Chemical Stability of Admixtures Combining Ziconotide With Baclofen During Simulated Intrathecal Administration

Ziconotide: a clinical update and pharmacologic review

“…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.…”

Ziconotide Combination Intrathecal Therapy: Rationale and Evidence

“…46 In vitro studies have been conducted to assess the stability of ziconotide when it is combined with a number of commonly used IT drugs. [23][24][25][26][27][28] Results from these studies show that the presence of other IT drugs often decreases the stability of ziconotide (Table 3). Ziconotide is more stable when combined with 1000 mcg/mL of either of the opioids fentanyl or sufentanil (90% stable for 26 and 33 days, respectively) 28 than it is when combined with 35 mg/mL of the opioid hydromorphone (90% stable for 19 d; Table 3), 24 suggesting that the stability of ziconotide varies depending on the IT agent with which it is combined.…”

“…6,14-22 (T. Deer, MD, unpublished data, March 2009) Although not detailed in this review, studies have also been conducted to specifically characterize the stability of ziconotide when combined with various IT drugs. [23][24][25][26][27][28] Ziconotide and Morphine Combination Therapy…”

“…Ziconotide is more stable when combined with 1000 mcg/mL of either of the opioids fentanyl or sufentanil (90% stable for 26 and 33 days, respectively) 28 than it is when combined with 35 mg/mL of the opioid hydromorphone (90% stable for 19 d; Table 3), 24 suggesting that the stability of ziconotide varies depending on the IT agent with which it is combined. In addition, results from the ziconotide and morphine stability studies show that increasing the concentration of morphine decreases the stability of ziconotide (90% stability was retained for 34, 19, or 8 d when combined with 10, 20, or 35 mg/mL morphine, respectively; Table 3) 23,24 ; further studies are needed to determine whether the relationship between the stability of ziconotide and the concentration of an adjunctive drug holds true for drugs other than morphine. Although more frequent pump refills will likely be required by patients treated with ziconotide combination therapy than by patients treated with ziconotide monotherapy, the frequency of pump refills could be decreased by using low concentrations of concomitant IT agents and by using powdered, rather than formulated, concomitant drugs.…”

“…There is a need for additional evidence-based investigations of ziconotide combination therapies, including long-term clinical trials. 25 20 Clonidine hydrochloride (2 mg/mL)w 26 >60 (extrapolated) Bupivacaine hydrochloride (5 mg/mL)w 27 22 Morphine sulfate (35 mg/mL)w+clonidine hydrochloride (2 mg/mL)w 26 6 Hydromorphone hydrochloride (35 mg/mL)w 24 19 Fentanyl citrate (1000 mcg/mL)w 28 26 Sufentanil citrate (1000 mcg/mL)w 28 33 *Time (in days) that the ziconotide concentration remained 90% of initial concentration.…”