DOSAGE AND ADMINISTRATION
IT PRIALT should be initiated at no more than 2.4 mcg/day (0.1 mcg/hr) and titrated to patient response. Doses may be titrated upward by up to 2.4 mcg/day (0.1 mcg/hr) at intervals of no more than 2–3 times per week, up to a recommended maximum of 19.2 mcg/day (0.8 mcg/hr) by Day 21. Dose increases in increments of less than 2.4 mcg/day (0.1 mcg/hr) and increases in dose less frequently than 2–3 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. Controlled studies of pain relief have not been conducted for longer than 3 weeks duration, although 977 patients have been treated with IT PRIALT in long-term open-label trials.
The dose of IT PRIALT should be adjusted according to the patient's severity of pain, their response to therapy, and the occurrence of adverse events. The effective dose of PRIALT for analgesia is variable. The average dose level at the end of the 21-day titration used in the slow titration clinical trial (see CLINICAL TRIALS) was 6.9 mcg/day (0.29 mcg/hr) and the maximum dose was 19.2 mcg/day (0.8 mcg/hr) on Day 21. Due to the frequency of adverse events, 19.2 mcg/day (0.8 mcg/hr) is the maximum recommended dose.
Because of the lower incidence of serious adverse events and discontinuations for adverse events associated with the slower titration (see ADVERSE REACTIONS), a faster titration schedule should only be used if there is an urgent need for analgesia that outweighs the risk to patient safety.
In clinical trials, no rebound or other adverse events related to discontinuation of PRIALT were noted, although treatment was almost always discontinued abruptly.
Vials of PRIALT should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
PRIALT should be administered intrathecally (IT) by or under the direction of a physician experienced in the technique of IT administration and who is familiar with the drug and device labeling. PRIALT is not intended for intravenous administration.
PRIALT is intended for IT delivery using a programmable implanted variable-rate microinfusion device or an external microinfusion device and catheter (see PRECAUTIONS-Meningitis and Other Infections). Refer to the manufacturer's manual for specific instructions and precautions for programming the microinfusion device and/or refilling the reservoir.
PRIALT is used for therapy undiluted (25 mcg/mL in 20 mL vial) or diluted (100 mcg/mL in 1, 2, or 5 mL vials). Diluted PRIALT is prepared with 0.9% Sodium Chloride Injection, USP (preservative free) using aseptic procedures to the desired concentration prior to placement in the microinfusion pump. The 100 mcg/mL formulation may be administered undiluted once an appropriate dose has been established. SALINE SOLUTIONS CONTAINING PRESERVATIVES ARE NOT APPROPRIATE FOR IT DRUG ADMINISTRATION AND SHOULD NOT BE USED. Refrigerate but do not freeze all PRIALT solutions after preparation and begin infusion within 24 hours. Discard any PRIALT solution with observed particulate matter or discoloration and any unused portion left in the vial.
Medtronic SynchroMed EL or SynchroMed II Infusion System (see PRECAUTIONS-Meningitis and Other Infections)
Refer to the manufacturer's manuals for specific instructions and precautions for performing a reservoir rinse, initial filling, refilling the reservoir, and programming.
Instructions for Use of PRIALT with Pump
1. Naïve Pump Priming (i.e., first time use with PRIALT)
Only the undiluted 25 mcg/mL formulation should be used 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.
2. Initial Pump Fill
Only the undiluted 25 mcg/mL formulation should be used for initial pump fill. Fill the naïve pump after priming as above with the appropriate volume of PRIALT at 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 the 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.
3. 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, it is recommended that the Medtronic refill kit be used. The pump contents should be emptied prior to refill with PRIALT.
If the internal infusion system must be surgically replaced while the person is receiving PRIALT, the replacement pump should be rinsed with PRIALT (No. 1 above), and this initial fill solution must be replaced within 14 days (No. 2 above). Subsequent refills should be done at least every 84 days if PRIALT is used undiluted or at least every 40 days if PRIALT is used diluted.
(ziconotide intrathecal infusion)
| Initial Fill|
|25 mcg/mL, undiluted||14 Days||84 Days|
|100 mcg/mL, undiluted||N/A||84 Days|
|100 mcg/mL, diluted||N/A||40 Days|
CADD-Micro ambulatory infusion pump (see PRECAUTIONS-Meningitis and Other Infections)
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 appropriate external microinfusion device 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 flow rate for the external microinfusion device usually starts at 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.