A promotional for Buclizine, marketed as Longifene by Mankind Pharma

New Delhi, Aug. 28: An unknown number of children in India have received an appetite stimulant that the country’s apex drug regulator approved for marketing five years ago without adequate evidence of its benefit and without mandatory trials, doctors have said.

The office of the Drug Controller General of India (DCGI) approved the medicine called Buclizine as an appetite stimulant, allowing it to be prescribed to young children despite the lack of approved clinical studies, the clinicians and paediatricians have said.

Buclizine was originally developed by the Belgium-based UCB Pharma as an anti-histamine and has been approved in several countries as treatment to prevent motion sickness and allergies but not to boost appetite or growth in children, they said.

“The DCGI has gone out of the way to approve Buclizine as an appetite stimulant,” said Chandra Gulhati, a specialist in drugs and therapeutics who is editor of the Monthly Index of Medical Specialities, India, an independent journal of drugs.

A detailed data sheet circulated by the company in Belgium suggests that Buclizine is not approved for appetite enhancement in Belgium, Gulhati said, in a commentary to appear in a forthcoming issue of the journal.

The sheet says that given the lack of approved clinical studies and scientific data, the benefit/risk for the use of Buclizine for appetite stimulation is negative. “If this drug is not good for Belgian children, how can it be safe and effective for Indian children?” Gulhati asked.

The New Delhi-based company marketing the drug, Mankind Pharma, said Buclizine had received the DCGI’s approval for its use as an appetite stimulant in June 2006, and as a treatment for motion sickness in January 2010. “There are many studies showing its use in appetite enhancement,” a Mankind spokesperson said.

The spokesperson said the company had acquired the license for Buclizine from UCB which had obtained approval in June 2006. “We do not know about clinical trials on appetite enhancement — please ask the DCGI about that,” the spokesperson said.

No one in the office of the DCGI was available for comment.

Some paediatricians have been concerned about what they describe as “aggressive promotion of the product” and widespread prescriptions of Buclizine by their own colleagues. “Parents worried about children not eating enough are often asked to give their kids this drug,” said Thirunavukkarasu Arun Babu, a paediatrician at the Sri Lakshmi Narayana Institute of Medical Sciences, Puducherry. “It is totally unscientific and done without the required evidence,” Babu said.

A senior Mankind official declined to say how much Buclizine is sold as an appetite stimulant in India. But paediatricians believe the number of children who receive the drug may run into several thousands each year.

“I prescribe it to three to five children each month,” said V. Thomas Varghese, a paediatrician in Kochi. In the out-patient department of the Sri Lakshmi Narayana Institute of Medical Sciences, Babu said, paediatricians routinely encounter old prescriptions listing Buclizine. “We see at least five a day,” he said.

Mankind Pharma markets the drug as Longifene and its promotional literature cites two medical studies published in the Indian Medical Gazette and another journal. Company officials said both papers show that the drug helps improve appetite.

However, in a paper published in the Indian Journal of Pharmacology this year, Babu said he had carried out a search of medical literature and clinical trial databases to look for evidence that Buclizine could be used as an appetite stimulant.

A search of PubMed — one of the largest databases cataloguing medical research — revealed no published papers on Buclizine and weight gain in the past 40 years, Babu said. “We didn’t find any registered clinical trials,” Babu said. “But weight gain has been reported as a side-effect of the drug when used to treat allergies.”

Gulhati has pointed out that under India’s drug laws, the DCGI’s approval of Buclizine as an appetite stimulant should have been preceded by clinical trials to demonstrate its efficacy in not less than 100 volunteers at three or four sites.

“As this is prescribed for young children, the trials should have also evaluated Buclizine in children.”

The commentary in the Monthly Index of Medical Specialties, India said the drug has not undergone clinical trials for its use in children anywhere in the world — and it remains unapproved in many countries, including Australia, Bangladesh, Canada, Japan, the European Union, and the US.

Several paediatricians say appetite stimulation is not the correct way to manage mild levels of malnutrition for which the drug is typically being prescribed. “The solution is to increase calorie intake,” Babu said.