(zi KOE no tide)
Management of severe chronic pain in patients requiring intrathecal therapy and who are intolerant or refractory to other therapies
Hypersensitivity to ziconotide or any component of the formulation; history of psychosis; IV administration
Intrathecal administration is contraindicated in patients with infection at the injection site, uncontrolled bleeding, or spinal canal obstruction that impairs CSF circulation
Severe psychiatric symptoms and neurological impairment may occur during treatment with ziconotide. Do not treat patients with a preexisting history of psychosis with ziconotide. Monitor all patients frequently for evidence of cognitive impairment, hallucinations, or changes in mood or consciousness. Ziconotide therapy can be interrupted or discontinued abruptly without evidence of withdrawal effects in the event of serious neurological or psychiatric signs or symptoms.
Chronic pain: Intrathecal: Initial dose: ≤2.4 mcg/day (0.1 mcg/hour)
Dose may be titrated by ≤2.4 mcg/day (0.1 mcg/hour) at intervals ≤2-3 times/week to a maximum dose of 19.2 mcg/day (0.8 mcg/hour) by day 21; average dose at day 21: 6.9 mcg/day (0.29 mcg/hour). A faster titration should be used only if the urgent need for analgesia outweighs the possible risk to patient safety.
Refer to adult dosing. Use with caution.
No dosage adjustment provided in manufacturer 's labeling (has not been studied).
No dosage adjustment provided in manufacturer 's labeling (has not been studied).
Preservative free NS should be used when dilution is needed.
CADD-Micro ‚ ® ambulatory infusion pump: Initial fill: Dilute to final concentration of 5 mcg/mL.
Medtronic SynchroMed ‚ ® EL or SynchroMed ‚ ® II infusion system: Prior to initial fill, rinse internal pump surfaces with 2 mL ziconotide (25 mcg/mL), repeat twice. Only the 25 mcg/mL concentration (undiluted) should be used for initial pump fill.
Not for IV administration.For intrathecal administration only using Medtronic SynchroMed ‚ ® EL, SynchroMed ‚ ® II Infusion System, or CADD-Micro ‚ ® ambulatory infusion pump.
Medtronic SynchroMed ‚ ® EL or SynchroMed ‚ ® II Infusion Systems:
Naive pump priming (first time use with ziconotide): Use 2 mL of undiluted ziconotide 25 mcg/mL solution to rinse the internal surfaces of the pump; repeat twice for a total of 3 rinses
Initial pump fill: Use only undiluted 25 mcg/mL solution and fill pump after priming. Following the initial fill only, adsorption on internal device surfaces will occur, requiring the use of the undiluted solution and refill within 14 days.
Pump refills: Contents should be emptied prior to refill. Subsequent pump refills should occur at least every 40 days if using diluted solution or at least every 84 days if using undiluted solution.
CADD-Micro ‚ ® ambulatory infusion pump: Refer to manufacturers manual for initial fill and refill instructions
Prior to use, store vials at 2 ‚ °C to 8 ‚ °C (36 ‚ °F to 46 ‚ °F). Once diluted, may be stored at 2 ‚ °C to 8 ‚ °C (36 ‚ °F to 46 ‚ °F) for 24 hours; refrigerate during transit. Do not freeze. Protect from light.
When using the Medtronic SynchroMed ‚ ® EL or SynchroMed ‚ ® II Infusion System, solutions expire as follows:
25 mcg/mL: Undiluted:
Initial fill: Use within 14 days.
Refill: Use within 84 days.
100 mcg/mL:
Undiluted: Refill: Use within 84 days.
Diluted: Refill: Use within 40 days.
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)
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy
Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
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 patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification
Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy
Dimethindene: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy
Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification
HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Consider starting with a 20% to 30% lower hydrocodone dose when using together with any other CNS depressant. Dose reductions in the other CNS depressant may also be warranted. Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. 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 adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy
Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: When oxycodone is combined with another CNS depressant, a dose reduction of one or both agents should be considered. The extended release oxycodone starting dose should be reduced 50% to 67% when initiated in patients already receiving CNS depressants. Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification
Piribedil [INT]: CNS Depressants may enhance the CNS depressant effect of Piribedil [INT]. Monitor therapy
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy
Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy
Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification
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. Consider therapy modification
Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Start tapentadol at a dose of one-third to one-half of the normal dose if being initiated in a patient who is taking another drug with CNS depressant effects. Monitor closely for evidence of excessive CNS depression. Consider therapy modification
Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification
Monitor for psychiatric or neurological impairment; signs and symptoms of meningitis or other infection; serum CPK (every other week for first month then monthly); pain relief
>10%:
Central nervous system: Dizziness (46%), confusion (15% to 33%), memory impairment (7% to 22%), somnolence (17%), ataxia (14%), speech disorder (14%), headache (13%), aphasia (12%), hallucination (12%; including auditory and visual)
Gastrointestinal: Nausea (40%), diarrhea (18%), vomiting (16%)
Neuromuscular & skeletal: Creatine kinase increased (40%; ≥3 times ULN: 11%), weakness (18%), gait disturbances (14%)
Ocular: Blurred vision (12%)
2% to 10%:
Cardiovascular: Hypotension, orthostatic hypotension, peripheral edema
Central nervous system: Abnormal thinking (8%), amnesia (8%), anxiety (8%), vertigo (7%), insomnia (6%), fever (5%), paranoid reaction (3%), delirium (2%), hostility (2%), stupor (2%), agitation, attention disturbance, balance impaired, burning sensation, coordination abnormal, depression, disorientation, fatigue, fever, hypoesthesia, irritability, lethargy, mental impairment, mood disorder, nervousness, pain, sedation
Dermatologic: Pruritus (7%)
Gastrointestinal: Anorexia (6%), taste perversion (5%), abdominal pain, appetite decreased, constipation, xerostomia
Genitourinary: Urinary retention (9%), dysuria, urinary hesitance
Neuromuscular & skeletal: Dysarthria (7%), paresthesia (7%), rigors (7%), tremor (7%), muscle spasm (6%), limb pain (5%), areflexia, muscle cramp, muscle weakness, myalgia
Ocular: Nystagmus (8%), diplopia, visual disturbance
Respiratory: Sinusitis (5%)
Miscellaneous: Diaphoresis (5%)
<2% (Limited to important or life-threatening): Acute renal failure, aspiration pneumonia (<1%), atrial fibrillation, cerebral vascular accident, ECG abnormalities, incoherence, loss of consciousness, mania, meningitis, myoclonus, psychosis (1%), psychotic disorder, respiratory distress, rhabdomyolysis, seizure (clonic and grand mal), sepsis, suicidal ideation, suicide attempt (<1%)
Concerns related to adverse effects:
- CNS toxicity: [U.S Boxed Warning]: Severe psychiatric symptoms and neurological impairment have been reported; interrupt or discontinue therapy if cognitive impairment, hallucinations, mood changes, or changes in consciousness occur. 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: With use, elevated serum creatine kinase can occur; particularly during the first 2 months of therapy. Consider dose reduction or discontinuing if combined with new neuromuscular symptoms (myalgias, myasthenia, muscle cramps, weakness) or reduction in physical activity.
- 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.
Concurrent drug therapy issues:
- CNS depressants: May have additive effects with ethanol and CNS-depressant medications.
- Opioids: May have additive CNS effects with opioids and may potentiate opioid-induced decreased GI motility; does not interact with opioid receptors or potentiate opioid-induced respiratory depression.
Special populations:
- Elderly: Use with caution in the elderly; may experience a higher incidence of confusion.
- Pediatric: Safety and efficacy have not been established in children.
Other warnings/precautions:
- Withdrawal: Will not prevent or relieve symptoms associated with opioid withdrawal; unlike opioids, ziconotide therapy can be interrupted abruptly or discontinued without evidence of withdrawal.
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Adverse events and maternal toxicity were observed in animal reproduction studies.
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.
Intrathecal: Vd: ~140 mL
Metabolized via endopeptidases and exopeptidases present on multiple organs including kidney, liver, lung; degraded to peptide fragments and free amino acids
IV: Urine (<1%)
IV: 1-1.6 hours (plasma); Intrathecal: 2.9-6.5 hours (CSF)
~50%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience dizziness, fatigue, diarrhea, or lack of appetite. Have patient report immediately to prescriber signs of depression (ie, suicidal ideation, anxiety, emotional instability, illogical thinking), illogical thinking, hallucinations, memory impairment, mood changes, change in alertness, seizures, change in balance, severe headache, severe nausea, vomiting, neck rigidity, difficulty speaking, muscle pain, dark urine, involuntary eye movements, vision changes, abnormal gait, tremors, difficult urination, loss of strength and energy, skin ulcers, or severe skin irritation (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.