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Dose correspondence between olanzapine long-acting injection and oral olanzapine: recommendations for switching

Detke, Holland C.; Zhao, Fangyi; Garhyan, Parag; Carlson, Janice; McDonnell, David

International Clinical Psychopharmacology:
doi: 10.1097/YIC.0b013e32834093d1
Original Articles
Abstract

Oral-to-depot dose correspondence was explored in a 24-week study of olanzapine long-acting injection (LAI). Patients with schizophrenia stabilized on oral olanzapine of 10, 15, or 20 mg/day (n=1065) were randomized to continue their oral treatment or switch directly to a fixed dose of olanzapine LAI [(mg/weeks) 45/4, 150/2, 405/4, or 300/2] without oral supplementation. Six-month relapse rates for each LAI-dose group stratified by earlier oral dose were analyzed using a Cox proportional hazard model assessing risk of relapse relative to each oral dose. Relapse rates for the therapeutic LAI doses (≥150 mg) varied depending on earlier oral dose, ranging from 1.5% (patients switched from 10 mg/day to 300 mg/2 weeks) to 18.8% (patients switched from 20 mg/day to 150 mg/2 weeks). Switching from 10 mg/day to 405 mg/4 weeks produced a comparable risk of relapse as remaining on that oral dose [Hazard ratio (HR)=1.03]. Switching from 15 or 20 mg/day to 300 mg/2 weeks produced comparable risk of relapse as remaining on those oral doses (HR=0.68 and 1.13, respectively). Pharmacokinetic modeling was conducted to evaluate the resulting dosing recommendations. Findings suggest that patients can be switched directly from oral to olanzapine LAI without the need for oral supplementation and with a low risk of relapse when initiated on an appropriate LAI dose.

Author Information

Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA

Correspondence to Holland C. Detke, PhD, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA Tel: +1 317 651 9043; fax: +1 317 277 0490; e-mail: detkehc@lilly.com

Received April 6, 2010

Accepted September 15, 2010

© 2011 Lippincott Williams & Wilkins, Inc.