This column was prepared by the Institute for Safe Medication Practices (ISMP), an ECRI affiliate.
Post-exposure prophylaxis (PEP) is used to prevent HIV infection in an HIV-negative person who has had a recent high-risk exposure to HIV. PEP is classified as nonoccupational (eg, sexual contact, injection drug use) or occupational (eg, needlestick injury). Centers for Disease Control and Prevention recommends a 28-day course of a three-drug antiretroviral regimen for PEP. The preferred regimen for nonoccupational PEP for most patients is Truvada® (emtricitabine and tenofovir disoproxil fumarate) once daily plus either Isentress® (raltegravir) twice daily or Tivicay® (dolutegravir) once daily. For occupational PEP, the preferred regimen for most patients is Truvada once daily and Isentress twice daily.
The challenge with this 28-day regimen is that Truvada is only available in bottles containing 30 tablets. Normally, this would not be a problem, as the pharmacy would only dispense 28 tablets and keep the remainder in its inventory. However, both the Truvada container label and the package insert (PI) state “dispense only in original container,” and neither provide any stability information about the product once the bottle is opened. So, if the prescriber orders a PEP regimen with a 28-day supply of Truvada, the pharmacy should open the bottle and dispense only 28 tablets. But how do they dispense these in the original container? And what do they do with the remaining two tablets? How long are the tablets stable once the manufacturer bottle is opened? Of course, if the prescriber writes for a PEP regimen containing a 30-day supply, the pharmacy would be able to dispense the entire, sealed bottle; however, the patient would be taking two extra days of medication, which are not indicated.
A specialty pharmacy recently reported this situation to Institute for Safe Medication Practices (ISMP). They had received a prescription for Truvada for PEP and could not locate any stability information for the drug once the manufacturer bottle was opened. So, they contacted Gilead Sciences, the drug manufacturer. Gilead informed the pharmacy that they do have additional stability information that is not included in the PI. The manufacturer provided the pharmacy with a “Truvada Storage and Stability” medical information sheet which states that Truvada is stable for a maximum of six weeks once the bottle is opened (depending on temperature and humidity). This information is currently only available via a direct request to Gilead, so many pharmacies may not be aware of the shortened expiration date for Truvada once the bottle is opened.
ISMP has contacted both Gilead and Food and Drug Administration (FDA) to encourage including updated stability and expiration data in the PI as soon as possible. Of course, this will not solve the issue of only having 30-count bottles available. FDA and manufacturers should work together, ideally prior to initial marketing approval, to ensure various packaging and package quantities are available to accommodate variations in dosing as well as support safe dispensing practices in various care settings. For example, the manufacturer, knowing that this product will be used in inpatient as well as outpatient settings, should offer unit-dose packaging. This would allow for both safe use in hospitals (rather than dispensing 30-count bottles to patient care areas) and provide flexibility for various dosing regimens in outpatient settings. For now, pharmacies should devise a plan for how to handle any extra tablets.