Beset by lawsuits and criticism in U.S., opioid makers eye new market in India

The sour grimace on the woman’s face, registering her bodily complaints to Dr. G.P. Dureja in his East Delhi office, would be recognized anywhere. Slouched shoulders, pinched forehead. She wore a willowy black kurta and cast a disapproving glance at the five pain physicians-in-training huddled behind Dureja, founder of Delhi Pain Management Centre and one of India’s pioneering pain physicians.

The five trainees, participants in the center’s acclaimed pain fellowship program, recorded the woman’s consultation on their smartphones, eager to see India’s famous pain doctor do his work. After their fellowships, they will return home, to Chennai, Kashmir, Rajasthan, ready to forge careers in India’s exploding pain industry.

The woman had been under Dureja’s care for some time now; he diagnosed her with fibromyalgia, a chronic neurological disorder of mysterious origin that causes pain throughout the body. But the regimen of Paracetamol and tramadol, an opioid analgesic, was not working and she was beyond fatigued. She wanted more relief.

Indians once thought of pain relief as an indulgence of the West, Dureja said after the woman left his office gripping her new prescriptions. The old way of thinking was, "Nobody has time to complain about pain in our country. But I’m getting five to seven new patients per day."

Storefront for-profit pain clinics like Delhi Pain Management Centre are opening by the score across Mumbai, Kolkata, Bangalore and other cities in this teeming nation. After decades of stringent narcotics laws, borne of debilitating opium epidemics of centuries past, India is a country ready to salve its pain.

And American pharmaceutical companies — architects of the opioid crisis in the United States and avid hunters of new markets — stand at the ready to feed and fuel that demand.

For Indian cancer patients who once writhed in agony, there are fentanyl patches from a subsidiary of Johnson & Johnson.

For the country’s vast army of middle-class office workers wracked with back and neck pain, there is buprenorphine from Mundipharma, a network of companies controlled by the Sackler family, owners of Connecticut-based Purdue Pharma.

And for the hundreds of millions of aging Indians with aching joints and knees, there are shots of tramadol from Abbott Laboratories.

Palliative care advocates, who recount stories of patients enduring excruciating cancer pain or dying in agony, have persuaded reluctant government officials to allow high-powered opioid painkillers into doctors’ offices and onto chemists’ shelves in this nation of 1.37 billion people.

But what began as a populist movement to bring inexpensive, Indian-made morphine to the diseased and dying poor has given rise to a pain management industry that promises countless new customers to American pharmaceutical companies facing a government crackdown and mounting lawsuits back home.

The lure of a pain-free life is a revelation in a country where incomes are rising for many city dwellers and 300 million to 400 million people are approaching the middle class. Like other markers of the country’s post-colonial sprint into modernity, newly minted pain doctors promise aspiring Indians that life has more to offer in a body free from pain, and foreign brands are worth the extra rupees.

"Don’t listen to your forefathers," Dureja said, a mantra for the shifting mindset. "They said you should tolerate pain, you should not complain, you should not take painkillers. Now, everybody wants a better quality of life, and everybody wants to get rid of pain early."

As major pharmaceutical companies look to capitalize on the opportunity, the playbook unfolding in India seems eerily familiar. Earnest advocates share heartbreaking stories of suffering patients; physicians and pharmaceutical companies champion pain relief for cancer patients and persuade regulators to grant greater access to ever more powerful opioids; well-meaning pain doctors open clinics; shady pain clinics follow; and a spigot of prescription opioids opens — first addressing legitimate medical uses but soon spilling into the streets and onto the black market.

A looming deluge of addictive painkillers terrifies some Indian medical professionals, who are keenly aware that despite government regulations most drugs are available for petty cash at the chemist shops that occupy nearly every city block and village center.

"Are people going to figure out every trick in the game to make [opioid painkillers] widely available?" asked Dr. Bobby John, a leading Indian public health expert based in New Delhi. "Of course it will happen."

‘The market for pain is good’

The headquarters of the Pain Clinic of India operates out of a closet-size office in Chembur, a tree-lined suburb in eastern Mumbai. The company’s presence on the internet is so prominent that Dr. Kailash Kothari, the clinic’s founder, has turned down requests from people in South Africa, Australia, Europe and the United States seeking prescription opioids.

Down an alleyway, the clinic’s small white-red-and-blue sign is difficult to spot. Around the side of a faded-pink building is a larger sign showing a shirtless, muscular white man gripping his back, another gripping his neck, another clutching his knee; a white woman with an excruciating headache presses her forehead and another grabs her shoulder. Back Pain. Neck Pain. Headache. Knee Pain. Shoulder Pain. Cancer Pain. The sign promises "Towards Pain Free Life."

One of the principal architects of pain medicine in India, Kothari runs several clinics in Mumbai, consults at numerous hospitals and flies to his clinic in Goa once a week. He co-founded the Indian Academy of Pain, an educational branch of the Indian Society for the Study of Pain that aims to create standardized training for pain medicine, in part by offering qualifying exams to prospective physicians. "This program is going to change the scenery of what we have in pain management," Kothari said.

Asserting control over who can call themselves a "pain medicine doctor" in this fledgling industry is an urgent question. Spread across the subcontinent are nearly 10 million licensed physicians and a massive number of untrained medical providers. (In rural India, 70% of health care providers have no formal medical training.)

"General practitioners have started prescribing these drugs," Dureja said. "And we’re not educating the population on when to use and not to use."

At Dureja’s clinics, as at most medical offices in India, patients pay cash for services and prescriptions. Delhi Pain Management charges $10 for a consultation; $10 for a Johnson & Johnson fentanyl patch; $10 for a Mundipharma buprenorphine patch. Dureja’s office takes a 15% cut of sales.

There are hints of American pharma’s fingerprints in a glass cabinet in the waiting room of his East Delhi clinic: awards from Johnson & Johnson honoring Dureja for symposia on pain management; a plaque for "his valuable contribution as a speaker" about tapentadol, an opioid marketed by Johnson & Johnson in 2009. The dispensing counter does a brisk business in Ultracet, branded tramadol tablets made by a Johnson & Johnson subsidiary.

Dureja’s training fellowships, like Kothari’s, are broadly considered on the level; but many others are shady, and none are regulated.

Each year, some 20 fellows attend Kothari’s three- to six-month training programs, and by his calculation, he has trained 150 aspiring pain doctors. "There are more than 50 people who already have their pain clinics in different parts of India," he said. Of those clinics, five or six "are training people, and it’s a chain reaction, which is going to benefit pain management as a specialty."

Kothari remembers when only a few hospitals in Mumbai treated cancer patients and had access to opioids. "But every year, we are accessing more of these kinds of drugs," he said. "Many chemists, hospitals and medical shops started acquiring the licenses for keeping these drugs, and availability is much, much better. Opioids are available in not just oral, but injectable, patches, syrups."

Most large Indian hospitals have added pain management as a specialty in recent years. At the insistence of the professional societies that accredit hospitals in India, Kothari said, nurses and doctors now are required to assess pain as a fifth vital sign, along with pulse, temperature, breathing and blood pressure.

The pharmaceutical industry has kept pace. Twenty years ago, only a few pharmaceutical companies marketed pain medicines in India, Kothari said. "Today, almost every company is having pain management as a separate division. In the last five years alone, I must have met more than 15 or 20 companies that have started separate pain management divisions."

A salesman for Sun Pharma, India’s largest drugmaker by sales, echoed the point during an interview in Chandigarh, the capital of Punjab and Haryana. The market for pain medications "has totally changed" in the past five years, he said. He shifted nervously and agreed to speak frankly only if his name wasn’t published, for fear of losing his job.

"Now everyone has a car, and [they get] back pain, and now they take medication." Growing obesity rates in India were also fueling demand, he said, as patients look for relief from weight-related knee and back pain. "So the market for pain is good."

Abbott Laboratories and Johnson & Johnson did not respond to requests for comment for this report.

Manmohan Singh, a vice president at Modi-Mundipharma in New Delhi, said opioid pain medications are an important therapeutic option, especially for cancer pain. He also said company promotions stress that physicians should familiarize themselves with product safety information. "Patients should be made aware of the clear treatment goals related to pain and function, as well as the potential opioid side effects and the potential for misuse, abuse and addiction," he said in a written statement.

One false step

The ascendance of pain management in India comes at a fortuitous political moment. Ahead of his reelection earlier this year, Prime Minister Narendra Modi invested heavily in health care. Last fall, the Indian government launched the world’s biggest public health insurance program, called Ayushman Bharat. Dubbed "Modicare," it guarantees half a billion poor Indians nearly $7,000 in hospital expenses, paid to private insurers, and, by 2020, the government is to open 150,000 primary care centers. The government has set aside $484 million to fund Modi’s signature program.

None of this would have been possible without the loosening of India’s strict narcotics laws.

The International Narcotics Control Board, established in 1968, and the Narcotic Drugs and Psychotropic Substances Act of 1985 codified the bureaucratic thicket for any doctor who wanted to prescribe opioid painkillers. Physicians feared fines, jail sentences and losing their medical license if they skirted regulations. While the government granted licenses to Indian farmers to grow poppies, most of the morphine produced from the crops was exported.

Dr. M.R. Rajagopal was a young medical student in Thiruvananthapuram at the time and remembers a neighbor with advanced cancer. "I [had] seen him screaming his way over weeks to death," Rajagopal said. "It was horrendous, and there was nothing being done about it." He chose to become an anesthesiologist because it was the only specialty then focused on pain.

Rajagopal is widely viewed as the father of palliative care in India; whispers of a Nobel Prize follow him. For decades, he has worked assiduously to convince national and state lawmakers that opioid medicines are not an indulgence but a humane refuge, and it is largely a function of his advocacy that morphine and other painkillers can be prescribed in India. "Two generations of doctors had not seen a tablet of morphine," he said.

The Narcotic Drugs and Psychotropic Substances Act, as amended in 2014, recognized that the need for pain relief was "an important obligation of the government." The revised law created a class of medicines called the "essential narcotic drugs" list, which includes morphine, fentanyl, methadone, oxycodone, codeine and hydrocodone.

Rajagopal’s days are filled with the tedious work of building a movement: speaking at colleges and public forums, penning editorials and medical papers about palliative care and overseeing Pallium India, a nonprofit medical center and training institute that is singularly focused on palliative care.

Pallium’s pharmacy is a testament to Rajagopal’s persistence. Drugs once banned now fill the shelves: fentanyl injections and patches, oral morphine and, most recently, methadone, approved for pain relief in 2018.

Rajagopal seems aware that one false step would invite the government to clamp down on the availability of opioids, reversing decades of his work. He does not advise using oxycodone or hydrocodone, though they are included on the "essential narcotic drugs" list, and he does not accept funding from pharmaceutical companies, instead putting his hand out to temple trustees and for donations from families cared for by Pallium’s home visiting teams.

But the pharmaceutical industry is a wily adversary. American activists made many of the same arguments decades ago as they sought relief for dying patients. Drugs now commonly prescribed for chronic pain first were approved for use by cancer patients. One of the first formulations of fentanyl, for example, was a lollipop because chemotherapy left cancer patients too nauseated to eat. In India, pain physicians now prescribe fentanyl patches to patients with chronic muscular pain.

Purdue Pharma’s international affiliate, Mundipharma, "is very good at co-opting regulators," said Keith Humphreys, a professor of psychiatry at Stanford University. "As happened in the U.S., they are easily converted into useful idiots."

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