Ziconotide Acetate (1 brand name, 1 dosage form, 1 route)
Available dosage forms: INJECTABLE.
Routes of administration: INTRATHECAL.
Brand Names
- PRIALT
Boxed Warning
PRIALT is contraindicated in patients with a preexisting history of psychosis. Severe psychiatric symptoms and neurological impairment may occur during treatment with PRIALT. Monitor all patients frequently for evidence of cognitive impairment, hallucinations, or changes in mood or consciousness. Discontinue PRIALT therapy in the event of serious neurological or psychiatric signs or symptoms.
Indications and Usage
PRIALT (ziconotide) solution, intrathecal infusion is indicated for the management of severe chronic pain in adult patients for whom intrathecal therapy is warranted, and who are intolerant of or refractory to other treatment, such as systemic analgesics, adjunctive therapies, or intrathecal morphine.
Contraindications
PRIALT is contraindicated in patients with a known hypersensitivity to ziconotide or any of its formulation components. PRIALT is contraindicated in patients with any other concomitant treatment or medical condition that would render intrathecal administration hazardous. Contraindications to the use of intrathecal analgesia include the presence of infection at the microinfusion injection site, uncontrolled bleeding diathesis, and spinal canal obstruction that impairs circulation of CSF. PRIALT is contraindicated in patients with a pre-existing history of psychosis.
Drug Interactions
Formal PK drug-drug interaction studies have not been performed with PRIALT. As ziconotide is a peptide, it is expected to be completely degraded by endopeptidases and exopeptidases (Phase I hydrolytic enzymes) widely located throughout the body, and not by other Phase I biotransformation processes (including the cytochrome P450 system) or by Phase II conjugation reactions. Thus, intrathecal administration, low plasma ziconotide concentrations, and metabolism by ubiquitous peptidases make metabolic interactions of other drugs with ziconotide unlikely. Further, as ziconotide is not highly bound in plasma (approximately 50%) and has low plasma exposure following intrathecal administration, clinically relevant plasma protein displacement reactions involving ziconotide and co-administered medications are unlikely. Over 90% of patients treated with intrathecal PRIALT used systemic opiates and in the slow titration study, 98% of patients received opioids. The combination of PRIALT with intrathecal opiates has not been studied in placebo-controlled clinical trials and is not recommended.
Mechanism of Action
Ziconotide binds to N-type calcium channels located on the primary nociceptive (A-δ and C) afferent nerves in the superficial layers (Rexed laminae I and II) of the dorsal horn in the spinal cord. Although the mechanism of action of ziconotide has not been established in humans, results in animals suggest that its binding blocks N-type calcium channels, which leads to a blockade of excitatory neurotransmitter release from the primary afferent nerve terminals and antinociception.
Overdosage
The maximum recommended intrathecal PRIALT dose is 19.2 mcg/day. The maximum intrathecal dose of PRIALT in clinical trials was 912 mcg/day. In some patients who received intrathecal doses greater than the maximum recommended dose, exaggerated pharmacological effects (e.g., ataxia, nystagmus, dizziness, stupor, unresponsiveness, spinal myoclonus, confusion, sedation, hypotension, word-finding difficulties, garbled speech, nausea, and vomiting) were observed. There was no indication of respiratory depression. Overdoses may occur due to pump programming errors or incorrect drug concentration preparations. In these cases, patients were observed and ziconotide was either temporarily discontinued or permanently withdrawn. Most patients recovered within 24 hours after withdrawal of drug. In the event of an overdose, elimination of ziconotide from CSF would be expected to remain constant (CSF t½=4.6 hours). Therefore, within 24 hours of stopping therapy, the ziconotide CSF concentration should be less than 5% of peak levels. There is no known antidote to ziconotide. General medical supportive measures should be administered to patients who receive an overdose until the exaggerated pharmacological effects of the drug have resolved. Treatment for an overdose is hospitalization, when needed, and symptom-related supportive care. Ziconotide does not bind to opiate receptors and its pharmacological effects are not blocked by opioid antagonists. In the event of an inadvertent intravenous or epidural administration, adverse reactions could include severe hypotension, which can be treated with a recumbent posture and blood pressure support as required. The half-life of PRIALT in serum is 1.3 hours.