Diabetologists in India are up in arms following
an unexpected decision by the government there to suspend sales of the
diabetes drug pioglitazone. The ruling came seemingly out of the
blue, and there is much concern among doctors about their patients with
type 2 diabetes who are currently taking this medication.
The government suspended the manufacture, sale, and distribution of
pioglitazone at the end of June, citing concerns over adverse effects,
particularly
bladder cancer, according to a report in
BMJ
and a
number of Indian
media outlets.
Vijay Panikar, MD, an endocrinologist from Lilavati Hospital, Bandra,
Mumbai, who is also the secretary of the Association for Diabetes Care
and Prevention, told
Medscape Medical News: "I think it's
unfortunate. Pioglitazone should not have been banned. The government
could have put some restrictions [on it] but still allowed marketing
of the drug because there is no clear-cut indication that it does cause
bladder cancer." In fact, he said, "there are new data coming,
which are probably in favor of pioglitazone, expected in 2014."
And the secretary general of the Indian Pharmaceutical Alliance,
which represents 19 research-based national pharmaceutical companies,
Beilib D.G. Shah, said his members are also infuriated by this
decision, which he says is wrong on a number of levels.
"First, the due process of law for suspensions was not followed," Shah told
Medscape Medical News,
adding that normally there is a procedure for this type of legislation,
with logical steps, none of which were followed in this case. Second,
"the government cites the fact that
pioglitazone is banned in France and Germany,"
but the French ban "was 3 years ago," Shah noted, and in Germany
"they have suspended sales to new patients" only, he said.
"This drug has been on the Indian market for 12 years, and there has
been no suggestion of a link with bladder cancer. This decision has put 3
million patients on pioglitazone at risk and has come so suddenly.
Now they will have to go to their diabetologist or doctor and discuss
what therapy to change to. One of their choices now is to move to a
new therapy, at 10 times the cost. There is a suspicion that some
foreign companies [have pressured for this] to switch patients from
safe low-cost treatments to newer therapies such as gliptins," he
asserted.
Medscape Medical News tried to
speak with a representative of the Indian government. But G.N. Singh,
PhD, the drugs controller general of India, was overseas and could not
be contacted, and Dr. Arun Panda, of the Ministry of Health and
Welfare, could not be reached for comment.
Pioglitazone "Cornerstone of Therapy" in India
The thiazolidinedione drug class, which includes rosiglitazone (
Avandia,
GlaxoSmithKline) as well as pioglitazone, has never been far from
controversy. Rosiglitazone was suspended by the European Union in 2010
and its use severely restricted in the United States because of concerns
about a possible increased risk of cardiovascular adverse effects,
although this assertion has recently been
challenged in the second in a high-profile Food and Drug Administration advisory committee meeting.
Shah told
Medscape Medical News that rosiglitazone was
removed from the Indian market around the same time as it was suspended
in Europe, leaving pioglitazone — originally developed by Takeda
Pharmaceuticals and marketed as
Actos but now widely available
as a generic medication — as the remaining thiazolidinedione. It,
too, has been associated with adverse effects, including fractures and
fluid retention, but bladder cancer is probably the greatest
concern. Although pioglitazone has remained on the market in many
countries, some — including France and Germany — have banned it or
severely restricted its use.
Indian patients are particularly well suited to pioglitazone, Dr. Panikar told
Medscape Medical News,
"because they have a lot of insulin resistance, so this drug is
ideal for that." In fact, pioglitazone "is the cornerstone of treatment
in most patients" in India, he stated.
Most in India are taking pioglitazone in combination with either
metformin or a sulfonylurea, with many using fixed-dose combination
products. Now that pioglitazone is suddenly unavailable, "the next
step is to give gliptins or insulin," he explained. However, gliptins
"are probably 10 times the price" of pioglitazone, so "a large
number of patients…cannot afford this at all," and they also say, "Why
should we take insulin…when all this time we were controlled without
insulin?" he observed.
He noted that pioglitazone is used in very low doses in India, 7.5 to
15 mg daily. "If you don't have a contraindication for the use of
pioglitazone, it should be used in a low dose," he asserted.
Dr. Panikar and others also stress that pioglitazone remains on the
market in the United States, the United Kingdom, and in many other
Western nations and that it is endorsed and recommended for diabetes
management by many respected organizations, including the American
Diabetes Association (ADA), the European Association for the Study
of Diabetes (EASD), and the International Diabetes Federation (IDF).
"We are worried, rather than being angry. We are concerned about our
patients. We are making appeals to the government to reconsider the
decision. Associations are in the process of putting together
appeals, which will be presented, and we are hopeful they will reverse
this decision," Dr. Panikar said.
Most Indians Cannot Afford Newer Medications
Pioglitazone has been available generically in India for some time,
but newer oral type 2 diabetes medications, such as the gliptins
(dipeptidyl peptidase-4 [DPP-4] inhibitors), are available only as
branded products from Western companies, said Shah, whose organization
represents domestic firms, such as Dr. Reddy's Laboratories and
Ranbaxy Laboratories. There is 1 exception to this, with the Indian
company Glenmark Pharmaceuticals, selling a cheaper version of one
of the gliptins, but this is being legally challenged, he noted.
He said that the Indian government ruling on pioglitazone
specifically cites that all "drug formulations containing pioglitazone
are likely to involve risk to human beings" and states that "safer
alternatives to the said drug are available."
While it is true that alternatives are available, many people simply
cannot afford them, he maintained. "Around a third" of existing patients
could probably afford to switch to newer diabetes medications, but
the remainder cannot, he explained.
The market for pioglitazone in India is estimated to be worth about
Rs7 billion ($120 million) a year, but the medication is cheap for
individual patients, priced as low as Re1 to Rs4 per tablet,
according to Indian reports.
But, "We haven't heard the last word yet," Shah asserted. Following
"strong protestations" from a number of quarters, the government has now
backtracked a little and agreed to a meeting of "technical experts"
to discuss the situation, possibly as early as next week, he told
Medscape Medical News.
