Health Canada takes baby steps toward drug safety

DRUG BUST Alan Cassels

If you thought we could get through these lazy days of summer without another major drug warning from Health Canada for a class of drugs taken by thousands of Canadians, think again.

The most recent advisory is among the more mystifying of the “adverse drug reactions” warnings I’ve seen lately; it warns of tendonitis and even tendon rupture linked to a commonly prescribed, relatively new class of antibiotics. And while the warning threatens to make me riff, for the umpteenth time, on the variety of ways in which drug regulators around the world – Health Canada not excepted – seem to go through the motions of monitoring and ensuring drug safety, there was also some good news. In a separate announcement, Health Canada advised it would provide some new seed money to help establish a drug safety research network in Canada.

This is very good news, but first, about the warning. The fluoroquinolone antibiotics, which include ciprofloxacin (Cipro) and other drugs whose generic names end in floxacin, have been under a dark cloud for a while now. More than two years ago, the drug watchdog group Public Citizen petitioned the US FDA to strengthen the warnings, stating, “…tendon ruptures associated with these drugs continue to occur at a disturbing rate, but could be prevented if doctors and patients were more aware of early warning signals.”

Last month, Health Canada was seemingly spurred into action by the US FDA’s ruling that makers of fluoroquinolone drugs had to issue a “black box” warning – the FDA’s strongest safety warning – on these drugs. Black box warnings don’t come along all that frequently and they usually emerge after much negotiation between the manufacturers and the regulator. A “black box” often precedes the removal of a drug from the market and it is a serious signal that the regulators are concerned about the drug’s toxicity.

For all you active individuals out enjoying the summer sunshine, the phrase “tendon rupture” is likely to strike fear in your heart. Tendon damage and perhaps a torn Achilles tendon could wreck anyone’s day. And this due to a drug you took for a simple infection? While the potential effects on your tendons from these drugs have been known for some time, what isn’t entirely clear is why any physician would prescribe the drug, being fully aware of the risk it carries when other antibiotics carry no such risk. As far as I can tell, there is no valid evidence that the fluoroquinolones are any better at treating most infections compared to the alternatives, such as older penicillin-type antibiotics.

My knee-jerk reaction is to suspect that the fluoroquinolone antibiotics have been widely prescribed – both mis-prescribed and over-prescribed – and only a little research confirms those suspicions. There is that perennial, but misapplied, axiom “newer equals better,” which has likely driven much of the marketing and subsequent prescribing of these drugs, and as with any newer treatment, the drug roars onto the scene with bells and whistles while the vital safety signals are spoken in whispers years later.

It is obvious to me that these drugs are marketed as being useful for indications for which they would, at best, be someone’s second choice. At least one manufacturer of this type of antibiotic has been slapped on the wrist by the US FDA for “…making false and misleading statements regarding the safety and efficacy” of the treatment in its advertising.

In terms of how well the drugs are being prescribed, one study involving 100 patients in two academic medical centres in the US found that 81 percent of the patients taking fluoroquinolone antibiotics had been given them for an inappropriate indication. In that same study, 43 percent of the patients received these antibiotics as a first-line treatment and 27 percent of recipients had no evidence of an infection. If this study, which was small and perhaps not applicable to the wider population, comes even close to representing the actual use of these drugs in the “real world,” it is a damning indictment of a serious failure in prescribing, made all the more serious because the drugs have the inconvenient capacity to cause “tendon rupture.”

Should we not expect Health Canada, as our drug regulator, to ensure that proper and timely prescribing information, especially safety information, is made available to guide our physicians? Sadly “too little and too late” seems to characterize the safety signals reaching physicians. After a new drug is approved, the marketers jump into action putting the new drug front and centre of our doctors, our hospitals and health clinics, plying them with free samples and glowing literature.

So what can we do to ensure that new drugs are used properly, rather than inadvertently inflicting tendon damage on the population?

Essentially, we need better “real world” data. It is slowly being recognized that Canada lacks the capacity to properly ensure that “real world” data is generated for new drugs, and that vital safety information about how drugs work in the world in which you and I live must be delivered to physicians in a timely manner. We hope that our physicians are acting in the most prudent manner possible when it comes to treating our infections. We also hope they will reserve newer drugs for patients for whom the older, more established classes of drugs clearly don’t work. Although hope is a pretty frail framework upon which to build a drug safety system.

The demand for “Real World Safety and Effectiveness” research around pharmaceuticals is a topic I’ve written about in the past (Common Ground, August, 2007). This need was initially enshrined in the National Pharmaceutical Strategy (NPS), a federal-provincial initiative boldly launched in September 2004, with the goal of providing Canadians with more equitable, sustainable and safer access to new drugs.

Almost four years later, I’m not the only one to notice that the NPS is largely a dud. Some have said that the “new” Conservative government’s mighty tendency to jettison those Liberal initiatives sounded the death knell for the NPS. Others have noted that provincial-federal wrangling over drug issues – the provinces want help to stanch the bleeding of red ink on the provincial drug file while the feds want to please the drug industry – means the NPS is going nowhere fast.

One of the things buried in the NPS’s objectives was a desire to “strengthen evaluation of real-world drug safety and effectiveness” and this recent announcement seems like it’s about to happen, albeit with baby steps.

With prescription drug spending now in excess of $22 billion per year, and a strong public appetite for more rigorous drug safety in Canada, Health Canada announced in mid-July it would provide the seed money needed to set up an independent research network to study the real world safety and effectiveness of prescription drugs in Canada. The business plan behind this network called for about $20 million per year, but Health Canada announced an immediate five percent of that ($1 million dollars) to get things up and running.

The hope is that the provinces will jump in with their own money and make the network a reality, a network that will likely link researchers in Canada, who are already doing “post-market” surveillance work, and allow them to cooperate in tracking real world drug use issues across the country.

No one can argue that Canadians must be protected from the unanticipated, adverse effects of prescription drugs, as the recent drug safety warning related to the fluoroquinolones has highlighted. Some, however, are insulted with the measly five percent Health Canada is kicking in, as it barely represents a down payment on the initiative.

Some have said that regardless of what form Bill C-51 ultimately takes, if it even survives, any promise of a “cradle-to-grave” surveillance of drugs in Canada will have to be bankrolled by “real world” drug data, and this money will ensure that Canadian researchers are organized and funded to use those data.

I say we give credit where credit is due. Health Canada has anted up so let’s wait and see if the provinces will come on board. Only time will tell if they will do their part to make this network fly. Or perhaps this initiative, like so many other important initiatives in the past, is destined to die from the lack of political will.

My strategy? I’m going to say a little prayer for those who are suffering needless Achilles damage this summer and I’ll feel a little guilty as I continue to enjoy running, jumping, hiking and walking. Because of our collective ignorance about a particular class of drugs, many Canadians won’t be enjoying the summer as I will.

It doesn’t have to be this way. Let’s make drug safety a priority this year and put the money behind that decision.

Alan Cassels is a pharmaceutical policy researcher at the University of Victoria and can be reached at; cassels@uivic.ca

If you think you have been injured by a prescription drug, you should call the Canada Vigilance Program at 1-866-234-2345. You can also submit an adverse reaction report on the Med Effect Canada website (www.hc-sc.gc.ca/dhp-mps/medeff/index_e.html).