Ziconotide, an intrathecal
analgesic for the management of chronic
intractable pain, binds with high affinity to
N-type calcium channels in neuronal tissue and obstructs neurotransmission. In three pivotal, well designed trials of 5-6 or 21 days' duration, titrated
ziconotide was significantly more effective than placebo in treating chronic malignant or nonmalignant
pain as assessed by mean percentage improvements from baseline in Visual Analogue Scale
Pain Intensity scores. Improvements in secondary endpoints (e.g. proportion of patients who responded or achieved
pain relief and the change in
opioid use) generally support the efficacy of
ziconotide over placebo.
Ziconotide maintains its
analgesic efficacy in preliminary results from long-term, open-label trials (data available for up to 12 months). Most
ziconotide-related adverse events are neurological, mild to moderate in severity, resolve over time and reverse without sequelae on
drug discontinuation. Low initial doses of
ziconotide and gradual titration to onset of
analgesia reduces the incidence and severity of adverse events. No evidence of
respiratory depression has been reported with intrathecal
ziconotide.