Peptide education
Ziconotide
Prialt · Ziconotide acetate
Ziconotide is a non-opioid prescription medicine for severe chronic pain. The U.S. product Prialt is reserved for adults whose pain warrants delivery into spinal fluid after other therapies have failed or caused unacceptable effects. It is administered through an intrathecal infusion device.
In a 3-week trial using slower titration, mean pain-score improvement was 14.7% with ziconotide and 7.2% with placebo. Dizziness, confusion, balance changes, and memory problems were among the adverse events reported with treatment.
Overview
Quick answer
Intrathecal delivery means the medicine reaches the fluid around the spinal cord. Prialt is not for intravenous administration. Its boxed warning addresses severe psychiatric symptoms and neurological impairment, and use is contraindicated in people with a preexisting history of psychosis.
Who is Prialt intended for?
The label covers adults whose severe, persistent pain warrants spinal-fluid infusion after other treatments have failed or proved intolerable. Those treatments include systemic analgesics, adjunctive therapies, and intrathecal morphine.
How is it delivered?
Prialt is infused into spinal fluid using a microinfusion device under the direction of a clinician experienced with intrathecal administration. It is not intended for an intravenous drip.
What does the U.S. label say about dosing?
The initial infusion is no more than 2.4 mcg per day. The label allows increases of up to 2.4 mcg per day no more than two or three times per week, according to response and adverse effects; its recommended maximum is 19.2 mcg per day.
What psychiatric risks matter?
Severe psychiatric symptoms or neurological impairment can occur. The label calls for frequent monitoring of cognition, hallucinations, mood, and consciousness, and excludes patients with a preexisting history of psychosis.
Is it an opioid?
No. Prialt is a non-opioid analgesic that binds N-type calcium channels. Its different drug class does not remove the need to monitor its own adverse effects.
Evidence
Evidence snapshot
Intrathecal treatment must be warranted after other treatments are not tolerated or have not worked.
Mean improvement in pain intensity at 3 weeks, ziconotide versus placebo.
Mean pain-score improvement in 108 evaluable patients after an initial 5-to-6-day titration, ziconotide versus placebo, in a separate rapidly titrated study.
The label warns about neuropsychiatric reactions and infection associated with the infusion system, including meningitis.
Claims
Common claims vs evidence
| Claim | Human evidence | Mechanistic evidence | Verdict |
|---|---|---|---|
| Intrathecal ziconotide can reduce severe pain. | Two placebo-controlled studies found greater average pain-score improvement with ziconotide, using different populations and titration schedules. | The drug binds N-type calcium channels in spinal pain pathways. The label says its mechanism of action in humans has not been established. | Supported for the selected severe chronic pain population in the label. |
| Non-opioid means free of serious neurological effects. | Confusion, hallucinations, changes in consciousness, and other neurological effects are addressed in the label's boxed warning. | False. The safety risks differ from opioid risks but remain significant. | |
| An intravenous injection is equivalent to the spinal infusion used in trials. | The studies and approved product use intrathecal infusion. The label says Prialt is not intended for intravenous administration. | No. Route and infusion-device controls are part of the treatment. |
Bottom line
Main takeaway
Prialt is delivered into spinal fluid for selected adults with severe chronic pain and needs close psychiatric and neurological monitoring.
The label sets a maximum starting rate, a titration limit, and a recommended maximum; the medicine is not for intravenous use.
The cancer or AIDS study used an accelerated titration, while the later 3-week study used a slower schedule and reported a smaller mean pain-score difference.
Identity
What it is
Ziconotide is a synthetic 25-amino-acid peptide modeled on a naturally occurring conopeptide. Prialt is a sterile solution for an intrathecal pump.
The label describes a non-opioid analgesic for selected adults with severe chronic pain, not a routine injection for ordinary pain.
Use context
Routes, doses, and cycle patterns
Prialt is delivered through an intrathecal device with dosing adjusted to response and adverse effects.
Human studies and product labels
Prialt U.S. label
- Purpose
- Severe chronic pain in selected adults
- Context
- Label-reported prescription use
- Route
- Continuous intrathecal infusion through a microinfusion device
- Amount
- Start at no more than 2.4 mcg/day; recommended maximum 19.2 mcg/day
- Frequency
- Increases of up to 2.4 mcg/day no more than 2 to 3 times per week
An experienced clinician directs administration and adjusts the dose to response and adverse effects.
Slower-titration chronic pain trial
- Purpose
- Change in pain intensity
- Context
- Randomized placebo-controlled study
- Route
- Intrathecal infusion
- Amount
- Initial rate 0.1 mcg/hour, equivalent to 2.4 mcg/day
- Frequency
- Gradual increases over 3 weeks
- Duration
- 3-week controlled comparison
Mean pain-score improvement was 14.7% versus 7.2% with placebo.
Cancer or AIDS pain trial
- Purpose
- Pain intensity after initial titration
- Context
- Randomized placebo-controlled study with faster titration
- Route
- Intrathecal infusion
- Amount
- An early cohort began at 0.4 mcg/hour; a later cohort began at 0.1 mcg/hour or less after the protocol was changed.
- Frequency
- Early increases were every 12 hours; later increases were once every 24 hours.
- Duration
- Initial titration over 5 to 6 days
The study used a faster titration than the current label describes.
Research
Research evidence
Randomized trials found greater average pain-score reductions than placebo in severe pain populations. The trials used different starting rates, titration speeds, populations, and follow-up periods, so their percentages are not interchangeable estimates for an individual patient.
| Study / evidence area | Population | Design | Product context | Main outcome | Limitations | Weight |
|---|---|---|---|---|---|---|
| Slower-titration chronic pain trial | 220 randomized adults with severe chronic pain | Double-blind, placebo-controlled trial | Intrathecal infusion beginning at 2.4 mcg/day | Mean pain-score improvement at week 3 was 14.7% versus 7.2% with placebo. | The blinded comparison lasted 3 weeks; neurological adverse events occurred. | Strong |
| Cancer or AIDS-related pain trial | 111 randomized adults with refractory pain and cancer or AIDS; 108 were evaluable (68 ziconotide, 40 placebo) | Double-blind, placebo-controlled trial | Intrathecal infusion with initial titration over 5 to 6 days | Mean pain-score improvement in the evaluable group was 53.1% with ziconotide versus 18.1% with placebo. | In the 111-patient intention-to-treat group, the figures were 51.4% versus 18.1%. Nearly all evaluable patients were taking opioids at baseline, and the initial comparison was short. | Strong |
Cautions
Safety and unknowns
- The boxed warning describes severe psychiatric symptoms and neurological impairment. A preexisting history of psychosis is a contraindication.
- Prialt is also contraindicated in people with hypersensitivity to ziconotide or its ingredients, or with another treatment or condition that makes intrathecal administration hazardous. Examples include infection at the infusion site, an uncontrolled bleeding disorder, or spinal canal obstruction that impairs spinal-fluid circulation.
- Dizziness, confusion, abnormal gait, memory problems, somnolence, and other neurological effects are listed in the label. Serious changes require prompt clinical assessment.
- Prialt may cause or worsen depression, including suicidal thoughts or behavior. The label calls for monitoring changes in mood and mental status.
- The label does not recommend combining Prialt with intrathecal opioids. Other medicines, including sedatives, can increase the risk of reduced alertness.
- Meningitis can occur through contamination or infection involving the infusion device or catheter. The label reports a higher risk with external systems.
- Creatine kinase (CK), an enzyme measured to assess muscle injury, can rise during treatment. The label recommends periodic CK monitoring, for example every other week for the first month and monthly as appropriate afterward. New muscle symptoms or reduced physical activity call for clinical assessment and CK testing. The label reports two cases of acute kidney failure associated with rhabdomyolysis, a severe breakdown of muscle, and very high CK.
- Pump programming errors or an incorrect concentration can cause overdose. The label calls for experienced clinicians and device-specific procedures.
Product quality
Product identity and quality
Prialt is a sterile intrathecal formulation used with an appropriate microinfusion device.
Route and device
The approved route is intrathecal; an incorrect route, concentration, or pump setting can cause harm.
Infection control
Device or catheter contamination can lead to meningitis.
Mechanism
How it is proposed to work
Ziconotide binds N-type calcium channels on pain-sensing nerve endings in the spinal cord. Animal findings suggest that this can reduce release of signals involved in pain; the label says the mechanism in humans is not established.
The drug does not bind opioid receptors, but it has its own psychiatric and neurological risks.
Details
Technical details
Sources
References
- 1.
DailyMed. Prialt prescribing information
- 2.
JAMA. Randomized intrathecal ziconotide trial in cancer or AIDS pain
doi:10.1001/jama.291.1.63 PMID:14709577
- 3.
PubMed. Randomized intrathecal ziconotide trial in cancer or AIDS pain, abstract
doi:10.1001/jama.291.1.63 PMID:14709577
- 4.
PubMed. Randomized slower-titration trial in severe chronic pain
doi:10.1016/j.jpainsymman.2005.10.003 PMID:16716870