SUMMARY

• No systematically collected clinical data is available on switching patients on INVEGA SUSTENNA to another antipsychotic. The decision of how to convert/switch antipsychotics must be based on clinical judgment, individual patient assessment, and pharmacokinetic (PK) properties of the drugs involved.
• If INVEGA SUSTENNA is discontinued, its prolonged-release characteristics must be considered. Following a single intramuscular (IM) dose of INVEGA SUSTENNA, the release of paliperidone starts as early as day 1 and lasts for as long as 126 days. The median apparent half-life of paliperidone following INVEGA SUSTENNA single-dose administration over the dose range of 39 mg - 234 mg ranged from 25 days - 49 days.¹
• If switching from INVEGA SUSTENNA to RISPERDAL CONSTA:
  • Upon initiating RISPERDAL CONSTA, sufficient antipsychotic coverage is required during a 3-week lag period until the main release of risperidone occurs. After a single RISPERDAL CONSTA injection, the release profile consists of a small initial release of risperidone, followed by a lag time of 3 weeks. The main release of risperidone starts from week 3 onwards, is maintained from 4 to 6 weeks, and subsides by week 7.²
• If switching from INVEGA SUSTENNA to oral paliperidone ER tablets:
  • PK modeling simulation data suggest that subjects would continue to have similar paliperidone plasma concentrations after discontinuation of INVEGA SUSTENNA 234 mg monthly maintenance dosing if they received oral paliperidone ER tablets according to the following schedule: 6 mg/day for the first month after discontinuation, 9 mg/day for the second month, and 12 mg/day thereafter.³
• If switching from INVEGA SUSTENNA to INVEGA TRINZA, initiate INVEGA TRINZA when the next INVEGA SUSTENNA dose is scheduled (see Table: INVEGA TRINZA Doses for Adult Patients Adequately Treated with INVEGA SUSTENNA).^4,5
  • In a prospective observational study, mean (standard deviation [SD]) plasma levels of paliperidone were 32.84 (15.21) ng/mL at the time of switching from INVEGA SUSTENNA to INVEGA TRINZA and 23.56 (11.98) ng/mL 28 days after INVEGA TRINZA administration. After steady-state paliperidone concentrations were achieved with INVEGA SUSTENNA treatment, the stability of plasma concentration of paliperidone was maintained during the transition to INVEGA TRINZA without oral supplementation of paliperidone.⁶
• If switching from INVEGA SUSTENNA to INVEGA HAFYERA, initiate INVEGA HAFYERA when the next INVEGA SUSTENNA dose is scheduled (see Table: INVEGA HAFYERA Doses for Adult Patients Adequately Treated with INVEGA SUSTENNA).⁷
• If switching from INVEGA SUSTENNA to subcutaneous risperidone, such as Perseris^® (risperidone) or Uzedy^® (risperidone), there are currently no head-to-head clinical studies examining this conversion and differences in formulation and route of administration must be considered.^8,9
  • Perseris^® and Uzedy^® are not Johnson & Johnson products. Please contact their respective manufacturer for more information.  

DOSAGE STRENGTH INFORMATION

Doses of paliperidone palmitate extended-release injectable suspension may be expressed in milligram equivalents of paliperidone (active moiety) or milligrams of paliperidone palmitate. Dosage information in this response has been converted to mg of paliperidone palmitate to reflect the commercially available dosage strengths in the United States. The conversion factor from mg eq. to mg is 1.56.

• INVEGA SUSTENNA doses expressed as 39, 78, 117, 156, and 234 mg of paliperidone palmitate are equal to 25, 50, 75, 100, and 150 mg eq. of paliperidone, respectively.
• INVEGA TRINZA doses expressed as 273, 410, 546, and 819 mg of paliperidone palmitate are equal to 175, 263, 350, and 525 mg eq. of paliperidone, respectively.
• INVEGA HAFYERA doses expressed as 1,092 and 1,560 mg of paliperidone palmitate are equal to 700 and 1,000 mg eq. of paliperidone respectively.

Treatment Discontinuation - Pharmacokinetic Modeling

Long-acting injectables have longer elimination times than their oral equivalents, and as with other long-acting formulations, active antipsychotic could therefore remain in the system for several months following discontinuation of INVEGA SUSTENNA. Samtani et al (2012)¹⁰ illustrated the active-moiety concentrations of oral risperidone, oral paliperidone, RISPERDAL CONSTA and INVEGA SUSTENNA upon treatment discontinuation, illustrating that active-moiety plasma concentrations persisted longest in subjects receiving INVEGA SUSTENNA (see the Figure below, Active-Moiety Concentrations from Oral Risperidone, Oral Paliperidone, Risperidone Long-Acting Injection, and Paliperidone Palmitate Upon Treatment Discontinuation, in which the arrows indicate last dose received for each product). This PK simulation compared the active moiety concentrations upon treatment discontinuation of:

• Risperidone (risperidone + 9-hydroxyrisperidone) among adults receiving either orally administered, immediate-release risperidone 3 mg/day or RISPERDAL CONSTA 37.5 mg/14 days.
• Paliperidone (9-hydroxyrisperidone) among adults receiving either orally administered paliperidone ER 6 mg/day or INVEGA SUSTENNA 117 mg/28 days.

Subjects at steady-state received their last dose on week -4 (4 weeks prior) for injectable INVEGA SUSTENNA, week -2 (2 weeks prior) for RISPERDAL CONSTA, or day -1 (1 day prior) for oral risperidone or oral paliperidone ER.

Pharmacokinetic Considerations if Switching to risperdal consta

Mannaert et al (2005)¹¹ illustrated the mean plasma concentration-time curve after single IM administration of 50 mg of RISPERDAL CONSTA (n=26) without oral supplementation, illustrating the main release of risperidone does not begin until three weeks after an injection (see Figure: Mean Plasma Concentration-Time Curve After Single Intramuscular Administration of RISPERDAL CONSTA 50 mg Without Oral Supplementation).¹²

In the absence of specific guidance/recommendations currently available for a switch from INVEGA SUSTENNA to RISPERDAL CONSTA, the decision must be based on clinical judgment and individual patient assessment, taking into account the variability in PK and pharmacodynamic properties of both products.

Dose Equivalency with risperdal consta - Pharmacokinetic Modeling

Samtani et al (2010)¹³ presented PK modeling simulations which suggest that patients previously stabilized with different doses of RISPERDAL CONSTA can attain similar steady-state exposure to active moiety during maintenance treatment with monthly doses of INVEGA SUSTENNA. The simulations were conducted to establish the strategy for switching from RISPERDAL CONSTA to INVEGA SUSTENNA (see Table: Doses of RISPERDAL CONSTA and INVEGA SUSTENNA Needed to Attain Similar Active Moiety Exposure at Steady-State). Please note that simulations have not been conducted to determine the strategy for switching from paliperidone palmitate to RISPERDAL CONSTA.

Dose Equivalency with oral paliperidone ER - Pharmacokinetic Modeling

A PK simulation depicted the expected paliperidone plasma concentration for subjects receiving INVEGA SUSTENNA 234 mg monthly maintenance doses at steady-state, and then converting to oral paliperidone ER (see Figure: Median Pharmacokinetic Profile After Conversion from INVEGA SUSTENNA 234 mg to Titration of Oral Paliperidone ER). All simulated subjects received INVEGA SUSTENNA 234 mg at -12, -8, and -4 weeks before a switch to paliperidone ER. The gray/orange line depicts the median expected paliperidone plasma concentration in subjects who continued to receive the INVEGA SUSTENNA 234 mg dose every 4 weeks. The black line depicts the median expected paliperidone plasma concentration in subjects who discontinued INVEGA SUSTENNA and switched to oral paliperidone ER 6 mg for weeks 0-4, paliperidone ER 9 mg for weeks 4-8, and finally continued on paliperidone ER 12 mg from weeks 8-20.³

PALIPERIDONE PLASMA LEVELS FOLLOWING TRANSITION FROM INVEGA SUSTENNA to invega trinza

Mauri et al (2022)⁶ conducted a prospective observational study to evaluate the maintenance of clinical efficacy and tolerability, and variation of paliperidone plasma levels during the transition from INVEGA SUSTENNA to INVEGA TRINZA.

Study Design/Methods

• Adult patients (N=22) aged 18-66 years with schizophrenia have been included since 2017, and observation is ongoing.
• Clinical assessments were performed at the time of the first INVEGA SUSTENNA administration and then every 28 days up to the time of switching to INVEGA TRINZA, followed by 28 days and 2 months after the first INVEGA TRINZA administration and then every 3 months until 9 months of the first INVEGA TRINZA administration.
• All patients were stabilized on INVEGA SUSTENNA for 4 months, following which patients were switched to INVEGA TRINZA.

Results

The mean age of patients was 46.91 years. The mean (SD) plasma levels of paliperidone were 32.84 (15.21) ng/mL at the time of switching from INVEGA SUSTENNA to INVEGA TRINZA and 23.56 (11.98) ng/mL 28 days after INVEGA TRINZA administration. At the time of switching to INVEGA TRINZA vs 28 days after INVEGA TRINZA administration, 75% vs 63% of patients had plasma levels of >20 ng/mL, 16% vs 18% had plasma levels of <20 ng/mL, and 1% vs 18% had plasma levels of <10 ng/mL. After the initial slight increase, the plasma levels were stabilized after the 4^th administration of INVEGA SUSTENNA, and a slight reduction in plasma levels (not statistically significant) was observed during treatment with INVEGA TRINZA.

After steady-state paliperidone concentrations were achieved with INVEGA SUSTENNA treatment, the stability of plasma concentration of paliperidone was maintained during the transition to INVEGA TRINZA without oral supplementation of paliperidone.

Dose Equivalency with INVEGA TRINZA and invega hafyera

Dose Initiation

• INVEGA TRINZA is indicated for the treatment of schizophrenia in patients after they have been adequately treated with INVEGA SUSTENNA for at least 4 months.^4,5
  • In order to establish a consistent maintenance dose, the last 2 doses of INVEGA SUSTENNA should be the same dosage strength before starting INVEGA TRINZA.
• Initiate INVEGA TRINZA when the next INVEGA SUSTENNA dose is scheduled with a INVEGA TRINZA dose based on the previous INVEGA SUSTENNA injection dose, using the equivalent 3.5-fold higher dose (see Table: INVEGA TRINZA Doses for Adult Patients Adequately Treated with INVEGA SUSTENNA).^4,5

• INVEGA HAFYERA is indicated for treatment of schizophrenia in patients after that have been adequately treated with INVEGA SUSTENNA for at least 4 months or INVEGA TRINZA for at least one 3-month cycle.⁷
  • The last 2 doses of INVEGA SUSTENNA should be the same dosage strength before starting INVEGA HAFYERA.
• Initiate INVEGA HAFYERA when the next INVEGA SUSTENNA dose is scheduled with a INVEGA HAFYERA dose based on the previous INVEGA SUSTENNA injection dose (see Table: INVEGA HAFYERA Doses for Adult Patients Adequately Treated with INVEGA SUSTENNA).⁷

Pharmacokinetic Considerations if Switching to SUBCUTANEOUS risperIDONE

Perseris^® (risperidone) and Uzedy^® (risperidone) are not Johnson & Johnson products. Perseris^® and Uzedy^® are subcutaneous, long-acting injectables available as once monthly and once monthly or once every 2 months, respectively. For questions on these products, please refer to their respective manufacturer.^8,9

There are currently no head-to-head studies examining the efficacy and safety of INVEGA SUSTENNA compared to the once monthly or once every 2 months subcutaneous risperidone injections. Differences in formulation and route of administration must be considered when transitioning a patient from INVEGA SUSTENNA to either medication.

Perseris (90 mg or 120 mg) is administered once monthly as a subcutaneous injection in the abdomen or back of the upper arm by a healthcare professional and is indicated for the treatment of schizophrenia in adults.⁹

Uzedy (50 mg, 75 mg, 100 mg, 125 mg, 150 mg, 200 mg, and 250 mg) is administered either once monthly or once every 2 months in the abdomen or upper arm via subcutaneous injection by a healthcare professional. Uzedy is indicated for the treatment of schizophrenia in adults.⁸

Case Report

Hsu et al (2013)¹⁴ reported the case of a 39-year-old Chinese female with a history of schizophrenia who developed tardive dyskinesia (TD) following the discontinuation of depot haloperidol and initiation of INVEGA SUSTENNA.

The patient was treated with depot haloperidol (40 mg/month) for 9 months but continued to experience prominent negative symptoms. Haloperidol was discontinued and INVEGA SUSTENNA was initiated with two 156 mg injections administered 7 days apart, followed by monthly maintenance doses of 156 mg for 2 months.

Subsequent to the 4^th INVEGA SUSTENNA 156 mg dose the patient experienced the first mild tongue protrusion. Over the next month symptoms progressed to moderate-severe involuntary tongue and jaw movements. INVEGA SUSTENNA was immediately discontinued while aripiprazole was initiated at 5 mg/day. Movement symptoms began to improve at 6 weeks and totally remitted at 3 months while her psychiatric symptoms remained controlled.

LITERATURE SEARCH

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 22 October 2024.