New Delhi: The popular antacid ranitidine, whose sales have been suspended for two years in several countries after it was found to contain cancer-causing properties, was omitted from the central government’s latest National List of Essential Medicines (NLEM), released Tuesday.
But this doesn’t mean that the drug, commonly known by the brand names Rantac and Zantac, will no longer be available in India.
Ranitidine has been under the scanner since 2019, when laboratory tests showed that it contained a potentially carcinogenic compound called N-Nitrosodimethylamine (NDMA).
By 2020, the sale of the drug was suspended by major drug regulators the world over, including the European Medicines Agency (EMA) and the US Food and Drug Administration (USFDA).
However, ranitidine remains freely available in India. There’s no need for a prescription either and most chemists will readily fish out a 40-tablet ranitidine strip, which costs a mere Rs 30.
All drugs in the NLEM have to be sold below a price specified by the government, but removal from the list doesn’t usually affect the availability of a drug, unless manufacturers choose to hike prices massively for some reason.
Despite the concerns swirling around ranitidine, data available with the All-Indian Origin Chemists & Distributors (AIOCD) Ltd, a pharma trade association, showed a dip of just 2 per cent in the drug’s sales between August 2021 and August 2022. Doctors continue to prescribe it too, albeit less than before.
Further, since the drug is available over the counter, consumers also buy it for self-medication. The low prices are a big draw, while many aren’t aware of the potential risks.
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Easily available, cheap, but sales marginally down
When ThePrint visited some pharmacies, ranitidine was easily available over the counter.
A person manning a pharmacy in Delhi’s Sarita Vihar recommended the drug with confidence. “We don’t have Zantac but I can give you Rantac 50. We sell many strips every day. It is an acidity drug, very effective. I do not know of any side effects,” he said.
Zantac was the brand name under which the British pharmaceutical giant GlaxoSmithKline sold ranitidine, a senior official of the AIOCD said.
In 2019, Glaxo had voluntarily recalled its ranitidine products in India, as well as other markets, citing the NDMA findings.
“After Glaxo withdrew the drug from the market, the sales aren’t what they used to be. I do not have ready data with me. Two or three Indian companies continue to manufacture the drug,” said Sandeep Nangia, AIOCD organising secretary.
However, AIOCD general secretary Rajiv Singhal clarified that though the sales had indeed gone down, it wasn’t by much. “I have looked at the data and there has just been a 2 per cent dip,” he said, speaking of the period between August 2021 and August 2022.
On the potential impact of the removal of the drug from the NLEM, which keeps the price capped at a certain level, Singhal said: “Most of the sale is over the counter. It is difficult to say what effect the removal from the NLEM will have. It depends on the company and whether they want to increase margins. But it is true that one of the reasons for the popularity of the drug is its price.”
Cost, side effects of alternatives drive prescriptions
Doctors that ThePrint spoke to said that ranitidine prescriptions, particularly in the big cities, have gone down significantly over the years.
A senior surgeon who works with a reputed private hospital chain said on condition of anonymity: “It is still prescribed but much less than earlier. Maybe if we were writing it for 10 patients earlier, now we write it for two.”
According to this doctor, the main reason to prescribe ranitidine is cost. “Alternatives like omeprazole and pantoprazole cost Rs 7-8 per tablet. This probably costs Rs 3-4 or sometimes even less than that. But it is used much more in hospitals and clinics where the patient base is mainly poor people.”
Other medical practitioners also pointed towards the side effects of some ranitidine alternatives like pantoprazole, which some studies indicate may be associated with the risk of kidney and bone damage.
Dr S. Chatterjee, internal medicine consultant at Indraprastha Apollo Hospitals, said ranitidine had seen an increase in popularity due to this reason.
“Ranitidine is a very old medicine that saw a revival when they found that long-term use of alternatives such as pantoprazole can cause bone and kidney issues. That is when people started moving away from the proton pump inhibitors (like pantoprazole) to ranitidine,” he said.
Chatterjee also said there was a need to avoid “knee-jerk” reactions to concerns about drugs since evidence keeps changing.
“In the last few years there have been some reports about [ranitidine] causing malignancies but rather than such knee jerk reactions of withdrawing one drug or the other, based on evidence that’s liable to change over time, the important thing is for people to consult their doctors before long-term use of any drug” he said.
“It is not as if there wasn’t sufficient evidence for the FDA’s action, but evidence also changes over time. We need to keep that in mind.”
Why FDA recalled ranitidine
The FDA initially issued a warning about ranitidine in 2019, asking people who were using it to move to other medicines in consultation with their doctors.
This advice was upgraded in April 2020 when the agency sought a recall because of the presence of NDMA, “a probable human carcinogen (a substance that could cause cancer)”, in ranitidine.
“In the summer of 2019, the FDA became aware of independent laboratory testing that found NDMA in ranitidine. Low levels of NDMA are commonly ingested in the diet, for example NDMA is present in foods and in water. These low levels would not be expected to lead to an increase in the risk of cancer. However, sustained higher levels of exposure may increase the risk of cancer in humans,” the FDA had said in its April 2020 statement.
Previously, the FDA hadn’t had enough evidence to make a recommendation as to whether people should continue or stop taking the drug, according to the statement. But now, “FDA testing and evaluation prompted by information from third-party laboratories confirmed that NDMA levels increase in ranitidine even under normal storage conditions, and NDMA has been found to increase significantly in samples stored at higher temperatures”.
The statement added that testing showed that the older a ranitidine product is, the greater the level of NDMA. “These conditions may raise the level of NDMA in the ranitidine product above the acceptable daily intake limit,” the statement said.
What is NDMA?
The National Library of Medicine categorises NDMA as a “volatile, combustible, yellow, oily liquid nitrosamine with a faint characteristic odor that decomposes when exposed to light and emits toxic fumes of nitrogen oxides when heated to decomposition.”
In the laboratory it is often used to induce tumours in animals used for experiments, but it can also form naturally during the cooking of cured meats. However, ingestion of low levels of NDMA may not be dangerous.
The EMA says that NDMA is classified as a carcinogen based on animal studies.
While ranitidine has been the focus of the NDMA discussion in India, there are many other drugs that contain variable amounts of the chemical.
An April 2020 article in the journal Chemical and Engineering News claimed that over the past few years, labs around the world have found NDMA and other N-nitrosamine contaminants in various drugs.
“In 2018, the first discovery was made in a drug containing the active pharmaceutical ingredient valsartan by the drug’s maker, Novartis. Valsartan is an angiotensin II receptor blocker (ARB) used to treat high blood pressure. Since this discovery, NDMA and similar compounds have been found in at least six drugs that are taken by tens of millions of people each year,” the article said.
(Edited by Asavari Singh)
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