Dosage & 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.
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Prialt Prescribing Information
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.
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.
General Information
PRIALT 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.
PRIALT is not intended for intravenous administration.
PRIALT is intended for intrathecal delivery using the Medtronic SynchroMed® II and SynchroMed® III Infusion System and CADD-Micro Ambulatory Infusion Pump [see Warnings and Precautions ]. Refer to the manufacturer's manual for specific instructions and precautions for programming the microinfusion device and/or refilling the reservoir.
PRIALT may be used for therapy undiluted (25 mcg/mL in 20 mL vial) or diluted (100 mcg/mL in 1 or 5 mL vials). The 100 mcg/mL formulation may be administered undiluted once an appropriate dose has been established.
Dilute PRIALT with 0.9% Sodium Chloride Injection, USP (preservative free) using aseptic procedures to the desired concentration prior to placement in the microinfusion pump.
- Saline solutions containing preservatives are not appropriate for intrathecal drug administration and should not be used due to risk of neurotoxicity.
- Refrigerate but do not freeze all PRIALT solutions after preparation and begin infusion within 24 hours.
Inspect vials of PRIALT visually for particulate matter and discoloration prior to administration whenever solution and container permit. Discard any PRIALT solution with observed particulate matter or discoloration and any unused portion left in the vial.
Dosing
Dose Initiation
Initiate dosing with PRIALT via intrathecal device at no more than 2.4 mcg/day (0.1 mcg/hr).
Dose Titration
Titrate doses by up to 2.4 mcg/day (0.1 mcg/hr) at intervals of no more than 2 to 3 times per week based on analgesic response and adverse events. Dose increases in increments of less than 2.4 mcg/day (0.1 mcg/hr) and less frequently than 2 to 3 times per week may be used. For each dose titration, assess the dosing requirements and adjust the pump infusion flow rate as required to achieve the new dosing.
The maximum recommended dose is 19.2 mcg/day (0.8 mcg/hr).
Adjust the dose of intrathecal PRIALT according to the severity of pain, the patient's response to therapy, and the occurrence of adverse reactions.
Instructions for Use with the Medtronic SynchroMed II and SynchroMed III Infusion System
Refer to the manufacturer's manuals for specific instructions and precautions for performing a reservoir rinse, initial filling, refilling the reservoir, and programming. [see Warnings and Precautions ]
Naïve Pump Priming (i.e., first time use with PRIALT)
Use only the undiluted 25 mcg/mL formulation for naïve pump priming. Rinse the internal surfaces of the pump with 2 mL of PRIALT at 25 mcg/mL. Repeat twice for a total of three rinses.
Initial Pump Fill
Use only the undiluted 25 mcg/mL formulation for the initial pump fill. Fill the naïve pump after priming with the appropriate volume of PRIALT 25 mcg/mL. Begin dosing at a delivery rate no higher than 2.4 mcg/day (0.1 mcg/hr). In a naïve pump, PRIALT is lost due to two 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, the pump reservoir should be refilled with PRIALT 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 PRIALT is used diluted. For undiluted PRIALT, fill the pump at least every 84 days. To ensure aseptic transfer of PRIALT into the device, use the Medtronic refill kit. Empty the pump contents prior to refill with PRIALT.
If the internal infusion system must be surgically replaced while the person is receiving PRIALT, rinse the replacement pump with PRIALT according to Naïve Pump Priming [see Dosage and Administration ], and replace the initial fill solution within 14 days according to Initial Pump Fill [see Dosage and Administration ].
| PRIALT (ziconotide) solution, intrathecal infusion | Initial Fill Expiry | Refill Expiry |
| 25 mcg/mL, undiluted | 14 Days | 84 Days |
| 100 mcg/mL, undiluted | N/A | 84 Days |
| 100 mcg/mL, diluted | N/A | 40 Days |
Instructions for Use in 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. The CADD-Micro Ambulatory Infusion Pump is filled for the first time with PRIALT solution at a concentration of 5 mcg/mL. This solution is prepared by diluting PRIALT with 0.9% Sodium Chloride, USP (preservative free).
The recommended initial flow rate for the external microinfusion is 0.02 mL/hr to deliver the initial dose rate of 2.4 mcg/day (0.1 mcg/hr) of PRIALT. Changes in dose rate are made by adjusting the flow rate of the infusion system and/or the concentration of PRIALT solution. [see Warnings and Precautions ]
PRIALT (ziconotide) solution, intrathecal infusion is supplied as a 25 mcg/mL concentration in single-use 20 mL glass vials and as a 100 mcg/mL concentration in single-use glass vials containing 1 mL or 5 mL of solution.
Pregnancy
Risk Summary
Available data from postmarketing reports are insufficient to identify a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In an animal reproduction study, ziconotide did not cause embryo-fetal toxicity when administered to pregnant rats and rabbits during the period of organogenesis by continuous intravenous infusion at 400- and 940-times, respectively, the maximum recommended human dose (MRHD) of 19.2 mcg/day. In a pre- and post-natal development study, ziconotide did not affect pup development or reproductive performance when administered to rats by continuous intravenous infusion at 3800-times the MRHD (see Data).
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Data
Animal Data
Ziconotide caused embryo-fetal mortality 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 embryo-fetal mortality in the rat was approximately 700-fold above the expected exposure resulting from the maximum recommended human daily intrathecal dose of 0.8 mcg/hr (19.2 mcg/day). Ziconotide did not result in malformations when administered to pregnant rats by continuous intravenous infusion at doses up to 30 mg/kg/day or to pregnant 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/hr (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 dose levels. Maternal toxicity in the rat led to reduced fetal weights and transient, delayed ossification of the pubic bones at doses ≥ 15 mg/kg/day, which is approximately 8900-fold higher than the expected exposure resulting from the maximum recommended human daily intrathecal dose of 0.8 mcg/hr (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/hr (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 3800-fold higher than the expected exposure resulting from the maximum recommended human daily intrathecal dose of 0.8 mcg/hr (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.
Lactation
Risk Summary
There are no data on the presence of ziconotide in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. Infants exposed to PRIALT through breast milk should be monitored for sedation which may result in respiratory depression and/or feeding problems. The developmental and health benefits of breastfeeding should be weighed against the mother´s clinical need for PRIALT and any potential adverse effect on the breastfed infant from PRIALT or from the underlying maternal condition.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
Geriatric Use
Of the total number of subjects in clinical studies of PRIALT, 22% were 65 and over, while 7% were 75 and over. In all trials, there was a higher incidence of confusion in older patients (42% for ≥ 65 year old versus 29% for < 65 year old subgroups). Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, the dose selection for an elderly 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.
- 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.