A review of intermittent subcutaneous apomorphine injections for the rescue management of motor fluctuations associated with advanced Parkinson's disease.
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, end-of-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 Cochrane Database 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 non-subcutaneous administration of apomorphine were excluded.


RESULTS
Intermittent subcutaneous administration of 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 approximately 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 approximately 3 rescue doses per day. Common adverse effects occurring in > or =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.
Chen
Jack J
JJ
Movement Disorders Center and School of Pharmacy, Loma Linda University, 1162 Campus Street-West Hall, Loma Linda, CA 92350, USA. jjchen@llu.edu
Obering
Crystal
C
D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001058:Apomorphine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004347:Drug Interactions; D017850:Economics, Pharmaceutical; D006801:Humans; D007279:Injections, Subcutaneous; D007980:Levodopa / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology
D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D007980:Levodopa; D001058:Apomorphine