Ziconotide Combination Intrathecal Therapy: Rationale and Evidence

Abstract

Although clinical and preclinical studies provide some support for the use of ziconotide in combination with morphine, hydromorphone, clonidine, or baclofen, strong evidence-based data are limited. Controlled, long-term clinical trials are warranted.

Ziconotide: a clinical update and pharmacologic review

“…Alicino et al demonstrated that ziconotide in combination with morphine could be helpful in opioid refractory cancer pain, with slow titration and a starting ziconotide dose of 1.2 µg/day and morphine calculated from oral equivalent [46]. Bupivacaine additions revealed no statistically significant difference [42]. Dupoiron et al demonstrated efficacy in cancer pain with slow titration and multidrug use, including morphine, ropivacaine, and clonidine, with reduced side effects [47].…”

“…Stability of ziconotide with admixtures reveals varying stability periods, as characterized by Shields [48][49][50][51][52][53], and summarized by Wallace [42]. See Table 3.…”

“…Reprinted with permission from [42,[48][49][50][51][52][53]. The manufacturer classifies the ziconotide as a pregnancy type C, with no known carcinogenicity.…”

“…Wallace et al [42] reported on ziconotide and combination therapy intrathecally to treat chronic, refractory pain, including morphine, hydromorphone, clonidine, bupivacaine, and baclofen. Additive or synergistic effects were demonstrated with morphine, clonidine, or baclofen [43][44][45].…”

Effects of arginine 10 to lysine substitution on ω‐conotoxin CVIE and CVIF block of Cav2.2 channels

“…However, their use in pain management is limited because of their poor absorption, poor stability (Craik and Adams, 2007) and frequently reported adverse actions and side effects in clinical trials (Schmidtko et al, 2010). Although case studies provide support for the use of ω-conotoxin MVIIA (ziconotide) in combination with morphine, baclofen or hydromorphone (Jaggi et al, 2011), strong evidence-based data are limited (Wallace et al, 2010). Better tolerated, improved and/or new N-type VGCC inhibitors are needed to help form the next generation of drugs to treat chronic pain.…”