Version May 2024
Ziconotide is contraindicated in patients with a preexisting history of psychosis. Severe psychiatric symptoms and neurological impairment may occur during treatment with ziconotide. Monitor all patients frequently for evidence of cognitive impairment, hallucinations, or changes in mood or consciousness. Discontinue ziconotide therapy in the event of serious neurological or psychiatric signs or symptoms.
Chronic pain, severe (intolerant or refractory to other therapies):
Trial dose (off label):
Bolus: Intrathecal: Initial: 1 to 2 mcg once; if needed, adjust additional trial doses based on response and tolerability. Monitor for ≥8 hours after each bolus (Mohammed 2013; PACC [Deer 2017a]; Pope 2015).
Co ntinuous infusion : Intrathecal: Initial: 0.5 to 1.2 mcg/day (0.02 to 0.05 mcg/hour); may increase as needed based on response and tolerability by ≤1.2 mcg/day (0.05 mcg/hour) (McDowell 2016; PACC [Deer 2017a]). Maximum: 19.2 mcg/day (0.8 mcg/hour) (PACC [Deer 2017b]).
Maintenance dose:
Continuous infusion: Intrathecal: Initial: 0.5 to 1.2 mcg/day (0.02 to 0.05 mcg/hour) (McDowell 2016). Some experts recommend initiating with ≤0.5 mcg/day (0.02 mcg/hour) (Prager 2014). May increase as needed by up to 0.5 mcg/day (0.02 mcg/hour) weekly based on response and tolerability (McDowell 2016; Prager 2014). Maximum: 19.2 mcg/day (0.8 mcg/hour). Note: Dosing in the prescribing information may not reflect current clinical practice; initiation and titration with a lower dose is preferred to improve tolerability (McDowell 2016; Prager 2014). The manufacturer's labeling recommends dose initiation with ≤2.4 mcg/day (≤0.1 mcg/hour); and titration up to 2 to 3 times weekly by up to 2.4 mcg/day.
Discontinuation of therapy: In the event of severe adverse effects, may discontinue therapy abruptly without risk of withdrawal.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Cognitive impairment: Reduce dose or discontinue. Effects are generally reversible within 3 to 15 days of discontinuation.
Neurologic or psychiatric adverse effects, severe: Interrupt or permanently discontinue therapy.
Reduced level of consciousness: Discontinue until event resolves.
CK elevation with neuromuscular symptoms, persistent: Consider dose reduction or discontinuation.
Refer to adult dosing; use with caution and start at the low end of the dosing range.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Central nervous system: Dizziness (46%), confusion (15% to 33%), memory impairment (7% to 22%), drowsiness (17%), abnormal gait (14%), ataxia (14%), speech disorder (14%), headache (13%), aphasia (12%), hallucination (12%; including auditory and visual)
Gastrointestinal: Nausea (40%), diarrhea (18%), vomiting (16%)
Neuromuscular & skeletal: Increased creatine phosphokinase (40%; ≥3 x ULN: 11%), weakness (18%)
Ophthalmic: Blurred vision (12%)
2% to 10%:
Cardiovascular: Hypotension, orthostatic hypotension, peripheral edema
Central nervous system: Abnormality in thinking (8%), amnesia (8%), anxiety (8%), dysarthria (7%), paresthesia (7%), rigors (7%), vertigo (7%), insomnia (6%), paranoia (3%), delirium (2%), hostility (2%), stupor (2%), absent reflexes, agitation, burning sensation, decreased mental acuity, depression, disorientation, disturbance in attention, fatigue, hypoesthesia, irritability, lethargy, loss of balance, mood disorder, myasthenia, nervousness, pain, sedation
Dermatologic: Pruritus (7%), diaphoresis (5%)
Gastrointestinal: Anorexia (6%), dysgeusia (5%), abdominal pain, constipation, decreased appetite, xerostomia
Genitourinary: Urinary retention (9%), dysuria, urinary hesitancy
Neuromuscular & skeletal: Tremor (7%), muscle spasm (6%), limb pain (5%), muscle cramps, myalgia
Ophthalmic: Nystagmus (8%), diplopia, visual disturbance
Respiratory: Sinusitis (5%)
Miscellaneous: Fever (5%)
<2%, postmarketing, and/or case reports: Acute renal failure, aspiration pneumonia (<1%), atrial fibrillation, attempted suicide (<1%), cerebrovascular accident, ECG abnormality, incoherence, loss of consciousness, mania, meningitis, myoclonus, psychosis (1%), respiratory distress, rhabdomyolysis, seizure (clonic and grand mal), sepsis, suicidal ideation
Hypersensitivity to ziconotide or any component of the formulation; history of psychosis; utilization in patients with any other concomitant treatment or medical condition that would render intrathecal administration hazardous (eg, infection at the injection site, uncontrolled bleeding diathesis, spinal canal obstruction that impairs circulation of cerebrospinal fluid).
Concerns related to adverse effects:
• CNS toxicity: Severe neurological impairment and psychiatric symptoms have been reported. May cause or worsen depression and/or risk of suicide. Cognitive impairment may appear gradually during treatment and is generally reversible after discontinuation (may take up to 2 weeks for cognitive effects to reverse). May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Elevated serum creatine kinase: Elevated serum creatine kinase may occur with use; particularly during the first 2 months of therapy.
• Meningitis: May occur with use of intrathecal pumps; monitor for signs of meningitis; treatment of meningitis may require removal of system and discontinuation of intrathecal therapy.
Disease-related concerns:
• Hepatic impairment: Safety and efficacy have not been established in patients with hepatic impairment.
• Renal impairment: Safety and efficacy have not been established in patients with renal impairment.
Special populations:
• Older adult: Use with caution in older adults; may experience a higher incidence of confusion.
• Pediatric: Safety and efficacy have not been established in children.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intrathecal, as acetate [preservative free]:
Prialt: 500 mcg/20 mL (20 mL); 100 mcg/mL (1 mL); 500 mcg/5 mL (5 mL)
No
Solution (Prialt Intrathecal)
100 mcg/mL (per mL): $1,309.84
500 mcg/20 mL (per mL): $310.78
500 mcg/5 mL (per mL): $1,243.12
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Intrathecal: For intrathecal administration only; do not administer IV.
Continuous infusion: Use approved intrathecal drug delivery systems (eg, Medtronic SynchroMed II Infusion System, CADD-Micro ambulatory infusion pump). Refer to product label and delivery system manufacturer's manual for specific instructions and precautions.
Chronic pain, severe (intolerant or refractory to other therapies): Management of severe chronic pain in patients requiring intrathecal therapy and who are intolerant or refractory to other therapies (eg, systemic analgesics, adjunctive therapies, intrathecal morphine).
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification
Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Doxylamine: CNS Depressants may enhance the CNS depressant effect of Doxylamine. Risk C: Monitor therapy
DroPERidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification
Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification
Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification
Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification
Zuranolone: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider therapy modification
Adverse events in the presence of maternal toxicity were observed in animal reproduction studies following continuous IV administration of ziconotide in doses greater than the equivalent maximum recommended human dose.
It is not known if ziconotide is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Infants potentially exposed to ziconotide via breast milk should be monitored for sedation, respiratory depression, and/or feeding problems.
Serum CPK (baseline, every other week for first month, then monthly); psychiatric or neurological impairment, hallucinations, changes in mood or consciousness; suicidality (PACC [Deer 2017b]; manufacturer's labeling).
Ziconotide selectively binds to N-type voltage-sensitive calcium channels located on the nociceptive afferent nerves of the dorsal horn in the spinal cord. This binding is thought to block N-type calcium channels, leading to a blockade of excitatory neurotransmitter release and reducing sensitivity to painful stimuli.
Distribution: Intrathecal: Vd: ~140 mL
Protein binding: ~50%
Metabolism: Metabolized via endopeptidases and exopeptidases present on multiple organs including kidney, liver, lung; degraded to peptide fragments and free amino acids
Half-life elimination: IV: 1 to 1.6 hours (plasma); Intrathecal: 2.9 to 6.5 hours (CSF)
Excretion: IV: Urine (<1%)
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