Important Safety Information
PRIALT is contraindicated in patients with:
- A known hypersensitivity to ziconotide or any of its formulation components.
- Any other concomitant treatment or medical condition that would render IT administration hazardous, such as the presence of infection at the microinfusion injection site, uncontrolled bleeding diathesis, and spinal canal obstruction that impairs circulation of cerebrospinal fluid (CSF).
- A pre-existing history of psychosis.
WARNINGS AND PRECAUTIONS
Cognitive and Neuropsychiatric Adverse Reactions
Severe psychiatric symptoms and neurological impairment may occur during treatment. Monitor all patients frequently for evidence of cognitive impairment, hallucinations, or changes in mood or consciousness. PRIALT may cause or worsen depression, with the risk of suicide in susceptible patients.
In clinical trials, 12% of patients reported hallucinations; other acute psychiatric events included paranoid reactions (3%), hostility (2%), delirium (2%), psychosis (1%), and manic reactions (0.4%). Management of psychiatric complications may need to include discontinuation of PRIALT, treatment with psychotherapeutic agents, and/or short-term hospitalization.
In clinical trials, cognitive adverse reactions included confusion (33%), memory impairment (22%), speech disorder (14%), aphasia (12%), thinking abnormal (8%), and amnesia (1%). Cognitive effects may appear gradually after several weeks of treatment and are generally reversible within 2 weeks after drug discontinuation. The elderly (≥65 years) are at higher risk for confusion. Concomitant use of central nervous system (CNS) depressants with PRIALT may have additive effects.
Meningitis and Other Infections
Meningitis can occur due to inadvertent contamination of the microinfusion device and other means. In clinical trials, the rate of meningitis was 3% (40 cases) in the PRIALT group using either internal or external microinfusion devices and 1% (1 case) with placebo. In patients with external microinfusion devices and catheters, meningitis occurred in 38 out of 41 patients (93%), 37 of whom received PRIALT and one who received placebo.
Patients, caregivers, and healthcare providers must be particularly vigilant for the signs and symptoms of meningitis including, but not limited to, fever, headache, stiff neck, altered mental status (eg, lethargy, confusion, disorientation), nausea or vomiting, and occasionally seizures.
Strict aseptic procedures must be used during the preparation of the PRIALT solution and refilling of the microinfusion device.
Reduced Level of Consciousness
In clinical trials, 2% of PRIALT-treated patients became unresponsive or stuporous. If reduced levels of consciousness occur, discontinue PRIALT until the event resolves, and other etiologies (eg, meningitis) must be considered.
Elevation of Serum Creatine Kinase
In clinical trials, serum creatine kinase (CK) levels above the upper limit of normal (ULN) were reported in 40% of patients, with 11% of patients having CK levels >3 times ULN. Incidences were higher during the first 2 months of treatment. Serum CK should be monitored periodically. If these symptoms continue and CK levels remain elevated or continue to rise, reduce the dose or discontinue the use of PRIALT.
Withdrawal From Opiates
PRIALT is not an opiate and cannot prevent or relieve the symptoms associated with the withdrawal of opiates. To avoid withdrawal syndrome when opiate withdrawal is necessary, do not abruptly reduce or withdraw opioid medications.
Driving and Operating Machinery
Use of PRIALT has been associated with cognitive impairment and decreased alertness/unresponsiveness. Caution patients against engaging in hazardous activities that require complete mental alertness or motor coordination.
MOST COMMON ADVERSE REACTIONS
The most frequently reported adverse reactions (≥25%) in clinical trials (n=1254 PRIALT-treated patients) were dizziness, nausea, confusional state, and nystagmus. Slower titration of PRIALT may result in fewer serious adverse reactions and discontinuations for adverse reactions.
ADDITIONAL IMPORTANT INFORMATION
- PRIALT should be administered intrathecally (IT) by or under the direction of a physician. PRIALT is not intended for intravenous (IV) administration. See full Prescribing Information for dosing and administration instructions.
- The combination of PRIALT with intrathecal opiates has not been studied in placebo-controlled clinical trials and is not recommended.
- PRIALT is for use only in the Medtronic SynchroMed® II Infusion System and the CADD-Micro Ambulatory Infusion Pump.
- Advise patients to contact a physician if they experience new or worsening muscle pain, soreness, or weakness with or without darkened urine.
Please see full Prescribing Information, including BOXED Warning.