Ziconotide (Prialt)

Summary

Ziconotide is an FDA approved synthetic cone snail peptide (Prialt, approved December 2004) given by continuous intrathecal infusion, a slow drip into the spinal fluid, through an implanted pump for severe chronic pain that has failed other treatments. In randomized trials, pain scores fell by about 15% to 53% more than placebo depending on how fast the dose was raised, and the drug carries a boxed warning, FDA's most serious label warning, for severe psychiatric symptoms and neurological impairment. It is available only through hospitals and pain clinics that manage intrathecal pumps, never as an injectable or oral product.

What is Ziconotide?

Ziconotide is a synthetic omega-conotoxin (25 amino acid peptide from the cone snail Conus magus), N-type calcium channel blocker. It is also known as Prialt, SNX-111, omega-conotoxin MVIIA, ziconotide intrathecal.

How does it work?

Ziconotide blocks N-type voltage gated calcium channels on the presynaptic terminals of primary nociceptive afferents in the dorsal horn of the spinal cord. This prevents the release of pain neurotransmitters such as glutamate, substance P, and CGRP. It does not act on opioid receptors, so it does not cause tolerance, respiratory depression, or dependence, but it must be delivered directly into cerebrospinal fluid because it does not cross the blood brain barrier.

FDA-approved uses of Ziconotide

Yes. Prialt was approved in December 2004. Its label covers the management of severe chronic pain in adults for whom intrathecal therapy (drug delivered into the spinal fluid) is warranted and who are intolerant of or refractory to (not helped by) other treatment, such as systemic analgesics (pain medicines taken by mouth or injection), adjunctive therapies, or intrathecal morphine. It is a non-opioid N-type calcium channel blocker, which blocks pain signals in the spinal cord, given only into the spinal fluid. [5]

What does the evidence say about Ziconotide?

Three randomized placebo controlled trials in about 590 patients with severe refractory pain. With fast titration, pain scores improved 53.1% versus 18.1% in cancer or AIDS pain (n = 111) and 31.2% versus 6.0% in non-malignant pain (n = 255), but adverse effects were frequent. With slow titration (n = 220), improvement was 14.7% versus 7.2%, statistically significant but modest. Psychiatric and cognitive adverse events limit use.

Human evidence

Staats 2004 (n = 111, cancer or AIDS pain): mean pain improvement 53.1% versus 18.1% on placebo, with 52.9% of ziconotide patients responding, but dizziness, nausea, nystagmus, and confusion were common with rapid titration. Wallace 2006 (n = 255, non-malignant pain): 31.2% versus 6.0% improvement. Rauck 2006 (n = 220, slow titration over 3 weeks to a mean 0.29 mcg per hour): 14.7% versus 7.2% improvement, with fewer severe adverse events. Long term open label data show that a subset of patients maintain benefit for years.

Animal evidence

Ziconotide produced dose dependent analgesia in rodent models of acute, inflammatory, and neuropathic pain when given intrathecally, without tolerance on repeated dosing. Animal work also established the N-type calcium channel mechanism and the lack of opioid receptor activity.

Key studies

Conditions studied

Is Ziconotide legal in the United States?

FDA and compounding status

FDA approved prescription drug (Prialt, approved December 28, 2004) for severe chronic pain in patients who need intrathecal therapy and are intolerant of or refractory to other treatments. Supplied as sterile solution for intrathecal pumps; hospital pharmacies may dilute it for pump filling. Not on any 503A bulks list and not sold as a research chemical for human use.

WADA status

Not WADA prohibited. Not named on the current prohibited list. Athletes should still confirm against the list in force for their season.

Regulatory timeline

1. Dec 28, 2004FDA

   FDA approves Prialt (ziconotide) for severe chronic pain

   FDA approved intrathecal ziconotide (Prialt), a synthetic cone snail peptide that blocks N-type calcium channels, for severe chronic pain in patients who need intrathecal therapy.

   Regulatory: FDA approvedSource: Drugs@FDA: Prialt (ziconotide) NDA 021060

Full tracker for Ziconotide or the category-wide tracker.

Ziconotide dose on the FDA label

Doses below are quoted from the FDA label for its approved uses, plus the doses used in the pivotal trials where noted. The prescriber sets the dose; PeptideAgent does not recommend doses or protocols.

FDA label (Prialt, DailyMed; intrathecal infusion through a programmable implanted or external microinfusion device, never intravenous): start at no more than 2.4 mcg per day (0.1 mcg per hour) and titrate by up to 2.4 mcg per day, no more than 2 to 3 times per week, to a recommended maximum of 19.2 mcg per day (0.8 mcg per hour) by day 21. The 25 mcg/mL strength is used undiluted; the 100 mcg/mL strength is diluted until a dose is established. The label carries a boxed warning for severe psychiatric symptoms and neurological impairment, and it is contraindicated with a history of psychosis.

Routes reported

What are the side effects and interactions of Ziconotide?

Side effects

Interactions

Contraindications

How do people access Ziconotide legally?

Typical cost: Drug cost is several thousand USD per month at list, plus the cost of pump implantation and refills. It is almost always billed through insurance as part of an intrathecal therapy program rather than paid in cash.

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Frequently asked questions

Decisions about starting, stopping, or combining any treatment belong with a licensed clinician who knows your history.

Sources

Numbered citations above point to these primary sources. PubMed entries link to the indexed abstract.