Drug Safety

, Volume 25, Issue 14, pp 1021–1033

Gastrointestinal Safety of an Extended-Release, Nondeformable, Oral Dosage Form (OROS®)1

A Retrospective Study
Original Research Article


Background: The OROS® osmotic (OSM) dosage form optimises extended-release oral administration by controlling the rate of drug release for a predetermined time, providing constant, patterned, or pulsed delivery profiles. OSM products include prescription medications for urology, CNS, and cardiovascular indications, as well as over-the-counter nasal/sinus congestion medications.

Methods: This retrospective study examines US gastrointestinal (GI) safety data for the OROS® dosage form following nearly two decades of use. Although GI injury and obstruction are known effects of oral medications, some reports have suggested that extended-release products pose a greater risk of GI injury and obstruction than other oral dosage forms. Products incorporating OROS® technology are being prescribed to an expanding range of patients; a review of the GI safety data for this dosage form thus seemed timely and appropriate. US safety information was obtained from three sources: (i) English language literature published from 1982 until June 1, 2000 from five major biomedical databases; (ii) postmarketing safety reports from January 1, 1983 until June 1, 2000 available through the Freedom of Information Act; and (iii) commercial safety information obtained directly from ALZA Corporation’s in-house safety database for those OSM products for which ALZA has reporting responsibility. US distribution data from IMS National Prescription Audit™ Plus data were used to estimate cumulative product distribution totals. These totals were combined with numbers of unique GI events to determine the estimated frequency of events.

Results: Nearly 13 billion OSM tablets are estimated to have been distributed in the US. The incidence of all clinically significant GI adverse events for OSM products (including intestinal, gastric, and oesophageal irritation, injury, and obstruction) reported in the US was approximately one case in >76 million tablets distributed. The majority (78%; estimated incidence: one case in 29 million tablets) of cases were reported in patients taking Procardia XL® (nifedipine). Oesophageal and lower GI obstruction were reported primarily in patients with pre-existing abnormalities or disease of the GI tract. Among paediatric patients, one obstruction was reported in an estimated 37.7 million tablets distributed. Reports of GI irritation associated with OSM products were consistent with known effects of the same drug substances in other dosage forms.

Conclusion: A review of long-term safety experience with products using OSM controlled-release technology yields a low incidence of clinically significant GI events. Properly prescribed, extended-release products provide substantial therapeutic and convenience benefits without additional risk.


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Copyright information

© Adis International Limited 2002

Authors and Affiliations

  • Dorsey M. Bass
    • 1
  • Mary Prevo
    • 2
  • Deborah S. Waxman
    • 2
  1. 1.Department of PediatricsStanford UniversityStanfordUSA
  2. 2.ALZA CorporationMountain ViewUSA

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