How often have we just popped in an antibiotic rather than visit a doctor? Or gone to a drugstore, told the pharmacist our symptoms, and trustingly taken the medicines he has given us? But do we really know what we are putting inside our system? Forty-four-year-old Ravi (name changed) was admitted to Max Hospital at Saket, Delhi, with severe diarrhoea. He was brought to Delhi from Alwar. Doctors at Alwar had suggested that he be taken to Delhi. “When Ravi came to us, his condition was very critical—due to loss of excessive water-salt, and many important nutrients. His blood pressure had come down drastically and he was on the verge of multiple organ failure,” says Dr R S Mishra, a senior internal medicine consultant at Max Hospital.
“The patient did not seem to be suffering from any infection. The investigations threw up a shocking fact. Due to indiscriminate use of Azithromycin—an antibiotic used to treat flu—he had developed serious side-effects. The frequent misuse had killed the good bacteria present in the body which are helpful in digestion,” Dr Mishra says and adds, “Patients get half-baked information from the internet and simply pop a pill for any ailment.”
While Ravi suffered due to his self-medication, there are a few who fall prey to ill-informed doctors. Jaijeet (34), from Agra, who was suffering from a stomach infection, consulted a neighbourhood doctor. The doctor prescribed Ornidazole for five days. Instead of improving, Jaijeet started to develop symptoms such as breathlessness, extreme weakness and seizures.He was referred to the Heart Care Foundation of India (HCFI), a charitable trust. “After various investigations, it was found that Jaijeet was suffering from rare but serious side-effects of the antibiotic, which was not at all needed in his case,” says Dr K K Aggarwal, senior medicine consultant and president, HCFI.
Delhi-based septuagenarian Neera (name changed) was admitted to Moolchand Hospital with severe pain in the joints and vomiting. After check-up, an antibiotic (Ciprofloxacin)—earlier prescribed for her upper respiratory infection—was withdrawn. “When we discontinued the medicine, she started recovering,” says Dr Shreekant Sharma, medicine consultant at Moolchand Hospital. In almost 85 per cent cases of upper respiratory problems, there is no need to start the course of an antibiotic, he adds.
There are many more such examples which we have heard, seen, even experienced in our day-to-day life. The consumption of antibiotics often creates many complications, proving hazardous.
Misuse of antibiotics is quite rampant in India. For every case that is recorded, there are many that go unnoticed. And doctors’ efforts could control such complications. “Ten out of 100 patients use antibiotics without any need. Self-medication worsens the problem. There are no rules to regulate sale of medicines. Even restricted drugs are easily available,” says Dr Ritesh Gupta, additional director and specialist in internal medicine and diabetes at Fortis, Nehru Place, Delhi.
Also, says Dr Sharma, many general physicians are in the habit of prescribing antibiotics at the approach of a sniff or a cough. Dr Aggarwal adds that many non-MBBS doctors and quacks operate in the market. Such professionals are quick to prescribe antibiotics as they are not aware of the harmful effects. Not just this. Even when patients visit a proper doctor and are given antibiotics only when needed, another problem arises. Pharmacists say that people often buy antibiotics for three days against the doctor’s prescription suggesting five days. The fact that the entire course of the medicine has not been completed renders it useless.
Patients today want quick results. But not everything is instant coffee. Many press a doctor for antibiotics or seek one who would prescribe antibiotics. “They think that antibiotics can help them get better faster,” says Sandeep Nagia, president, Retail Distribution Chemists Alliance.
“Viral fever, diarrhoea, upper respiratory infections, common cough and cold, flu, and mild chest infection, are the commonest ailments where antibiotics are mostly misused,” says Dr Sharma. Experts say side-effects of the antibiotics vary from patient to patient. While for some it might be mild, for others it could become quite serious.
The most common antibiotics that are misused are Azithromycin, Ciprofloxacin, Augmentin, Ornidazole, Norfloxacin, Levofloxacin, Metronidazole, Ofloxacin, Amoxicillin, and Doxycycline.
According to Dr Gupta, a very disturbing trend is the misuse of high-end antibiotics drugs only used in hospitals. These drugs are only given intravenously and are generally misused by small hospitals and nursing homes. “They are used for life-threatening infections, when normal antibiotics fail.
For example, Piperacillin and Meropenem are used in case of severe pneumonia, sepsis, meningitis,” says Dr Gupta. The most dangerous side-effect of misuse of such antibiotics is that the body becomes immune to it. And when the time to actually use the medicine arrives, it no longer has the desired effect. He explains how Ciprofloxacin, once an effective antibiotic for treatment of urine infection, is no longer working on patients. Similarly Azithromycin—good for chest infections—is not showing positive results on many.
Recently, a study conducted by Sir Gangaram Hospital, Delhi, reveals that certain bacteria have developed resistance against fourth generation of antibiotics. The survey was done on 201 patients for two-and-a-half years, suffering from community-acquired infections. These patients had not come in contact with any health facility in the last three months or more.“We observed that two/three of the patients suffering due to E.coli and Klebsiella pneumoniae bacteria did not respond to strong antibiotics.
This happens due to easy availability and overuse of antibiotics. At every level, misuse/overuse of antibiotics is being observed and it’s dangerous,” says Dr Sumit Ray, vice-chairman, department of critical care, Sir Gangaram Hospital and head of the research team.Another study of global trends in antibiotic consumption conducted by a team of scientists from Princeton University reveals that between 2000 and 2010, there has been a 76 per cent increase in the consumption of antibiotics, especially in BRICS countries—Brazil, Russia, India, China, and South Africa. Studies also reveal that India has the biggest market for antibiotics followed by China and the US. A study from the Centres for Disease Control and Prevention says almost 50 per cent of the antibiotics are prescribed without any need.
And it is not just humans who are suffering. Misuse of antibiotics in animals at poultry farms are spreading resistance bacteria into the environment. They are also infecting humans and creating resistance against certain antibiotics, a study of the Centre for Science and Environment reveals. The study was based across 12 poultry farms located in Punjab, Rajasthan, Haryana and Uttar Pradesh.
Over the years, large-scale manufacturing and sale of fixed dose combination (FDC) drugs has made the problem of misuse/overuse and resistance against antibiotics more dangerous. These FDC drugs have been used for serious and chronic illnesses but many a time fail to give results because of resistance problem.
Shyam Sundar (32), from Agra district, was suffering from non-responding complicated typhoid fever with bleeding in the small intestine. His blood culture came positive for typhoid but it was resistant to conventional antibiotics. He was brought to Delhi for treatment. HCFI offered to help. “He was not responding to classical typhoid drug Ciprofloxacin started two weeks back,” says Dr Aggarwal. Investigations revealed that Shyam had often used Ciprofloxacin and Tinidazole for irritable bowel syndrome which actually required no antibiotics. Over the years, he developed resistance towards Ciprofloxacin group of drugs.
Twenty-three-year-old Anamika Sethi from Delhi had always been conscious about her beauty and skin. So when she developed small rashes on her face, she was quick to visit a neighbourhood doctor. She was advised to use Betnovate GM, a combination of a steroid with an antibiotic and an anti-fungal cream. Since it helped her, Anamika would often use it even later for any small rash and would also prescribe it to her friends. Two years later she developed a bad skin infection that refused to respond to topical antibiotics due to resistance to rampant use of antibiotic cream. It had to be treated with systemic fourth generation antibiotics.
Dr Mira Shiva, founder and co-ordinator of All India Drug Action Network, says: “We have been fighting a long battle to ensure safe medication for consumers.” They have also gone to court against what they term the sale of irrational FDC drugs. “One component present in FDC pill should be taken once a day, but another component present in the same pill has to be taken twice a day—this is irrational combination of drugs,” she explains. Most of the consumers are not aware of the common fact that if they are taking two FDC pills in a day, they are actually consuming six or even more drugs in a day. This might include two or more antibiotics combination, depending on how many combinations of drugs the pill contains.It is scary even to imagine that there is a long list of FDC drugs which has been consumed by us over the years. Most of these are not approved by the Central Drug Standard Control Organisation (CDSCO), the official regulatory authority. The trial of these drugs never took place, no one knows about their side-effects, adverse drug interaction and other consequences.
As few studies reveal that FDC drugs are causing not only more adverse drug reaction but also adverse drug interaction. When there are combinations of so many drugs in one pill, the chances of adverse drug interaction rise by almost 40 per cent. A recent report published in the British Journal of Clinical Pharmacology says 64 per cent of antibiotics in India—under FDC category—are not approved by the authority concerned. In their study, they took 118 different formulations of FDC that were in the market during 2007-2012. Of these, only 43 were approved by the Central drug authority.
“It’s shocking that drugs which have been banned by other countries, and not even approved by our own ‘authority’, are easily available in our market,” says Dr Shiva. Experts also believe that unapproved FDC antibiotics not only are creating resistance problems but can be dangerous for life as there is no trial and no record of their efficacy and safety. “Sometimes doctors prescribe reputed, good medicines but it won’t work. One reason that can be assumed is that the medicine is either substandard or falsified,” says Dr Aggarwal.
According to a recent WHO study, one of 10 medical products available in low and mid-income countries such as India are either substandard or fake. The study also pinpoints that these products not only fail to respond to diseases but are causing serious complications and even death. Similarly, a CDSCO survey in 2015 reveals that 4.5 per cent drugs in the market are substandard. The big question is: Why are companies manufacturing and promoting these drugs? Why is the government not stopping this malpractice?
“From time to time, the government revises the national list of essential drugs and puts a price cap to make them accessible to all sections of people. Due to this price control, many pharma companies prefer to manufacture non-essential drugs which are mostly FDC and earn a good margin of profit,” says a senior doctor at AIIMS-Delhi, requesting anonymity. According to the Drugs and Cosmetics Act, FDC is treated as a new drug in India because combination of two or more drugs may change the safety, efficacy of the individual active pharmaceutical ingredient (API). CDSCO is the licensing authority under the Act. Once the rationality of FDC drugs, and their safety and efficacy after clinical trial are proved, the permission to manufacture and market the FDC drug is granted.
The Act says that for manufacturing or sale of any new drug, every pharma company has to take permission from the Central authority. But since the laws are more stringent, companies approach the state governments. Experts say this malpractice is the sole reason many unapproved FDC drugs are available in the Indian market.
Over the years the government too has woken up to this menace. “The government is fully aware of these malpractices. Many strict actions have been taken in the past and in continuation to penalise companies making and selling new drugs without proper permission,” claims a senior Union Health Ministry official. To check the rampant sale of irrational FDC drugs, a committee under Chandrakant Kokate, vice-chancellor of KLE University, Karnataka, was set up by the government in 2014. The purpose was to review more than 6,000 FDC drugs available in the market. The report revealed that many FDCs were irrational, and posed health risks.
Of these, the government banned sale of 344 FDC drugs in 2016. Many popular drugs such as Corex, Saridon,Vicks Action 500, Amoxycillin, Nimorazole, Nimesulide, D’cold, Benadryl and Phensedyl were included in the list. But pharma companies went to the High Court against the order. They argued that these drugs were there in the market for over 15-20 years and there is no data available to prove their harmful effects. Secondly, there was no prior notice or warning given to the companies. The court quashed the order and almost all the drugs came back into the market. The Government of India has approached the Supreme Court, which has asked the Drugs Technical Advisory Board (DTAB) to review all the drugs again.
“We are committed to providing safe medication to our population. The government will go to any extent to safeguard public health,” says A K Pradhan, deputy drug controller of India. Recently, the DTAB formed a committee to review the safety, efficacy and therapeutic value of 344 drugs before recommending any action.
The government is also running many awareness programmes for consumers and to educate doctors for minimal use of antibiotics and check adverse drug reaction. To facilitate the same, the Pharmacovigilance Program of India (PvPI) was launched by the Health Ministry. The Indian Pharmacopoeia Commission (IPC)—an autonomous body under the ministry—suggests standards for identity and purity of drugs. It also promotes rational use of generic drugs. “Earlier we were totally dependent on foreign agencies to learn about the adverse drug reaction of different drugs, but now we are working independently with the help of the WHO,” a senior scientist of IPC says. There is a long list of drugs on the website of the IPC that is updated every month. This indicates drug name, usage, and the adverse drug reaction.
Also a new pharmaceutical policy has been drafted to address not only price control of medicines but also that drugs should be sold under generic names and not under differently-priced brands. “Currently our drug policy is market-based. It promotes manufacturers. If the new drug policy addresses patient benefit, it will be a great achievement,” says Dr Shiva.
Experts also believe that lack of clarity between the state and Central drug authority affects implementation of laws. Absence of stern policies, rules, vigilance programmes, frequent checks on the efficacy of the drugs make the situation worse. “Doctors prescribe only licensed drugs. It is not the doctor’s job to curb this malpractice in India,” says Dr Aggarwal. But, at the same time, they should discourage promotional tactics of companies manufacturing irrational FDC drugs, he says, adding that companies try to lure doctors to promote new drugs.
Dr Ray suggests that regular training of doctors should be conducted to create awareness on antibiotics use. Also doctors can raise the flag against irrational FDC antibiotics. Dr Mishra adds that the government must make an ‘Antibiotics Policy’ mandatory for every hospital and nursing home to minimise their use. Doctors should be made accountable when using antibiotics. Experts also are of the opinion that more power and fixed accountability to drug regulatory bodies is a must to safeguard against powerful antibiotics being sold over the counter. Also, there is a need to have more research and data on increasing problem of drug resistance. “Computerised updated lists of manufacturers, licences granted and inspections done could discourage the sale of unapproved drugs,” says a senior officer of Safe Medicines India, an industry watchdog.
Meanwhile, pharma companies offer a different view. “Most of the drugs come under essential list of medicines and have a price cap, so margin of profit is minimised. How can the companies survive? It has been observed over the years that there is consistent shortage of essential drugs as companies are reluctant to manufacture these with minimum profit. There is no research-trial of new drugs as this becomes an expensive venture. Resistance to drugs is shooting up but there is no new drug in the market to solve the problem,” opines a senior director in one of the top pharma companies. He adds there should be some support policy by the government to promote companies that are manufacturing essential medicines and are keen to work in the research field.
According to experts, many FDC drugs give miracle result in the treatment of serious and chronic diseases. It has been observed that FDC drugs improve patient compliance. Instead of taking four pills or more, a patient can take just one. It reduces pill burden and is low-cost too.Finally, it is all about public health. There is a pressing need for a joint effort made by the Central and state governments to provide safe medication to the masses. Rampant checking of licence and quality of drugs creates a sense of fear and accountability among culprits and law-breakers. Hospitals and doctors should be encouraged to minimise use of antibiotics and maximise use of single dose, rational FDC and generic drugs.
At the same time, the drug policy should not just be manufacturer-friendly. It should also take into consideration benefit of the patients. To combat scarcity, pharma companies should be given incentives on making essential drugs and promoting research work.
Antimicrobial resistance
It takes place when microorganisms such as bacteria, viruses, fungi change when there is a lot
of exposure to the drugs such as antibiotics, antivirals and antifungals.
Adverse drug interaction
The side-effects of a combination of two or more drugs inside the body.
Adverse drug reaction
Is hardly known. Different patients react against a drug differently. For example, if a drug causes heart problem in one patient, it can spike another’s BP. Sometimes, they even prove fatal.
Side-effects
Mostly known by the doctors. They can warn patients against these; most of these are
not serious in nature.
64% of antibiotics under FDC category in India are not approved by the authorities. Of 118 different formulations of antibiotics studied between 2007 and 2012, only 43 were approved by the Central Drugs Standard Control Organisation. 75 formulations had no licence from the regulatory authority. The 118 FDC drugs were sold out through almost 3,300 different brand-names and manufactured by about 500 pharma companies. A British Journal Of ClinicalPharmacology study
Between 2000 and 2010, there were 76 percent increase in the consumption of antibiotics, especially in BRICS countries (Brazil, Russia, India, China and South Africa). Studies also reveal that India has the biggest market for antibiotics drugs followed by China and the US. A Centre for Disease Control and Prevention study says almost 50 percent of the antibiotics drugs are prescribed without any need. Even duration of the time and doses are not followed properly.
10 Commonly Misused Antibiotics
1. Azithromycin: Used to treat certain bacterial infections, bronchitis, pneumonia, lung infections, infection of the ears and many others
Side-effects: Vomiting, acidity, nausea, severe diarrhea, serious allergic reaction (rare)
2. Ciprofloxacin: Used for typhoid; lung and urinary infections, and other bacterial infections.
Side-effects: Severe dizziness, loss of movement in joints, severe pain in joints, low BP
3. Augmentin: Used for pneumonia, urinary infection, severe chest infection, sinusitis, infection of the skin
Side-effects: Itching, redness on skin. In rare cases, it causes seizures and fever
4. Ornidazole: Used to treat some protozoa infections, stomach and urinary infections
Side-effects: Dizziness, vomiting, severe difficulty in breathing, unusual weakness, headache
5. Norfloxacin: Used to treat urinary tract infections, gynaecological infections
Side-effects: Nausea, diarrhoea, headache, change in the quantity of urine
6. Levofloxacin: Used for sinusitis, pneumonia, prostate
Side-effects: Constipation, vomiting, abdominal pain
7. Metronidazole: Used to treat infections of the vagina, stomach, liver, respiratory tract
Side-effects: Agitation, numbness, back pain and much more
8. Ofloxacin: Used to treat pneumonia, cellulitis, urinary tract infection
Side-effects: Upset stomach, problems in sleeping, dizziness, persistent diarrhoea
9. Amoxicillin: First line treatment for middle ear infection, throat infections, tonsillitis, gonorrhea
Side-effects: Nausea, vomiting; may cause serious intestinal condition. Serious allergy reaction is rare.
10. Doxycycline: Used to treat acne, cholera, syphilis, and pneumonia
Side-effects: Diarrhoea, vomiting; may cause pressure inside the skull, and has many more serious side effects
Useful TIPS
For consumers
■ Stop using banned, hazardous and irrational drugs
■ Avoid combination drugs, and buy single ingredient drugs
■ Look at the expiry date before purchasing
■ Report shortage of essential and life-saving drugs
■ Ask your doctor in detail about how to take the drug, how often, and about the side-effects
■ Report side-effects to the doctor
■ Take full course of the medicine
For health professionals
■ Suggest antibiotics when needed
■ Educate patients about useless and alternative drugs
■ Minimise the prescription of antibiotics
■ Learn and speak about irrational FDC drugs
■ Inform patients as well as ADR centres about it
Suspected Drugs
A list of these drugs has been prepared after thorough clinical trial and published on the website of the Indian Pharmacopoeia Commission. Updated every month, the list is for awareness of doctors and consumers.
Terbinafine: Used for treatment of fungal infections
Adverse reaction: Acute generalised exanthematous pustulosis (pus problem on the skin)
Nitrofurantoin: Used for urinary tract infections
Adverse reaction: Vasculitis (vessels inflammation)
Losartan: Used for heart failure, reduction of stroke risk
Adverse reaction: Burning micturition (painful urination)
Paracetamol: Used for mild to moderate pain, headache Adverse reaction: baboon syndrome
Mebeverine: Used for irritable bowel syndrome
Adverse reaction: Retrosternal pain (in between chest pain)
Fluoxetine: Used for psychological disorder, premature ejaculation
Adverse reaction: Urinary incontinence (leakage of urine)
The Misused FDC Antibiotics
Studies have revealed that Fixed Dose Combination (FDC) drugs cause not only more adverse drug reaction but also adverse drug interaction. When there are combination of two-six drugs in one pill, the chances of adverse drug interaction rises by almost 40 percent.
Azithromycin+Cefixime Typhoid
Amoxicillin+Dicloxacillin Viral fevers
Azithromycin+Levofloxacin Typhoid
Cefixime+Linezolid Skin infections
Amoxicillin+Cefixime+
Potassium Clavulanic Acid Typhoid
Ofloxacin+Nitazoxanide Viral diarrhoea
Metronidazole+Norfloxacin Viral diarrhoea
Roxithromycin+
Serratiopeptidase Flu