The x-axis represents time in weeks. Dosage labels along the x-axis represent individual injections. Squares represent the two INVEGA SUSTENNA® initiation doses and circles represent INVEGA SUSTENNA® maintenance doses. Circles represent INVEGA TRINZA® doses.
The injection location (deltoid muscle) and dosage strength (234 mg) of the first INVEGA SUSTENNA® initiation dose is fixed and unable to be adjusted per the INVEGA SUSTENNA® Prescribing Information. The first INVEGA SUSTENNA® initiation dose occurs on Day 1 (on the x-axis).
The injection location (deltoid muscle) and dosage strength (156 mg) of the second INVEGA SUSTENNA® initiation dose is fixed and unable to be adjusted per the INVEGA SUSTENNA® Prescribing Information. While the INVEGA SUSTENNA® Prescribing Information does permit a dosing window of ±4 days to avoid a missed dose, in the illustrative scenarios, the timing of the second INVEGA SUSTENNA® dose cannot be adjusted.
According to the INVEGA SUSTENNA® Prescribing Information, monthly maintenance doses can be administered in either the deltoid or gluteal muscle. However, for illustrative purposes only, once you select the deltoid or gluteal muscle for an INVEGA SUSTENNA® maintenance dose, the site of injection will remain constant for all remaining INVEGA SUSTENNA® maintenance doses.
The last two doses of INVEGA SUSTENNA® must be the same dosage strength in order to establish a consistent maintenance dose before starting INVEGA TRINZA®. INVEGA TRINZA® is to be used only after INVEGA SUSTENNA® has been established as adequate treatment for at least four months, ensuring the last two doses of INVEGA SUSTENNA® are the same strength. In most of the scenarios, an additional INVEGA SUSTENNA® maintenance dose is also displayed for illustrative purposes only.
Initiate INVEGA TRINZA® when the next INVEGA SUSTENNA® dose is scheduled with a 3.5-fold higher dose in either the deltoid or gluteal muscle.
While the INVEGA TRINZA® Prescribing Information does permit a dosing window to avoid a first INVEGA TRINZA® missed dose, in most illustrative scenarios, the timing of the first INVEGA TRINZA® dose is locked and cannot be adjusted ±7 days.
Following the initial INVEGA TRINZA® dose, INVEGA TRINZA® should be administered every 3 months (±2 weeks) in either the deltoid or gluteal muscle. INVEGA TRINZA® dose adjustment can be made every 3 months in increments within the range of 273 mg to 819 mg based on individual patient tolerability and/or efficacy.
However, for illustrative purposes only, all INVEGA TRINZA® maintenance doses are locked based upon the first INVEGA TRINZA® dosage strength and site of injection selection. Additionally, in most illustrative scenarios, the timing of the INVEGA TRINZA® doses are locked and cannot be adjusted ±2 weeks to help avoid a missed dose.
This axis represents the typical paliperidone plasma concentration in nanograms per milliliter (ng/mL). Since efficacy and specific levels will vary from patient to patient, the concentration depicted is not intended to represent or imply therapeutic blood levels of paliperidone.
Clicking on these thought bubbles will reveal additional educational information about the scenario.
Patients may transition from every 2-week RISPERDAL CONSTA® at steady state (with an initial 3 weeks of oral supplementation) to monthly INVEGA SUSTENNA® (with adequate treatment for at least 4 months) to every 3-month INVEGA TRINZA®. Since paliperidone is the active metabolite of risperidone, the cumulative plasma level curve will reflect the plasma level contributions from the RISPERDAL CONSTA® treatment in this scenario. See the respective Prescribing Information for complete information.
Patients may transition from a monthly Long-Acting Injectable Antipsychotic (at steady-state) to monthly INVEGA SUSTENNA® (with adequate treatment for at least 4 months) to every 3-month INVEGA TRINZA®. Since other LAI antipsychotics are not related to the paliperidone compound, the cumulative plasma level curve will not reflect the plasma level contributions from the previous LAI antipsychotic treatment in this scenario. See the respective Prescribing Information for complete information.
When the Switch to INVEGA SUSTENNA® scenario is selected from the INVEGA TRINZA® Schizophrenia section of the Educational Dose Illustrator website, the recommended INVEGA SUSTENNA® dose is outlined by the INVEGA TRINZA® Prescribing Information, and is driven by last dose of INVEGA TRINZA® administered. The cumulative paliperidone plasma level curve will reflect the plasma level contributions from INVEGA TRINZA® and INVEGA SUSTENNA® in this scenario.
Daily oral INVEGA® ER doses should be started 3 months after the last INVEGA TRINZA® dose and transitioned over the next several months. The cumulative paliperidone plasma level curve will reflect the plasma level contributions from INVEGA TRINZA® and oral INVEGA® ER in this scenario. See the respective product’s Prescribing Information for complete information.
When the Single Dose Curve scenario is selected, the plasma levels from a single dose of INVEGA TRINZA® will be displayed in addition to the 5 months of previous INVEGA SUSTENNA® treatment for illustrative purposes. As stated in the INVEGA TRINZA® Prescribing Information, INVEGA TRINZA® is to be used only after INVEGA SUSTENNA® has been established as adequate treatment for at least four months.
The top menu is a list of all available dosing scenarios in the INVEGA TRINZA® Prescribing Information.
The legend dropdown indicates what each graph element represents.
Clicking this button will show additional background information about the dosing scenario available below the graph.
A blue vertical line is used to indicate when a switch in treatment has occurred (e.g., a switch from INVEGA SUSTENNA® to INVEGA TRINZA®).
INVEGA TRINZA® data simulations end abruptly as the plasma levels were not followed to final elimination from the body. The median apparent half-life of paliperidone following INVEGA TRINZA® administration over the dose range of 273-819 mg ranged from 84-95 days following deltoid injections and 118-139 days following gluteal injections.
The Educational Dose Illustrator can be used to visualize how dosing affects paliperidone plasma concentrations following administration of INVEGA SUSTENNA® and INVEGA TRINZA®. This resource simulates the paliperidone plasma concentrations over time resulting from different dosing scenarios that are set forth in the Prescribing Information for INVEGA SUSTENNA® and INVEGA TRINZA®.
The Educational Dose Illustrator is intended to be used as a resource to foster a better understanding and educate healthcare professionals about the dosing recommendations provided in the Prescribing Information for INVEGA SUSTENNA® and INVEGA TRINZA®. It is intended for educational purposes only. It is not intended to influence prescribing practices. It is not intended to be used to determine patient prescribing dosages, treatment, or dosing strategies. Because the simulated patient blood plasma levels of INVEGA SUSTENNA® and INVEGA TRINZA® shown in the dosing scenarios are based upon aggregated pharmacokinetic information from clinical studies, the simulations may not be representative of individual patient response.
The simulations were conducted using a 1-compartment model with parallel zero and first-order absorption to describe the pharmacokinetics of INVEGA SUSTENNA® 1 and a 1-compartment model with two saturable absorption processes described the pharmacokinetics of INVEGA TRINZA®2.
This information is for educational purposes only and is not intended to advise prescribing decisions or dosing strategies.
1. Samtani MN, Vermeulen A, Stuyckens K. Population pharmacokinetics of intramuscular paliperidone palmitate in patients with schizophrenia: a novel once-monthly, long-acting formulation of an atypical antipsychotic. Clin Pharmacokinet 2009;48(9):585-600.
2. Magnusson MO, Samtani MN, Plan EL, et al. Population pharmacokinetic simulations of two paliperidone palmitate formulations. Poster presented at the Population Approach Group In Europe; June 2-5, 2015; Crete, Greece.
The pharmacokinetic characteristics of paliperidone when administered as a single1 and multiple2 injections of paliperidone palmitate 3-month were well captured by the developed population pharmacokinetic model3 for paliperidone palmitate 3-month.
This information is for educational purposes only and is not intended to advise prescribing decisions or dosing strategies.
1. Ravenstijn P, Remmerie B, Savitz A, et al. pharmacokinetics, safety, and tolerability of paliperidone palmitate 3-month formulation in patients with schizophrenia: a phase-1, single-dose, randomized, open-label study. J Clin Pharmacol 2015 doi: 10.1002/jcph.597. [Epub ahead of print]
2. Berwaerts J, Liu Y, Gopal S, et al. Efficacy and safety of the 3-month formulation of paliperidone palmitate vs placebo for relapse prevention of schizophrenia - a randomized clinical trial. JAMA Psychiatry 2015;72(8):830-839.
3. Magnusson MO, Samtani MN, Plan EL, et al. Population pharmacokinetic simulations of two paliperidone palmitate formulations. Poster presented at the Population Approach Group In Europe; June 2-5, 2015; Crete, Greece.