IS INDIA A DUMP YARD FOR HAZARDOUS DRUGS?

Honey J. Ambanatu*

 

D-cold, Nimesulide and Analgin are common household drugs. We give these drugs to our children when they have fever; doctors prescribe them as painkillers. What we do not know is that many of these drugs are banned in the developed countries, but are sold in our markets. This paper will focus on some of the common drugs and branded formulations sold in Indian pharmacies but banned in many developed countries. It will also discuss the reported side effects of these drugs and the state of drug regulation in India.

NIMESULIDE

Nimesulide is widely available in India under the brand names Nise (Dr Reddy?s) and Nimulid (Panacea Biotech). There are more than 80 brands of nimesulide currently marketed in India with no restrictions on their sales. The total market for single ingredient nimesulide brands is about Rs 300 crore. The top brand, Nise, of Dr Reddy’s Laboratory, alone has sales of Rs 60 crore or more. Apart from this, there are a dozen irrational combinations of nimesulide with paracetamol floating in the market. Nimesulide obtained government approval in India in 1994 for use in painful inflammatory febrile disorders. Various state drug regulatory authorities have been issuing licences for the manufacture of these irrational combinations from 1998 onwards, despite specific guidelines from the Drugs Controller General of India (DCGI) cautioning about their irrationality.

Nimesulide is licensed for use in some forty countries. Surprisingly, the USA, where the drug originated, is not one of them. Nimesulide was discovered by 3M Pharmaceuticals, an American manufacturer. All other products discovered by 3M Pharmaceuticals are being marketed in the USA. 3M Riker, the parent company of 3M Pharmaceuticals, sold the molecule to a small private company in Switzerland called Helsinn. Instead of launching nimesulide in Switzerland, Helsinn licensed the drug to Boehringer in Italy, where it was launched in 1985. Why was nimesulide not marketed in USA? Why it was not submitted for approval by the U. S. Federal Drug Administration (US FDA)?

The safety of nimesulide has been a matter of public concern worldwide for some years because of its serious side effects and decreasing use in several countries. The adverse effects of nimesulide on the liver have been known for some years, though not adequately publicized. According to researchers at the Zurich University Hospital, hepatotoxicity represents an important risk factor in nimesulide usage. Several laboratory, animal and human studies in Canada and the USA have shown that nimesulide is not gastro-protective. This was one of the reasons for aborting an attempt to get US FDA approval in 1998.

The National Agency for Medicines of Finland ordered the suspension of the sale of nimesulide within 72 hours, indicating the urgency and seriousness of the measure. Within two months, Spain followed suit and took action that was even more drastic. All stocks lying in the distribution channel were recalled and patients were instructed not to consume any nimesulide. Turkey has also prohibited its use. Two children, who were given nimesulide, died of Reye’s syndrome in Portugal, leading to a ban on the drug’s pediatric suspension in that country in 1999. The drug is not approved in Britain, Australia, New Zealand, and Canada and was banned in Spain and Finland in 2001.

Following an observational study of nimesulide covering 9,000 patients, Ireland issued an official warning to all prescribers to adhere strictly to the approved indications and dosage schedule, keeping in mind nimesulide’s potential for liver damage. In May 2007, the competent authority in Ireland suspended the marketing authorizations for medicines containing nimesulide based on reports of serious side effects affecting the liver. The European Medicines Agency (EMEA) undertook an independent assessment of the liver toxicity risk following safety concerns by the Irish authority. As is the usual procedure in European countries, the nimesulide issue was referred to the European Council’s scientific advisory body, the Committee for Proprietary Medicinal Products (CPMP), for final adjudication. The CPMP concluded that while there was no need to suspend the marketing authorizations, they need to be changed to the extent that the information provided to the doctors and patients should suitably be amended to limit the risk of liver injury. The guidelines issued by CPMP provide that the nimesulide treatment should be advised after a comprehensive risk assessment and limited to a maximum of 15 days and that all packs containing more than 30 doses should be removed from the market.

In South East Asia (Thailand, Malaysia, Singapore etc), nimesulide is permitted to be used only in adults for musculo-skeletal inflammation, accompanied by hyperpyrexia (temperature above 106.7 degree F), and in no other condition. In Italy, it is licensed for use in musculo-skeletal inflammation and accompanying pain only. Its use in children below 6 years is prohibited. Nimesulide was launched in Switzerland, the home country of Helsinn, in 1995 on the strength of human data from Italy. The Swiss Government permitted its use only in adults. Its use in children below 12 years is prohibited.

In India’s immediate neighbourhood, the drug has failed to obtain approval in Bangladesh, Pakistan and Sri Lanka. Nimesulide is primarily meant for musculo-skeletal disorders. However, it is used in India as a first-line drug for fever, that too in children. India seems to be the only country where nimesulide drops are marketed for use in neonates and infants. The only other country beside Italy, where the use of nimsulide is permitted in children, is Brazil, where it is prohibited for children below 3 years. It is generally agreed that despite its inherent antipyretic properties, nimesulide should not be recommended as a first-line fever therapy. The real cause of fever may be a life-threatening condition that could get masked because of the use of nimesulide.

According to Dr. C.M. Gulhati, editor of Monthly Index of Medical Specialities, only two formulations are approved in India, viz. 100 mg tablet and 50 mg/ 5 ml suspension. The following formulations are being marketed here without DCGI permission: 50 mg tablets for kids, 25 mg/ml drops, 200 mg tablets, 400 mg tablets, 100 mg EF tablets, 100 mg MD tablets. Even where a particular company has obtained permission for a formulation, another company would need fresh DCGI approval, if introducing the same drug within 4 years. As per Rule 122 (E) of the Drugs & Cosmetics Act, read with Schedule Y, all drugs require mandatory prior permission from the DGCI. A fresh permission is required if a new formulation of an approved drug is to be launched, such as a sustained release tablet. However, nimesulide is being marketed in India in combination with other agents. Over 170 companies in India are marketing nimesulide in single ingredient formulations without the mandatory DCGI approval. All fixed-dose combinations of nimesulide with other agents such as paracetamol, diclofenac, tizanidine etc are being marketed without DCGI approval. This fact has been admitted by the DCGI in reply to a starred question in Lok Sabha on August 20, 2000.

The Delhi High Court sought the expert opinion of the Drugs Technical Advisory Board (DTAB), on nimesulide in December 2002 during the hearing of a public interest litigation. The DTAB, a statutory body under the Drugs and Cosmetics Act, opined that there was no ground for banning of nimesulide for adult or paediatric use. The drug regulatory authorities claimed that no “adverse drug reaction” (ADR) Report had been received on the use of nimesulide in the country to necessitate a review. The DGCI permitted the oral suspension of nimesulide to be marketed based on a report submitted by the Indian Academy of Pediatricians.

Among the countries where nimesulide is being marketed, very few have well run post-marketing surveillance system for drugs. As a result, there are very few unbiased independent clinical trials. In fact, most trials on nimesulide have been sponsored, financed, or conducted by manufacturers and associated investigators. They are unreliable, if not biased. There is a strong opinion that most of the studies submitted to the DCGI by manufacturers of nimesulide were sponsored and financed by Helsinn; many of them were actually written by Helsinn employees.

At last, due to the untiring efforts of some NGOs and Pharma Vigilantes, the Government of India has put nimesulide under focused surveillance by the authorities in the National Pharmacovigilance Programme.

PIPERAZINE (Brand name: Piperazine)

Drugs containing Benzylpiperazine (BZP) have been declared illegal by the UK drug regulator because they contain a dangerous anti-worming agent. Research by the Medicines and Healthcare Products Regulatory Agency (MHRA) found that BZP could not only cause the same high as amphetamines, but also induce side effects, including vomiting, abdominal pain, seizures and abnormal heart rhythms. In extreme cases, it can even cause death. BZP is used as an anti-worming agent to tackle parasites in cattle. Piperazine-based products are classified as medicinal and must only be sold under licence in a pharmacy. However, BZP pills are unlicensed and there is no safeguard over the quality or safety of the drug. It is banned in the US and many other countries, but it is sold in India with certain restrictions.

PHENYLBUTAZONE/ OXYPHENBUTAZONE (Brand name: Sioril)

Andrew Williams, an Ottawa based communications expert specializing in third world countries, has done an extensive study on these drugs. According to him, although banned or restricted in many developed countries, phenylbutazone/ oxyphenbutazone are still being actively marketed in the Third World, and widely prescribed by doctors apparently ill informed about their toxicity. The situation is aggravated by the fact that the companies adopt different standards in labeling and marketing their products in developing countries.

The two drugs, phenylbutazone and oxyphenbutazone, have been withdrawn from the market or their use severely restricted in Europe and the U.S.A., as they have been linked with life-threatening blood disorders, gastrointestinal bleeding, ulceration, leukemia, and the Steven-Johnson Syndrome. Nearly 1200 people worldwide have died from these drug-related disorders, according to a leaked internal report from Ciba- Giegy, the largest producer of the painkillers. Over I0, 000 persons have also been reported to have suffered serious side effects. In the aftermath of the leaking of the Ciba-Giegy document early in 1984, many governments moved to ban or heavily restrict the use of these drugs.

In Britain, where at least 1500 patients are estimated to have died in the last 25 years on ingesting the drugs, the government banned phenylbutazone for general use and the company manufacturing these drugs voluntarily withdrew oxyphenbutazone soon after. The two drugs have also been banned in Norway and in Bangladesh, a developing country that, unlike Malaysia, has a drug control ordinance to regulate the manufacture, import, distribution, and sale of pharmaceuticals. According to Andrew Williams, the failure of the drug companies adequately to warn consumers and doctors in the Third World against using the drugs for minor ailments or for treatment of the young and elderly is evidence of double standards in marketing.

In the United States, the Physicians’ Desk Reference warns that the Tanderil brand of oxyphenbutazone should not be given to children below the age of 14. However, in Malaysia, the drug insert for the same brand recommends its use for infants from 12 months onwards. The two drugs are widely prescribed by Malaysian doctors even for such minor ailments as headache and stomachache. This predilection is disturbing, because the toxic side effects of phenylbutazone are quite common and occur in 25 to 40 percent of users.

According to a Ciba-Giegy memorandum, 20 out of 100 patients using phenylbutazone and 7 out of 100 patients using oxyphenbutazone are affected. Nevertheless, the Drug Index for Malaysia and Singapore lists 18 brands of phenylbutazone and 6 brands of oxyphenbutazone being sold in Malaysia. A Malaysian university lecturer almost died when his doctor gave him phenylbutazone to treat a stiff neck. He suffered from rashes, which later erupted, leaving raw flesh. The tissues of his eyes were affected and his nails dropped away. His condition was diagnosed as Steven-Johnson Syndrome induced by a reaction to the drug.

In India, the drug is allowed to be sold with certain restrictions.

FURAZOLIDONE (Brand name: Furoxone, Lomofen)

Furazolidone, an antimicrobial drug that is used to treat bacterial infections, is used in several veterinary products meant for chickens and pigs in New Zealand. The drug has been banned in the European Union and in the USA after the US FDA found that it could induce cancer in humans and other animals. It is illegal to feed furazolidone and dimetridazole to food producing animals such as pigs and chickens as they are considered carcinogenic. In August 1991, Lebanon restricted the use in children of products containing loperamide, diphonoxylate, diphenoxine, and furazolidone. This was followed by deregistration and banning of associated products.

In India, the drug is under the pharmacovigilance scrutiny of the DCGI.

ANALGIN (Brand name: Novalgin)

Analgin is a white crystalline powder with a scarcely perceptible yellowish tinge. It is an anti-inflammatory and anti-pyretic drug. Metamizole/ analgin/ Novalgin were banned in Sweden in 1974 and in the United States in 1977. More than 30 countries, including Japan, Australia, Iran, and some countries in the European Union, have followed suit. In these countries, metamizole is still occasionally used as a veterinary drug. In Germany, it became a prescription drug. In Sweden, metamizole was re-approved in 1995 based on the results from an International Agranulocytosis and Aplastic Anaemia study. However, the drug was again suspended in April 1999 based on Swedish ADR.

Some European pharmaceutical companies, notably Hoechst and Merck, continue to develop metamizole-containing drugs and market them in the countries that allow their use. In Spain, Mexico, India, Brazil, Russia, Bulgaria, Romania, Israel and several Third World countries, metamizole is still freely available over-the-counter (OTC). It remains one of the most popular analgesics and plays an important role in selfmedication. Metamizole and metamizole-containing drugs account for 80% of the OTC analgesic market in Russia, whereas Ibuprofen accounts for 2.5%. In Nepal, analgin (metamizole) and its combinations have been banned since January 1998.

In Brazil, metamizole (novalgina) products, although sold OTC, carry warnings to avoid usage by those less than 19 years old. Information is also given about early detection and treatment of agranulocytosis. Although the Brazilian government did not impose a ban on the drug, its use has seen a decline in the past few years as pharmaceutical companies doctors increasingly opted for aspirin, paracetamol, and ibuprofen based products as replacement, especially for pediatric use. Amongst adults, it is still widely used. Some of the most widely available metamizole-containing products still in use in Brazil are Buscopan plus (under the name of Buscopan Composto), novalgina, and neosaldina.

Generic dipyrone is also available. The National Agency for Food and Drug Administration and Control (NAFDAC) of Brazil announced a ban on the manufacture and importation into the country of all drugs containing dipyrone, including novalgina and analgin, with effect from September 1, 2005. The blanket ban followed the discovery of two major cases of severe ADR involving two secondary school students in Ibuzor, Delta State. From January 1, 2006, the sale and use of dipyrone have also been disallowed in Nigeria. Dipyrone should be used with caution, and never as a first line analgesic or antipyretic agent. It should only be used when other antipyretic or analgesic agents are found unsuitable.

Because of hectic campaigning by activists, and after a long battle in court, the Government of India finally banned the combination of analgin with any other drug. The sale of Baralgan was eventually discontinued. Hoechst, heavily hit by the loss of business from one of its bestsellers, hit upon a brilliant idea. It started marketing ‘Baralgan M’, which contains only 500 mg of analgin. It is also continuing to market the brand Novalgin (which also contains analgin 500 mg). The drug literature accompanying the box of ‘Baralgan M’ says that Baralgan M is a non-narcotic analgesic, antipyretic, anti-inflammatory, and antispasmodic agent. So the company markets Novalgin (analgin 500 mg) as an analgesic, antipyretic and anti-inflammatory, and Baralgan M (analgin 500 mg) as an antispasmodic besides the above three indications.

CISAPRIDE (Brand name: Ciza, Syspride)

Propulsid (Cisapride) helps push food through the stomach. The adverse side effects of this drug were reported in the US, France and Germany and it was decided by the US FDA to withdraw it from the US market. The US FDA action came in the wake of investigation into 341 reports of cardiac toxicity of cisapride made by Medwatch, a US based consumer action group. The investigation had confirmed that 80 deaths were caused during the period June 1993 and March 2000 because of the cardiac toxicity of cisapride. In Germany and France also, the use of the drug has been severely restricted after similar investigations. The restrictions stipulate that the patients should have failed in all the standard therapeutic modalities and have undergone an appropriate diagnostic evaluation. According to Janssen Pharmaceutica and the FDA, propulsid (cisapride) can cause fatal heart rhythm problems. Indeed, at least 111 people have died because of propulsid related conditions, and nearly 400 have developed heart abnormalities. Of the 70 deaths originally reported by the US FDA, 11 were children. It was also reported that 20 children suffered heart rhythm disturbances.

Cases of serious heart arrhythmia, including ventricular fibrillation, ventricular arrhythmia and torsades de pointe and QT prolongation, cardiac arrest and sudden death, have been observed in people taking cisapride (propulsid). In rare cases, seizures have also been reported. Nervous system side effects have included headaches, dizziness, and fatigue. Although propulsid was approved for adult use, many children, mostly infants and premature babies, were given propulsid and some of them died or suffered irregular heartbeats.

Currently, seven major brands of cisapride are sold in the Indian market. These include Cisade, manufactured and marketed by Unichem; Cislone, made by Sigma Laboratories; Unipride, manufactured by Torrent; Cisanorm of Sufic Pharma; Cisapro, manufactured and marketed by Zydus Cadila Healthcare, Cisawal of Wallace; and Ciza, made by Lutas Pharmaceuticals. Consumer Education & Research Centre (CERC), a consumer organization working for detecting adulteration and toxicity in food and drugs marketed in India, has drawn the attention of the DCGI and the authorities concerned to this issue and urged them to ban the sale of cisapride with immediate effect.

According to CERC, cisapride, an original discovery of Janssen Pharmaceuticals, is reported to have caused irregular heartbeats, bloating, radical variations in blood pressure and intestinal disorders. A study by CERC has shown that at least 80 deaths have been caused by the use of the drug in recent years. Cisapride is now under the pharmacovigilance scrutiny of DCGI.

PHENYLPROPANOLAMINE (PPA) (Brand name: Vicks Action 500)

The term phenylpropanolamine might not catch the attention of a lay man, but the brand name Vicks Action 500 certainly does. The major component of this tablet is PPA, which has been banned by the US FDA on account of an increased stroke risk. PPA was commonly used in OTC weight control products and in prescription/ OTC cold and coughs products as a nasal decongestant. Since 1979, over 30 published case reports have described the occurrence of intracranial hemorrhage after PPA ingestion. Early reports involved diet pills including both PPA and caffeine, a combination that was removed from the market in 1983 because of its abuse potential. Later reports involved the use of PPA alone, often as a first ever dose.

In the Hemorrhagic Stroke Project (HSP) of subjects between ages 18 and 49 years, PPA use was found to be associated with an increased risk for hemorrhagic stroke. The increased risk was evident for PPA used as an appetite suppressant as well as for first use exposure. Because the first uses of PPA in the HSP always involved cough-cold remedies, the risk for hemorrhagic stroke is present in both the customary indications for PPA (as a cough-cold remedy and as an appetite suppressant). A study conducted by scientists at Yale University School of Medicine for the drug companies also revealed that there was an increased risk of hemorrhagic stroke in people who took PPA. In India, the drug is under the pharmacovigilance scrutiny of the DCGI.

Along with these drugs, we have to contend with more than 60,000 branded formulations, which are being marketed in India. Under the drug laws, when two or more drugs are combined, the resultant product is required to be registered with the DCGI. The state governments do not have the power to approve any new combination. In actual practice, a number of drugs banned in one state are available in the others. Only a few of these formulations are lifesaving and essential; most of them have side effects at the therapeutic level, as well as toxic effects. Recently, the DCGI has ordered the removal of over 30 combination drugs from the market and proposed the review of over 1,000 combination drugs. The Central Drug Standard Control Organization (CDSCO) has said that only irrational combinations would be removed after the review. Manufacturing licenses for these banned products would also be withdrawn.

DRUG REGULATION IN INDIA

In India, the DTAB is the final authority on imposing a ban. An executive committee examines the harmful effects of the drugs and reports the result to the DTAB. The government bans a drug if it is found to have harmful effects. The DCGI notifies all state drug authorities, chemist associations, and manufacturers of the ban. Under the Drugs and Cosmetics Act, licenses of chemists stocking banned drugs can be revoked.

What India lacks is a viable ADR data capturing system. India’s contribution to the worldwide collection of data on the side effects of different drugs is almost nil. According to a Health Ministry source, the monitoring of ADR is not included in the curriculum of medical students in India and the majority of doctors do not maintain detailed records of patients. The DCGI requires a two-year post-marketing surveillance of patients on new drugs. But that may be inadequate. As per ORG-MARG data, nonsteroidal anti-inflammatory drugs (NSAIDs) have a huge profit margin. These are not the cheapest analgesic or antipyretic remedies. Drug companies in India resist any move to impose extensive safety trials. Hence, there is a need for an effective reporting system for monitoring side effects. Such a system would necessarily involve doctors, patients, and drug companies. As it may not always be possible to assess all adverse effects of a new drug before marketing permission is granted, post marketing surveillance is expected to be done by the pharmaceutical companies. That is not done by most of the companies in India.

The establishment of the National Pharmacovigilance Advisory Committee (NPAC) in 2004 under the chairmanship of the Director General of Health Services was with the objective of building a comprehensive pharmacovigilance data system in the country. Now the NPAC is in place, but it has to be fast enough to generate credible data of ADR of new drugs so that the DCGI can act in time. Some would claim that simply because a drug is not being marketed in the United States or Britain, it does not mean that it is not good. This is a simplistic argument designed to confuse and confound the issue.

Though India is the world’s fourth-largest drug market by volume, its decisions to approve or ban medicines depend heavily on Western regulators. This is because the drugs sold here have mostly been discovered abroad. In India, copycats of such drugs are marketed after perfunctory safety trials, if at all. If the Western regulators are lax in their duty, patients in India are also affected. We have the example of Vioxx, (rofecoxib), which has voluntarily been withdrawn by Merck & Co. from the US and other developed countries due to safety concerns of an increased risk of cardiovascular events, including heart attack and strokes.

Many of the drugs are permitted to be sold in the Indian market with certain restriction. In practice, these restrictions are generally overlooked. Serious measures need to be undertaken to deal with this problem. There should be a regular surveillance of distributors, wholesalers, and retailers to ensure that restricted drugs are not freely available in the market. The drug regulatory authority has to be strengthened to play its supervisory and monitoring role. Legal action should be taken against anyone found violating the regulation. The DCGI should create a database of new information and guidelines given by the international medical agencies. The database should be up to date and available to doctors, pharmaceutical companies, and the patients. There needs to be a wider understanding among the medical fraternity itself on the rational use of drugs and evidence-based practice. Combination drugs mostly benefit the pharma companies and are useful to the patients only in rare cases. Pharmaceutical corporates should be made to realize their social responsibility. The civil society has to make a constant effort to persuade them to withdraw hazardous and irrational drugs from the Indian market. We also need to increase people’s awareness about irrational combinations and hazardous drugs. The technical names of drugs are not easy for a common man to understand. He tends to take anything prescribed by a doctor as God’s own word. Patients should be encouraged to question their doctor on the safety status of the drugs that are prescribed for them. They should develop the habit of going through the database to access the latest information on the medicines prescribed.

When numerous developed countries have banned the medicines discussed above, why are we still permitting them to be sold in India? Is India condemned to be the dump yard of hazardous drugs? While the Government of India has put some of these drugs under pharmacovigilance, the process prescribed is time consuming. Meanwhile, the side effects of the drugs under surveillance are posing a serious health hazard. Moreover, not all hazardous drugs are under the surveillance system. The need of the hour is a joint effort by all the elements of the civil society to create public awareness about this hazard and to keep the issue in sharp focus by agitating it from all possible platforms. Our health is precious and requires all the attention that it can get.

Follow up of the conclusions of the research on Hazardous Drugs

In the light of the findings of the research summarized in the preceding article, we thought it fit to approach some of the leading pharmaceutical companies marketing nimesulide and its combinations with other drugs and request them voluntarily to withdraw their products in the larger social interest.

We wrote at first to Dr. Anji Reddy of Dr. Reddy’s Laboratories, which has a number of successful corporate social responsibility initiatives to its credit. Unfortunately, our letter, which is reproduced below, failed to evoke any response despite a reminder.

Letter dated October 30, 2007 from Mr. K. K. Jaswal to Dr. Anji Reddy, Chairman, Dr. Reddy’s Laboratories Ltd, Greenlands, Ameerpet, Hyderabad 500 016.

“I am writing this letter on behalf of Common Cause, an organization dedicated to ventilating common problems of the people and seeking relief from the authorities, or the higher judiciary, as required by the circumstances of each case. Our initiatives in public interest litigation for redressing public grievances have greatly contributed to the evolution of this instrument and its adoption on a wide scale.

At the outset, I would like to express my admiration for the innovative and highly effective initiatives launched by Dr. Reddy’s Laboratories under their corporate social responsibility programme. During my last innings in the Government of India as Member Secretary, National Commission for Enterprises in the Unorganized Sector, I had the occasion to work closely with Ms. Nalini Gangadharan, who was with Dr. Reddy’s Foundation at that time. I was greatly impressed by the path breaking work done by the Foundation in Hyderabad, Kurukshetra, Kaithal and other places in imparting marketable skills to the underprivileged youth under its Livelihood Advancement Business School (LABS) initiative. As Chairman of the Commission’s Task Force on Skill Formation, I had inducted Nalini in the Working Group on policy formulation. The policy prescriptions of the Commission in this domain bear the imprint of the LABS programme.

It is, therefore, all the more disconcerting for me to find that a company like Dr. Reddy’s Laboratories, which goes beyond its legal obligations to undertake diverse social initiatives and which swears by the credo of ‘Safety, Health & Environment’, should be marketing a drug like Nimesulide, which has been banned in a large number of developed and developing countries. There is a considerable body of evidence coming from countries placed at various stages of the development continuum that the administration of Nimesulide in certain situations has posed a serious health hazard, particularly to children. The fact that in India the jury is still out on the safety of Nimesulide and that the drug is still under surveillance should not come in the way of a voluntary withdrawal of the drug from the market. It would be cynical to demand that the health hazard in the use of Nimesulide should be proved beyond the shadow of doubt. We are concerned here with the lives of millions of trusting and vulnerable people, and not with a criminal trial. The standards of proof required in the two situations are quite different.

In India, Nimesulide is sold over the counter and is freely used for treating fever in children and in self medication. The mass of incriminating evidence against it has been summarized in the enclosed report compiled by our research team. It warrants the immediate withdrawal of the drug from the market, even though the Drug Controller General of India (DCGI) may not have issued a fiat in this regard, because the requirements of the procedure are yet to be satisfied.

Common Cause would urge that as a socially responsible corporate, Dr. Reddy’s Laboratories should set an example of voluntarism before the industry and withdraw Nimesulide from the market, without waiting for a ban by the DCGI. The drug may, of course, be reintroduced in the market once its safety has been established beyond doubt.

I would eagerly await your response.”

Similar letters were also addressed to Zydus Cadila, Intas, Panacea Biotec, Cipla ltd., Mankind Pharma Ltd. and Aalembic Ltd. Replies were received from Panacea Biotec, Cipla and Intas. These are being reproduced below with a view to giving an insight into the mindset of the Indian pharmaceutical industry on an issue of great social responsibility.

Reply dated December 4, 2007 from Mr. P.S. Panwar, Manager (IP & Legal Affairs), Panacea Biotec, B-1 Extension/ A.27, Mohan Co-op. Industrial Estate, Mathura Road, New Delhi.

“With reference to your above cited letter, we have to state as under:-

At the outset, it is pertinent to point out that the above cited letter is not based on true facts. Anything contained in the above cited letter which may be inconsistent with what is hereinafter stated by us is hereby specifically denied and controverted as if the same is set out herein and denied in seriatim.

Admittedly, the safety aspect of the Nimesulide have been gone into by the statutory body namely Drugs Technical Advisory Board, and therefore, it is now well established. Admittedly, the matter has been judicially examined by the Hon’ble High Court in PIL. Therefore, the matter stands concluded and cannot be re-agitated.

Thanking you”.

Letter dated December 3, 2007 received from Mr. R. Chandrashekhar, Senior Vice President – Global Marketing, Intas Biopharmaceuticals Ltd., Ahmedabad.

“I am in receipt of your letter dated 6 November 2007 and 22 November 2007. Since I am looking after marketing and business development of Biotech / Oncology Products only, your letter of concern on the referred product (Nimesulide) has been passed on to my counterpart at Intas Pharmaceuticals Ltd.

This is for your information”.

Letter dated November 29, 2007 from Cipla Ltd., Mumbai Central, Mumbai-400 008.

“Sub: Voluntary withdrawal of Nimesulide based drugs. We are in receipt of your letters dated 6 November 2007 and 22 November 2007 addressed to our Chairman & Managing Director, Dr. Y.K. Hamied on the above subject. We would like to bring to your attention the following:

  1. Formulations of Nimesulide have been sold in India for more than a decade now and it has been extensively used in a number of patients both adults and paediatric. It is pertinent to note that The Indian Medical Association has come to the conclusion that Nimesulide was “safe and effective in all age groups starting with day 0 to over 60 years” for a variety of conditions including fever.
  2. Nimesulide has been approved in over 50 countries and has been in the market for over 22 years. The Committee for Medicinal Products for Human Use (CHMP), Europe has recently issued a favourable opinion on the drug and is most likely the re-approve the marketing of the drug in Europe since the innovator has demonstrated that benefits outweigh the risks.
  3. The government of India has already put in place a mechanism to carry out pharmaco-vigilance studies to ascertain the possible side effect of Nimesulide. The DCGI had in the past ordered the withdrawal of Nimesulide drops and our company was the first to withdraw the formulation from the market.
  4. As an ongoing process, the DCGI regularly reviews the post-marketing data on various drugs and have announced the withdrawal of numerous drugs after the same were originally approved for marketing in the country. Recent drug withdrawals announced by the DCGI relates to Valdecoxib, Rofecoxib, Rosiglitazone etc.
  5. The drug approval process in every country is different and any drug approved in a particular country need not be approved in another country. All the countries need not and have not approved all the drugs that are marketed currently in the world. Therefore, it is misleading to argue that Nimesulide is approved only in 50 countries and hence should not be marketed in India.

Cipla is fully aware of its corporate social responsibility and as in the past, would abide by the directives of the Health Ministry in this regard.

Thanking you”.

We also wrote the following letter to Secretary to Government of India, Ministry of Health & Family Welfare, without eliciting any response.

Letter dated November 6, 2007 to Shri Naresh Dayal, IAS, Secretary to Government of India, Ministry of Health & Family Welfare, Nirman Bhavan, New Delhi

“I am writing this letter on behalf of Common Cause, an organization dedicated to ventilating common problems of the people and seeking relief from the authorities, or the higher judiciary, as required by the circumstances of each case. Our initiatives in public interest litigation for redressing public grievances have greatly contributed to the evolution of this instrument and its adoption on a wide scale.

Of late,Common Cause has been taking a keen interest in matters concerning public health and the hazards posed to it by the prevalence of ineffective/harmful drugs and combination of drugs in the market. A status note on the subject compiled by our research team is enclosed. The issues posed in this note must be engaging your attention, as is evident from the recent clamp-down on combination drugs, which have flooded the Indian markets.

It has been reported that some time ago, the Drugs Controller General of India (DGCI) took the long overdue step of directing the state drug regulators to withdraw from the market 294 combination drugs sold under 1100 different brand names, for which manufacturing licences had been granted without the mandatory approvals. It is a happy augury that the domestic pharmaceutical industry has agreed to withdraw 120 combination drugs from the market in partial compliance of the directives from state drug regulators. I hope that the matter will be pursued by the DGCI to its logical corollary and the industry will be prevailed upon to withdraw the remaining 174 combination drugs from the market. The DGCI may concurrently focus his attention on the drugs/combination drugs, which have been banned in many developed countries, and some of the developing countries as well, for their deleterious effects, particularly on children, but are freely being sold in India.

I would also request that an exhaustive study of the malpractices prevalent in the manufacture and marketing of drugs may be entrusted to an independent expert body, which may work closely with consumer organizations and medical research institutes. This body may also study the functioning of the institution of Drugs Controller General of India and its counterpart in the states and recommend systemic reforms with a view to bringing the Indian drugs regulatory bodies to the level of the best of the breed globally.

I would eagerly await your response”.

Jan-March, 2008