Non-opioid analgesics: other: Safety assessment of intrathecal ziconotide treatment for chronic malignant and nonmalignant pain

Abstract

The objective of this work was to investigate the safety of intrathecal (IT) ziconotide (PRIALTTM) in patients with refractory malignant or chronic nonmalignant pain across multiple studies. This analysis includes safety data from 10 different multicenter studies. Ziconotide titration regimens varied, including forced titration regimens as well as conservative titration to effectiveness. The overall safety of IT ziconotide was examined by monitoring adverse events (AEs) and serious adverse events (SAEs, defined according to FDA criteria). In the 10 studies, 1048 patients were treated with ziconotide. Overall, 88.8% of patients reported at least 1 AE considered by the investigator to be related to ziconotide. The most frequently reported ziconotide-related AEs include abnormal gait (19.2%), memory impairment (19.6%), confusion (28.5%), nystagmus (29.3%), and dizziness (47.5%). SAEs related to ziconotide were reported in 147 patients; meningitis (0.9%), stupor (1.0%), urinary retention (1.0%), dizziness (1.1%), and confusion (3.5%) were the most frequently reported. Four hundred fifty-nine patients discontinued treatment early due to intolerable AEs. Nausea (5.3%), dizziness (6.7%), and confusion (11.7%) most commonly led to discontinuation. Overall, the most common ziconotide-related AEs are nervous system related, as might be expected based on the pharmacology of the drug at higher centers in the central nervous system. Across all studies, most patients in these very refractory populations experienced AEs. There were many early discontinuations, although for a substantial number of patients the risk of AEs was tolerable based on the analgesic benefit of the drug.