Has heartburn pill that has been given to millions harmed patients?

When UK drug-maker Glaxo launched the heartburn medicine Zantac in 1981, the drug became one of the nation’s greatest pharmaceutical successes — not least for its effectiveness in treating heartburn, which affects up to a quarter of British adults.

The medicine’s active ingredient, ranitidine, reduces the amount of acid that the stomach produces. It can act as an effective salve for acid reflux and heartburn (the pain acid reflux causes), and can also be used to prevent and treat stomach ulcers.

As a preventive, patients were told to take one tablet with a glass of water 15 to 60 minutes before eating food or drinking beverages that cause heartburn.

By 1985, worldwide Zantac sales had reached £432 million, turning Glaxo from a mid-sized British company to a global pharmaceutical giant. And the medicine’s popularity continued to soar. In 1988 it became the world’s best-selling drug, earning more than a billion dollars in annual sales.

Zantac is a histamine blocker. Cells in the stomach wall are stimulated by histamine to produce digestive acids; Zantac works by blocking this action.

Other commonly used heartburn drugs are proton-pump inhibitors (PPIs), which target tiny pumps that secrete acid through stomach cells. PPIs have been linked to illnesses such as kidney disease, gastric infections and an increased risk of stomach cancer.

But now, in courts across the U.S., more than 3,700 legal actions have been filed by people who claim that taking Zantac and other ranitidine-based medications has caused them to develop cancers. The most commonly cited are bladder, stomach, oesophageal, pancreatic and liver cancers.

Concern about Zantac first emerged three years ago, when American scientists at the Connecticut-based laboratory Valisure studied commercially available samples of Zantac and warned that these contained ‘extremely high levels’ of a chemical called N-Nitrosodimethylamine (NDMA), thought to cause cancer.

The scientists reported to the U.S. regulator, the Food and Drug Administration (FDA), that the ranitidine in Zantac can degrade over time into NDMA. The risk is particularly high, they added, if the medicine is stored in hot and humid conditions.

The FDA has set a safe limit for daily exposure to NDMA at 96 nanograms. Lab testing by the FDA and Valisure revealed that Zantac samples contained as many as three million nanograms of NDMA.

The FDA issued a safety recall of all ranitidine-based products on April 1, 2020. Seven months later, safety concerns over NDMA prompted the UK regulator, the Medicines and Healthcare products Regulatory Agency (MHRA), to issue an alert for all healthcare professionals and retailers to stop supplying ranitidine medications.

This included Zantac, generic versions of the drugs on prescription and low-dose versions available over the counter from pharmacies. (Glaxo’s patent for ranitidine expired in 1997.)

Zantac is a histamine blocker. Cells in the stomach wall are stimulated by histamine to produce digestive acids; Zantac works by blocking this action. A file photo is used above

The first legal case against Zantac-type drugs in the U.S. came to an early end in August this year, when lawyers agreed a pre-court settlement of about £450,000.

Joseph Bayer, from Illinois, had launched the case 12 months earlier, claiming that taking Zantac had caused him to develop cancer of the oesophagus.

His lawsuit was aimed at GlaxoSmithKline (Glaxo became GlaxoSmithKline, or GSK, in 2000) and several companies that had made generic versions of the drug.

Before the case came to trial, the generic drug makers agreed to co-fund an out-of-court settlement, and Joseph Bayer dropped the case.

GlaxoSmithKline was not part of the settlement. A spokesman says: ‘GSK did not settle Mr Bayer’s claim and has not paid anything in exchange for the voluntary case dismissal.’

Nevertheless, other claimants continue to press for compensation from GSK and the drug’s generic makers.

One, Joseph Galimidi, a 57-year-old rabbi from South Florida, is suing for compensation for injuries, pain and suffering after developing breast cancer in 2013. The disease is rare in men — about 350 men are diagnosed each year in the UK, according to Cancer Research UK.

Joseph Galimidi says he had been regularly taking Zantac for heartburn over the previous four years.

And Mark Allan Blake, of Colorado, has filed a lawsuit claiming that Zantac, which he began using four times weekly in 1996, is responsible for causing the bladder cancer he developed in 2018.

Among the U.S. court cases naming GSK, a trial is due to begin in California in February 2023. Another, in Madison County, Illinois, is scheduled the same month.

There are several class legal actions and in excess of 100 personal injury cases being brought against GSK in Canada, along with a class action in Israel.

In Britain, there are no known compensation cases being pursued over Zantac. Research into the potential health risk from ranitidine here is scant, although last year a study of 17,000 Scottish people’s health records, published in the American Journal of Gastroenterology, suggested a link.

Scientists at Queen’s University Belfast and Aberdeen University used the records to compare differences in bladder cancer incidence between people taking prescribed ranitidine drugs and those who weren’t.

It found that those who had taken the drugs for more than three years had a nearly one-and-a-half times greater risk of developing bladder tumours.

Professor Chris Cardwell, a public health statistician at Queen’s University Belfast, who led the study, told Good Health that while the finding is interesting, it should be treated with caution until further studies are performed into the possible association.

It could perhaps be a statistical quirk, he says.

‘Alternatively, it could be that the ranitidine users were different from non-ranitidine users in ways that we could not adjust for, such as family history or occupational exposures,’ he adds.

Other recent research supports a potential cancer link. Last month, investigators compared the health records of more than 55,000 people who’d regularly taken prescribed ranitidine drugs with the records of another 55,000 people who had never taken them.

The researchers in Taiwan reported in the International Journal of Environmental Research and Public Health that the ranitidine-takers had significantly raised risks of developing lung, liver, pancreatic and stomach cancers.

Those who’d used ranitidine drugs at higher doses for longer periods were most at risk, the study concluded, though it added that more research is needed to explain the possible association.

GSK continues to dismiss any suggestion of a Zantac-cancer link. In a statement in August it said: ‘The overwhelming weight of the scientific evidence supports the conclusion that there is no increased cancer risk associated with the use of ranitidine. Suggestions to the contrary are therefore inconsistent with the science and GSK will vigorously defend itself against all meritless claims alleging otherwise.’

The MHRA told Good Health the licences for ranitidine-based medicines will remain suspended until it is ‘reassured’ that each marketing authorisation holder has carried out the ‘necessary investigations and analytical work to fully address the conditions’ set by the European Commission in 2020.