Patient Safety

FAQs - Clinical Considerations

In simplest possible terms, what has changed in the Unfractionated Heparin (UFH) products - -what caused this change -- how does this change help in ensuring purity and safety?

With the objective of ensuring purity of Unfractionated Heparin and patient safety in response to the 2008 adulteration problem (involving another manufacturer's heparin products), USP has implemented several changes to the current standard, effective October 1, 2009. These changes essentially update test methods used to identify the contents of UFH and to characterize the potency and purity of the Active Pharmaceutical Ingredient (API) and resultant Finished Product. In addition, USP is harmonizing their reference standard with the International Standard. This is creating a shift in apparent potency by approximately 10%1.

These changes are required of all manufacturers of heparin marketed in the United States.

Please clarify the USP statement that there has been an estimated drift of 10% between the USP unit and the International Unit (IU) for Unfractionated Heparin (UFH) over the past 30 years. In which direction has the 10% potency change been?

The USP has noted that UFH finished product prepared with current USP standards has averaged 10% higher potency (a range of 7% to 13%) than drug prepared with the International standards (International Units)1.

The new heparin standard now aligns the USP potency unit with the International Unit.

How will UFH prepared with the new USP standard differ in potency from heparin prepared under the previous USP standard?

The USP has noted that UFH finished product prepared with the new International Standard has averaged an approximately 10% decrease in potency (range 7% to 13%) in comparison with UFH prepared with the previous USP standard1.

Do we need to use a conversion factor when considering dose modifications between UFH prepared with the old USP standard in comparison with UFH prepared with the new USP standard?

A specific conversion factor cannot be recommended due to the inherent bioavailability of heparin, in addition there continues to be variability from lot to lot of UFH. As with all UFH use, careful clinical and laboratory monitoring of the patient's response, with dose adjustment as appropriate continues to be recommended.

Do you expect heparin prepared with the new standard to result in a higher or lower activated partial thromboplastin time (aPTT) or activated clotting time (ACT) than heparin prepared with the previous standard?

Heparin prepared according to the new International Standard has been successfully used in Europe, Canada, and other countries for many years. A few studies suggest that in comparison with heparin prepared in accordance with the previous USP standard, use of heparin prepared with the new International Standard may result in decreased activated clotting times (ACT) in some patients and a resultant decrease in clinical effect2, 3. Therefore, APP Pharmaceuticals is committed to communicating the changes to health care practitioners to allow them to make informed decisions regarding dosing.

How can health care providers prepare for the changes?

The following is a suggested UFH readiness checklist:

[  ] Plan for transition
[  ] Consider USP changes and potential effects
[  ] Use as an opportunity to review all potentially affected protocols
[  ] Reevaluate aPTT and ACT targets for new lots
[  ] Monitor for changes
[  ] Provide ongoing support4

References:

  1. http://www.usp.org/hottopics/heparin.html
  2. Dyck L and Friesen RM. Do Different Heparin Brands Influence Activated Clotting Times? J Extra Corpor Technol. 1998; 30:73-6.
  3. Hamilton M, MacDonald W, Levely A, et al. A rose is a rose - or is it? The 1993 Compendium of the Canadian Society of Clinical Perfusion, Scientific Sessions, October 1993.
  4. Nutescue E.Readiness for the New USP Standards for Unfractionated Heparin (UFH). Webinar, September 23, 2009.
  5. Smythe MA, Nutescu EA, Wittkowsky AK. Changes in the USP Heparin Monograph and Implications for Clinicians.Pharmacotherapy 2010;30(5):428–431.