Overview
11 DESCRIPTION PRIALT contains ziconotide, a synthetic equivalent of a naturally occurring conopeptide found in the piscivorous marine snail, Conus magus. Ziconotide is a 25 amino acid, polybasic peptide containing three disulfide bridges with a molecular weight of 2639 daltons and a molecular formula of C 102 H 172 N 36 O 32 S 7 .
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 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. 12.2 Pharmacodynamics Interaction with Opioids Ziconotide does not bind to opioid receptors and its pharmacological effects are not blocked by opioid antagonists.
Indications
- 1 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. PRIALT (ziconotide) solution, intrathecal infusion is an 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...
Common Doses
- 25 mcg
- 100 mcg
- 2.4 mcg
- 0.1 mcg
Dosage
2 DOSAGE AND ADMINISTRATION PRIALT is a non-opioid and non-NSAID analgesic agent used for the management of severe and chronic pain. Administer PRIALT intrathecally 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. ( 2 ) PRIALT is not for intravenous administration. ( 2.1 ) PRIALT is delivered using a programmable implanted variable-rate microinfusion device or an external microinfusion device and catheter. ( 2.1 ) PRIALT 25 mcg/mL is used undiluted.
Black Box Warning
WARNING: NEUROPSYCHIATRIC ADVERSE REACTIONS 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.
Contraindications
- 4 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.
Side Effects
- 6 ADVERSE REACTIONS The most frequently reported adverse reactions (≥ 25%) in clinical trials were dizziness, nausea, confusional state, nystagmus. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact TerSera Therapeutics at 1-844-344-4035 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates in clinical practice.
Interactions
- 7 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.