In October 2010, the Food and Drug Administration (FDA) approved a new direct thrombin inhibitor—dabigatran etexilate mesylate (Pradaxa)—for the prevention of strokes and blood clots in patients with nonvalvular atrial fibrillation (see Drug Watch, February). The FDA has now issued a safety communication explaining that the requirements for safe storage of dabigatran may not be well recognized by health care professionals or patients.
Although the original label states that dabigatran should be stored in its original packaging to protect it from moisture, that information isn't emphasized or displayed prominently in the package insert. Despite this relative lack of information in the labeling, the FDA has taken steps to prevent exposure of the product to moisture. Dabigatran comes in blister packs or a 60-pill bottle (a month's supply) with a desiccant cap to minimize product breakdown from moisture, an unusual and expensive packaging option. (The United States is the only country where a bottle is used to dispense dabigatran. In all other markets, dabigatran comes only in blister packs.) The related FDA Drug Safety Communication (http://1.usa.gov/hGJG0z) provides some information on the effect of moisture on the drug's efficacy: "Pradaxa capsules will hydrolyze [decompose] over time when exposed to humidity, causing a breakdown of active ingredient, and rendering the medication less effective." And dabigatran's label states that once the bottle is opened, the product must be used within 30 days (unlike most medications, which don't lose any efficacy until after a year).
The FDA is currently reviewing data suggesting that there may be no significant loss of potency for as long as 60 days after the bottle is opened, as long as dabigatran is stored in the original bottle and the handling requirements are met. The exact concern of the FDA over this issue is unclear, nor is it known precisely how much potency is lost from exposure to the environment if the drug isn't used within 30 days, how much is lost if the drug isn't kept in the original container, or whether the loss is great enough to place the patient at risk for blood clots and stroke. A search of the FDA's MedWatch site doesn't yield any case reports specifically noting a loss of potency and efficacy from improper storage.
Until more information is available, it would seem prudent for nurses and other health professionals to include the following in their instructions to patients:
* Store dabigatran in its original bottle or blister pack. Don't remove the pills from their original packaging for storage in a pill box or pill organizer.
* Keep the lid of the bottle closed except when you remove a capsule. If you have the blister pack, remove each capsule only at the time you'll be swallowing it.
* Keep the bottle away from excessive heat, moisture, or cold (for example, don't keep it in the bathroom medicine cabinet, over the stove, or in the refrigerator).
* Open only one bottle of 60 capsules at a time.
* If you receive more than one bottle per filled prescription, label the bottles to show which one is used first.
* Date the opened bottle to show that it expires 30 days after you open it.
* Read the medication guide each time you receive a filled prescription.
Nurses who note any loss of drug effectiveness or other adverse effects in a patient receiving dabigatran should contact the FDA's MedWatch program at www.fda.gov/Safety/MedWatch.