A review of intermittent subcutaneous apomorphineinjections for the rescue management of motor fluctuations associated with advanced Parkinson's disease

Abstract

Background: As Parkinson's disease (PD) progresses,despite optimized pharmacotherapy, patients experience more frequent fluctuations between symptomatic improvement (“on” times) and the return of motor features (“off” times). Apomorphine, the first injectable dopamine agonist available in the United States, is indicated for the acute treatment of “off” episodes (eg, endof-dose wearing-off episodes, unpredictable “on/off” episodes) in patients with advanced PD who are receiving medically optimal antiparkinsonian therapy. Objective: This article reviews the pharmacology,clinical efficacy, and tolerability of intermittent subcutaneous apomorphine injections for the management of “off” episodes in patients with PD. Methods: MEDLINE (1966–July 2005), the CochraneDatabase of Systematic Reviews, and International Pharmaceutical Abstracts (1970–July 2005) were searched for original research and review articles published in English. The search terms were apomorphine and Parkinson's disease. The reference lists of articles were also consulted, as was selected information provided by the manufacturer of apomorphine. All relevant identified studies on intermittent subcutaneous administration of apomorphine were included in the review; trials of continuous subcutaneous infusion and nonsubcutaneous administration of apomorphine were excluded. Results: Intermittent subcutaneous administrationof apomorphine produced consistent rescue from “of” episodes in patients with advanced PD, with a symptomatic motor improvement between the predose “off” state and postdose “on” state similar to that achieved with levodopa. The onset of effect occurred within 20 minutes, and the duration of effect was ∼100 minutes. The therapeutic rescue dose ranged from 2 to 6 mg. During the clinical development program for subcutaneously injected apomorphine, patients required a mean of ∼3 rescue doses per day. Common adverse effects occurring in ≥20% of patients were injection-site reaction, yawning, dyskinesias, drowsiness, nausea and vomiting, dizziness or postural dizziness, and rhinorrhea. Conclusions: The available clinical studies indicate that apomorphine is effective in providing prompt and consistent rescue from “off” episodes in patients with PD. Antiemetic prophylaxis and close medical supervision are recommended when initiating apomorphine therapy.