PRIALT ziconotide acetate 500 ug/5mL Injection, Solution
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the N-type Calcium Channel Antagonist class.
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UNII AE28F7PNPL
Methionine is an amino acid used as a nutrient supplement and pH buffer in medicines. It helps stabilize the formulation and supports the product's overall composition.
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UNII 451W47IQ8X
Sodium chloride is common table salt. It's used in medicines as a buffer to maintain proper pH, as a filler to add bulk, or to adjust the osmotic balance in liquid formulations.
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| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Prialt 500 ug/5mLthis 68118-0722-10 | ESTEVE | 1 vial | — | — | FDA listed | — |
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 68118-0722-10 You're viewing this | 1 VIAL, GLASS in 1 CARTON (68118-722-10) / 5 mL in 1 VIAL, GLASS | 2019-08-15 | Active |
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| FDA label (SPL via DailyMed) | ✓ Available |
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| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
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| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: NEUROPSYCHIATRIC ADVERSE REACTIONS PRIALT is contraindicated in patients with a preexisting history of psychosis. Severe psychiatric symptoms and neurological impairment may occur during treatment with PRIALT. Monitor all patients frequently for evidence of cognitive impairment, hallucinations, or changes in mood or consciousness.
Discontinue PRIALT therapy in the event of serious neurological or psychiatric signs or symptoms. WARNING: NEUROPSYCHIATRIC ADVERSE REACTIONS See full prescribing information for complete boxed warning Severe psychiatric symptoms and neurological impairment may occur during treatment with PRIALT. Do not treat patients with a pre-existing history of psychosis with PRIALT
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE 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.
( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION 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 )
2.1General 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 ) ].
Refer to the manufacturer's manual for specific instructions and precautions for programming the microinfusion device and/or refilling the reservoir. PRIALT may be used for therapy undiluted (25 mcg/mL in 20 mL vial) or diluted (100 mcg/mL in 1 or 5 mL vials). The 100 mcg/mL formulation may be administered undiluted once an appropriate dose has been established.
Dilute PRIALT with 0.9% Sodium Chloride Injection, USP (preservative free) using aseptic procedures to the desired concentration prior to placement in the microinfusion pump. Saline solutions containing preservatives are not appropriate for intrathecal drug administration and should not be used due to risk of neurotoxicity. Refrigerate but do not freeze all PRIALT solutions after preparation and begin infusion within 24 hours.
Inspect vials of PRIALT visually for particulate matter and discoloration prior to administration whenever solution and container permit. Discard any PRIALT solution with observed particulate matter or discoloration and any unused portion left in the vial.
2.2Dosing Dose Initiation Initiate dosing with PRIALT via intrathecal device at no more than 2.4 mcg/day (0.1 mcg/hr). Dose Titration Titrate doses by up to 2.4 mcg/day (0.1 mcg/hr) at intervals of no more than 2 to 3 times per week based on analgesic response and adverse events. Dose increases in increments of less than 2.4 mcg/day (0.1 mcg/hr) and less frequently than 2 to 3 times per week may be used.
For each dose titration, assess the dosing requirements and adjust the pump infusion flow rate as required to achieve the new dosing. The maximum recommended dose is 19.2 mcg/day (0.8 mcg/hr). Adjust the dose of intrathecal PRIALT according to the severity of pain, the patient's response to therapy, and the occurrence of adverse reactions.
2.3Instructions for Use with the Medtronic SynchroMed II and SynchroMed III Infusion System Refer to the manufacturer's manuals for specific instructions and precautions for performing a reservoir rinse, initial filling, refilling the reservoir, and programming. [ see Warnings and Precautions ( 5.2 ) ] Naïve Pump Priming (i.e., first time use with PRIALT) Use only the undiluted 25 mcg/mL formulation for naïve pump priming. Rinse the internal surfaces of the pump with 2 mL of PRIALT at 25 mcg/mL. Repeat twice for a total of three rinses.
Initial Pump Fill Use only the undiluted 25 mcg/mL formulation for the initial pump fill . Fill the na…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS PRIALT (ziconotide) solution, intrathecal infusion is supplied as a 25 mcg/mL concentration in single-use 20 mL glass vials and as a 100 mcg/mL concentration in single-use glass vials containing 1 mL or 5 mL of solution. Intrathecal solution ( 3 ): 25 mcg/mL 100 mcg/mL
⛔ Contraindications ▾
4 CONTRAINDICATIONS 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. Contraindications to the use of intrathecal analgesia include the presence of infection at the microinfusion injection site, uncontrolled bleeding diathesis, and spinal canal obstruction that impairs circulation of CSF.
PRIALT is contraindicated in patients with a pre-existing history of psychosis. Patients with a known hypersensitivity to ziconotide or any of its formulation components and in patients with any other concomitant treatment or medical condition that would render intrathecal administration hazardous. ( 4 ) Patients with a pre-existing history of psychosis with ziconotide.
( 4 ) Contraindications to the use of intrathecal analgesia include conditions such as the presence of infection at the microinfusion injection site, uncontrolled bleeding diathesis, and spinal canal obstruction that impairs circulation of cerebrospinal fluid (CSF). ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS 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 )
5.1Cognitive 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. Events of acute psychiatric disturbances such as hallucinations (12%), paranoid reactions (3%), hostility (2%), delirium (2%), psychosis (1%), and manic reactions (0.4%) have been reported in patients treated with PRIALT. Patients with pretreatment psychiatric disorders may be at an increased risk.
PRIALT may cause or worsen depression with the risk of suicide in susceptible patients. In placebo-controlled trials, there was a higher incidence of suicide, suicide attempts, and suicide ideations in PRIALT-treated patients than in the placebo group (0.27/patient year for PRIALT patients and 0.10/patient year for placebo patients). Management of psychiatric complications may need to include discontinuation of PRIALT, treatment with psychotherapeutic agents and/or short-term hospitalization.
Before drug is reinitiated, careful evaluation must be performed on an individual basis. Use of PRIALT has been associated with cognitive impairment and decreased alertness/unresponsiveness. The following cognitive adverse reaction rates were reported: confusion (33%), memory impairment (22%), speech disorder (14%), aphasia (12%), thinking abnormal (8%), and amnesia (1%).
Cognitive impairment may appear gradually after several weeks of treatment. Reduce the dose of PRIALT or discontinue the use of PRIALT if signs or symptoms of cognitive impairment develop, but other contributing causes must also be considered. The cognitive effects of PRIALT are generally reversible within 2 weeks after drug discontinuation.
The median time to reversal of the individual cognitive effects ranged from 3 to 15 days. The elderly (≥ 65 years of age) are at higher risk for confusion. [ see Use in Specific Populations ( 8.5 ) ] There may be additive effects on cognitive impairment and decreased alertness when PRIALT is used in conjunction with other CNS-depressant drugs that may necessitate dosage adjustments.
5.2Meningitis and Other Infections Meningitis can occur due to inadvertent contamination of the microinfusion device and other means such as CSF seeding due to hematogenous or direct spread from an infected pump pocket or catheter tract. While meningitis is rare with an internal microinfusion device and surgically-implanted catheter, the incidence increases substantially with external devices. In PRIALT clinical trials, meningitis occurred in 3% (40) of patients in the PRIALT group using either internal or external microinfusion devices and 1% (1 case) of patients in the plac…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS 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
6.1Clinical 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. Incidence of Adverse Reactions in Slow Titration Placebo-Controlled Trial by Percent (Events That Occurred in ≥ 5% of Patients and More Commonly with PRIALT than with Placebo) MedDRA System Organ Class MedDRA Preferred term PRIALT N=112 Placebo N=108 Percentage of Patients Any AE 93 82 Ear and Labyrinth Disorders Vertigo 7 0 Eye Disorders Vision Blurred 12 3 Gastrointestinal Disorders Diarrhea 18 15 Nausea 40 29 Vomiting 16 14 General Disorders and Administration Site Conditions Asthenia 18 6 Gait Abnormal 14 2 Pyrexia 5 3 Rigors 7 5 Infections and Infestations Sinusitis 5 2 Metabolism and Nutrition Disorders Anorexia 6 2 Musculoskeletal and Connective Tissue Disorders Muscle Spasms 6 4 Pain in Limb 5 2 Nervous System Disorders Amnesia 8 0 Ataxia 14 1 Dizziness 46 13 Dysarthria 7 0 Dysgeusia 5 5 Headache 13 11 Memory Impairment 7 1 Nystagmus 8 0 Somnolence 17 10 Tremor 7 3 Psychiatric Disorders Anxiety 8 3 Confusional State 15 5 Insomnia 6 9 Renal and Urinary Disorders Urinary Retention 9 0 Skin and Subcutaneous Disorders Pruritis 7 7 Sweating Increased 5 6 Other Adverse Reactions Observed During Clinical Studies of PRIALT The following adverse reactions assessed as related to PRIALT have been reported in 2% or greater of patients participating in the clinical studies: EYE DISORDERS: diplopia, visual disturbance GASTROINTESTINAL DISORDERS: abdominal pain, constipation, dry mouth, nausea aggravated GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS: fall, fatigue, lethargy, edema peripheral INVESTIGATIONS: blood creatine phosphokinase increased METABOLISM AND NUTRITION DISORDERS: appetite decreased MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS: muscle cramp, muscle weakness, myalgia, pain in limb NERVOUS SYSTEM DISORDERS: aphasia, areflexia, balance impaired, burning sensation, coordination abnormal, disturbance in attention, dizziness postural, dysarthria, dysgeusia, hypoaesthesia, mental impairment, paraesthesia, sedation, speech disorder PSYCHIATRIC DISORDERS: agitation, anxiety, cognitive disorder, confusional state, depression, depression aggravated, disorientation, hallucination, hallucination auditory, hallucination visual, insomnia, irritability, mood disorder, nervousness, paranoia RENAL AND URINARY DISORDERS: dysuria, urinary hesitation VASCULAR DISORDERS: hypotension, orthostatic hypotension.
The following medically important adverse reactions occurred in less than 2% of patients were assessed by the clinical investigators as related to PRIALT: acute renal failure , atrial fibrillation, cerebrovascular accident, sepsis, meningitis,…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Formal PK drug-drug interaction studies have not been performed with PRIALT. As ziconotide is a peptide, it is expected to be completely degraded by endopeptidases and exopeptidases (Phase I hydrolytic enzymes) widely located throughout the body, and not by other Phase I biotransformation processes (including the cytochrome P450 system) or by Phase II conjugation reactions. Thus, intrathecal administration, low plasma ziconotide concentrations, and metabolism by ubiquitous peptidases make metabolic interactions of other drugs with ziconotide unlikely.
Further, as ziconotide is not highly bound in plasma (approximately 50%) and has low plasma exposure following intrathecal administration, clinically relevant plasma protein displacement reactions involving ziconotide and co-administered medications are unlikely. Over 90% of patients treated with intrathecal PRIALT used systemic opiates and in the slow titration study, 98% of patients received opioids. The combination of PRIALT with intrathecal opiates has not been studied in placebo-controlled clinical trials and is not recommended.
Combination of PRIALT with intrathecal opiates is not recommended. ( 7 ) Patients taking concomitant antiepileptics, neuroleptics, sedatives, or diuretics may be at higher risk of depressed levels of consciousness. ( 5.3 ) The use of PRIALT may be associated with an increased incidence of CNS adverse reactions such as dizziness and confusion.
( 7.1 )
7.1Interaction with CNS Depressants Almost all patients in the PRIALT clinical trials received concomitant non-intrathecal medication. Most patients received several concomitant drugs, including antidepressants (66%), anxiolytics (52%), antiepileptics (47%), neuroleptics (46%), and sedatives (34%). The use of drugs with CNS-depressant activities may be associated with an increased incidence of CNS adverse reactions such as dizziness and confusion [ see Warnings and Precautions ( 5 ) ].
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS 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 )
8.1Pregnancy 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.
Data Animal Data Ziconotide caused embryo-fetal mortality in rats when given as a continuous intravenous infusion during the major period of organogenesis as evidenced by significant increases in post-implantation loss because of an absence or a reduced number of live fetuses. Estimated exposure for embryo-fetal mortality in the rat was approximately 700-fold above the expected exposure resulting from the maximum recommended human daily intrathecal dose of 0.8 mcg/hr (19.2 mcg/day). Ziconotide did not result in malformations when administered to pregnant rats by continuous intravenous infusion at doses up to 30 mg/kg/day or to pregnant rabbits up to 5 mg/kg/day during the major period of organ development.
Estimated exposures in the female rat and rabbit were approximately 26,000-fold and 940-fold higher than the expected exposure resulting from the maximum recommended human daily dose of 0.8 mcg/hr (19.2 mcg/day) based on plasma exposure. Maternal toxicity in the rat and rabbit, as evidenced by decreased body weight gain and food consumption, was present at all dose levels. Maternal toxicity in the rat led to reduced fetal weights and transient, delayed ossification of the pubic bones at doses ≥ 15 mg/kg/day, which is approximately 8900-fold higher than the expected exposure resulting from the maximum recommended human daily intrathecal dose of 0.8 mcg/hr (19.2 mcg/day) based on plasma exposure.
The no observable adverse effect level (NOAEL) for embryo-fetal development in rats was 0.5 mg/kg/day and in rabbits was 5 mg/kg/day. Estimated NOAEL exposures in the rat and rabbit were approximately 400-fold and 940-fold higher than the expected exposure resulting from the maximum recommended human daily intrathecal dose of 0.8 mcg/hr (19.2 mcg/day) based on plasma exposure. In a pre- and post-natal study in rats, ziconotide given as a continuous intravenous infusion did not affect pup development or reproductive performance up to a dose of 10 mg/kg/day, which is approximately 3800-fold higher than the expected exposure resulting from the maximum recommended human daily intrathecal dose of 0.8 mcg/hr (19.2 mcg/day) based on plasma exposure.
Maternal toxicity, as evidenced by clinical observations, and decreases in body weight gain and food consumption were observed at all doses.
8.2Lactation Risk Summary There are no data on the presence of ziconotide in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. Infants exposed to PRIALT through breast milk should be monitored for sedation which may result in respiratory depression and/or feeding problems. The developmental and health benefits of breastfeeding sho…
🤰 Pregnancy ▾
8.1Pregnancy 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.
Data Animal Data Ziconotide caused embryo-fetal mortality in rats when given as a continuous intravenous infusion during the major period of organogenesis as evidenced by significant increases in post-implantation loss because of an absence or a reduced number of live fetuses. Estimated exposure for embryo-fetal mortality in the rat was approximately 700-fold above the expected exposure resulting from the maximum recommended human daily intrathecal dose of 0.8 mcg/hr (19.2 mcg/day). Ziconotide did not result in malformations when administered to pregnant rats by continuous intravenous infusion at doses up to 30 mg/kg/day or to pregnant rabbits up to 5 mg/kg/day during the major period of organ development.
Estimated exposures in the female rat and rabbit were approximately 26,000-fold and 940-fold higher than the expected exposure resulting from the maximum recommended human daily dose of 0.8 mcg/hr (19.2 mcg/day) based on plasma exposure. Maternal toxicity in the rat and rabbit, as evidenced by decreased body weight gain and food consumption, was present at all dose levels. Maternal toxicity in the rat led to reduced fetal weights and transient, delayed ossification of the pubic bones at doses ≥ 15 mg/kg/day, which is approximately 8900-fold higher than the expected exposure resulting from the maximum recommended human daily intrathecal dose of 0.8 mcg/hr (19.2 mcg/day) based on plasma exposure.
The no observable adverse effect level (NOAEL) for embryo-fetal development in rats was 0.5 mg/kg/day and in rabbits was 5 mg/kg/day. Estimated NOAEL exposures in the rat and rabbit were approximately 400-fold and 940-fold higher than the expected exposure resulting from the maximum recommended human daily intrathecal dose of 0.8 mcg/hr (19.2 mcg/day) based on plasma exposure. In a pre- and post-natal study in rats, ziconotide given as a continuous intravenous infusion did not affect pup development or reproductive performance up to a dose of 10 mg/kg/day, which is approximately 3800-fold higher than the expected exposure resulting from the maximum recommended human daily intrathecal dose of 0.8 mcg/hr (19.2 mcg/day) based on plasma exposure.
Maternal toxicity, as evidenced by clinical observations, and decreases in body weight gain and food consumption were observed at all doses.
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established.
🧓 Geriatric Use ▾
8.5Geriatric Use Of the total number of subjects in clinical studies of PRIALT, 22% were 65 and over, while 7% were 75 and over. In all trials, there was a higher incidence of confusion in older patients (42% for ≥ 65 year old versus 29% for < 65 year old subgroups). Other reported clinical experience has not identified differences in responses between elderly and younger patients.
In general, the dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.
🆘 Overdosage ▾
10 OVERDOSAGE 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. General medical supportive measures should be administered to patients who receive an overdose until the exaggerated pharmacological effects of the drug have resolved. Treatment for an overdose is hospitalization, when needed, and symptom-related supportive care.
Ziconotide does not bind to opiate receptors and its pharmacological effects are not blocked by opioid antagonists. In the event of an inadvertent intravenous or epidural administration, adverse reactions could include severe hypotension, which can be treated with a recumbent posture and blood pressure support as required. The half-life of PRIALT in serum is 1.3 hours.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action 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.
12.2Pharmacodynamics Interaction with Opioids Ziconotide does not bind to opioid receptors and its pharmacological effects are not blocked by opioid antagonists. In animal models, intrathecal ziconotide potentiated opioid-induced reduction in gastrointestinal (GI) motility, but did not potentiate morphine-induced respiratory depression. In rats receiving ziconotide, additive analgesic effects were observed with concurrent administration of morphine, baclofen, or clonidine.
Concurrent administration of intrathecal ziconotide and morphine did not prevent the development of morphine tolerance in rats.
12.3Pharmacokinetics 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. Both intrathecal and intravenous data are shown below ( Table 2 ).
Table 2. PRIALT PK Parameters (Mean ± SD) Route Fluid N CL (mL/min) Vd (mL) T 1/2elim (hr) Intrathecal CSF 23 0.38 ± 0.56 155 ± 263 4.6 ±
0.9Intravenous Plasma 21 270 ± 44 30,460 ± 6366 1.3 ±
0.3Following one-hour intrathecal administration of 1 to 10 mcg of PRIALT, both total exposure (AUC; range: 83.6 to 608 ng•h/mL) and peak exposure (C max ; range: 16.4 to 132 ng/mL) values in the CSF were variable and dose-dependent, but appeared approximately dose-proportional. During 5 or 6 days of continuous intrathecal infusions of PRIALT at infusion rates ranging from 0.1 to 7.0 mcg/hr in patients with chronic pain, plasma ziconotide levels could not be quantified in 56% of patients using an assay with a lower limit of detection of approximately 0.04 ng/mL.
Predictably, patients requiring higher intrathecal infusion dose rates were more likely to have quantifiable ziconotide levels in plasma. Plasma ziconotide levels, when detectable, remain constant after many months of intrathecal PRIALT infusion in patients followed for up to 9 months. Distribution Ziconotide is about 50% bound to human plasma proteins.
The mean CSF volume of distribution (Vd) of ziconotide following intrathecal administration approximates the estimated total CSF volume (140 mL). Elimination Metabolism Ziconotide is cleaved by endopeptidases and exopeptidases at multiple sites on the peptide. Following passage from the CSF into the systemic circulation during continuous intrathecal administration, ziconotide is expected to be susceptible to proteolytic cleavage by various ubiquitous peptidases/proteases present in most organs (e.g., kidney, liver, lung, muscle, etc.), and thus readily degraded to peptide fragments and their individual constituent free amino acids.
Human and animal CSF and blood exhibit minimal hydrolytic activity toward ziconotide in vitro. The biological activity of the various expected proteolytic degradation products of ziconotide has not been assessed. Excretion Minimal amounts of ziconotide (< 1%) were recovered in human urine following intravenous infusion.
The terminal half-life of ziconotide in CSF after an intrathecal administration was around 4.6 hours (range 2.9 to 6.5 hours). Mean CSF clearance (CL) of ziconotide approximates adult human CSF turnover rate (0.3 to 0.4 mL/min). Specific Populations No formal studies were conducted to assess the effect of demographic factors (age, race, gender, and weight), renal or hepatic dysfunction, or to assess the effect of con…
🧬 Mechanism of Action ▾
12.1Mechanism of Action 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.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied PRIALT is supplied as a 25 mcg/mL solution in a single-use 20 mL glass vial and as a 100 mcg/mL solution in single-use glass vials containing 1 mL or 5 mL of solution. One vial is packaged per carton. Presentation (NDC) 25 mcg/mL: 20 mL vial (70720-723-10). Only the undiluted 25 mcg/mL formulation should be used for PRIALT naïve pump priming. 100 mcg/mL: 1 mL vial (70720-720-10) 5 mL vial (70720-722-10)
16.2Storage Refrigerate PRIALT during transit. Store PRIALT at 2°C to 8°C (36°F to 46°F). PRIALT, once diluted aseptically with saline, may be stored at 2°C to 8°C for 24 hours. Do NOT freeze PRIALT. Protect from light.
📦 Storage and Handling ▾
16.2Storage Refrigerate PRIALT during transit. Store PRIALT at 2°C to 8°C (36°F to 46°F). PRIALT, once diluted aseptically with saline, may be stored at 2°C to 8°C for 24 hours. Do NOT freeze PRIALT. Protect from light.
📋 Description ▾
11 DESCRIPTION PRIALT contains ziconotide, a synthetic equivalent of a naturally occurring conopeptide found in the piscivorous marine snail, Conus magus. Ziconotide is a 25 amino acid, polybasic peptide containing three disulfide bridges with a molecular weight of 2639 daltons and a molecular formula of C 102 H 172 N 36 O 32 S 7 . The amino acid sequence and disulfide bridging pattern are given below: Ziconotide is a hydrophilic molecule that is freely soluble in water and is practically insoluble in methyl t-butyl ether.
PRIALT is formulated as a sterile, preservative-free, isotonic solution for intrathecal administration using an appropriate microinfusion device [ see Dosage and Administration ( 2 ) ]. Each 1 or 5 mL vial of PRIALT (100 mcg/mL) respectively contains 100 or 500 mcg of ziconotide acetate, and the 20 mL vial of PRIALT (25 mcg/mL) contains 500 mcg of ziconotide acetate, with L-methionine and sodium chloride as excipients at pH 4.0–5.0. Each vial is intended for single use only, either undiluted or after dilution to the appropriate concentration with 0.9% Sodium Chloride Injection, USP (preservative free).
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💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise patients that psychiatric symptoms (paranoia, hostility, mania, depressive, suicidal) and cognitive symptoms (confusion, memory problems, speech disorder) may occur during treatment with PRIALT. Caution patients against engaging in hazardous activity requiring complete mental alertness or motor coordination such as operating machinery or driving a motor vehicle during treatment with PRIALT. Caution patients about possible combined effects with other CNS-depressant drugs.
Dosage adjustments may be necessary when PRIALT is administered with such agents because of the potentially additive effects. Advise patients to contact a physician if the patient experiences new or worsening muscle pain, soreness, weakness with or without darkened urine. Instruct patients and their caregivers to contact a physician immediately if the patient has any of the following A change in mental status (e.g., lethargy, confusion, disorientation, decreased alertness) A change in mood, perception (hallucinations, including unusual tactile sensations in the oral cavity) Symptoms of depression or suicidal ideation Nausea, vomiting, seizures, fever, headache, and/or stiff neck, as these may be symptoms of developing meningitis Decreased level of consciousness, unresponsiveness or stupor New muscular symptoms (e.g., muscle cramps, myalgias) Withdrawal symptoms (e.g., nausea, insomnia, flu-like symptoms) as a result of abruptly discontinuing opioid therapy Development of serious skin reaction (e.g., bullous dermatitis, skin ulcers, skin exfoliation) Lactation: Advise mothers who have been administered PRIALT to monitor neonates for signs of sedation which may result in respiratory depression and/or feeding problems [ see Use in Specific Populations ( 8.2 ) ] For use only in the Medtronic SynchroMed ® II and SynchroMed ® III Infusion System.
Distributed by: Esteve Pharmaceuticals, S.A. Barcelona, Spain © 2026 Esteve Pharmaceuticals, S.A. PRIALT ® is a registered trademark of Esteve Pharmaceuticals, S.A..
SynchroMed ® is a registered trademark of Medtronic, Inc. U.S. Patent Nos.
5,364,842; 5,795,864; and 5,891,849