicants can use the CHMPs scientific opinion as a basis when applying for a marketing authorization in countries outside of the EU. The scientific opinion also facilitates the WHO prequalification process. Due to concerns about severe liver problems associated with repeated use,Pyramax should only be used as a single 3-day treatment course in areas of low transmission with evidence of decreased efficacy of other oral artemisininbased combination therapies, consistent with WHO recommendations. Pyramax should only be used at controlled sites where a patients liver function can be systematically monitored and where exhaustive collection of adverse events as well as reliable information on resistance can be ensured. Reference: European Medicines Agency.Press Release, EMA/CHMP/114875/2012. 17 February 2012 at http://www.ema.europa.eu Free medicines for all from October 2012 in India India's ambitious policy to provide free medicines to all patients attending a government health facility across the country will be rolled out from October. Strongly backed by Prime Minister Manmohan Singh himself, the free-medicines-for-all scheme being referred to as the "real game changer" has received its first financial allocation of Rs 100 crore from the Planning Commission for 2012-13. The entire programme, however, is estimated to cost Rs 28,560 crore over the 12th five year plan. At present, the public sector provides healthcare to 22% of the country's population. The ministry estimates that this will increase to 52% by 2017 once medicines are provided for free from 1.6 lakh sub-centres, 23,000 primary health centres, 5,000 community health centres and 640 district hospitals. The ministry has sent the National List of Essential Medicines, 2011, (348 drugs which includes anti-AIDS, analgesics, anti-ulcers, anti psychotic, sedatives, anesthetic agents, lipid lowering agents, steroids and anti platelet drugs) to all the states to use as reference. The states,however, have been asked to create their own Essential Drugs List (EDL),

3 keeping in mind the diseases that worst affect them. Around 75% of the funds under the scheme will be borne by the Centre, while the rest will be the state's responsibility. Around 5% of the district funds will be allowed to be used to purchase drugs outside the EDL. The Cabinet has approved the setting up of a Central Procurement Agency (CPA) for bulk procurement of drugs. The PMO has asked the ministry to set up the CPA as early as possible. At present, 78% of the entire health expenditure in India is from out of pocket (OOP). Purchasing drugs alone accounts for 72% of this OOP expenditure. Additional secretary in the ministry L C Goyal said a scientific committee will have to draw up the EDL list for the states. They have also been asked to devise standard treatment protocols in order to avoid unnecessary and irrational treatments. Goyal said, "The states will procure drugs directly from manufacturer or importer through an open tender. Companies applying for the tenders will have to have GMP compliance certificate, a no conviction certificate and should have a specified annual turnover. The drugs must carry a not-for-sale label printed on the packaging." He added, "We plan to roll out the game changing programme from October." Goyal said a district-level state-of-the-art warehouse will have to be set up by states to store the drugs and a passport driven system will move the medicines to district hospitals, CHCs and PHCs will then send the drugs to the sub centres. He added, "It is being made mandatory for all doctors in the public sector to prescribe generic drugs and salt names and not brands. Action will be taken against doctors found prescribing brands." Tamil Nadu has been providing free medicines in its public health centres for the past 15 years, while Rajasthan introduced it last October. Both these states have a corporation that runs the show with complete functional autonomy. A Planning Commission panel had said drug prices have shot up by 40% between 1996 and 2006. It said that during the same period the price of controlled drugs rose by 0.02%, while those in the EDL increased by 15%. The price of drugs that were neither under price control, nor under the EDL grew by 137%. The Commission says 39 million Indians are pushed to poverty because of ill health every year. Around 30% in rural India didn't go for any treatment for financial constraints in 2004. In urban areas, 20% of ailments were untreated for financial problems the same year. About 47% and 31% of hospital admissions in rural and urban India, respectively, were financed by loans and sale of assets. States have cut down on spending to purchase drugs, adding to aam aadmi's woes. A study by the Public Health Foundation of India recently found that while India's per capita OOP expenditure to pay for healthcare costs has gone up from Rs 41.83 in 2005 to Rs 68.63 in 2010, the per capita spending on drugs increased from 29.77% to 46.86% during the same period, while hospitalization costs went up from 11.20% to 22.47%. Outpatient expenditure also increased from 30.63% to 46.16%. Catastrophic spending, or percentage of households spending more than 10% of their overall income on healthcare, is nearly 15% in states that have

4 insurance in place as against 11% in states that lack such policies. Source: http://timesofindia.indiatimes.com/india/Fr ee-medicines-for-all-fromOctober/articleshow/14347633.cms GlaxoSmithKline to pay $3B in settlement GlaxoSmithKline will pay $3 billion to resolve investigations of the companys sales, marketing, and pricing practices, according to an announcement by the U.S. Justice Department on Monday. The company said in a news release that the agreement was with the U.S. Government, multiple states and the District of Columbia, and was the result of negotiations agreed to in principle in November. "This action constitutes the largest health care fraud settlement in United States history," said James M. Cole, deputy attorney general, at a press conference held in Washington D.C. on Monday, according to a news release. According to the justice department, the company agreed to plead guilty to criminal charges and to pay $1 billion in criminal fines and forfeitures for the alleged illegal marketing and promotion of the drugs Paxil and Wellbutrin for uses not approved by the U.S. Food and Drug Administration. The company also allegedly failed to report important clinical data about the drug Avandia to the administration, according to the department. The company said it was pleading guilty to misdemeanor violations related to aspects of the marketing of Paxil for pediatric use, and Wellbutrin for certain uses, and for failure to include information about the initiation studies. or status of certain Avandia

The justice department also said GlaxoSmithKline will pay an additional $2 billion to resolve civil allegations that it caused false claims to be submitted to federal health care programs for those drugs, and others, as a result of the companys illegal promotional practices and payments to physicians, the justice department said. The settlement also resolves a civil investigation of the companys alleged underpayment of rebates that were required under the Medicaid Drug Rebate Program, the justice department said. The company added that it has entered into a corporate integrity agreement with the Office of Inspector General of the U.S. Department of Health and Human Services, and has made "fundamental changes" to its procedures for compliance, marketing and selling in the United States over the last few years. Since January of last year, the company has put in place a new incentive compensation system for professional sales representatives who work directly with health care professionals, the company said. The new system is meant to eliminate individual sales targets as a basis for bonuses, and instead bases incentive compensation on the quality of the service these representatives deliver to customers to support improved patient health. "In the US, we have taken action at all levels in the company," said GlaxoSmithKlines CEO Andrew Witty in a prepared statement. "We have fundamentally changed our procedures for compliance, marketing and selling. When necessary, we have removed employees who have engaged in misconduct."