Ziconotide acetate is available as a 100-mcg/mL solution in 1- and 5-mL single-use vials and as a 25-mcg/mL solution in 20-mL single-use vials.3167 The formulation also contains L-methionine and sodium chloride excipients, but is preservative free.3167
pH
From 4 to 5.3167
Osmolarity
Ziconotide acetate in sodium chloride 0.9% at concentrations ranging from 0.25 to 1 mcg/mL had an osmolarity of 308 mOsm/L.3170
Trade Name(s)
Prialt
Ziconotide acetate is administered intrathecally either undiluted (using the 25-mcg/mL solution) or diluted (using the 100-mcg/mL solution) using a programmable implanted variable-rate microinfusion device or an external microinfusion device and catheter.3167 The 100-mcg/mL solution must be diluted only in preservative-free sodium chloride 0.9%; saline solutions containing preservatives are not appropriate for intrathecal drug administration.3167 Once an appropriate dose has been established, the 100-mcg/mL solution may be administered undiluted.3167
The drug is intended for use only with the Medtronic SynchroMed II Infusion System or the CADD-Micro Ambulatory Infusion Pump.3167
When using the Medtronic SynchroMed II Infusion System, only the undiluted 25-mcg/mL solution should be used for the initial priming of a new pump.3167 Three 2-mL rinses of the internal surfaces of the new pump should be performed using the undiluted 25-mcg/mL solution.3167 After performing the initial rinses of a new pump, only the undiluted 25-mcg/mL solution should be used for the first fill of the pump.3167 The new pump should be refilled within 14 days of the first fill in order to ensure appropriate dose administration because of initial losses of the drug due to both sorption to titanium internal surfaces and dilution in the residual space of the pump.3167 Losses resulting from these 2 factors do not occur upon subsequent refill.3167 For subsequent refills, the pumps should be filled at least every 84 days if the drug is used undiluted or at least every 40 days if the drug is diluted.3167 The remaining pump contents should be emptied prior to refilling.3167 A Medtronic refill kit should be used to ensure aseptic transfer of the drug solution into the pump.3167 The pump manufacturer's manual should be consulted for specific instructions and precautions on rinsing the reservoir, initial filling of the reservoir, refilling the reservoir, and programming the infusion system.3167
When using the CADD-Micro Ambulatory Infusion Pump, the pump initially should be filled with ziconotide acetate solution that has been diluted in preservative-free sodium chloride 0.9% to a concentration of 5 mcg/mL.3167 The pump manufacturer’s manual should be consulted for specific instructions and precautions on initial filling of the reservoir, refilling the reservoir or replacing the drug cartridge, and operation of the pump.3167
Ziconotide acetate injection is not intended for intravenous administration.3167
Intact vials of ziconotide acetate should be stored under refrigeration and protected from light and freezing.3167 Ziconotide acetate diluted in preservative-free sodium chloride 0.9% may be stored at 2 to 8°C for up to 24 hours prior to beginning the infusion.3167
pH Effects
In a study evaluating the influence of pH and temperature on the stability of ziconotide, admixtures of ziconotide acetate, morphine sulfate, and ropivacaine hydrochloride were prepared in a range of concentrations and stored in syringes (Plastipak, BD) at 4 or 20°C or Medtronic SynchroMed II pumps at 37°C.3168 The resulting pH of the admixtures was influenced by the morphine concentration and the storage temperature.3168 Admixtures with lower morphine concentrations resulted in a higher pH; admixtures stored at lower temperatures resulted in a lower pH.3168 Ziconotide prepared in admixtures with lower morphine concentrations and stored at 37°C demonstrated improved ziconotide stability.3168 Admixtures with a pH exceeding 4.5 demonstrated improved ziconotide stability compared with admixtures with a pH less than 4.5.3168
Ambulatory Pumps
Ziconotide acetate is intended for use with the CADD-Micro Ambulatory Infusion Pump.3167
Implantable Pumps
Ziconotide acetate is intended for use with the Medtronic SynchroMed II Infusion System.3167 The manufacturer of ziconotide states that the initial fill of a new pump with 25 mcg/mL of undiluted solution expires in 14 days; subsequent refills with undiluted 25- or 100-mcg/mL solutions of the drug expire in 84 days.3167 Refills using diluted solutions prepared from the 100-mcg/mL formulation of the drug expire in 40 days.3167
In November 2012, Medtronic Neuromodulation warned that intermittent or permanent pump motor stalling due to corrosion has occurred in SynchroMed infusion systems after use of unapproved drugs and drug formulations (i.e., drugs not listed in the device's labeling, including admixtures, compounded drugs, and unapproved drug concentrations).3169 Medtronic has confirmed through returned product analysis and in vitro testing that such permanent pump motor stalling has been caused by admixtures containing drugs such as baclofen, bupivacaine, clonidine, fentanyl, hydromorphone, morphine, and sufentanil.3169 Some antimicrobial or antioxidant preservatives (e.g., sodium metabisulfite) are known to cause pump damage, while some admixtures may have increased the rates of permeation of corrosive agents; admixtures with a pH of 3 or less and those requiring additives to maintain the solubility of a particular concentration also may not be compatible with the infusion system.3169 Pump problems from previous use of an unapproved drug formulation may persist even if an approved drug formulation is used subsequently.3169 Medtronic states that only those drugs and drug formulations for which the SynchroMed infusion system is approved should be used to minimize the potential for damage to the internal pump components.3169
Clonidine hydrochloride and morphine sulfate powders were dissolved in ziconotide acetate (Elan) injection to yield concentrations of 2 and 35 mg/mL and 25 mcg/mL, respectively.2752 Stored at 37°C in Medtronic SynchroMed II pumps, 11% ziconotide loss in 7 days, 4% clonidine loss in 20 days, and no morphine loss in 28 days occurred.2752
For a list of references cited in the text of this monograph, search the monograph titled References.