Ziconotide is an intrathecal 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. Ziconotide is not intended for intravenous administration. Severe psychiatric symptoms and neurological impairment may occur during treatment with ziconotide. All patients treated with ziconotide require frequent monitoring for evidence of cognitive impairment, hallucinations, or changes in mood or consciousness. Meningitis can occur due to inadvertent contamination of the microinfusion device and other means such as cerebrospinal fluid 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. Patients have become unresponsive or stuporous while receiving ziconotide; there is no known pharmacologic antagonist for this effect. Ziconotide is not an opioid and cannot prevent or relieve the symptoms associated with opioid withdrawal. The combination of ziconotide with intrathecal opioids has not been studied in placebo-controlled clinical trials and is not recommended.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Discard any ziconotide solution with observed particulate matter or discoloration and any unused portion left in the vial.
Intrathecal Administration
-Ziconotide 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.
-Ziconotide is intended for intrathecal delivery using the Medtronic SynchroMed II Infusion System and CADD-Micro Ambulatory Infusion Pump. Refer to the manufacturer's manual for specific instructions and precautions for programming the microinfusion device and/or refilling the reservoir.
-Ziconotide may be used for therapy undiluted (25 mcg/mL) or diluted (100 mcg/mL). The 100 mcg/mL formulation may be administered undiluted once an appropriate dose has been established.
Dilution
-Dilute ziconotide with preservative free 0.9% Sodium Chloride Injection using aseptic procedures to the desired concentration prior to placement in the microinfusion pump.
-Storage: Refrigerate but do not freeze all ziconotide solutions after preparation and begin infusion within 24 hours.
Continuous intrathecal infusion with the Medtronic SynchroMed II Infusion System
-Naive pump priming: Use only the undiluted 25 mcg/mL formulation for naive pump priming. Rinse the internal surfaces of the pump with 2 mL of ziconotide at 25 mcg/mL. Repeat twice for a total of 3 rinses.
-Initial pump fill: Use only the undiluted 25 mcg/mL formulation for the initial pump fill. Fill the naive pump after priming with the appropriate volume of ziconotide 25 mcg/mL. In a naive pump, ziconotide is lost due to 2 factors that do not occur upon subsequent refills: adsorption on internal device surfaces, such as titanium, and by dilution in the residual space of the device. Consequently, refill the pump reservoir with ziconotide within 14 days of the initial fill to ensure appropriate dose administration.
-Pump refills: For subsequent pump refills, fill the pump at least every 40 days if ziconotide is used diluted. For undiluted ziconotide, fill the pump at least every 84 days. To ensure aseptic transfer of ziconotide into the device, use the Medtronic refill kit. Empty the pump contents prior to refill with ziconotide.
-If the internal infusion system must be surgically replaced while the person is receiving ziconotide, rinse the replacement pump with ziconotide according to naive pump priming, and replace the initial fill solution within 14 days according to initial pump fill.
Continuous intrathecal infusion with the CADD-Micro Ambulatory Infusion Pump
-Refer to the manufacturer's manuals for specific instructions and precautions for performing the initial filling, refilling of the reservoir or replacement of the drug cartridge, and operation.
-Initial pump fill: The CADD-Micro Ambulatory Infusion Pump is filled for the first time with ziconotide solution at a concentration of 5 mcg/mL. This solution is prepared by diluting ziconotide with preservative free 0.9% Sodium Chloride.
Severe neurological impairment may occur during treatment with ziconotide. Cognitive adverse reactions reported with ziconotide include confusion (15% to 33%), memory impairment (7% to 22%), speech disorder (14%), aphasia (12%), thinking abnormal (8%), and amnesia (1% to 8%). Cognitive disorder and disorientation have been reported in 2% or more of ziconotide-treated patients in clinical trials. Cognitive impairment may appear gradually after several weeks of treatment. Reduce the dose of ziconotide or discontinue the use of ziconotide if signs or symptoms of cognitive impairment develop, but other contributing causes must also be considered. The cognitive effects of ziconotide 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. Use of ziconotide has been associated with impaired cognition and decreased alertness/unresponsiveness. The incidence of loss of consciousness or stupor in clinical trials was 2% in ziconotide-treated patients. During these episodes, patients sometimes appear to be conscious and breathing is not depressed. If reduced levels of consciousness occur, discontinue ziconotide until the event resolves, and other etiologies must be considered. There is no known pharmacologic antagonist for this effect. Other nervous system disorders reported with ziconotide in clinical trials include ataxia (14%), dizziness (46%), drowsiness (17%), dysarthria (7%), dysgeusia (5%), headache (13%), nystagmus (8%), tremor (7%), and vertigo (7%). Areflexia, impaired balance, burning sensation, abnormal coordination, disturbance in attention, postural dizziness, hypoesthesia, mental impairment, paresthesias, sedation, and stroke have been reported in 2% or more of ziconotide-treated patients, and seizures (clonic and grand mal convulsions) have been reported in less than 2% of ziconotide-treated patients.
Severe psychiatric symptoms may occur during treatment with ziconotide. Events of acute psychiatric disturbances such as hallucinations (12%), paranoia (3%), hostility (2%), delirium (2%), psychosis (1%), and mania (0.4%) have been reported in patients treated with ziconotide. Ziconotide 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 suicidal ideation in ziconotide-treated patients than in the placebo group (0.27/patient year for ziconotide patients and 0.10/patient year for placebo patients). Other psychiatric adverse reactions reported with ziconotide in clinical trials include anxiety (8%) and insomnia (6%). Agitation, depression, aggravated depression, mood disorder, and nervousness have been reported in 2% or more of ziconotide treated patients; psychotic disorder and suicidal ideation have been reported in less than 2% of ziconotide-treated patients, and suicide attempt has been reported in less than 1% of ziconotide-treated patients. Management of psychiatric complications may need to include discontinuation of ziconotide, treatment with psychotherapeutic agents, and/or short-term hospitalization. Before ziconotide is reinitiated, careful evaluation must be performed on an individual basis.
Gastrointestinal adverse events reported with ziconotide in clinical trials include anorexia (6%), diarrhea (18%), nausea (40%), and vomiting (16%). Abdominal pain, aggravated nausea, constipation, and xerostomia have been reported in 2% or more of ziconotide-treated patients in clinical trials.
General adverse events reported with ziconotide in clinical trials include asthenia (18%), gait disturbance (14%), fever (5%), and rigors (7%). Falls, fatigue, lethargy, and peripheral edema have been reported in 2% or more of ziconotide-treated patients in clinical trials.
In clinical studies, 40% of ziconotide-treated patients had serum creatine kinase (CK) concentrations above the upper limit of normal (ULN), and 11% had CK concentrations that were more than 3 times the ULN. In cases where CK was fractionated, only the muscle isoenzyme (MM) was elevated. The time to occurrence was sporadic, but the greatest incidence of CK elevation was during the first 2 months of treatment. A case of symptomatic myopathy with EMG findings, and 2 cases of acute renal failure associated with rhabdomyolysis and extreme CK elevations (17,000 to 27,000 IU/L) have been reported in ziconotide-treated patients. Monitor serum CK in patients undergoing treatment with ziconotide periodically (e.g., every other week for the first month and monthly as appropriate thereafter). Evaluate patients clinically and obtain CK measurements in the setting of new neuromuscular symptoms (e.g., myalgias, myasthenia, muscle cramps, asthenia) or a reduction in physical activity. If these symptoms continue and CK concentrations remain elevated or continue to rise, reduce the dose or discontinue the use of ziconotide. Myalgia (2% or more), muscle cramps (2% or more), muscle spasms (6%), myasthenia (2% or more), limb pain (2% to 5%), rhabdomyolysis (less than 2%), and acute renal failure (less than 2%) have been reported in ziconotide-treated patients in clinical trials.
In ziconotide clinical trials, meningitis occurred in 3% of patients in the ziconotide group using either internal or external microinfusion devices and 1% of patients in the placebo group. The risk of meningitis was particularly high in patients with external microinfusion devices and catheters, occurring in 38 out of 41 patients (93%), 37 of whom received ziconotide and 1 who received placebo. Serious infection or meningitis can occur within 24 hours of a breach in sterility such as a disconnected catheter, the most common cause of meningitis with external microinfusion devices. In suspected cases (especially in immuno-compromised patients) or in confirmed cases of meningitis, cerebrospinal fluid (CSF) cultures must be obtained and appropriate antibiotic therapy must be promptly instituted. Treatment of meningitis usually requires removal of the microinfusion system, catheter, and any other foreign body materials within the intrathecal space and, therefore, discontinuation of ziconotide therapy. Sinusitis (5%), sepsis (less than 2%), and fatal aspiration pneumonia (less than 1%) have also been reported in ziconotide-treated patients in clinical trials.
Eye disorders reported with ziconotide in clinical trials include blurred vision (12%), diplopia (2% or more), and visual disturbance (2% or more).
Cardiovascular adverse events reported with ziconotide in clinical trials include hypotension (2% or more) and orthostatic hypotension (2% or more). Atrial fibrillation and abnormal electrocardiogram have been reported in less than 2% of ziconotide-treated patients in clinical trials.
Dermatologic adverse events reported with ziconotide in clinical trials include pruritus (7%) and diaphoresis (5%). Hypersensitivity reactions including angioedema and serious skin reactions including bullous rash, skin ulcer, skin exfoliation (exfoliative dermatitis), and burning skin sensation have been reported with ziconotide in postmarketing experience. Respiratory distress has been reported in 2% or more of ziconotide-treated patients in clinical trials.
Urinary retention has been reported in 9% of ziconotide-treated patients in clinical trials; dysuria and urinary hesitation have been reported in 2% or more of ziconotide-treated patients.
Ziconotide is contraindicated in patients with a known hypersensitivity to ziconotide or any of its formulation components.
Ziconotide is contraindicated in patients with any other concomitant treatment or medical condition that would render intrathecal administration hazardous, including the presence of infection at the microinfusion injection site, uncontrolled bleeding diathesis, and spinal cord compression or any spinal canal obstruction that impairs cerebrospinal fluid (CSF) circulation. 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. The risk of meningitis was particularly high in patients with external microinfusion devices and catheters. Strict aseptic procedures must be used during the preparation of the ziconotide solution and refilling of the microinfusion device to decrease the risk of introducing contaminants or other environmental pathogens into the reservoir.
Ziconotide is contraindicated for use in patients with a pre-existing history of psychosis. A severe, adverse psychiatric event and neurologic events may occur during treatment with ziconotide. Patients with pretreatment psychiatric disorders may be at an increased risk. Ziconotide may cause or worsen depression with the risk of suicidal ideation in susceptible patients. Monitor all patients frequently for evidence of cognitive impairment, hallucinations, or changes in mood or consciousness.
Advise patients against engaging in hazardous activities that require complete mental alertness or motor coordination such as driving or operating machinery due to ziconotide use being associated with cognitive impairment and decreased alertness/unresponsiveness.
Ziconotide administration requires an experienced clinician in the technique of intrathecal administration and who is familiar with the drug and device labeling.
In all trials, there was a higher incidence of confusion in patients older than 65 years. In general, the dose selection for a geriatric 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.
Use ziconotide during pregnancy only if the potential benefit to the mother justifies risk to the fetus. No adequate and well-controlled studies with ziconotide have been conducted in pregnant women. Ziconotide was embryolethal 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 embryolethality in the rat was approximately 700-fold above the expected exposure resulting from the maximum recommended human daily intrathecal dose of 0.8 mcg/hour (19.2 mcg/day). Ziconotide was not teratogenic in female rats when given as a continuous intravenous infusion at doses up to 30 mg/kg/day or in female 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/hour (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 doses. Maternal toxicity in the rat led to reduced fetal weights and transient, delayed ossification of the pubic bones at doses of 15 mg/kg/day or more, which is approximately 8,900-fold higher than the expected exposure resulting from the maximum recommended human daily intrathecal dose of 0.8 mcg/hour (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/hour (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 3,800-fold higher than the expected exposure resulting from the maximum recommended human daily intrathecal dose of 0.8 mcg/hour (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.
Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for ziconotide and any potential adverse effects on the breast-fed infant from ziconotide or the underlying maternal condition. Monitor infants exposed to ziconotide through breast milk for sedation, which may result in respiratory depression and/or feeding problems. There are no data on the presence of ziconotide in human milk, the effects on the breast-fed infant, or the effects on milk production.
For the treatment of chronic, severe 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:
Intrathecal infusion dosage:
Adults: 2.4 mcg/day (0.1 mcg/hour) continuous intrathecal infusion, initially. Titrate by up to 2.4 mcg/day (0.1 mcg/hour) at intervals of no more than 2 to 3 times per week based on severity of pain, the patient's response to therapy, and the occurrence of adverse reactions. Dose increases in increments of less than 2.4 mcg/day (0.1 mcg/hour) and less frequently than 2 to 3 times per week may be used. Max: 19.2 mcg/day (0.8 mcg/hour).
Maximum Dosage Limits:
-Adults
19.2 mcg/day (0.8 mcg/hour) intrathecally.
-Geriatric
19.2 mcg/day (0.8 mcg/hour) intrathecally.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Acetaminophen; Chlorpheniramine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Acetaminophen; Codeine: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Acetaminophen; Diphenhydramine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Acetaminophen; Hydrocodone: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Acetaminophen; Oxycodone: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Acrivastine; Pseudoephedrine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Alfentanil: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Amiloride: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Amitriptyline: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as tricyclic antidepressants. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Amobarbital: (Moderate) CNS depressant medications, such as barbiturates, may increase drowsiness, dizziness, and confusion that are associated with ziconotide. Dosage adjustments may be necessary if ziconotide is used with a barbiturate.
Amoxapine: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as amoxapine. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide. If altered consciousness occurs, consider discontinuation of either agent.
Anxiolytics; Sedatives; and Hypnotics: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as anxiolytics, sedatives, and hypnotics. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide. Patients taking sedatives with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of sedative cessation is warranted in addition to ziconotide discontinuation.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) CNS depressant medications, such as barbiturates, may increase drowsiness, dizziness, and confusion that are associated with ziconotide. Dosage adjustments may be necessary if ziconotide is used with a barbiturate.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) CNS depressant medications, such as carisoprodol, may increase drowsiness, dizziness, and confusion that are associated with ziconotide. Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects. (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Aspirin, ASA; Oxycodone: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Atenolol; Chlorthalidone: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Azilsartan; Chlorthalidone: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Barbiturates: (Moderate) CNS depressant medications, such as barbiturates, may increase drowsiness, dizziness, and confusion that are associated with ziconotide. Dosage adjustments may be necessary if ziconotide is used with a barbiturate.
Belladonna; Opium: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Benzhydrocodone; Acetaminophen: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Brompheniramine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Brompheniramine; Phenylephrine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Brompheniramine; Pseudoephedrine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Bumetanide: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Buprenorphine: (Moderate) Concurrent use of ziconotide and opiate agonists-antagonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Buprenorphine; Naloxone: (Moderate) Concurrent use of ziconotide and opiate agonists-antagonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Buspirone: (Moderate) CNS depressant medications, such as buspirone, may increase drowsiness, dizziness, and confusion that are associated with ziconotide. Dosage adjustments may be necessary if ziconotide is used with buspirone.
Butalbital; Acetaminophen: (Moderate) CNS depressant medications, such as barbiturates, may increase drowsiness, dizziness, and confusion that are associated with ziconotide. Dosage adjustments may be necessary if ziconotide is used with a barbiturate.
Butalbital; Acetaminophen; Caffeine: (Moderate) CNS depressant medications, such as barbiturates, may increase drowsiness, dizziness, and confusion that are associated with ziconotide. Dosage adjustments may be necessary if ziconotide is used with a barbiturate.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) CNS depressant medications, such as barbiturates, may increase drowsiness, dizziness, and confusion that are associated with ziconotide. Dosage adjustments may be necessary if ziconotide is used with a barbiturate. (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) CNS depressant medications, such as barbiturates, may increase drowsiness, dizziness, and confusion that are associated with ziconotide. Dosage adjustments may be necessary if ziconotide is used with a barbiturate. (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Butorphanol: (Moderate) Concurrent use of ziconotide and opiate agonists-antagonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Carbinoxamine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Carisoprodol: (Moderate) CNS depressant medications, such as carisoprodol, may increase drowsiness, dizziness, and confusion that are associated with ziconotide. Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects.
Celecoxib; Tramadol: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Chlophedianol; Dexbrompheniramine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Chlorcyclizine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Chlordiazepoxide; Amitriptyline: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as tricyclic antidepressants. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Chlorothiazide: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Chlorpheniramine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Chlorpheniramine; Codeine: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists. (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Chlorpheniramine; Dextromethorphan: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Chlorpheniramine; Hydrocodone: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists. (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Chlorpheniramine; Phenylephrine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Chlorpheniramine; Pseudoephedrine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Chlorpromazine: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as phenothiazines. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Chlorthalidone: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Clemastine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Clomipramine: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as tricyclic antidepressants. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Clozapine: (Moderate) Clozapine has CNS depressant effects and may increase drowsiness, dizziness, and confusion that are associated with ziconotide if coadministered.
Codeine: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Codeine; Guaifenesin: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Codeine; Phenylephrine; Promethazine: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists. (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as phenothiazines. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Codeine; Promethazine: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists. (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as phenothiazines. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Cyproheptadine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Desipramine: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as tricyclic antidepressants. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Dexbrompheniramine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Dexchlorpheniramine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Dimenhydrinate: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Diphenhydramine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Diphenhydramine; Ibuprofen: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Diphenhydramine; Naproxen: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Diphenhydramine; Phenylephrine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Doxepin: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as tricyclic antidepressants. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Doxylamine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Doxylamine; Pyridoxine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Droperidol: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as droperidol. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Eszopiclone: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as anxiolytics, sedatives, and hypnotics. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide. Patients taking sedatives with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of sedative cessation is warranted in addition to ziconotide discontinuation.
Ethacrynic Acid: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
Fentanyl: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Fluphenazine: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as phenothiazines. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Furosemide: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Haloperidol: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as haloperidol. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Homatropine; Hydrocodone: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Hydrochlorothiazide, HCTZ: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Hydrocodone: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Hydrocodone; Ibuprofen: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Hydromorphone: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Hydroxyzine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Ibuprofen; Oxycodone: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Imipramine: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as tricyclic antidepressants. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Levorphanol: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Loop diuretics: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Mannitol: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Maprotiline: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as maprotiline. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Meclizine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Meperidine: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Meprobamate: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as anxiolytics, sedatives, and hypnotics. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide. Patients taking sedatives with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of sedative cessation is warranted in addition to ziconotide discontinuation.
Methadone: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Methocarbamol: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as methocarbamol. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Methohexital: (Moderate) CNS depressant medications, such as barbiturates, may increase drowsiness, dizziness, and confusion that are associated with ziconotide. Dosage adjustments may be necessary if ziconotide is used with a barbiturate.
Metolazone: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Mirtazapine: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as mirtazipine. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Molindone: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as molindone. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Morphine: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Morphine; Naltrexone: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Nalbuphine: (Moderate) Concurrent use of ziconotide and opiate agonists-antagonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Nefazodone: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as nefazodone. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Nortriptyline: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as tricyclic antidepressants. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Olanzapine: (Moderate) Olanzapine is a CNS depressant medication that may increase drowsiness, dizziness, and confusion that are associated with ziconotide. If altered consciousness occurs, consider treatment discontinuation.
Olanzapine; Fluoxetine: (Moderate) Olanzapine is a CNS depressant medication that may increase drowsiness, dizziness, and confusion that are associated with ziconotide. If altered consciousness occurs, consider treatment discontinuation.
Olanzapine; Samidorphan: (Moderate) Olanzapine is a CNS depressant medication that may increase drowsiness, dizziness, and confusion that are associated with ziconotide. If altered consciousness occurs, consider treatment discontinuation.
Oliceridine: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Opiate Agonists: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Opiate Agonists-Antagonists: (Moderate) Concurrent use of ziconotide and opiate agonists-antagonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Oxycodone: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Oxymorphone: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Pentazocine; Naloxone: (Moderate) Concurrent use of ziconotide and opiate agonists-antagonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Pentobarbital: (Moderate) CNS depressant medications, such as barbiturates, may increase drowsiness, dizziness, and confusion that are associated with ziconotide. Dosage adjustments may be necessary if ziconotide is used with a barbiturate.
Perphenazine: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as phenothiazines. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Perphenazine; Amitriptyline: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as phenothiazines. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide. (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as tricyclic antidepressants. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Phenobarbital: (Moderate) CNS depressant medications, such as barbiturates, may increase drowsiness, dizziness, and confusion that are associated with ziconotide. Dosage adjustments may be necessary if ziconotide is used with a barbiturate.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) CNS depressant medications, such as barbiturates, may increase drowsiness, dizziness, and confusion that are associated with ziconotide. Dosage adjustments may be necessary if ziconotide is used with a barbiturate.
Phenothiazines: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as phenothiazines. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Pimozide: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as pimozide. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Potassium-sparing diuretics: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Pramipexole: (Moderate) Pramipexole is a CNS depressant medication that may increase drowsiness, dizziness, and confusion that are associated with ziconotide. Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects.
Primidone: (Moderate) CNS depressant medications, such as barbiturates, may increase drowsiness, dizziness, and confusion that are associated with ziconotide. Dosage adjustments may be necessary if ziconotide is used with a barbiturate.
Prochlorperazine: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as phenothiazines. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Promethazine: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as phenothiazines. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Promethazine; Dextromethorphan: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as phenothiazines. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Promethazine; Phenylephrine: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as phenothiazines. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Protriptyline: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as tricyclic antidepressants. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Pseudoephedrine; Triprolidine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Quetiapine: (Moderate) Quetiapine is a CNS depressant medication that may increase drowsiness, dizziness, and confusion that are associated with ziconotide. Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Remifentanil: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Risperidone: (Moderate) Risperidone is a CNS depressant medication that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Ropinirole: (Moderate) Ropinirole is a CNS depressant medication that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Secobarbital: (Moderate) CNS depressant medications, such as barbiturates, may increase drowsiness, dizziness, and confusion that are associated with ziconotide. Dosage adjustments may be necessary if ziconotide is used with a barbiturate.
Sedating H1-blockers: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Spironolactone: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Sufentanil: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Tapentadol: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Thiazide diuretics: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Thioridazine: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as phenothiazines. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Torsemide: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Tramadol: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Tramadol; Acetaminophen: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Trazodone: (Moderate) Trazodone is a CNS depressant medication that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Triamterene: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Tricyclic antidepressants: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as tricyclic antidepressants. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Trifluoperazine: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as phenothiazines. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Trimipramine: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as tricyclic antidepressants. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Triprolidine: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Zaleplon: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as anxiolytics, sedatives, and hypnotics. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide. Patients taking sedatives with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of sedative cessation is warranted in addition to ziconotide discontinuation.
Zolpidem: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as anxiolytics, sedatives, and hypnotics. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide. Patients taking sedatives with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of sedative cessation is warranted in addition to ziconotide discontinuation.
Ziconotide binds to N-type calcium channels located on the primary nociceptive 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.
Ziconotide is administered by continuous intrathecal infusion. Ziconotide is about 50% bound to human plasma proteins. The mean cerebrospinal fluid (CSF) Vd of ziconotide after intrathecal administration approximates the estimated total CSF volume (140 mL). Ziconotide is cleaved by endopeptidases and exopeptidases at multiple sites on the peptide. After 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 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. 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 of ziconotide approximates adult human CSF turnover rate (0.3 to 0.4 mL/minute).
-Route-Specific Pharmacokinetics
Other Route(s)
Intrathecal Route
The cerebrospinal fluid (CSF) pharmacokinetics of ziconotide have been studied after 1-hour intrathecal infusions of 1 to 10 mcg of ziconotide to patients with chronic pain; Vd was 155 +/- 263 mL, clearance was 0.38 +/- 0.56 mL/minute, and half-life was 4.6 +/- 0.9 hours. Both total exposure (AUC; range: 83.6 to 608 ng x hour/mL) and peak exposure (Cmax; 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 ziconotide at infusion rates ranging from 0.1 to 7 mcg/hour in patients with chronic pain, plasma ziconotide concentrations 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 concentrations in plasma. Plasma ziconotide concentrations, when detectable, remain constant after many months of intrathecal ziconotide infusion in patients followed for up to 9 months.
-Special Populations
Hepatic Impairment
No formal studies were conducted to assess the effect of hepatic dysfunction on the pharmacokinetics of ziconotide.
Renal Impairment
No formal studies were conducted to assess the effect of renal dysfunction on the pharmacokinetics of ziconotide.
Geriatric
No formal studies were conducted to assess the effect of age on the pharmacokinetics of ziconotide.
Gender Differences
No formal studies were conducted to assess the effect of gender on the pharmacokinetics of ziconotide.
Ethnic Differences
No formal studies were conducted to assess the effect of race on the pharmacokinetics of ziconotide.
Obesity
No formal studies were conducted to assess the effect of weight on the pharmacokinetics of ziconotide.