Invega Sustenna

INVEGA SUSTENNA (paliperidone palmitate) is indicated for the treatment of:

• Schizophrenia in adults
  
  
  [see
  
  

  14.1 Schizophrenia

  Short-Term Monotherapy (Studies 1, 2, 3, 4)

  The efficacy of INVEGA SUSTENNA in the acute treatment of schizophrenia was evaluated in four short-term (one 9-week and three 13-week) double-blind, randomized, placebo-controlled, fixed-dose studies of acutely relapsed adult inpatients who met DSM-IV criteria for schizophrenia. The fixed doses of INVEGA SUSTENNA in these studies were given on days 1, 8, and 36 in the 9-week study, and additionally on day 64 of the 13-week studies, i.e., at a weekly interval for the initial two doses and then every 4 weeks for maintenance.

  Efficacy was evaluated using the total score on the Positive and Negative Syndrome Scale (PANSS). The PANSS is a 30-item scale that measures positive symptoms of schizophrenia (7 items), negative symptoms of schizophrenia (7 items), and general psychopathology (16 items), each rated on a scale of 1 (absent) to 7 (extreme); total PANSS scores range from 30 to 210.

  In Study 1 (PSY-3007), a 13-week study (n=636) comparing three fixed doses of INVEGA SUSTENNA (initial deltoid injection of 234 mg followed by 3 gluteal or deltoid doses of either 39 mg/4 weeks, 156 mg/4 weeks or 234 mg/4 weeks) to placebo, all three doses of INVEGA SUSTENNA were superior to placebo in improving the PANSS total score.

  In Study 2 (PSY-3003), another 13-week study (n=349) comparing three fixed doses of INVEGA SUSTENNA (78 mg/4 weeks, 156 mg/4 weeks, and 234 mg/4 weeks) to placebo, only 156 mg/4 weeks of INVEGA SUSTENNA was superior to placebo in improving the PANSS total score.

  In Study 3 (PSY-3004), a third 13-week study (n=513) comparing three fixed doses of INVEGA SUSTENNA (39 mg/4 weeks, 78 mg/4 weeks, and 156 mg/4 weeks) to placebo, all three doses of INVEGA SUSTENNA were superior to placebo in improving the PANSS total score.

  In Study 4 (SCH-201), the 9-week study (n=197) comparing two fixed doses of INVEGA SUSTENNA (78 mg/4 weeks and 156 mg/4 weeks) to placebo, both doses of INVEGA SUSTENNA were superior to placebo in improving PANSS total score.

  A summary of the mean baseline PANSS scores along with the mean changes from baseline in the four short-term acute schizophrenia studies are provided in Table 14.

  Table 14: Schizophrenia Short-term Studies

  Study Number	Treatment Group	Primary Efficacy Measure: PANSS Total Score
  		Mean Baseline Score (SD)	LS Mean Change from Baseline (SE)	Placebo-subtracted DifferenceDifference (drug minus placebo) in least-squares mean change from baseline. (95% CI)
  SD: standard deviation; SE: standard error; LS Mean: least-squares mean; CI: unadjusted confidence interval.
  Study 1	INVEGA SUSTENNA (39 mg/4 weeks)p<0.05 (Doses statistically significantly superior to placebo).	86.9 (11.99)	-11.2 (1.69)	-5.1 (-9.01, -1.10)
  	INVEGA SUSTENNA (156 mg/4 weeks)	86.2 (10.77)	-14.8 (1.68)	-8.7 (-12.62, -4.78)
  	INVEGA SUSTENNA (234 mg/4 weeks)	88.4 (11.70)	-15.9 (1.70)	-9.8 (-13.71, -5.85)
  	Placebo	86.8 (10.31)	-6.1 (1.69)	--
  Study 2 Because an insufficient number of subjects received the 234 mg/4 weeks dose, results from this group are not included.	INVEGA SUSTENNA (78 mg/4 weeks)	89.9 (10.78)	-6.9 (2.50)	-3.5 (-8.73, 1.77)
  	INVEGA SUSTENNA (156 mg/4 weeks)	90.1 (11.66)	-10.4 (2.47)	-6.9 (-12.12, -1.68)
  	Placebo	92.4 (12.55)	-3.5 (2.15)	--
  Study 3	INVEGA SUSTENNA (39 mg/4 weeks)	90.7 (12.25)	-19.8 (2.19)	-6.6 (-11.40, -1.73)
  	INVEGA SUSTENNA (78 mg/4 weeks)	91.2 (12.02)	-19.2 (2.19)	-5.9 (-10.76, -1.07)
  	INVEGA SUSTENNA (156 mg/4 weeks)	90.8 (11.70)	-22.5 (2.18)	-9.2 (-14.07, -4.43)
  	Placebo	90.7 (12.22)	-13.3 (2.21)	--
  Study 4	INVEGA SUSTENNA (78 mg/4 weeks)	88.0 (12.39)	-4.6 (2.43)	-11.2 (-16.85, -5.57)
  	INVEGA SUSTENNA (156 mg/4 weeks)	85.2 (11.09)	-7.4 (2.45)	-14.0 (-19.51, -8.58)
  	Placebo	87.8 (13.90)	6.6 (2.45)	--

  Maintenance Monotherapy Treatment (Study 5: PSY-3001)

  The efficacy of INVEGA SUSTENNA in maintaining symptomatic control in schizophrenia was established in a longer-term double-blind, placebo-controlled, flexible-dose study involving adult subjects who met DSM-IV criteria for schizophrenia. This study included a minimum 12-week, fixed-dose stabilization phase, and a randomized, placebo-controlled phase to observe for relapse. During the double-blind phase, patients were randomized to either the same dose of INVEGA SUSTENNA they received during the stabilization phase, i.e., 39 mg, 78 mg, or 156 mg administered every 4 weeks, or to placebo. A total of 410 stabilized patients were randomized to either INVEGA SUSTENNA or to placebo until they experienced a relapse of schizophrenia symptoms. Relapse was pre-defined as time to first emergence of one or more of the following: psychiatric hospitalization, ≥ 25% increase (if the baseline score was > 40) or a 10-point increase (if the baseline score was ≤ 40) in total PANSS score on two consecutive assessments, deliberate self-injury, violent behavior, suicidal/homicidal ideation, or a score of ≥ 5 (if the maximum baseline score was ≤ 3) or ≥ 6 (if the maximum baseline score was 4) on two consecutive assessments of the specific PANSS items. The primary efficacy variable was time to relapse. A pre-planned interim analysis showed a statistically significantly longer time to relapse in patients treated with INVEGA SUSTENNA compared to placebo, and the study was stopped early because maintenance of efficacy was demonstrated. Thirty-four percent (34%) of subjects in the placebo group and 10% of subjects in the INVEGA SUSTENNA group experienced a relapse event. There was a statistically significant difference between the treatment groups in favor of INVEGA SUSTENNA. A Kaplan-Meier plot of time to relapse by treatment group is shown in Figure 3. The time to relapse for subjects in the placebo group was statistically significantly shorter than for the INVEGA SUSTENNA group. An examination of population subgroups did not reveal any clinically significant differences in responsiveness on the basis of gender, age, or race.

  Figure 3: Kaplan-Meier Plot of Cumulative Proportion of Subjects with Relapse Over Time (Schizophrenia Study 5)

  

  Figure 3

  Long-Term Comparative Monotherapy Treatment versus Oral Antipsychotic Therapy (Study 6: SCH-3006)

  The efficacy of INVEGA SUSTENNA in delaying time to treatment failure compared with selected oral antipsychotic medications was established in a long-term, randomized, flexible-dose study in subjects with schizophrenia and a history of incarceration. Subjects were screened for up to 14 days followed by a 15-month treatment phase during which they were observed for treatment failure.

  The primary endpoint was time to first treatment failure. Treatment failure was defined as one of the following: arrest and/or incarceration; psychiatric hospitalization; discontinuation of antipsychotic treatment because of safety or tolerability; treatment supplementation with another antipsychotic because of inadequate efficacy; need for increase in level of psychiatric services to prevent an imminent psychiatric hospitalization; discontinuation of antipsychotic treatment because of inadequate efficacy; or suicide. Treatment failure was determined by an Event Monitoring Board (EMB) that was blinded to treatment assignment. A total of 444 subjects were randomly assigned to either INVEGA SUSTENNA (N = 226; median dose 156 mg) or one of up to seven pre-specified, flexibly-dosed, commonly prescribed oral antipsychotic medications (N = 218; aripiprazole, haloperidol, olanzapine, paliperidone, perphenazine, quetiapine, or risperidone). The selection of the oral antipsychotic medication was determined to be appropriate for the patient by the investigator. A statistically significantly longer time to first treatment failure was seen for INVEGA SUSTENNA compared with oral antipsychotic medications. The median time to treatment failure was 416 days and 226 days for INVEGA SUSTENNA and antipsychotic medications, respectively. A Kaplan-Meier plot of time to first treatment failure is shown in Figure 4. The frequencies of first treatment failure events by type are shown in Table 15. The time to first arrest and/or incarceration or psychiatric hospitalization was also statistically significantly longer for the INVEGA SUSTENNA group compared to the oral antipsychotic group.

  Figure 4: Kaplan-Meier Plot of Time to First Treatment Failure in a Long-Term, Randomized, Flexible-Dose Study in Subjects with Schizophrenia and a History of Incarceration (Schizophrenia Study 6)

  

  *

  Median time to first treatment failure: 416 days with INVEGA SUSTENNA; 226 days with oral antipsychotics

  Table 15: Components of Composite Endpoint in a Long-Term, Randomized, Flexible-Dose Study in Subjects with Schizophrenia and a History of Incarceration (Schizophrenia Study 6)

  Event Type	INVEGA SUSTENNA N=226 frequency (%)	Oral Antipsychotics N=218 frequency (%)	Hazard RatioHazard ratio of INVEGA SUSTENNA to Oral Antipsychotics based on Cox regression model for time-to-event analysis. Note that the hazard ratio did not appear constant throughout the trial. [95% CI]
  First Treatment Failures	90 (39.8%)	117 (53.7%)	0.70 [0.53, 0.92]
  First Treatment Failure Component Events
  Arrest and/or incarceration	48 (21.2%)	64 (29.4%)
  Psychiatric hospitalization	18 (8.0%)	26 (11.9%)
  Discontinuation of antipsychotic treatment because of safety or tolerability	15 (6.6%)	8 (3.7%)
  Treatment supplementation with another antipsychotic because of inadequate efficacy	5 (2.2%)	6 (2.8%)
  Need for increase in level of psychiatric services to prevent an imminent psychiatric hospitalization	3 (1.3%)	4 (1.8%)
  Discontinuation of antipsychotic treatment because of inadequate efficacy	1 (0.4%)	9 (4.1%)
  Suicide	0	0
  Arrest and/or Incarceration or Psychiatric Hospitalization Events, regardless of whether they were first events Analysis results, which incorporated relevant events collected after discontinuation for those who discontinued, were consistent with the results from the pre-specified analysis of this secondary endpoint.	76 (33.6%)	98 (45.0%)	0.70 [0.52, 0.94]

  Figure 4

  ].
  
  
• Schizoaffective disorder in adults as monotherapy and as an adjunct to mood stabilizers or antidepressants
  
  
  [see
  
  

  14.2 Schizoaffective Disorder

  Maintenance Treatment – Monotherapy and as Adjunct to Mood Stabilizer or Antidepressant (SAff Study 1: SCA-3004)

  The efficacy of INVEGA SUSTENNA in maintaining symptom control in schizoaffective disorder was established in a long-term double-blind, placebo-controlled, flexible-dose randomized-withdrawal study designed to delay relapse in adult subjects who met DSM-IV criteria for schizoaffective disorder, as confirmed by the Structured Clinical Interview for DSM-IV Disorders. The population included subjects with schizoaffective bipolar and depressive types. Subjects received INVEGA SUSTENNA either as monotherapy or as an adjunct to stable doses of antidepressant or mood stabilizers.

  This study included a 13-week, open-label, flexible-dose (INVEGA SUSTENNA 78 mg, 117 mg, 156 mg, or 234 mg) lead-in period which enrolled a total of 667 subjects who had 1) acute exacerbation of psychotic symptoms; 2) score ≥4 on ≥3 PANSS items of delusions, conceptual disorganization, hallucinatory behavior, excitement, suspiciousness/persecution, hostility, uncooperativeness, tension, and poor impulse control; and 3) prominent mood symptoms ≥16 on the Young Mania Rating Scale (YMRS) and/or the Hamilton Rating Scale for Depression, 21-item version (HAM-D-21). Subjects were 19 to 66 years old (mean 39.5 years) and 53.5% were male. The mean scores at open-label enrollment of PANSS total was 85.8 (range 42 to 128), HAM-D-21 was 20.4 (range 3 to 43), YMRS was 18.6 (range 0 to 50), and CGI-S-SCA was 4.4 (range 2 to 6).

  After the 13-week open-label flexible-dose INVEGA SUSTENNA treatment, 432 subjects met stabilization criteria (PANSS total score ≤70, YMRS ≤12, and HAM-D-21 ≤12) and continued into the 12-week open-label fixed-dose stabilization period.

  A total of 334 subjects who met stabilization criteria for 12 consecutive weeks were randomized (1:1) to continue the same dose of INVEGA SUSTENNA or to placebo in the 15-month, double-blind, maintenance period. For the 164 subjects who were randomized to INVEGA SUSTENNA, dose distribution was 78 mg (4.9%), 117 mg (9.8%), 156 mg (47.0%), and 234 mg (38.4%). The primary efficacy variable was time to relapse. Relapse was defined as the first occurrence of one or more of the following: 1) psychiatric hospitalization; 2) intervention employed to avert hospitalization; 3) clinically significant self-injury, suicidal or homicidal ideation or violent behavior; 4) a score of ≥6 (if the score was ≤4 at randomization) of any of the individual PANSS items: delusions, conceptual disorganization, hallucinatory behavior, excitement, suspiciousness/persecution, hostility, uncooperativeness, or poor impulse control; 5) on two consecutive assessments within 7 days: ≥25% increase (if the score at randomization was >45) or ≥10-point increase (if the score at randomization was ≤45) in total PANSS score; a score of ≥5 (if the score was ≤3 at randomization) of any of the individual PANSS items: delusions, conceptual disorganization, hallucinatory behavior, excitement, suspiciousness/persecution, hostility, uncooperativeness, or poor impulse control; an increase of ≥2 points (if the score was 1 [not ill] to 3 [mildly ill] at randomization) or increase of ≥1 point (if the score was ≥4 [moderately ill or worse] at randomization) in CGI-S-SCA overall score.

  There was a statistically significant difference in time to relapse between the treatment groups in favor of INVEGA SUSTENNA. A Kaplan-Meier plot of time to relapse by treatment group is shown in Figure 5.

  Figure 5: Kaplan-Meier Plot of Cumulative Proportion of Subjects with Relapse Over Time (SAff Study 1)

  

  Table 16 summarizes the number of subjects with relapse in the overall population, by subgroup (monotherapy vs. adjunctive therapy), and by symptom type at the first occurrence of relapse.

  Table 16: Summary of Relapse Rates (SAff Study 1).

  	Number (Percent) of Subjects Who Relapsed
  	Placebo N=170	INVEGA SUSTENNA N=164
  All Subjects	57 (33.5%)	25 (15.2%)
  Monotherapy subset	N=73 24 (32.9%)	N=78 9 (11.5%)
  Adjunct to Antidepressants or Mood Stabilizer subset	N=97 33 (34.0%)	N=86 16 (18.6%)
  Psychotic Symptoms 8 subjects experienced a relapse without psychotic symptoms.	53 (31.2%)	21 (12.8%)
  Mood Symptoms 16 subjects experienced a relapse without any mood symptoms.
  Any Mood Symptoms	48 (28.2%)	18 (11.0%)
  Manic	16 (9.4%)	5 (3.0%)
  Depressive	23 (13.5%)	8 (4.9%)
  Mixed	9 (5.3%)	5 (3.0%)

  Figure 5

  ].
  
  

• For intramuscular injection only. (
  
  2.1 Administration Instructions

  Each injection must be administered only by a healthcare professional.

  Parenteral drug products should be inspected visually for foreign matter and discoloration prior to administration, whenever product and container permit.

  INVEGA SUSTENNA is intended for intramuscular use only. Do not administer by any other route. Avoid inadvertent injection into a blood vessel. 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 SUSTENNA must be administered using only the needles that are provided in the INVEGA SUSTENNA kit.

  The recommended needle size for administration of INVEGA SUSTENNA into the deltoid muscle is determined by the patient's weight:

  • For patients weighing less than 90 kg, the 1-inch, 23 gauge needle is recommended.
  • For patients weighing 90 kg or more, the 1½-inch, 22 gauge needle is recommended.

  Deltoid injections should be alternated between the two deltoid muscles.

  The recommended needle size for administration of INVEGA SUSTENNA into the gluteal muscle is the 1½-inch, 22 gauge needle regardless of patient weight.

  Administer into the upper-outer quadrant of the gluteal muscle. Gluteal injections should be alternated between the two gluteal muscles.
  )
  
• Each injection must be administered only by a healthcare professional. (
  
  2.1 Administration Instructions

  Each injection must be administered only by a healthcare professional.

  Parenteral drug products should be inspected visually for foreign matter and discoloration prior to administration, whenever product and container permit.

  INVEGA SUSTENNA is intended for intramuscular use only. Do not administer by any other route. Avoid inadvertent injection into a blood vessel. 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 SUSTENNA must be administered using only the needles that are provided in the INVEGA SUSTENNA kit.

  The recommended needle size for administration of INVEGA SUSTENNA into the deltoid muscle is determined by the patient's weight:

  • For patients weighing less than 90 kg, the 1-inch, 23 gauge needle is recommended.
  • For patients weighing 90 kg or more, the 1½-inch, 22 gauge needle is recommended.

  Deltoid injections should be alternated between the two deltoid muscles.

  The recommended needle size for administration of INVEGA SUSTENNA into the gluteal muscle is the 1½-inch, 22 gauge needle regardless of patient weight.

  Administer into the upper-outer quadrant of the gluteal muscle. Gluteal injections should be alternated between the two gluteal muscles.
  )
  
• For deltoid injection, use 1-inch 23G needle for patients weighing less than 90 kg or 1½-inch 22G needle for patients weighing 90 kg or more. For gluteal injection, use 1½-inch 22G needle regardless of patient weight. (
  
  2.1 Administration Instructions

  Each injection must be administered only by a healthcare professional.

  Parenteral drug products should be inspected visually for foreign matter and discoloration prior to administration, whenever product and container permit.

  INVEGA SUSTENNA is intended for intramuscular use only. Do not administer by any other route. Avoid inadvertent injection into a blood vessel. 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 SUSTENNA must be administered using only the needles that are provided in the INVEGA SUSTENNA kit.

  The recommended needle size for administration of INVEGA SUSTENNA into the deltoid muscle is determined by the patient's weight:

  • For patients weighing less than 90 kg, the 1-inch, 23 gauge needle is recommended.
  • For patients weighing 90 kg or more, the 1½-inch, 22 gauge needle is recommended.

  Deltoid injections should be alternated between the two deltoid muscles.

  The recommended needle size for administration of INVEGA SUSTENNA into the gluteal muscle is the 1½-inch, 22 gauge needle regardless of patient weight.

  Administer into the upper-outer quadrant of the gluteal muscle. Gluteal injections should be alternated between the two gluteal muscles.
  )
  

• For patients naïve to oral paliperidone or oral or injectable risperidone, establish tolerability with oral paliperidone or oral risperidone prior to initiating treatment with INVEGA SUSTENNA. (
  
  2.2 Schizophrenia and Schizoaffective Disorder

  For patients who have never taken oral paliperidone or oral or injectable risperidone, it is recommended to establish tolerability with oral paliperidone or oral risperidone prior to initiating treatment with INVEGA SUSTENNA.

  The recommended dosing of INVEGA SUSTENNA for each approved indication is displayed in Table 1. The recommended initiation of INVEGA SUSTENNA is with a dose of 234 mg on treatment day 1 and 156 mg one week later, both administered in the deltoid muscle. Following the second initiation dose, monthly maintenance doses can be administered in either the deltoid or gluteal muscle.

  Table 1: Recommended Dosing of INVEGA SUSTENNA for Adults with Schizophrenia or Schizoaffective Disorder

  Indication	Initiation Dosing (deltoid)		Monthly Maintenance DoseAdministered 5 weeks after the first injection. (deltoid or gluteal)	Maximum Monthly Dose
  	Day 1	Day 8
  Schizophrenia	234 mg	156 mg	39–234 mgThe recommended maintenance dose for treatment of schizophrenia is 117 mg. Some patients may benefit from lower or higher maintenance doses within the additional available strengths (39 mg, 78 mg, 156 mg, and 234 mg).	234 mg
  Schizoaffective disorder	234 mg	156 mg	78–234 mgAdjust dose based on tolerability and/or efficacy using available strengths. The 39 mg strength was not studied in the long-term schizoaffective disorder study.	234 mg

  Adjustment of the maintenance dose may be made monthly. When making dose adjustments, the prolonged-release characteristics of INVEGA SUSTENNA should be considered

  [see Clinical Pharmacology (12.3)]

  , as the full effect of the dose adjustment may not be evident for several months.
  )
  
• Missed Doses: To manage either a missed second initiation dose or a missed monthly maintenance dose, refer to the Full Prescribing Information. (
  
  2.3 Missed Doses

  Avoiding Missed Doses

  It is recommended that the second initiation dose of INVEGA SUSTENNA be given one week after the first dose. To avoid a missed dose, patients may be given the second dose 4 days before or after the one-week time point. Similarly, the third and subsequent injections after the initiation regimen are recommended to be given monthly. To avoid a missed monthly dose, patients may be given the injection up to 7 days before or after the monthly time point.

  Management of a Missed Second Initiation Dose

  If the target date for the second INVEGA SUSTENNA injection (one week ± 4 days) is missed, the recommended reinitiation depends on the length of time which has elapsed since the patient's first injection. In case of a missed second initiation dose follow the dosing instructions provided in Table 2.

  Table 2: Management of a Missed Second Initiation Dose

  TIMING OF MISSED SECOND INITIATION DOSE	DOSING
  Less than 4 weeks since first injection	Administer the second initiation dose of 156 mg in the deltoid muscle as soon as possible. It is recommended to administer a third injection of 117 mg in either the deltoid or gluteal muscle 5 weeks after the first injection (regardless of the timing of the second injection). Thereafter, resume regular monthly dosing in either the deltoid or gluteal muscle.
  4 to 7 weeks since first injection	Resume dosing with two injections of 156 mg in the following manner: Administer a deltoid injection as soon as possible. Administer a second deltoid injection 1 week later. Thereafter, resume regular monthly dosing in either the deltoid or gluteal muscle.
  More than 7 weeks since first injection	Restart dosing with recommended initiation (see Section 2.2, Table 1) : Administer a 234 mg deltoid injection on Day 1. Administer a 156 mg deltoid injection 1 week later. Thereafter, resume regular monthly dosing in either the deltoid or gluteal muscle.

  Management of a Missed Maintenance Dose

  In case of a missed maintenance dose follow the dosing instructions provided in Table 3.

  Table 3: Management of a Missed Maintenance Dose

  TIMING OF MISSED MAINTENANCE DOSE	DOSING
  4 to 6 weeks since last injection	Resume regular monthly dosing as soon as possible at the patient's previously stabilized dose, followed by injections at monthly intervals.
  More than 6 weeks to 6 months since last injection	Resume the same dose the patient was previously stabilized on (unless the patient was stabilized on a dose of 234 mg, then the first 2 injections should each be 156 mg) in the following manner: Administer a deltoid injection as soon as possible. Administer a second deltoid injection 1 week later at the same dose. Thereafter, resume administering the previously stabilized dose in the deltoid or gluteal muscle 1 month after the second injection.
  More than 6 months since last injection	Restart dosing with recommended initiation ( see Section 2.2, Table 1 ) : Administer a 234 mg deltoid injection on Day 1. Administer a 156 mg deltoid injection 1 week later. Thereafter, resume administering the previously stabilized dose in the deltoid or gluteal muscle 1 month after the second injection.
  )
  
• Moderate to severe renal impairment (creatinine clearance < 50 mL/min):
  INVEGA SUSTENNA is not recommended. (
  
  2.5 Dosage Adjustments

  Patients with Renal Impairment

  INVEGA SUSTENNA has not been systematically studied in patients with renal impairment

  [see Clinical Pharmacology (12.3)]

  .

  For patients with mild renal impairment (creatinine clearance ≥ 50 mL/min to < 80 mL/min [Cockcroft-Gault Formula]), initiate INVEGA SUSTENNA with a dose of 156 mg on treatment Day 1 and 117 mg on Day 8, both in the deltoid muscle. Follow with the recommended monthly maintenance dose of 78 mg, administered in either the deltoid or gluteal muscle. Adjust monthly maintenance dose based on tolerability and/or efficacy within the strengths of 39 mg, 78 mg, 117 mg, or 156 mg. The maximum monthly dose is 156 mg for patients with mild renal impairment

  [see Use in Specific Populations (8.6)and Clinical Pharmacology (12.3)]

  .

  INVEGA SUSTENNA is not recommended in patients with moderate or severe renal impairment (creatinine clearance < 50 mL/min)

  [see Use in Specific Populations (8.6)and Clinical Pharmacology (12.3)]

  .

  Coadministration with Strong CYP3A4/P-glycoprotein (P-gp) Inducers

  Avoid using a strong inducer of CYP3A4 and/or P-gp (e.g., carbamazepine, rifampin, St John's Wort) during the 1-month dosing interval for INVEGA SUSTENNA, if possible. If administering a strong inducer is necessary, consider managing the patient using paliperidone extended release tablets

  [see Drug Interactions (7.1)and Clinical Pharmacology (12.3)]

  .
  )
  
• Mild renal impairment (creatinine clearance ≥ 50 mL/min to < 80 mL/min):
  Administer 156 mg on treatment Day 1 and 117 mg on Day 8, both in the deltoid muscle. Follow with the recommended monthly maintenance dose of 78 mg, administered in the deltoid or gluteal muscle. Adjust monthly maintenance dose based on tolerability and/or efficacy within the strengths of 39 mg, 78 mg, 117 mg, or 156 mg. The maximum monthly dose is 156 mg for patients with mild renal impairment. (
  
  2.5 Dosage Adjustments

  Patients with Renal Impairment

  INVEGA SUSTENNA has not been systematically studied in patients with renal impairment

  [see Clinical Pharmacology (12.3)]

  .

  For patients with mild renal impairment (creatinine clearance ≥ 50 mL/min to < 80 mL/min [Cockcroft-Gault Formula]), initiate INVEGA SUSTENNA with a dose of 156 mg on treatment Day 1 and 117 mg on Day 8, both in the deltoid muscle. Follow with the recommended monthly maintenance dose of 78 mg, administered in either the deltoid or gluteal muscle. Adjust monthly maintenance dose based on tolerability and/or efficacy within the strengths of 39 mg, 78 mg, 117 mg, or 156 mg. The maximum monthly dose is 156 mg for patients with mild renal impairment

  [see Use in Specific Populations (8.6)and Clinical Pharmacology (12.3)]

  .

  INVEGA SUSTENNA is not recommended in patients with moderate or severe renal impairment (creatinine clearance < 50 mL/min)

  [see Use in Specific Populations (8.6)and Clinical Pharmacology (12.3)]

  .

  Coadministration with Strong CYP3A4/P-glycoprotein (P-gp) Inducers

  Avoid using a strong inducer of CYP3A4 and/or P-gp (e.g., carbamazepine, rifampin, St John's Wort) during the 1-month dosing interval for INVEGA SUSTENNA, if possible. If administering a strong inducer is necessary, consider managing the patient using paliperidone extended release tablets

  [see Drug Interactions (7.1)and Clinical Pharmacology (12.3)]

  .
  )
  

INVEGA SUSTENNA is available as a white to off-white aqueous extended-release injectable suspension for intramuscular injection in dose strengths of 39 mg/0.25 mL, 78 mg/0.5 mL, 117 mg/0.75 mL, 156 mg/mL, and 234 mg/1.5 mL paliperidone palmitate in single-dose prefilled syringes.