Do the potential benefits outweigh the risks? An update on the use of ziconotide in clinical practice

Abstract

Ziconotide is a selective and potent blocker of N-type voltage-gated calcium channels. It was approved by the Food and Drug Administration in 2004 and by the European Medicines Agency in 2005 for the treatment of severe chronic pain in patients needing intrathecal analgesia (ITA). The aim of this paper is to provide a practitioner-oriented, educational, narrative, up-to-date review on the use of ziconotide in clinical pain medicine. Of special concern regarding safety is the partial incongruity between dosing statements in the Summary of Product Characteristics and novel low-dosage, slow uptitration recommendations. Even though ziconotide has obvious advantages compared to opioids, pain practitioners pondering the use of ziconotide nonetheless have to balance its proved potential analgesic effect against its neurological side effects, with special consideration being given to dosing and neuropsychiatric dangers. Using a seesaw analogy, the paper discusses what factors pain physicians should weigh in when considering ziconotide as ITA drug, the non-opioid advantages of ziconotide being counterbalanced by its potential psychiatric side effects. Ziconotide is an important part of the armamentarium of modern interventional pain medicine. If ITA is deemed necessary, ziconotide is a rational alternative, at least in chronic (neuropathic) non-cancer pain. However, in many European countries, ziconotide treatment is only available in a few (if any) centres. The safety profile of ziconotide is not fundamentally more worrying than that of opioids or cannabinoids; it is just different. This paper provides a concise, up-to-date and clinically-oriented summary of the use of ziconotide in clinical practice, not least concerning safety and dosage issues.

Ziconotide for spinal cord injury‐related pain

“…This implies that while for some patients discontinuation of treatment may be avoided by slower titrations in others this is unavoidable rendering ITZ unusable for them. Newer recommendation on the use of ITZ (Bäckryd, ) are in the sense of slow titration and the low rate of drug related adverse effects (none declared by the patients in the post‐implantation period) are probably related to this prudent use of the drug.…”

Animal toxins — Nature’s evolutionary-refined toolkit for basic research and drug discovery

“…Ziconotide is administered by intrathecal infusion, which limits its use to patients with intractable chronic pain that have failed on frontline analgesic drugs such as morphine. While ziconotide set a landmark as the first venom-derived drug with a neuronal target, its limited market acceptance due to its mode of administration and neuropsychiatric side-effects [237] has caused venom researchers to focus attention on analgesic targets in peripheral nociceptors rather than central neurons, as outlined in Section 4.2.…”

Intrathecal pain management with ziconotide: Time for consensus?

“…Morphine ITA was the gold standard for several years but ziconotide ITA has been far more widely investigated (reviewed in Bäckryd, 2018; Deer et al., 2019). With a greater depth of data comes a clear understanding of the potential position of this agent in the severe, refractory pain‐management paradigm.…”

“…Trialing ziconotide ITA using an external syringe pump is a widely used strategy (reviewed in Bäckryd, 2018), but there are concerns about this approach. Firstly, no external pump can reproduce the efficiency of an internal drug‐delivery system for ITA: syringe pumps exhibit different flow rates, which alter the pharmacodynamic parameters of ziconotide and therefore affect its efficacy and tolerability responses, as indicated for bolus dosing above.…”