INVEGA TRINZA PROLONGED RELEASE SUSPENSION FOR IM INJECTION 525MG/2.625ML

INJECTION, SUSPENSION, EXTENDED RELEASE

**Dosage and Administration** INVEGA TRINZA® is to be used only after the 1-month paliperidone palmitate injectable product has been established as adequate treatment for at least four months. In order to establish a consistent maintenance dose, it is recommended that the last two doses of the 1-month injection be the same dosage strength before starting INVEGA TRINZA®. **Dosage** Initiate INVEGA TRINZA® at the time when the next 1-month paliperidone palmitate dose was to be scheduled with a INVEGA TRINZA® dose based on the previous 1-month injection dose as shown in Table 1. INVEGA TRINZA® may be administered up to 7 days before or after the monthly time point of the next scheduled paliperidone palmitate 1-month dose.  Following the initial INVEGA TRINZA® dose, INVEGA TRINZA® should be administered every 3 months. If needed, dose adjustment can be made every 3 months in increments within the range of 175 mg to 525 mg based on individual patient tolerability and/or efficacy. Due to the long-acting nature of INVEGA TRINZA®, the patient’s response to an adjusted dose may not be apparent for several months (see _Pharmacokinetic Properties_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). **Missed dose(s)** _Dosing Window_. Missing doses of INVEGA TRINZA® should be avoided. However, on exceptional occasions, patients may be given the injection up to 2 weeks before or after the 3-month time point. _Missed Dose > 3½ Months up to 4 Months_. If more than 3½ months (up to 4 months) have elapsed since the last injection of INVEGA TRINZA®, the previously administered INVEGA TRINZA® dose should be administered as soon as possible, then continue with the 3-month injections following this dose. _Missed Dose > 4 Months up to 9 Months_. If more than 4 months (up to 9 months) have elapsed since the last injection of INVEGA TRINZA®, do NOT administer the next dose of INVEGA TRINZA®. Instead, use the re-initiation regimen shown in Table 2.  _Missed Dose > 9 Months_. If more than 9 months have elapsed since the last injection of INVEGA TRINZA®, re-initiate treatment with the 1-month paliperidone palmitate injectable product as described in the prescribing information for that product. INVEGA TRINZA® can then be resumed after the patient has been adequately treated with the 1-month paliperidone palmitate injectable product for at least 4 months. **Administration information** Parenteral drug products should be inspected visually for foreign matter and discoloration prior to administration. **Within 5 minutes prior to administration of INVEGA TRINZA® to the patient, it is important to shake the syringe vigorously for at least 15 seconds to ensure a homogeneous suspension** (see _Instructions for Use and Handling and Disposal_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). INVEGA TRINZA® is intended for intramuscular use only. Do not administer intravascularly or subcutaneously. Avoid inadvertent injection into a blood vessel. Each injection must be administered only by a health care professional. Administer the dose in a single injection; do not administer the dose in divided injections. Inject slowly, deep into the deltoid or gluteal muscle. INVEGA TRINZA® must be administered using only the thin wall needles that are provided in the INVEGA TRINZA® pack. Needles from the 1-month paliperidone palmitate injectable product pack or other commercially-available needles are not to be used when administering INVEGA TRINZA®. The recommended needle size for administration of INVEGA TRINZA® into the deltoid muscle is determined by the patient’s weight. For those ≥ 90 kg (≥ 200 lbs), the 1½-inch, 22 gauge thin wall needle is recommended. For those < 90 kg (< 200 lbs), the 1-inch, 22 gauge thin wall needle is recommended. Administer into the center of the deltoid muscle. Deltoid injections should be alternated between the two deltoid muscles. The recommended needle size for administration of INVEGA TRINZA® into the gluteal muscle regardless of body weight is the 1½-inch, 22 gauge thin wall needle. Administer into the upper-outer quadrant of the gluteal muscle. Gluteal injections should be alternated between the two gluteal muscles. Since paliperidone is the active metabolite of risperidone, caution should be exercised when INVEGA TRINZA® is coadministered with risperidone or with oral paliperidone for extended periods of time. Safety data involving concomitant use of INVEGA TRINZA® with other antipsychotics is limited. _Incomplete Administration_. To avoid an incomplete administration of INVEGA TRINZA®, ensure that the prefilled syringe is **shaken vigorously for at least 15 seconds within 5 minutes prior to administration to ensure a homogeneous suspension** (see _Instructions for Use and Handling and Disposal_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). However, in the event of an incompletely administered dose, do **not** re-inject the dose remaining in the syringe and do **not** administer another dose. Closely monitor and treat the patient appropriately until the next scheduled 3-month injection of INVEGA TRINZA®. **Special populations** _**Pediatrics (less than 18 years of age)**_ Safety and effectiveness of INVEGA TRINZA® in patients < 18 years of age have not been studied. _**Elderly (65 years of age and older)**_ In general, recommended dosing of INVEGA TRINZA® for elderly patients with normal renal function is the same as for younger adult patients with normal renal function. As elderly patients may have reduced renal function, see _Renal impairment_ below for dosing recommendations in patients with renal impairment. Efficacy and safety in elderly >65 years of have not been established. _**Renal impairment**_ INVEGA TRINZA® has not been systematically studied in patients with renal impairment (see _Pharmacokinetic Properties_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). For patients with mild renal impairment (creatinine clearance ≥ 50 to < 80 mL/min), dose adjustment is done when initiating treatment with the 1-month paliperidone palmitate injectable product; no dose adjustment of INVEGA TRINZA® is required. Transition to INVEGA TRINZA® is with a dose in a 3.5 to 1 ratio to the previous stabilized 1-month paliperidone palmitate injectable product as described in _Dosage_ above. The maximum recommended dose of INVEGA TRINZA® in patients with mild renal impairment is 350 mg. INVEGA TRINZA® is not recommended in patients with moderate or severe renal impairment (creatinine clearance < 50 ml/min). _**Hepatic impairment**_ INVEGA TRINZA® has not been studied in patients with hepatic impairment. Based on a study with oral paliperidone, no dose adjustment is required in patients with mild or moderate hepatic impairment. Paliperidone has not been studied in patients with severe hepatic impairment. (See _Pharmacokinetic Properties_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_) _**Other populations**_ No dose adjustment for INVEGA TRINZA® is recommended based on gender, race, or smoking status. (For pregnant women and nursing mothers, see _Pregnancy and Breast-feeding_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_.) **Switching from other antipsychotic agents** INVEGA TRINZA® is to be used only after the patient has been adequately treated with the 1-month paliperidone palmitate injectable product for at least 4 months (see _Indications_ and _Dosage and Administration_). If INVEGA TRINZA® is discontinued, its prolonged-release characteristics must be considered. As recommended with other antipsychotic medications, the need for continuing existing extrapyramidal symptoms (EPS) medication should be re-evaluated periodically. **Switching from INVEGA TRINZA® to the 1-Month Paliperidone Palmitate Injectable Product** For switching from INVEGA TRINZA® to the 1-month paliperidone palmitate injectable product, the 1-month paliperidone palmitate injectable product should be administered at the time the next INVEGA TRINZA® dose was to be administered using the equivalent 3.5-fold lower dose as shown in Table 3. The 1-month paliperidone palmitate injectable product should then continue dosed at monthly intervals.  **Switching from INVEGA TRINZA® to Oral Paliperidone Extended-Release Tablets** For switching from INVEGA TRINZA® to oral paliperidone extended-release tablets, the daily dosing of the paliperidone extended-release tablets should be started 3 months after the last INVEGA TRINZA® dose and transitioned over the next several months following the last INVEGA TRINZA® dose as described in Table 4. Table 4 provides dose conversion regimens to allow patients previously stabilized on different doses of INVEGA TRINZA® to attain similar paliperidone exposure with once daily paliperidone extended-release tablets.