Finding Information about Drug Side Effects   (December 24, 2011)

Someone recently asked whether the side effects of Januvia (sitagliptin, a medication for T2DM) include "1) heart attack; 2) stroke; and 3) death. Is this true? I came across an article about Januvia that said that, but I can't find the article again." I couldn't recall any information that Januvia causes a higher-than-anticipated risk of heart attack, stroke, or death in people with diabetes (who are, of course, prone to have these events in any case), and so decided to look it up in what I consider one of the most definitive ways possible: using the Internet.

Not just by wandering around Google or Wikipedia, which I frequently do when looking up odd information, but by reviewing the drug's FDA-approved labeling information (commonly called the package insert or the prescribing information, or USPI). The reason I use the FDA-approved label is simple: the FDA insists on any side effect of importance being included in the label, either as an "adverse reaction" or in a warning or precaution or elsewhere in the label. And the manufacturers keep their on-line versions of the label up-to-date.

For those of you who haven't played this game, here's how I do it:

First, type in the brand name of the medication (in this case, Januvia), wherever your webbrowser takes new hyperlinks (the domain name of the website you're looking for), and follow it with ".com" - so in this case, type in "januvia.com". Once in a while, you'll have to add "www." in front, so you might have to type "www.januvia.com" to get there. For almost every name-brand medication, at least for recent ones, this trick will take you to the homepage for the product (although sometimes it will land you at the website of the manufacturer, and you'll have to look further to find the drug of interest). Once you're at the home page for the drug, look around for a phrase like "Prescribing Information" and click on it: it'll usually lead you directly to a PDF of the prescribing information.

In rare instances, this method fails, but you can find the label at the FDA website, at "www.labels.fda.gov". Click on "Proprietary Name Search" if you know the brand name (Januvia), or on "Active Ingredient Search" if you know the generic name (sitagliptin). Problem with this website is that you'll often have multiple choices of which label to review, and obviously you'll want the most current one. For drugs approved elsewhere in the world, but not in the US, you can find the labels on-line at other websites: For the UK, it's the  electronic Medicines Compendium, at www.medicines.org.uk/emc/; the labels are called a different jargon: Summaries of Product Characteristics (known as SPCs or SmPCs).

Once you get to the current label, you may find it's set up in either of two ways, as the FDA changed the formatting guidance a few years ago. But the titles of the sections to look through are CONTRAINDICATIONS (a recommendation to not use the drug if it has something listed here), WARNINGS AND PRECAUTIONS (strong advice to watch out for side effects listed here), and -ADVERSE REACTIONS (side effects that either occurred in clinical trials or that have been reported since the drug was approved, which are called "postmarketing reports").

Remember that lay terms like "heart attack" are probably described in the label as "myocardial infarction", stroke as "cerebrovascular accident", and both of these terms are "macrovascular" so searching for these various medical terms as well as the lay terms might find the words of concern. For Januvia, none of these yield any mention of such side effects with the drug.

If you are having trouble deciphering the label, ask your pharmacist or physician or diabetes nurse educator to help you. If they are unsure about some wording or concept as described in the label, they can call the Medical Information department of the drug's manufacturer, who can look up additional information to help sort things out for you.

Could there be a very recent article announcing new side effects with a drug that haven't yet made it into the label? Sure, but if some new side effect is of major concern (e.g., bladder cancer increased risk on Actos) it shows up in the label within months.

Hope this helps!