Health Canada nixes constipation med. What now for IBS-C?

By Jennifer Lalibert�

The constipation drug tegaserod has been pulled off the shelves after researchers discovered an increased cardiac risk — including MI and stroke — in patients taking the drug.

The drug was approved in Canada in 2002 for women with irritable bowel syndrome with constipation (IBS-C), and later for men and women under 65 with chronic idiopathic constipation. You should advise all your patients to stop taking tegaserod immediately, according to a recommendation issued by the manufacturer, Novartis. Health Canada, which along with the FDA ordered the med's withdrawal, advises physicians to refrain from issuing new tegaserod scripts and to review treatment of patients currently taking it.

Tegaserod was a real breakthrough when it first hit the market. It was the first prokinetic — a medication that stimulates the muscles in the gut to contract — to work in the lower portion of the GI tract. In clinical trials, it was shown to improve bowel function by increasing the activity of serotonin, which has prokinetic actions in the gut.

"My success with it has been about 50/50," admits Dr Arni Sekar, a gastroenterologist at the Ottawa Hospital, noting it was really only appropriate for a minority of patients on a short-term basis. But he says it does leave a big gap in constipation treatment. "There really aren't any other drugs we can use at this point," says Dr Sekar. "We have to stop it and basically go backwards."

He adds that he had high hopes that the best was yet to come. "We saw this as a precursor for bigger and better things. It's really a shame that it has these cardiovascular effects, because the concept was great," he says.

THE FACTS
Health Canada and the FDA recommended Novartis suspend sales of tegaserod because the drug's benefits, they found, no longer outweighed the risks. During a routine safety review, Swiss drug officials found that in 29 studies, 13 of 11,614 patients taking tegaserod experienced cardiac problems, resulting in one death. On the other hand, cardiac problems cropped up only once among 7,031 placebo subjects.

The important thing to remember, says Dr Sekar, is that all those affected had pre-existing cardiovascular disease and/or risk factors. "We don't know what the mechanisms are at this point," he says. "Maybe we'll find out that in a subgroup of healthy patients, it might be quite safe. But for right now, we have to explore other options."

WHAT NOW?
Limited choice Pharmacologically speaking, options are limited. "We have domperidone, but that only works on the upper GI, not the colon," says Dr Sekar. And that's about it. The mainstays of IBS treatment — a proper diet with plenty of fibre, exercise, relaxation techniques and biofeedback are what most patients have to fall back on (see "Simple tips for IBS-C patients,"). "These are chronic conditions, they're not going to go away with a few months of pharmacotherapy," points out Dr Sekar, who admits he's a bit of a minimalist when it comes to prescribing.

Special access In the US, the FDA has agreed to allow Novartis to re-submit an application specifically for patients who have no other viable treatment option — and the same will likely be possible here. The agency has also said it will consider re-introducing the drug for certain subgroups of patients at a later date, provided there's adequate data to safely support its use in certain patients. But not yet. "For now, the best thing is to stop completely," Dr Sekar says.