The Indian pharmaceutical industry is a pioneer among developing countries with capabilities in the competitive field of drug manufacture and technology. The Indian pharma industry is estimated to be worth $ 4.5 billion, growing at a pace of 8 to 9 per cent annually. The country is noted for its capability, technology, quality and range of medicines manufactured. From simple drugs to sophisticated molecules for anticancer and biotherpuetics is now made indigenously. The Indian pharmaceutical sector is highly fragmented with more than 20,000 registered units. However, the leading 250 pharmaceutical companies control 70 per cent of the market with market leader Ranbaxy holding nearly 7 per cent of the market share.
It is an extremely intensive market with severe price competition and government price control. The pharmaceutical industry in India meets around 70 per cent of the country's demand for bulk drugs, drug intermediates, pharmaceutical formulations, chemicals, tablets, capsules, orals and injectibles. Despite of advances in industrial production of formulations, the Indian public are not safe due to poor regulatory scenario, as for the distribution and sale of the medicines are concerned. The country may boost of its advances in the area of US FDA approved manufacturing units, however, when it comes to the question of management of distribution and sale of ethical products, poor administration and regulation of drugs are the major concern, which endangers public health at large.
The drugs need to be handled carefully and regulated properly. The pharmacoviglence is a new buzz word of recent times often heard in the Indian pharmaceutical arena. There is a renewed interest in the adverse drug reactions and its documentation. It is a good development and before we organise the pharmacovigilence in our country, there is a need to look into the banned drug marketed in the country. A large number of drugs that are banned abroad are freely available in the Indian market. It is expected that physicians need to update themselves continuously on the new adverse effects of drugs. It is practically impossible to keep track on these affairs as some of the reputed companies continue to sell the banned drugs in Indian market due to laxity of regulations.
The laxity on part of the he government and the selfish interests of the manufacturers in influencing the policy decisions with regard to banning of dangerous drugs is a an issue which needs to be addressed immediately. The banning of drugs in developed countries will be enforced only after gaining substantial evidence regarding potential hazards on humans and live stock. It is very unfortunate to see some of the very dangerous drugs banned in most of the part of the developed world continue to be manufactured and sold in the Indian market with out much concern to the public hazard.
Process of banning drugs in India is done by the Drugs Technical Advisory Board (DTAB), which is the final authority on imposing a ban. An executive committee examines the harmful effects of the drugs and reports the results to the DTAB. If any drug is found to have harmful side effects, the government issues the ban order and all manufacturers and wholesalers are asked not to stock the particular medicine.
The drug controller general of India (DCGI) notifies all state drug authorities, chemist associations and manufacturers about the ban on the drug. Authorities are instructed to carry out inspections and control the misuse of banned drug.
India is a vast country with multi-ethnic population and with not so alert public. The public are inactive and there is no collective thinking or action when a matter of public issue like patient safety is engendered. In this background, with limited control over industrialists, drugs are freely sold with out concern for consequences of misuse or drug related accidents. The Indian Central Drugs Regulatory Authority has recently set up a vibrant pharmacovigilance programme in the country. Its functions include assessing the benefit, harm, effectiveness and risk of medicines, encouraging their safe, rational and proper use, improving patient care and safety in relation to the use of medicines and all medical and para-medical interventions.
In the Indian scenario the prevalence of hazardous drugs that are banned continues to compound, largely due to lack of adequately trained professionals in drug regulation. The prime stake holders in sale of medicines are general practitioners and pharmacists, who can influence the consumption of drugs. As for the general practitioners are concerned, it so happens many times that they are not aware of the potential risk to their patients. The medical schools do not adequately emphasise on teaching and training in rational use of drugs and drug utilisation, which has positive impact on prescribing habits of a young doctor. Instead, the young medicos get influenced by the marketing executives who are likely to hide controversial hazardous side effects of the drugs, which can influence the prescriptions.
If doctors over-prescribe drugs, companies can have more money for gifts and promotion, reinforcing doctors' belief that they are doing the right thing. The pharmaceutical industry, instead of sponsoring research, education and promotion of ethical prescription, is entering into unhealthy collaborations to promote sale of drugs.
It is quite interesting to review how the banning of Refecoxib was handled in our country recently. Due to serious ADR, Merck announced a worldwide withdrawal of their molecule Rofecoxib, branded as Vioxx. However, in India the drug was sold with impunity - despite of the litigation, warnings and media coverage of the adverse affects of the drug, it continued to be sold in the country. Recently, in relation to the ban on Vioxx, the government issued an order to ban another Cox-2 drug, Valdecoxib. Nevertheless, this drug is also being stocked and distributed by many chemists. But, there are a number of other drugs that have got a red light in other countries, but are allowed to circulate freely in the Indian market with government approval.
Drugs like Analgin, a simple looking painkiller that can cause bone-marrow depression, is available in Indian market. Also, Cisapride, a prokinetic agent and Droperidol, an anti-depressant agent, which can cause serious cardiac problems like irregular heartbeat are available in the domestic market. Apart, Furazolidone, an anti-diarrhoeal, Nitrofurazone, an anti-bacterial cream and Phenolphthalein laxative are some of the drugs that can lead to cancer and is present in the country's market. Other drugs with hazardous effects available in India include Nimesulide (popular pain-killer that can cause fatal liver failure), Piperazine (anti-worms, which can damage nerve) and Quiniodochlor (anti-diarrhoeal, which can cause permanent damage to sight, apart from irreversible visual disability). Analgin, Furazolidone and Nitrofurazone are banned for use even in animals in US.
In many countries, Nimesulide is banned for use in both adults and children, but the Indian government has turned a blind eye and duff ear to the entire issue. The European Agency for Evaluation of Medicinal Products (EMEA) has prohibited the use of the drug in children below 12 years. Earlier, countries such as Finland, Spain and Portugal suspended the use of Nimesulide, as it is very dangerous to liver and its adverse effects can lead to hepatotoxicity.
Why prescribe banned medicines?
A surprising aspect regarding banned drugs is lack of knowledge among medical practitioners. While doctors in big hospitals are aware of the ban on the drugs, many private practitioners do not keep track of the latest developments. The establishment of a National Pharmacovigilance Commission and other proposed changes in drug regulation are positive steps, but much remains to be done. Banned drugs are a nuisance in today's Indian clinical scenario. Drugs are banned only after establishing their hazardous impact on the public at large. Developed countries such as US, European Union, Japan and Australia identify unsafe drugs through a systematic programme of pharmacovigilance. After further investigation, regulatory authorities like US FDA initiate the banning process within their jurisdiction.
This survey reviews a grim situation with respect to the availability and use of banned drugs throughout the country. It is not true that there are no alternatives available for a banned drug. There exist many safer alternatives. Despite of this, banned drugs continue to be manufactured, promoted, prescribed and consumed. The government is expected to play its role by alerting the public regarding the ill effects of using banned drugs through social messages.
It has been recently pointed out that Indian drug regulatory authorities have refused to ban the sale of 11 drugs, including Furazolidone, Phenylpropanolamine, Cisapride and Nimuselide, apart from over 80 drug combinations that are prohibited in many other countries. This clearly indicates the regulatory favoritism for industry over public interest. Furthermore, many single ingredient drugs and fixed dose combinations such as Aceclofenac and Paracetamol or Alprazolam and Atenolol, which are irrational, have penetrated the Indian market without having undergone mandatory clinical trials.
All these point to the fact that in India the drug regulatory system has geared up to protect the interests of industry. We have conducted a survey of dangerous drugs that are banned in developed countries but active in India. Drugs with banned status in developed countries, which are listed in drug index books and therapeutic guides and referred by medical practitioners in the country are collected and subjected to graphical representation. In it Nimesulide tops the list. Nimesulide is the drug that is marketed the most under various brand names followed by Cisapride.
The banned drugs are also combined with other drugs with a claim of improved therapeutic efficacy and less adverse actions. These combinations are not made internationally and available only in Indian market. This calls for action by all the concerned people to act and ban these dangerous preparations from the market. In this category, again Nimesulide tops the list.
These drugs may not be causing immediate causality, but are capable for causing potential danger on long term use, may be 15 years latter like diethyl stibosterol. It is high time that we adopt a rational and sensitive policy for banning of dangerous drugs from Indian market.
(The authors are with Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal University)