PPIs are drugs that work by inhibiting acid secretions in the stomach. It brings fast relief in cases of peptic ulcers and episodes of gastroesophageal reflux disease (GERD). GERD is stomach acids flowing back into the tube connecting the mouth and the esophagus. PPIs are available as tablets, capsules and injections and are becoming as ubiquitous as a Crocin to manage fever.
The reason for the popularity of PPIs among doctors and patients is not tough to gauge. With unhealthy lifestyles and dietary habits, acidity is common among Indians. While many brands of PPIs are sold almost over-the-counter, Pan, Pantop, Omez and Rablet fly off the chemist’s shelves.
Pai has raised two red flags. First, he objects to irresponsible prescriptions by doctors. Second, he warns those who habitually pop such medicines. He says there are clear age-specific conditions that require a therapy and then there are cases for which we cannot give drugs like PPIs. He says pantoprazole is prescribed for children but warns that it cannot be recommended to anyone below the age of 1 year.
Pantoprazole leads in PPI categories. Amit Mookim, MD of IQVIA South Asia, which tracks prescription trends, says while many new brands have entered this segment, the top players have consolidated their positions. Pantoprazole and its combination products contribute nearly 50% of the market and are growing. One of the key factors driving increased usage, he says, is co-prescription of PPI molecules with amoxicillin & clavulanate fixed dose combination and paracetamol and its fixed dose combination, which has increased significantly over the last five years. Co-prescription refers to a medicine that a doctor adds to increase or suppress the effects of a drug used to address the actual illness.PAN-INDIAN PROBLEM
The leading pantoprazole brands are Pan, Pantop and Pantocid. Sales of pantoprazole drugs in India stands at over Rs 1,800 crore for the 12 months ending April 2024. Mumbai-based drug maker Alkem leads with its single-brand sales at Rs 617 crore. The second spot is taken by Aristo’s Pantop with sales of Rs 370 crore, followed by Sun Pharma’s Pantocid, with sales worth Rs 289 crore.Pai says PPI provides fast relief, but going by the US FDA’s guidelines, it is not safe beyond approved indications and an upper limit of six to eight weeks. “There is data to back it up,” he says.
Pai is not alone in pushing for a rational use of PPIs. Research papers have piled up that show overuse of PPIs can lead to adverse events.
A report in the Indian Journal of Gastroenterology last year detailed guidelines for optimising the use of PPIs. It says, “They (PPIs) are freely available and based on current evidence, use of PPIs for inappropriate indications and duration appears to be common. Over the years, concerns have been raised on the safety of PPIs as they have been associated with several adverse effects. Hence, there is a need for PPI stewardship to promote the use of PPIs for appropriate indication and duration.”
According to the US FDA, PPIs are approved for the treatment of GERD, dyspepsia, erosive esophagitis, peptic ulcer and hypersecretory conditions such as Zollinger-Ellison syndrome and for managing certain inflammations. But in India those guidelines are seldom followed by doctors, pharmaceutical companies, or patients.
Take lansoprazole, a smaller category of PPI drugs, which had sales worth Rs 118 crore (12-month MAT till April 2024). Cipla’s brand Junior Lanzol had sales of Rs 96 crore. The brand is prescribed for a wide range of conditions, including diarrhoea and gastroenteritis, acute upper respiratory infections, viral infections, constipation, fever and asthma. “Of the total prescriptions, only 18% were for approved indications,” says an advisor in pharma marketing. On a lighter note, he says, “If you are ill, you take pills and if you are not ill, take more pills.”
USE, DON’T OVERUSE
While the overuse of such drugs is rampant, some experts say PPI works as a coprescription drug. In cases where nausea or acidity is caused by a medicine, it may be needed. Mandar Kubal, an expert in respiratory drugs, says in malaria, chloroquine may cause nausea or vomiting and, therefore, a PPI with domperidone has a clear role.
Similarly, an orthopaedic expert may prescribe a PPI with the painkiller aceclofenac for sprain or backache. Doctors prescribe non-steroidal anti-inflammatory drugs (NSAIDs), but Kubal says these may lead to peptic ulcers. In such cases, he adds, short-term use of PPIs for three to five days is not unreasonable. “Other than by gastroenterology specialists, writing PPIs for the long term is not desirable,” says Kubal.
In practice, such principles are not followed. A recent study by the Indian Council of Medical Research shows pantoprazole among the most randomly prescribed drugs. A few other medicines examined from 7,800 prescriptions that were labelled as “unacceptable” include combinations of rabeprazole and domperidone.
Dr Cyriac Abby Philips, a hepatologist based in Aluva, Kerala, objects to the indiscriminate use of PPIs. Philips, who works at the Liver Institute in Rajagiri Hospital, says irrational prescriptions of “gas medications” such as PPIs are the reason why patients get “hooked on” to this seemingly benign but dangerous group of drugs. Known to be vocal, Philips has a strong following on X.
“Many physicians are to be blamed for the illogical and unwarranted use of this group of drugs in patients,” says Philips. He admits that drugs such as omeprazole, esomeprazole, pantoprazole, lansoprazole, dexlansoprazole and rabeprazole are so potent that the World Health Organization has included them on the list of Essential Medicines. But their use, he says, beyond approved indications is where things may worsen. “People prefer self-medication for heartburn or indigestion symptoms such as fullness, bloating, stomach pain and excessive burping but it is recommended that PPIs be used for no more than 14 days,” he adds.
Philips says when such drugs are over-used, they are known to reduce magnesium levels in the body that can predispose a person to muscle weakness, seizures and heart rate abnormalities. “Since the acidic environment of the stomach serves as a protective barrier against infections and use of PPIs disrupts that barrier, long-term use of these medications predisposes people to severe infections, especially those with underlying liver disease or cancer,” says Philips.
“The non-recommended use of PPIs is contraindicated in people with cirrhosis, especially a terrible condition called ‘spontaneous bacterial peritonitis’ which is associated with high risk of death in liver patients,” Philips adds.
The excessive use of PPIs may also cause vitamin and iron deficiency and even possibly bone fractures. “PPIs have been notorious to cause a dreadful clinical complication in cirrhosis patients, called hepatic encephalopathy where brain failure happens in the presence of high ammonia and infections,” says Philips.
However, Philips desists from creating fear among people. “The over-the-counter use of PPIs must be curbed or limited to less than 14 days while the actual reasons for abdominal complaints/symptoms can be sought and treated,” he says.
Dr Pavan Dhoble, a gastroenterology consultant in Mumbai’s PD Hinduja Hospital, says he regularly sees patients who have been on PPIs for over a decade. Dhoble and his senior Dr Philip Abraham are drafting a set of guidelines, taking lessons from their practice. Dhoble says the bigger issue is the easy availability of drugs from medical shops without prescriptions.
Almost 90% cases of bloating and gas are functional, but physicians are in a hurry to write medicines. “When patients see relief and no harm, popping pills becomes a habit,” he says, adding that regulatory bodies should take action against the OTC sale of such medicines.
In 2019, the Drug Controller General of India issued orders directing drug producers to include a package insert that shows Acute Kidney Injury (AKI) as an adverse reaction caused by PPIs. But that is not seen as an effective countermeasure. Dhoble says such inserts, literature or monographs carry everything from head to toe, but people pay little heed to them. Doctors, he says, should identify high-risk patients with underlying conditions such as diabetes or chronic kidney disease as there could be transient issues for them.
A few years ago, he says, PPIs came in strengths of 10 mg, but most drug makers have moved on to 20 mg, 40 mg and 80 mg pills. “Why was that change needed?” he asks. “For doctors, tapering off PPIs has now become tougher.”
