Ziconotide

Ziconotide binds to N-type calcium channels located on the primary nociceptive (A-δ and C) afferent nerves in the superficial layers (Rexed laminae I and II) of the dorsal horn in the spinal cord. Although the mechanism of action of ziconotide has not been established in humans, results in animals suggest that its binding blocks N-type calcium channels, which leads to a blockade of excitatory neurotransmitter release from the primary afferent nerve terminals and antinociception.

• PRIALT (ziconotide) solution, intrathecal infusion is indicated for the management of severe chronic pain in adult patients for whom intrathecal therapy is warranted, and who are intolerant of or refractory to other treatment, such as systemic analgesics, adjunctive therapies, or intrathecal morphine. PRIALT (ziconotide) solution, intrathecal infusion is an N-type calcium channel antagonist indicated for the management of severe chronic pain in patients for whom intrathecal therapy is warranted, and who are intolerant of or refractory to other treatment, such as systemic analgesics, adjunctive therapies, or intrathecal morphine.

• PRIALT is contraindicated in patients with a known hypersensitivity to ziconotide or any of its formulation components. PRIALT is contraindicated in patients with any other concomitant treatment or medical condition that would render intrathecal administration hazardous.contraindicated

PRIALT is a non-opioid and non-NSAID analgesic agent used for the management of severe and chronic pain. Administer PRIALT intrathecally by or under the direction of a physician experienced in the technique of intrathecal administration and who is familiar with the drug and device labeling. ( 2 ) PRIALT is not for intravenous administration. ( 2.1 ) PRIALT is delivered using a programmable implanted variable-rate microinfusion device or an external microinfusion device and catheter. ( 2.1 ) PRIALT 25 mcg/mL is used undiluted. The 100 mcg/mL formulation must be used diluted until an appropriate dose has been established. ( 2.1 ) Saline solutions containing preservatives must not be used. ( 2.1 ) Refrigerate but do not freeze all PRIALT solutions after preparation. Begin infusion within 24 hours. ( 2.1 ) Initiate PRIALT at no more than 2.4 mcg/day (0.1 mcg/hr) and titrated to patient response. Doses may be titrated upward by up to 2.4 mcg/day (0.1 mcg/hr) at intervals of no more than 2–3 times per week, up to a recommended maximum of 19.2 mcg/day (0.8 mcg/hr) by Day 21. ( 2 ) 2.1 General Information PRIALT is intended for administration by or under the direction of a physician experienced in the technique of intrathecal administration and who is familiar with the drug and device labeling. PRIALT is not intended for intravenous administration. PRIALT is intended for intrathecal delivery using the Medtronic SynchroMed ® II and SynchroMed ® III Infusion System [ see Warnings and Precautions ( 5.2 ) ].

Cognitive and neuropsychiatric adverse reactions – Cognitive impairment and severe neuropsychiatric symptoms may occur with PRIALT use. ( 5.1 ) Meningitis and other infections – Patients, caregivers, and healthcare providers must be aware of the signs and symptoms of meningitis, including but not limited to fever, headache, stiff neck, altered mental status (e.g., lethargy, confusion, disorientation), nausea or vomiting, and occasionally seizures. ( 5.2 ) Reduced level of consciousness – Patients may become unresponsive or stuporous while receiving PRIALT. ( 5.3 ) Elevation of serum creatine kinase – Patients taking PRIALT may experience elevations in creatine kinase. Monitor serum CK in patients undergoing treatment with PRIALT periodically. ( 5.4 ) Withdrawal from opiates : Patients must not be abruptly withdrawn from opiates and must be gradually tapered over a few weeks and replaced with a pharmacologically equivalent dose of oral opiates. ( 5.5 ) 5.1 Cognitive and Neuropsychiatric Adverse Reactions Severe psychiatric symptoms and neurological impairment may occur during treatment with PRIALT. PRIALT is contraindicated in patients with a pre-existing history of psychosis. Monitor all patients frequently for evidence of cognitive impairment, hallucinations, or changes in mood or consciousness. PRIALT therapy can be interrupted or discontinued abruptly without evidence of withdrawal effects in the event of serious neurological or psychiatric signs or symptoms.

The most frequently reported adverse reactions (≥ 25%) in clinical trials were dizziness, nausea, confusional state, nystagmus. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact TerSera Therapeutics at 1-844-344-4035 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates in clinical practice. A total of 1254 adult patients received PRIALT as a continuous infusion in acute and severe chronic pain trials with an exposure of 662 patient-years. The mean duration of treatment was 193 days with 173 patients (14%) treated for at least 1 year. The average final dose was 17.6 mcg/day (0.73 mcg/hr). The most frequently reported adverse reactions (≥ 25%) in clinical trials were dizziness, nausea, confusional state and nystagmus. Slower titration of PRIALT may result in fewer serious adverse reactions and discontinuation of PRIALT for adverse reactions [ see Clinical Studies ( 14 ) and Dosage and Administration ( 2 ) ]. Adverse reactions during the slow titration placebo-controlled trial that occurred in 5% or greater of patients and more commonly with PRIALT than with placebo are summarized in Table 1 . Table 1.

Geriatric Use : There is a higher incidence of confusion in elderly patients. The dose selection for an elderly patient should be cautious, starting at the low end of the dosing range. ( 8.5 ) 8.1 Pregnancy Risk Summary Available data from postmarketing reports are insufficient to identify a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In an animal reproduction study, ziconotide did not cause embryo-fetal toxicity when administered to pregnant rats and rabbits during the period of organogenesis by continuous intravenous infusion at 400- and 940-times, respectively, the maximum recommended human dose (MRHD) of 19.2 mcg/day. In a pre- and post-natal development study, ziconotide did not affect pup development or reproductive performance when administered to rats by continuous intravenous infusion at 3800-times the MRHD (see Data ) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Metabolism

The cerebrospinal fluid (CSF) pharmacokinetics (PK) of ziconotide have been studied after one-hour intrathecal infusions of 1 to 10 mcg of PRIALT to patients with chronic pain. The plasma PK following intravenous infusion (0.3 to 10 mcg/kg/day) have also been studied.

The maximum recommended intrathecal PRIALT dose is 19.2 mcg/day. The maximum intrathecal dose of PRIALT in clinical trials was 912 mcg/day. In some patients who received intrathecal doses greater than the maximum recommended dose, exaggerated pharmacological effects (e.g., ataxia, nystagmus, dizziness, stupor, unresponsiveness, spinal myoclonus, confusion, sedation, hypotension, word-finding difficulties, garbled speech, nausea, and vomiting) were observed. There was no indication of respiratory depression. Overdoses may occur due to pump programming errors or incorrect drug concentration preparations. In these cases, patients were observed and ziconotide was either temporarily discontinued or permanently withdrawn. Most patients recovered within 24 hours after withdrawal of drug. In the event of an overdose, elimination of ziconotide from CSF would be expected to remain constant (CSF t ½ =4.6 hours). Therefore, within 24 hours of stopping therapy, the ziconotide CSF concentration should be less than 5% of peak levels. There is no known antidote to ziconotide.

• Dec 28, 2004NDANDA021060Esteve

1. 1Pain36215%
2. 2Device Issue31313%
3. 3Off Label Use30012%
4. 4Drug Ineffective2419.9%
5. 5Confusional State2048.4%
6. 6Nausea2048.4%
7. 7Hallucination1666.8%
8. 8Dizziness1576.5%
9. 9Headache1365.6%
10. 10Hallucination, Auditory1335.5%
11. 11Memory Impairment1044.3%
12. 12Fall1014.2%
13. 13Vomiting984.0%
14. 14Somnolence953.9%
15. 15Drug Withdrawal Syndrome913.7%

The 10 most recently updated of 13 ClinicalTrials.gov registrations naming Ziconotide as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Intrathecal Ziconotide in Chemotherapy Induced Peripheral Neuropathy
  Not yet recruiting · Observational · 24 enrolled · Christian Hospital Northeast Northwest
  NCT07499882updated 2026-03-30
• OP2C : Prialt® Observatory in Clinical Practice
  Recruiting · Observational · 300 enrolled · Institut Cancerologie de l'Ouest
  NCT04321408updated 2025-08-17
• Ziconotide for Non-cancer Pain by Intrathecal Administration
  Recruiting · Observational · 85 enrolled · ESTEVE Pharmaceuticals SAS
  NCT06541184updated 2025-02-27
• Safety and Activity Study of Intrathecally Administered Ziconotide for Neuropathic Pain in Patients With Cancer
  Unknown · Phase 2 · Interventional · 16 enrolled · National Cancer Institute, Naples
  NCT00996983updated 2023-03-24
• Ziconotide as First-Line IDT
  Completed · Phase 4 · Interventional · 13 enrolled · Albany Medical College
  NCT03321955updated 2021-01-12
• Intrathecal Ziconotide Antalgic Efficacy for Severe Refractory Neuropathic
  Unknown · Phase 3 · Interventional · 44 enrolled · Hospices Civils de Lyon
  NCT03942848updated 2019-05-08
• Patient Registry of Intrathecal Pain Management in Europe for Prialt (Ziconotide Intrathecal Infusion) and Alternative Drugs for the Management of Severe, Chronic Pain.
  Completed · Observational · 219 enrolled · Eisai Limited
  NCT02268812updated 2018-10-25
• Single Shot Intrathecal Ziconotide for Painful Neuropathy or Myelopathy
  Withdrawn · Phase 4 · Interventional · 0 enrolled · Aaron Boster
  NCT01992562updated 2018-09-18
• Patient Registry of Intrathecal Ziconotide Management(PRIZM)
  Completed · Observational · 93 enrolled · Jazz Pharmaceuticals
  NCT01888120updated 2017-03-16
• Prialt (Ziconotide) In Severe Chronic Pain
  Completed · Phase 3 · Interventional · 220 enrolled · Elan Pharmaceuticals
  NCT00047749updated 2015-12-14

Frequently asked questions

How does Ziconotide work?

Ziconotide binds to N-type calcium channels located on the primary nociceptive (A-δ and C) afferent nerves in the superficial layers (Rexed laminae I and II) of the dorsal horn in the spinal cord. Although the mechanism of action of ziconotide has not been established in humans, results in animals suggest that its binding blocks N-type calcium channels, which leads to a blockade of excitatory neurotransmitter release from the primary afferent nerve terminals and antinociception.

What is Ziconotide used for?

According to FDA labeling, Ziconotide carries indications including: PRIALT (ziconotide) solution, intrathecal infusion is indicated for the management of severe chronic pain in adult patients for whom intrathecal therapy is warranted, and who are intolerant of or refractory to other treatment, such as systemic analgesics, adjunctive therapies, or intrathecal morphine. PRIALT (ziconotide) solution, intrathecal infusion is an N-type calcium channel antagonist indicated for the management of severe chronic pain in patients for whom intrathecal therapy is warranted, and who are intolerant of or refractory to other treatment, such as systemic analgesics, adjunctive therapies, or intrathecal morphine.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Ziconotide?

Ziconotide is classified as Other analgesics and antipyretics, N-type Calcium Channel Antagonist, N-Calcium Channel Receptor Antagonists, Neurotransmitter & Neuromuscular Transmitter Activity Alteration.

What are the brand names for Ziconotide?

Ziconotide is marketed under brand names including Prialt.

What are the contraindications for Ziconotide?

Ziconotide labeling lists contraindications including: PRIALT is contraindicated in patients with a known hypersensitivity to ziconotide or any of its formulation components. PRIALT is contraindicated in patients with any other concomitant treatment or medical condition that would render intrathecal administration hazardous.. Always consult the full prescribing information and a clinician.