The decision to ban 300-odd fixed-dose combination drugs brings down the curtain on Indians’ obsession for self-medication through codeine-based cough syrups

The fall from grace for codeine — once the world’s most lauded cough medicine — had begun nearly half a century ago before it was formally tombstoned by India earlier this week. Corex, a cough syrup whose most important element is codeine and one of pharma major Pfizer’s most profitable drugs in India, >was banned along with 300-odd so-called fixed-dose combination (FDC) drugs on March 14.

Until the early 20th century, when the world had yet to discover antibiotics and pneumonia and tuberculosis were major killers, physicians often chose to alleviate suffering and prescribed narcotics to address cough, especially the racking, convulsive variety that characterised tuberculosis. When the hallucinogenic morphine seemed to be the only effective solution, codeine emerged in 1832, in the lab of French chemist Pierre Robiquet, as a white knight that promised a restful, relaxed sleep. It was also a breakthrough in chemistry and among the first artificially synthesised drugs educed from opium. Over time, however, its side effects — of being extremely addictive and inducing drowsiness — became such a problem that Heroin (the highly regulated narcotic of today) and a drug developed by German drug manufacturer Bayer was actually sold as the “non-addictive” version of codeine and “10 times more effective as cough medicine”, according to Richard Askwith, in The Sunday Times (U.K.) of September 1998.

Relief at a high cost

Coughs usually occur when people catch a cold and they are nature’s method of protecting our airways, of inducing a reflex response to any irritation in our throat. A cough can linger for up to two weeks as the upper airways are inflamed by the cold virus and mucus trickling down the back of the throat. Cough syrups either try to suppress it or help cough up phlegm. Cough suppressants such as codeine and dextromethorphan directly act on the brain regions responsible for triggering the coughing reflex.

Their mechanism may be simple but while promoted as agents of relief by drug companies, the onset of antibiotics to cure infectious diseases that often had cough as a symptom, also began to throw up a body of medical literature in the 1950s that showed that cough syrups did little to help with the underlying causes of disease and could do more harm than good.

Once ingested, codeine could be rapidly converted to morphine within the body and that could dangerously spike blood levels, especially in children, and reports also started to emerge of its role in hypoxia — or decreased oxygen supply to the brain.

Worse, given its opioid ancestry there were always clinical observations that cough syrups in high doses caused hallucinations, dizziness and were extremely addictive and reports also began to emerge of its popularity as a street drug because of its easy availability in pharmacies. A comprehensive review last year by the U.S. National Institute of Drug Abuse says: “Abusing Dextromethorphan, or DXM (a cough suppressant developed in the ’50s as an alternative to codeine formulations), can cause impaired motor function, numbness, nausea or vomiting, increased heart rate and blood pressure, and at high doses, extreme agitation, increased body temperature, and a build-up of excess acid in body fluids.”

“Cough syrups have been out of the medical curriculum for over three decades and shown to be ineffective,” says Dr. Amit Sengupta of Jan Swasthya Abhiyan, an organisation that works on public health, “and yet they are freely available at the chemist’s.”

Corex’s recent ouster is connected to a large crackdown by the government on FDCs that are medicines in which two or more active pharmaceutical ingredients (APIs) are combined to form a single drug. Though the combined action of multiple drugs ought to mean improved efficacy, critics says that a combination is a new drug that could lead to unknown side effects.

What’s even more worrying is that were an adverse reaction to happen in a patient, it is often difficult to isolate the offending ingredient. In several countries access to cough syrups is regulated but India is an outlier.

A socio-cultural problem?

For one, say medical practitioners, Indians are psychologically addicted to prescriptions. Dr. C.M. Gulhati, editor, Monthly Index of Medical Specialities (India), an influential reference guide on drugs and clinical trials, has for several years been arguing that India is “unique” among all the countries in its fixation with “irrational” drug combinations. “In my experience, several patients are dissatisfied if they haven’t been prescribed a certain number of medicines and think a doctor is unfit if he asks for tests before prescribing pills,” he says, “and that’s got to do with doctor fees being usually more than the cost of recommended medicines.”

The World Bank notes that over 85 per cent of the out-of-pocket expenditure of Indians is on private health care. Moreover, to save on a visit to the doctor, Indians are notoriously prone to what Dr. Gulhati terms the “disease” of self-medication. “The combination of poverty, privatised health care and corruption is what’s responsible for the rise of irrationally prescribed medicines in India.” Coupled with lax laws governing the regulation of drugs in India, this opens to the door to pharmaceutical companies entering the doctor-patient interface and significantly influencing the medicines that are being consumed, he adds.

Dr. Gulhati says India was also unique in that there were branded cough syrups available which were advertised both as expectorants and suppressants: “That’s north and south… expectorants are supposed to induce coughing and suppressants the opposite. How do you explain such negligence?”

Listing what is permissible

While addressing foundational problems with the state of Indian health care may take time, a more rational way would be for India’s drug regulator to get its act together. “Instead of banning drug formulations, a better way would be list out permissible drug formulations by basing it on efficacy and potency,” says Dr. Sengupta. There are nearly 6,000 FDCs available across the country and imprecise legislation over the years has meant that States — and not the Centre — have usually had the power to vet which formulations were permissible. They gained in popularity due to laws in the 1980s that made it more profitable for companies to sell FDCs than single drugs, though such caps have now been lifted.

In the meantime, there are better ways to treat cough. Dr. Gulhati says that the aim of most cough medication is to soothe the throat and that can be achieved through home remedies such as honey and warm water. For relief, there are always the single-dose formulations available. “We could begin by having the doctor treat you the proper way,” he says.