How India tackles adverse drug reactions - By ignoring data

A 17yearold Kolkata boy was prescribed Dapsone an antibiotic for a skin problem and developed severe potentially fatal side effects The doctor could not diagnose the condition Dapsone syndrome nor did he report the side effects to the Pharmacovigilance Programme of India a government watchdog It took visits to two speciality hospitals a fortnightrsquos stay in an intensivecare unit and a week in a ward to bring the boy back from the brink of deathWith 10 of 363 trillion medicines popped worldwide in 2015 India is the worldrsquos thirdlargest medicine market It stands to scientific reason that these drugs will have side effects Yet in 2013 India reported no more than 2 of globally occurring adverse drug reactions ADRs jargon for side effects of medicines logged in Vigibase a database maintained by the Uppsala Monitoring Centre a World Health Organisation collaborating centre for international drug monitoringAn Indiaspendorg story It isnrsquot as if drugs have fewer side effects in India Serious effects were seen in 67 of patients a 2014 study reported Other studies have cited drug side effects as the reason for 34 of hospital admissions in India 37 hospital readmissions and 18 mortality In the developed world adverse reactions are believed to be the fourthleading cause of death Within India the ADR reporting rate ADRs reported per million population has almost doubled in the last three years to 40 but it is lower than 130 the average ADR reporting rate for highincome countries and clearly disproportionate to the countryrsquos population and medicine consumption An update on the Pharmacovigilance Programme of India Pharmacovigilance Programme of IndiaIn other words India addresses the problem of adverse drug reactions by ignoring or not reporting the data That could prove costly said experts if it isnrsquot already Ignoring Indian data makes drugs more unsafeldquoADR reporting is important because it gives Indian regulatory authorities realistic data to base drug usage decisions onrdquo said Y K Gupta professor and head Department of Pharmacology All India Institute of Medical Sciences AIIMS and national scientific coordinator Pharmacovigilance Programme of India ldquoUsing only global evidence without Indian data isnrsquot an ideal situation because people of different ancestry may respond differently to medicationrdquo Reporting the side effects of a drug could help determine if the medicine should stay or be pulled off shelves A medicine labelled safe for clinical use after trials could still be found to be dangerousndashas it happened with Rofecoxib a nonsteroidal antiinflammatory drug a runaway success after its 1999 launch Between its launch and 2004 Rofecoxib reportedly caused between 88000 and 140000 cardiac events This forced Merck a pharma multinational and the drugrsquos maker to voluntarily withdraw it from the US market in turn prompting a ban in India although no significant cardiac event was reported as a side effect In 2004 pharmacovigilance in India existed only on paper although formal monitoring began 18 years before that in 1986 and India signed up to the WHO Programme for International Drug Monitoring in 1997 Reporting was lax until the launch of the Pharmacovigilance Programme of India in 2010 ldquoADR reporting is still too low visagravevis the countryrsquos 128 billion populationrdquo said Harihar Dikshit head Department of Pharmacology Indira Gandhi Institute of Medical Sciences IGIMS Patna one of 150 Indian ADR Monitoring Centres Carelessness insensitivity among reasons for Indiarsquos poor reporting of side effects Some key reasons behind Indiarsquos poor track record in reporting ADRs gtgt Nurses who are most likely to see a patient suffer a side effect are expected to inform the treating doctor but seldom do ldquoReporting ADRs is not mandatory for doctors in India nor is staying updated with ADRsrdquo said Akram Ahmad previously of the Department of Pharmacy Practice Annamalai University where he conducted some of the studies quoted in this storygtgt ldquoDoctors in India are careless in prescribing medicines because they know they will not be held accountable for their actions and are equally careless about reporting ADRsrdquo said Kunal Saha a USbased doctor who has waged a decadelong legal battle after his wife Anuradha Saha died of side effects of a drug overdose when she was being treated for a skin allergy in 1998 Settling Saharsquos case the Supreme Court ruled that medical negligence includes not informing patients about the possible side effects of a drug ldquoPhysicians prescribe new drugs at the behest of medical representatives even without reading the drug pharmacology driven by the promise of gifts despite this being illegalrdquo said Saha ldquoPatients are prescribed excessive doses unwarranted drugs or unwarranted combinationsrdquogtgt Some doctors donrsquot know that drug side effects should be reported to any one of 150 ADR monitoring centres across India nor are they adept at recognising a drug side effectgtgt Half of Indiarsquos population depends on drug stores not run by pharmacists and on doctors holding alternative medicine qualifications who arenrsquot permitted to prescribe allopathic medicines in many states said Ahmad ldquoNeither of these two will report ADRsrdquogtgt ldquoDoctors are focused on growing their practice They spend very little time diagnosing patientsrsquo symptoms let alone explaining the drug regimen and asking them to report back any adverse reactionrdquo said AhmadScarce data preclude regulatory action on questionable drugs Drug side effects in India are scarcely reported even in scientific literature A 65yearold woman with cardiovascular disease developed chest pain after being put on Nimesulide a popular painkiller for fracturerelated pain as this 2003 study reported Swapping Nimesulide with an alternative Ibuprofen quickly alleviated the chest pain A 78yearold man with heart disease was prescribed Nimesulide for a wrist injury He developed breathlessness blue pallor and restlessness and quickly succumbed to further complications another 2004 study reported On the Naranjo scalemdasha scale developed by Canadian pharmacologist Claudio Naranjo and others to assess the causality for an adverse drug reactionmdashthe complications the 78yearold patient developed after taking Nimesulide scored two indicating the drug could lsquopossiblyrsquo have been the cause of cardiac artery insufficiency a shortage of blood in one or more coronary arteries These events arenrsquot recent They occurred in Jawaharlal Nehru Medical College Hospital JNMCH Aligarh Muslim University in 2003 well before the Indian government started to take pharmacovigilance seriously ldquoI observed those adverse drug reactions and have never prescribed Nimesulide sincerdquo said Syed Ziaur Rahman associate professor Department of Pharmacology and deputy medical superintendent JNMCH Aligarh Muslim University Nimesulide has been available in India since 1997 It currently sells as Nice listed as a lsquotop brandrsquo on Dr Reddyrsquos Laboratories and Nimulid MD on Panacea Biotech Nimesulide has never been licensed for use in the US UK Australia New Zealand and Canada ldquoHoping to drive further investigation on the drug I presented these cases in academic conferences But all that happened was Nimesulide became a lsquohotrsquo topic of discussion in academic meetings for some timerdquo said Rahman Over a decade later a group of experts ruled that Nimesulide adversely affects the liver in children and should not be prescribed said Gupta So Nimesulide was banned for children in 2011 the Panacea website still lists Nimulid MD Kid as being available To ban or not to ban India needs datadriven action Reporting adverse drug reactions makes the experience of a few physicians available to the entire country ldquoThe occurrence of serious ADRs could lead a drug to be banned or suspended pending the generation of more evidence or confined for use in a specific population age group condition or doserdquo said Gupta Or the manufacturer could be asked to add further information on the drug label or insert For instance in 2015 Indian authorities recommended the inclusion of advisory notes mentioning hepatotoxicity haemorrhage and cardiovascular events as possible side effects of Sunatinib Malate an anticancer drug and cardiac dysfunction as a possible side effect of Pazopanib HCl another anticancer drug However sometimes in India a drug ban has been reversed in court or by the regulatory authority In 1996 the Indian government banned the combination of the painkiller Analgin with any other drugs Globally such combinations have been banned for being less safe than Analgin alone Analgin per se is banned in the US Australia Japan and Canada An India ban on Analgin came through in June 2013 But the government revoked the suspension in March 2014 permitting sales as long as the product carried a specific warning Vigiaccessorg the database of globally occurring side effects lists 2005 ADRs of Analgin as being of Asianorigin presumably including India Ideally the drugmaker should be informed of such ADRs ldquoNo adverse side effects for our product have been reported to usrdquo said a Sanofi India spokesperson Phenylpropanolamine an ingredient of popular cold medicines was banned in 2011 but the Madras High Court has stayed the banmdashldquofor want of Indiaspecific datardquo said Gupta Watch out for side effects with a slow onset Side effects are usually thought of as an immediate adverse drug reaction Thatrsquos not always the case For instance a blockbuster diabetes drug Metformin reduces the absorption of Vitamin B12 from dietary sources according to this 2014 study ldquoA deficiency of vitamin B12 can in turn cause mental disabilities slowness forgetfulness and most significantly exacerbate the onset and progression of diabetic neuropathy a disease of the nerves that commonly occurs in advanced diabetes patientsrdquo said study coauthor Atul Gogia consultant Internal Medicine at Sir Ganga Ram Hospital New Delhi While his finding has not led Gogia to change his prescriptions for diabetes patients it has made him more conscious about the potential impact of his prescriptions ldquoVegetarian diabetes patients could especially be at high risk of developing vitamin B12 deficiency because of the combination of their diet and prescriptionrdquo said Gogia ldquoNow we get patientsrsquo vitamin B12 levels tested and prescribe them supplements if neededrdquo