Fixed-dose combination drugs like Zimnic AZ aren’t unique to India. They are used worldwide to improve patients’ compliance in complicated courses of treatment for such conditions as HIV, tuberculosis and malaria. It’s easier to get patients to take one drug than a number of different pills.
Combination drugs are also useful in increasing compliance among the many Indian patients who can’t read, said Sanjay Sikaria, director of drugmaker Suncare Formulations Private Ltd in Uttarakhand state. “FDCs (Fixed dose combinations) are not bad,” he said. “Rampant misuse of these drugs is bad.”
That’s the problem in India, where there has been an explosion of combination drugs. They have become a way to boost sales and increase market share: More and more companies have tacked on ingredients to existing drugs so they can peddle a new product to doctors and chemists, say people in the country’s highly competitive pharmaceutical sector.
Combination drugs are profitable because of high demand from doctors, who see them as a way to ensure patient compliance, say people in the pharmaceutical industry. Many doctors also see them as providing “quick-fix solutions” that cover multiple possible symptoms with a single pill, said a physician employed by a pharmaceutical company. “The market needs it and demands it,” he said.
Between 2011 and 2014, India’s fixed-dose combination market grew more than 40% in rupee terms, according to IMS Health.
A study published in the journal of Public Library of Science (PLOS) in May found that over 70% of non-steroidal anti-inflammatory drug (NSAID) combinations, which are used as painkillers, were being marketed in India without central government approval. The authors recommended that unapproved drug combinations be banned immediately.
“We have fixed-dose combinations in every category of drug,” said Anurag Bhargava, professor of medicine at Yenepoya Medical College in the southern state of Karnataka. “The single ingredient versions are harder to find.”
Delhi takes ‘longer’
FDCs have grown rapidly in India, in part because over the years pharmaceutical companies have procured licenses from a state to manufacture new drugs, without obtaining central government approval.
The Abbott combination won approval this way, according to Akums Drugs & Pharmaceuticals Ltd, which manufactures Zimnic AZ in Uttarakhand, a state known for its Himalayan peaks and thriving drug manufacturing industry. In 2010, Uttarakhand’s state drug licensing authority granted approval to Akums to manufacture the combination of cefixime and azithromycin, the components of Zimnic AZ, according to the company. Each of those drugs is individually approved by the government. Akums said it also makes the combination for an Indian drug company.
Asked why Akums was manufacturing a drug without the approval of the central government, former company chairman DC Jain said state authorities were as qualified as the central government to assess a drug, and that the process of applying for approval from a state and the central government was similar.
Since getting a state license, Akums said it has filed an application to New Delhi for the combination.
Getting a green light from New Delhi takes “a little longer,” said Jain, who is now a consultant at Akums.
Akums did not respond to a request for a copy of the document showing that the combination of cefixime and azithromycin had been approved by the state. During a visit at the state drug controller’s office in Uttarakhand, staff could not find a record of the license.
One of several committees convened by the drug controller to review drug cocktails in 2014 recommended that the combination of these two antibiotics should not be approved. The panel found that the drug was “not a standard antibiotic combination” and that “the misuse potential is very high,” according to the committee’s recommendation, a copy of which was obtained by Reuters through a freedom of information request.
After years of intermittent efforts to limit the sale of state-licensed FDC drugs, the government is making another attempt to weed out those it considers “irrational.” More than 3,000 different brands of combination drugs are currently under review in New Delhi, a drug regulatory official said.
Asked about the status of the cefixime-azithromycin combination, GN Singh, the drugs controller general, said he could not comment on a specific case. But the drug regulatory official said the combination was “under the scanner” because pairing the two drugs that make up Zimnic AZ “is not appropriate.”
