Skip to Content

Paliperidone

Medically reviewed by Drugs.com. Last updated on Jul 31, 2020.

Pronunciation

(pal ee PER i done)

Index Terms

  • Paliperidone Palmitate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Suspension, Intramuscular, as palmitate:

Invega Sustenna: 39 mg/0.25 mL (0.25 mL); 78 mg/0.5 mL (0.5 mL); 117 mg/0.75 mL (0.75 mL); 156 mg/mL (1 mL); 234 mg/1.5 mL (1.5 mL) [contains polyethylene glycol]

Invega Trinza: 410 mg/1.315 mL (1.315 mL); 273 mg/0.875 mL (0.875 mL); 546 mg/1.75 mL (1.75 mL); 819 mg/2.625 mL (2.625 mL) [contains polyethylene glycol]

Tablet Extended Release 24 Hour, Oral:

Invega: 1.5 mg, 3 mg, 6 mg, 9 mg

Generic: 1.5 mg, 3 mg, 6 mg, 9 mg

Brand Names: U.S.

  • Invega
  • Invega Sustenna
  • Invega Trinza

Pharmacologic Category

  • Second Generation (Atypical) Antipsychotic

Pharmacology

Paliperidone is considered a benzisoxazole atypical antipsychotic as it is the primary active metabolite of risperidone. As with other atypical antipsychotics, its therapeutic efficacy is believed to result from mixed central serotonergic and dopaminergic antagonism. The addition of serotonin antagonism to dopamine antagonism (classic neuroleptic mechanism) is thought to improve negative symptoms of psychoses and reduce the incidence of extrapyramidal side effects (Huttunen 1995). Similar to risperidone, paliperidone demonstrates high affinity to α1, α2, D2, H1, and 5-HT2A receptors and low affinity for muscarinic receptors. In contrast to risperidone, paliperidone displays nearly 10-fold lower affinity for α2 and 5-HT2A receptors, and nearly three- to fivefold less affinity for 5-HT1A and 5-HT1D, respectively.

Absorption

IM: Slow release (Monthly: Begins on day 1 and continues up to 126 days; 3-month: Begins on day 1 and continues up to 18 months)

Distribution

Vd: Oral: 487 L; Monthly IM: 391 L; 3-month IM: 1960 L

Metabolism

Hepatic via CYP2D6 and 3A4 (limited role in elimination); minor metabolism (<10% each) via dealkylation, hydroxylation, dehydrogenation, and benzisoxazole scission

Excretion

Urine (80%; 59% as unchanged drug); feces (11%)

Time to Peak

Oral: ~24 hours; Monthly IM: 13 days; 3-month IM: 30 to 33 days

Half-Life Elimination

Oral: 23 hours; 24 to 51 hours with renal impairment (CrCl <80 mL/minute)

Monthly IM (following a single-dose administration): Range: 25 to 49 days

3-month IM: Deltoid injection range: 84 to 95 days; gluteal injection range: 118 to 139 days

Protein Binding

74%

Special Populations: Renal Function Impairment

Elimination of paliperidone decreased with decreasing estimated creatinine clearance.

Special Populations: Gender

Slower monthly IM absorption observed in women.

Use: Labeled Indications

Schizophrenia: Treatment of schizophrenia.

Schizoaffective disorder (oral and monthly IM paliperidone): Treatment of schizoaffective disorder as monotherapy and as an adjunct to mood stabilizers or antidepressants.

Contraindications

Hypersensitivity to paliperidone, risperidone, or any component of the formulation

Dosing: Adult

Note: Paliperidone is a major, active metabolite of risperidone.

Schizophrenia and schizoaffective disorder:

Oral: Initial: 6 mg once daily; may adjust daily dose based on response and tolerability in increments of 3 mg every ≥5 days up to a maximum of 12 mg/day. Usual dosage range: 6 to 12 mg/day. Note: According to manufacturer’s labeling, 3 mg/day may be effective for some patients (eg, those who do not tolerate 6 mg/day).

IM:

Note: Formulation contains paliperidone palmitate. Dosing in the US labeling is based on paliperidone palmitate; dosing in the Canadian labeling is based on paliperidone base (paliperidone palmitate 1 mg is equivalent to paliperidone base ~0.64 mg).

Monthly paliperidone (Invega Sustenna): Note: Before starting monthly IM paliperidone, establish tolerability with a test dose of oral paliperidone or oral risperidone. After initiating monthly IM paliperidone, overlap with oral antipsychotics is not necessary (Lauriello 2020).

Initiation: 234 mg (150 mg as base) on treatment day 1 followed by 156 mg (100 mg as base) 1 week later, with both doses administered in the deltoid muscle. The second dose may be administered 4 days before or after the 1-week time point. Note: When converting from other long-acting injectable antipsychotics (at steady state), initiation doses are not required.

Managing Missed Paliperidone Dose: Second Initiation Dose

Time since first injection

Instructions

<4 weeks

Administer 156 mg (100 mg as base) in the deltoid muscle as soon as possible, followed by 117 mg (75 mg as base) in either the deltoid or gluteal muscle 5 weeks after the first injection (regardless of when 156 mg dose was administered). Then begin monthly maintenance dose 4 weeks later.

4 to 7 weeks

Administer 156 mg (100 mg as base) in the deltoid muscle as soon as possible, followed by another 156 mg (100 mg as base) dose in the deltoid muscle 1 week later. Then begin monthly maintenance dose 4 weeks later.

>7 weeks

Reinitiate entire dose titration.

Maintenance: Five weeks after the first initiation dose, begin a maintenance dose of 39 to 234 mg (25 to 150 mg as base) every month administered in either the deltoid or gluteal muscle. See the “Dose Conversions That Attain Similar Steady-State Paliperidone Exposure During Maintenance Treatment” table to identify an appropriate maintenance dose based on previous oral paliperidone dose or risperidone dose. The monthly maintenance dose may be administered 7 days before or after the monthly time point.

Managing Missed Paliperidone Dose: Monthly IM Maintenance Dose

Time since last injection

Instructions

4 to 6 weeks

Administer the missed dose as soon as possible. Then resume usual monthly maintenance dose 4 weeks later.

>6 weeks to 6 months

Maintenance dose 39 to 156 mg (25 to 100 mg as base): Administer 2 maintenance doses in the deltoid muscle 1 week apart. Then resume usual monthly maintenance dose 4 weeks later.

Maintenance dose 234 mg (150 mg as base): Administer 156 mg (100 mg as base) in the deltoid muscle as soon as possible, followed by another 156 mg (100 mg as base) in the deltoid muscle 1 week later. Then resume usual monthly maintenance dose 4 weeks later.

>6 months

Reinitiate entire dose titration.

Dosage adjustments: Adjustments may be made monthly based on response and tolerability; the full effect from dose adjustments may not be apparent for several months.

3-month paliperidone (Invega Trinza): Note: 3-month IM paliperidone is to be used only after monthly IM paliperidone (Invega Sustenna) has been established as adequate treatment for at least 4 months. The last 2 doses of monthly IM paliperidone should be the same dosage strength before starting 3-month IM paliperidone.

Conversion from monthly IM paliperidone to 3-month IM paliperidone: Initiate 3-month IM paliperidone when the next monthly IM paliperidone dose is scheduled. Base the 3-month dose on the previous monthly dose, using the “Dose Conversions That Attain Similar Steady-State Paliperidone Exposure During Maintenance Treatment” table. 3-month IM paliperidone may be administered up to 7 days before or after the next monthly dose is due. Following the initial injection, administer every 3 months. Maintenance injections may be administered up to 2 weeks before or after the 3-month time point.

Managing Missed Paliperidone Dose: 3-month IM Maintenance Dose

Time since last injection

Instructions

3.5 to <4 months

Administer the missed dose as soon as possible. Then resume usual maintenance dose 3 months later.

4 to 9 months

Maintenance dose 273 mg (175 mg as base): Administer 78 mg (50 mg as base) of monthly IM paliperidone (Invega Sustenna) into the deltoid muscle on days 1 and 8. One month following the second injection, administer 273 mg (175 mg as base) of 3-month IM paliperidone (Invega Trinza) into the deltoid or gluteal muscle and resume usual dosing at 3-month intervals.

Maintenance dose 410 mg (263 mg as base): Administer 117 mg (75 mg as base) of monthly IM paliperidone (Invega Sustenna) into the deltoid muscle on days 1 and 8. One month following the second injection, administer 410 mg (263 mg as base) of 3-month IM paliperidone (Invega Trinza) into the deltoid or gluteal muscle and resume usual dosing at 3-month intervals.

Maintenance dose 546 mg (350 mg as base): Administer 156 mg (100 mg as base) of monthly IM paliperidone (Invega Sustenna) into the deltoid muscle on days 1 and 8. One month following the second injection, administer 546 mg (350 mg as base) of 3-month IM paliperidone (Invega Trinza) into the deltoid or gluteal muscle and resume usual dosing at 3-month intervals.

Maintenance dose 819 mg (525 mg as base): Administer 156 mg (100 mg as base) of monthly IM paliperidone (Invega Sustenna) into the deltoid muscle on days 1 and 8. One month following the second injection, administer 819 mg (525 mg as base) of 3-month IM paliperidone (Invega Trinza) into the deltoid or gluteal muscle and resume usual dosing at 3-month intervals.

>9 months

Reinitiate treatment with monthly IM paliperidone (Invega Sustenna). 3-month IM paliperidone (Invega Trinza) can be resumed after the patient has been adequately treated with monthly IM paliperidone for at least 4 months.

Dosage adjustments: Incremental dose adjustment can be made every 3 months based on response and tolerability to achieve usual dose of 273 to 819 mg (175 to 525 mg as base); response to an adjusted dose may not be apparent for several months.

Dose Conversions That Attain Similar Steady-State Paliperidone Exposure During Maintenance Treatment

Paliperidone ER tablet

Paliperidone palmitate monthly injection (Invega Sustenna)

Paliperidone palmitate 3-month injection (Invega Trinza)

Risperidone ER injection (Risperdal Consta)

Risperidone tablet

Converting from 3-month IM paliperidone to paliperidone ER tablets: Do not use above table to determine appropriate dose, which is based on injection dose and weeks since last administration. Refer to the “Conversion From 3-Month IM Paliperidone to Paliperidone ER Tablets” table to determine oral dose.

Converting from 3-month IM paliperidone to monthly IM paliperidone: Initiate monthly IM paliperidone when the next 3-month IM paliperidone dose is scheduled. Base the monthly dose on the previous 3-month dose. Following the initial injection, administer once monthly.

Converting from other oral antipsychotics to long-acting injectable paliperidone: There are no systematically collected data to address switching patients from other oral antipsychotics to IM paliperidone.

Converting from other long-acting injectable antipsychotics (at steady state) to monthly IM paliperidone: Initiate monthly IM paliperidone in the place of the next scheduled injection and continue at monthly intervals. The 2 initiation doses are not required in these patients.

3 mg/day

39 mg (25 mg as base) every month

Has not been studied

No information available

1 mg/day

78 mg (50 mg as base) every month

273 mg (175 mg as base) every 3 months

25 mg every 2 weeks

2 mg/day

6 mg/day

117 mg (75 mg as base) every month

410 mg (263 mg as base) every 3 months

37.5 mg every 2 weeks

3 mg/day

9 mg/day

156 mg (100 mg as base) every month

546 mg (350 mg as base) every 3 months

50 mg every 2 weeks

4 mg/day

12 mg/day

234 mg (150 mg as base) every month

819 mg (525 mg as base) every 3 months

No information available

5 mg/day

Conversion from 3-month IM paliperidone to paliperidone ER tablets: Initiate paliperidone ER tablets ≥3 months after the last dose of 3-month IM paliperidone. Base the once-daily ER tablet dose on the last 3-month injection dose and weeks since last administered, using the following table:

Converting From 3-month IM Paliperidone to Paliperidone ER Tablets

Weeks since last 3-month IM injection

≥12 weeks to 18 weeks

>18 weeks to 24 weeks

>24 weeks

Last 3-month IM injection dose

Daily dose of oral paliperidone ER tablet

273 mg (175 mg as base)

3 mg

3 mg

3 mg

410 mg (263 mg as base)

3 mg

3 mg

6 mg

546 mg (350 mg as base)

3 mg

6 mg

9 mg

819 mg (525 mg as base)

6 mg

9 mg

12 mg

Discontinuation of therapy: Gradual dose reduction of oral therapy is advised to avoid withdrawal symptoms (ie, insomnia, headache, GI symptoms), unless discontinuation is due to significant adverse effects. In general, when discontinuing oral antipsychotic therapy for a chronic psychiatric disorder (eg, schizophrenia), decreasing the dose very gradually over weeks to months with close monitoring is suggested to allow for detection of prodromal symptoms of disease recurrence (APA [Lehman 2004]; CPA 2005). A taper is unnecessary when discontinuing long-acting injectable paliperidone.

Switching antipsychotics: An optimal universal strategy for switching antipsychotic drugs has not been established. Strategies include cross-titration (gradually discontinuing the first antipsychotic while gradually increasing the new antipsychotic) and abrupt change (abruptly discontinuing the first antipsychotic and either increasing the new antipsychotic gradually or starting it at a treatment dose). In patients with schizophrenia at high risk of relapse, the current medication may be maintained at full dose as the new medication is increased (ie, overlap); once the new medication is at therapeutic dose, the first medication is gradually decreased and discontinued over 1 to 2 weeks (Cerovecki 2013; Remington 2005; Takeuchi 2017). Based upon clinical experience, some experts generally prefer cross-titration and overlap approaches rather than abrupt change (Post 2019; Stroup 2019).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing; use with caution. Additional monitoring of renal function and orthostatic BP may be warranted.

Dosing: Pediatric

Irritability associated with autistic disorder: Limited data available: Children ≥12 years and Adolescents: Oral: Extended-release tablet: Initial: 3 mg once daily; titrate on a weekly basis in 3 mg/day increments until clinical response or intolerance; maximum daily dose: 12 mg/day. Dosing based on an open-label trial of 25 patients (mean age: 15.3 years; age range: 12 to 21 years); therapeutic response was reported in 84% of patients at a mean final dose: 7.1 mg/day (Stigler 2012).

Schizoaffective disorder:

Oral: Extended-release tablet: Adolescents ≥18 years: Usual: 6 mg once daily (administered in the morning in clinical trials); titration not required, though some may benefit from lower or higher doses (range: 3 to 12 mg daily). If exceeding 6 mg daily, increases of 3 mg daily are recommended at intervals of more than 4 days, up to a maximum daily dose: 12 mg/day.

Parenteral: Adolescents ≥18 years: Monthly paliperidone injection (Invega Sustenna): IM: Note: Prior to initiation of monthly IM paliperidone, patients naive to oral paliperidone or oral or injectable risperidone should have tolerability established with a test dose of oral paliperidone or oral risperidone. Previous oral antipsychotic regimen can be gradually discontinued at the time of initiation of monthly IM paliperidone.

Initiation of therapy (2-dose series):

Initial: 234 mg on treatment day 1 followed by 156 mg 1 week later with both doses administered in the deltoid muscle. The second dose may be administered 4 days before or after the weekly time point.

Missed second initiation dose: If the target administration date of 1 week ± 4 days for the second dose is missed, catch-up dosing depends on the time elapsed since the first dose.

Time elapsed since last first dose

Catch-up dose for therapy initiation

<4 weeks

Administer the missed dose 156 mg (in the deltoid) as soon as possible, followed by a third dose of 117 mg (in either the deltoid or gluteal muscle) 5 weeks after the first injection (regardless of when the second injection was administered), then begin normal monthly maintenance dosing.

≥4 weeks to ≤7 weeks

Administer a dose of 156 mg (in the deltoid) as soon as possible, followed by another 156 mg dose (in the deltoid) 1 week later, then begin normal monthly maintenance dosing

>7 weeks

Reinitiate following dosing recommendations for initiation of therapy

Maintenance: First maintenance injection should be administered 5 weeks after the first injection of the initial series. Adjust the dose based on response and tolerability and begin a maintenance dose of 78 to 234 mg (every month administered in either the deltoid or gluteal muscle). The monthly maintenance dose may be administered 7 days before or after the monthly time point.

Missed maintenance dose: Dose and interval dependent upon time since last dose, see table:

Time elapsed since last monthly maintenance injection

Catch-up dosing

≥4 weeks to ≤6 weeks

Administer the missed dose as soon as possible and continue therapy at monthly interval

>6 weeks to ≤6 months and dose <234 mg

Administer the same dose the patient was previously stabilized on in the deltoid as soon as possible, followed by a second equivalent dose in the deltoid 1 week later, then resume maintenance dose at monthly intervals.

>6 weeks to ≤6 months and dose 234 mg

Administer a 156 mg dose in the deltoid as soon as possible, followed by a second dose of 156 mg in the deltoid 1 week later, then resume maintenance dose at monthly intervals.

>6 months

Reinitiate following dosing recommendations for initiation of therapy.

Conversion from oral extended-release paliperidone to monthly IM paliperidone:

Initiate monthly IM paliperidone as described using the 1-week initiation regimen. Patients previously stabilized on oral doses can expect similar steady state exposure during maintenance treatment with monthly IM paliperidone using the following conversion:

Oral extended release once daily dose

Monthly maintenance IM dose(Invega Sustenna)

3 mg

39 to 78 mg

6 mg

117 mg

9 mg

156 mg

12 mg

234 mg

Conversion from other oral antipsychotics to monthly IM paliperidone: There is no systematically collected data to address switching patients from other oral antipsychotics to monthly IM paliperidone.

Switching from other long-acting injectable antipsychotics (at steady-state) to monthly IM paliperidone: Initiate monthly IM paliperidone in the place of the next scheduled injection and continue at monthly intervals; may be administered in the deltoid or gluteal muscle. The two initiation doses are not required in these patients.

Dosage adjustments: Adjustments may be made monthly (full effect from adjustments may not be seen for several months)

Schizophrenia:

Oral: Extended-release tablet:

Children ≥12 and Adolescents <18 years: 3 mg once daily; titration not necessary; if after clinical assessment a dosage increase is required, may increase dose in 3 mg/day increments at least every 5 days; maximum daily dose is weight dependent: <51 kg: 6 mg/day; ≥51 kg: 12 mg/day; Note: During adolescent clinical trials, higher doses were not associated with greater efficacy, but increased risk of adverse effects.

Adolescents: ≥18 years: Usual dose: 6 mg once daily (administered in the morning in clinical trials); titration not required, though some may benefit from lower or higher doses (range: 3 to 12 mg daily). If exceeding 6 mg daily, increases of 3 mg daily are recommended no more frequently than every 5 days, up to a maximum of 12 mg daily.

Parenteral: Adolescents ≥18 years:

Monthly paliperidone injection (Invega Sustenna): IM: Note: Prior to initiation of monthly IM therapy, tolerability should be established with oral paliperidone or oral risperidone; may require test dose of oral paliperidone or risperidone. Previous oral antipsychotics can be discontinued at the time of initiation of IM therapy.

Initiation of therapy (2-dose series):

Initial: 234 mg on treatment day 1 followed by 156 mg 1 week later with both doses administered in the deltoid muscle. The second dose may be administered 4 days before or after the weekly time point.

Missed second initiation dose: If the target administration date of 1 week ± 4 days for the second dose is missed, catch-up dosing depends on the time elapsed since the first dose.

Time elapsed since last first dose

Catch-up dose for therapy initiation

<4 weeks

Administer the missed dose of 156 mg (in the deltoid) as soon as possible, followed by a third dose of 117 mg (in either the deltoid or gluteal muscle) 5 weeks after the first injection (regardless of when the second injection was administered), then begin normal monthly maintenance dosing.

≥4 weeks to ≤7 weeks

Administer a dose of 156 mg (in the deltoid) as soon as possible, followed by another 156 mg dose (in the deltoid) 1 week later, then begin normal monthly maintenance dosing

>7 weeks

Reinitiate following dosing recommendations for initiation of therapy

Maintenance: First maintenance injection should be administered 5 weeks after the first injection of the initial series. Begin with a maintenance dose 117 mg every month administered in either the deltoid or gluteal muscle. Some patients may benefit from higher or lower monthly maintenance doses (monthly maintenance dosage range: 39 to 234 mg). The monthly maintenance dose may be administered 7 days before or after the monthly time point.

Missed maintenance dose: Dose and interval dependent upon time since last dose, see table:

Time elapsed since last monthly maintenance injection

Catch-up dosing

≥4 weeks to ≤6 weeks

Administer the missed dose as soon as possible and continue therapy at monthly interval

>6 weeks to ≤6 months and dose <234 mg

Administer the same dose the patient was previously stabilized on in the deltoid as soon as possible, followed by a second equivalent dose in the deltoid 1 week later, then resume maintenance dose at monthly intervals.

>6 weeks to ≤6 months and dose 234 mg

Administer a 156 mg dose in the deltoid as soon as possible, followed by a second dose of 156 mg in the deltoid 1 week later, then resume maintenance dose at monthly intervals.

>6 months

Reinitiate following dosing recommendations for initiation of therapy.

Conversion from oral paliperidone to IM paliperidone monthly injection: Initiate IM therapy as described using the 1-week initiation regimen. Patients previously stabilized on oral doses can expect similar steady state exposure during maintenance treatment with IM therapy using the following conversion:

Oral extended release once daily dose

Monthly maintenance IM dose

3 mg

39 to 78 mg

6 mg

117 mg

9 mg

156 mg

12 mg

234 mg

Switching from other long acting injectable antipsychotics to IM paliperidone: Initiate IM paliperidone in the place of the next scheduled injection and continue at monthly intervals. The 1-week initiation regimen is not required in these patients.

Dosage adjustments: Adjustments may be made monthly (full effect from adjustments may not be seen for several months)

Three-month paliperidone (Invega Trinza): IM: Note: 3-month IM paliperidone is to be used only after monthly IM paliperidone (Invega Sustenna) has been established as adequate treatment for at least 4 months. The last 2 doses of monthly IM paliperidone should be the same dosage strength before starting 3-month IM paliperidone.

Conversion from monthly injection and 3-month injection:

Monthly to 3-month injections: Initiate 3-month IM paliperidone when the next monthly IM paliperidone dose is scheduled. Base the 3-month dose on the previous monthly dose, using the equivalent 3.5 times higher dose (see following table). Three-month IM paliperidone may be administered up to 7 days before or after the next monthly dose date. Following the initial injection, administer every 3 months. Patients may be given the injection up to 2 weeks before or after the 3-month time point.

Three-month to monthly injections: Initiate monthly IM paliperidone when the next 3-month IM paliperidone dose is scheduled. Base the monthly dose on the previous 3-month dose, using the equivalent 3.5 times lower dose (see following table). After initial injection, administer once monthly.

Monthly IM paliperidone dose

(Invega Sustenna)

3-month paliperidone dose

(Invega Trinza)

Note: Conversion from monthly IM paliperidone (Invega Sustenna) 39 mg to 3-month IM paliperidone (Invega Trinza) has not been studied.

78 mg

273 mg

117 mg

410 mg

156 mg

546 mg

234 mg

819 mg

Conversion from 3-month IM paliperidone to oral paliperidone extended-release tablets: Initiate paliperidone extended-release tablets at least 3 months after the last dose of 3-month IM paliperidone. Base the once daily extended-release tablet dose on the last 3-month injection dose and weeks since last administered. Use the following conversion.

3-month paliperidone dose

(Invega Trinza)

Time elapsed since last IM dose

Oral extended release once daily dose

273 mg

≥12 weeks

3 mg

410 mg

12 weeks to ≤24 weeks

3 mg

>24 weeks

6 mg

546 mg

12 to ≤18 weeks

3 mg

>18 to ≤24 weeks

6 mg

>24 weeks

9 mg

819 mg

12 to ≤18 weeks

6 mg

>18 to ≤24 weeks

9 mg

>24 weeks

12 mg

Dosage adjustments: Dosage adjustments can be made every 3 months in increments within the range of 273 to 819 mg based on response and tolerability. Due to the long-acting nature, the patient's response to an adjusted dose may not be apparent for several months.

Missed doses: Dose and interval dependent upon time since last dose; use of the monthly dosage form (Invega Sustenna) may be necessary in some cases; see table:

Time elapsed since last 3 month maintenance dose

Catch-up dosing

31/2 months to 4 months

Administer the previous 3-month dose as soon as possible and continue with normal dosing

4 months to 9 months and dose 273 mg

Administer 78 mg of monthly IM paliperidone (Invega Sustenna) into the deltoid muscle. Repeat same dose of monthly IM paliperidone (Invega Sustenna) 1 week later. One month following the second injection, administer 273 mg of 3-month IM paliperidone (Invega Trinza) into the deltoid or gluteal muscle and resume normal dosing at 3-month intervals

4 months to 9 months and dose 410 mg

Administer 117 mg of monthly IM paliperidone (Invega Sustenna) into the deltoid muscle. Repeat same dose of monthly IM paliperidone (Invega Sustenna) 1 week later. One month following the second injection, administer 410 mg of 3-month IM paliperidone (Invega Trinza) into the deltoid or gluteal muscle and resume normal dosing at 3-month intervals.

4 months to 9 months and dose 546 mg

Administer 156 mg of monthly IM paliperidone (Invega Sustenna) into the deltoid muscle. Repeat same dose of monthly IM paliperidone (Invega Sustenna) 1 week later. One month following the second injection, administer 546 mg of 3-month IM paliperidone (Invega Trinza) into the deltoid or gluteal muscle and resume normal dosing at 3-month intervals.

4 months to 9 months and dose 819 mg

Administer 156 mg of monthly IM paliperidone (Invega Sustenna) into the deltoid muscle. Repeat same dose of monthly IM paliperidone (Invega Sustenna) 1 week later. One month following the second injection, administer 819 mg of 3-month IM paliperidone (Invega Trinza) into the deltoid or gluteal muscle and resume normal dosing at 3-month intervals.

>9 months

Re-initiate treatment with monthly IM paliperidone (Invega Sustenna). Three-month IM paliperidone can be resumed after the patient has been adequately treated with monthly IM paliperidone for at least 4 months.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Administration

Oral: Administer without regard to meals. ER tablets should be swallowed whole with liquids; do not crush, chew, or divide.

Bariatric surgery: Tablet, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. An IM formulation of Invega is available. If safety and efficacy can be effectively monitored, no change in formulation or administration is required after bariatric surgery; however, close clinical monitoring is advised in the immediate postoperative phase for the theoretical circumstance of reduced absorption after bariatric surgery.

IM injection: Administer by IM route only as a single injection (do not divide); do not administer by any other route. Avoid inadvertent injection into vasculature.

Monthly paliperidone (Invega Sustenna): Do not mix with any other product or diluent. Prior to injection, shake syringe for at least 10 seconds to ensure a homogenous suspension. Administer using only the needles that are provided in the kit. The 2 initial injections should be administered in the deltoid muscle using a 11/2 inch, 22-gauge needle for patients ≥90 kg, and a 1 inch, 23-gauge needle for patients <90 kg. The 2 initial deltoid intramuscular injections help attain therapeutic concentrations rapidly. Alternate deltoid injections (right and left deltoid muscle). The second dose may be administered 4 days before or after the weekly time point. Monthly maintenance doses can be administered in either the deltoid or gluteal muscle. Administer injections in the gluteal muscle using a 11/2 inch, 22-gauge needle (regardless of patient weight) in the upper-outer quadrant of the gluteal area. Alternate gluteal injections (right and left gluteal muscle). The monthly maintenance dose may be administered 7 days before or after the monthly time point.

Three-month paliperidone (Invega Trinza): Prior to injection, shake syringe for with tip pointing up at least 15 seconds to ensure a homogenous suspension. Inject within 5 minutes of shaking vigorously. Inject slowly, deep into the deltoid or gluteal muscle. Must be administered using only the thin wall needles that are provided in the pack. Do not use needles from monthly IM paliperidone or other commercially-available needles to reduce the risk of blockage. Administer into the center of the deltoid muscle using a 11/2 inch, 22-gauge thin wall needle for patients ≥90 kg, and a 1 inch, 22-gauge thin wall needle for patients <90 kg. Alternate deltoid injections (right and left deltoid muscle). Administer injections in the gluteal muscle using a 11/2 inch, 22-gauge thin wall needle (regardless of patient weight) in the upper-outer quadrant of the gluteal area. Alternate gluteal injections (right and left gluteal muscle). 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 with oral supplementation as clinically appropriate until the next scheduled 3-month injection.

Storage

Oral, Monthly IM: Store at ≤25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect tablets from moisture.

3-month IM: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Do not mix with any other product or diluent.

Drug Interactions

Acetylcholinesterase Inhibitors (Central): May enhance the neurotoxic (central) effect of Antipsychotic Agents. Severe extrapyramidal symptoms have occurred in some patients. Monitor therapy

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Amifampridine: Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. Monitor therapy

Amisulpride (Oral): May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk of neuroleptic malignant syndrome may be increased. Avoid combination

Amphetamines: Antipsychotic Agents may diminish the stimulatory effect of Amphetamines. Monitor therapy

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Anti-Parkinson Agents (Dopamine Agonist): Antipsychotic Agents (Second Generation [Atypical]) may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Management: Consider avoiding atypical antipsychotic use in patients with Parkinson disease. If an atypical antipsychotic is necessary, consider using clozapine, quetiapine, or ziprasidone at lower initial doses, or a non-dopamine antagonist (eg, pimavanserin). Consider therapy modification

Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Consider therapy modification

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromopride: May enhance the adverse/toxic effect of Antipsychotic Agents. Avoid combination

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Consider therapy modification

BuPROPion: May enhance the neuroexcitatory and/or seizure-potentiating effect of Agents With Seizure Threshold Lowering Potential. Monitor therapy

Cabergoline: May diminish the therapeutic effect of Antipsychotic Agents. Avoid combination

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy

Deutetrabenazine: May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk for akathisia, parkinsonism, or neuroleptic malignant syndrome may be increased. Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Consider therapy modification

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Consider therapy modification

Guanethidine: Antipsychotic Agents may diminish the therapeutic effect of Guanethidine. Monitor therapy

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Haloperidol. Monitor therapy

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Inducers of CYP3A4 (Strong) and P-glycoprotein: May decrease the serum concentration of Paliperidone. Management: Monitor for reduced paliperidone effects when combined with strong inducers of both CYP3A4 and P-gp. Avoid use of these inducers with extended-release injectable paliperidone and instead manage patients with paliperidone extended-release tablets. Monitor therapy

Iohexol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Consider therapy modification

Iomeprol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Consider therapy modification

Iopamidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Consider therapy modification

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Consider therapy modification

Lithium: May enhance the neurotoxic effect of Antipsychotic Agents. Lithium may decrease the serum concentration of Antipsychotic Agents. Specifically noted with chlorpromazine. Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mequitazine: Antipsychotic Agents may enhance the arrhythmogenic effect of Mequitazine. Management: Consider alternatives to one of these agents when possible. While this combination is not specifically contraindicated, mequitazine labeling describes this combination as discouraged. Consider therapy modification

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Consider therapy modification

Methylphenidate: Antipsychotic Agents may enhance the adverse/toxic effect of Methylphenidate. Methylphenidate may enhance the adverse/toxic effect of Antipsychotic Agents. Monitor therapy

Metoclopramide: May enhance the adverse/toxic effect of Antipsychotic Agents. Avoid combination

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

MetyroSINE: May enhance the adverse/toxic effect of Antipsychotic Agents. Monitor therapy

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Consider therapy modification

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Piribedil: Antipsychotic Agents may diminish the therapeutic effect of Piribedil. Piribedil may diminish the therapeutic effect of Antipsychotic Agents. Management: Use of piribedil with antiemetic neuroleptics is contraindicated, and use with antipsychotic neuroleptics, except for clozapine, is not recommended. Avoid combination

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

Quinagolide: Antipsychotic Agents may diminish the therapeutic effect of Quinagolide. Monitor therapy

RisperiDONE: May enhance the adverse/toxic effect of Paliperidone. Management: Additive paliperidone exposure is expected with this combination. Consider using an alternative combination when possible. Consider therapy modification

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Serotonergic Agents (High Risk): May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Monitor therapy

St John's Wort: May decrease the serum concentration of Paliperidone. Management: Monitor for reduced paliperidone effects when combined St. John's wort. Avoid use of St. John's wort with extended-release injectable paliperidone and instead manage patients with paliperidone extended-release tablets. Monitor therapy

Sulpiride: Antipsychotic Agents may enhance the adverse/toxic effect of Sulpiride. Avoid combination

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tetrabenazine: May enhance the adverse/toxic effect of Antipsychotic Agents. Monitor therapy

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Valproate Products: May increase the serum concentration of Paliperidone. Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Unless otherwise noted, frequency of adverse effects is reported for the oral/IM formulation in adults.

>10%:

Cardiovascular: Tachycardia (adolescents and adults: 3% to 14%)

Central nervous system: Drowsiness (oral, adolescents: 13% to 26%; adults: 5% to 12%), extrapyramidal reaction (oral, adolescents and adults: 5% to 23%; IM: 2% to 5%), akathisia (adolescents and adults: 4% to 17%), headache (adolescents and adults: 4% to 15%), parkinsonian-like syndrome (adolescents and adults: 2% to 15%), dystonia (adolescents and adults: 1% to 14%)

Endocrine & metabolic: Increased serum prolactin (males: ≤56%; females: ≤44%), decreased HDL cholesterol (oral; adolescents and adults: 23% to 29%; IM: 14% to 16%), increased LDL cholesterol (adolescents and adults: 4% to 14%), weight gain (oral: adults: 3% to 9%, adolescents: 2% to 19%; IM: 6% to 13%), increased serum triglycerides (adolescents and adults: 6% to 13%), increased serum cholesterol (adolescents and adults: 4% to 11%), hyperglycemia (adolescents and adults: 3% to 11%)

Gastrointestinal: Vomiting (adolescents and adults: 5% to 11%)

Neuromuscular & skeletal: Hyperkinesia (oral, adolescents and adults: 6% to 17%; IM: 4% to 5%), tremor (oral, adolescents and adults: 4% to 12%; IM: 1%)

1% to 10%:

Cardiovascular: Orthostatic hypotension (oral: 2% to 4%; IM: <1%), bundle branch block (3%), first degree atrioventricular block (2%), hypertension (adolescents and adults: ≤2%), sinus arrhythmia (oral: ≤2%), bradycardia (adolescents and adults: <2%), edema (adolescents and adults: <2%), palpitations (adolescents and adults: <2%)

Central nervous system: Agitation (IM: 8% to 10%; oral: adolescents and adults: <2%), anxiety (adolescents and adults: 8% to 9%), sedation (IM: 5% to 7%), dizziness (adolescents and adults: 2% to 6%), dysarthria (1% to 4%), lethargy (adolescents: 3%), fatigue (adolescents and adults: 2% to 3%), sleep disorder (oral: 2% to 3%), nightmares (adolescents and adults: ≤2%), insomnia (adolescents and adults: <2%), opisthotonus (oral, adolescents and adults: <2%)

Dermatologic: Pruritus (adolescents and adults: <2%), skin rash (adolescents and adults: <2%)

Endocrine & metabolic: Amenorrhea (adolescents and adults: 2% to 6%), galactorrhea (IM, women: 1% to 4%), gynecomastia (adolescents and adults: 3%), decreased libido (IM: 1%)

Gastrointestinal: Nausea (4% to 8%), dyspepsia (5% to 6%), sialorrhea (adolescents and adults: 1% to 6%), constipation (4% to 5%), abdominal distress (≤4%), upper abdominal pain (≤4%), diarrhea (IM: 3%), swollen tongue (adolescents: 3%), increased appetite (2% to 3%), toothache (IM: 2% to 3%), xerostomia (adolescents and adults: 2% to 3%), stomach discomfort (oral: 2%), decreased appetite (1% to 2%), flatulence (adolescents and adults: <2%)

Genitourinary: Urinary tract infection (adolescents and adults: ≤3%), breast tenderness (adolescents and adults: <2%), irregular menses (adolescents and adults: <2%), retrograde ejaculation (adolescents and adults:<2%), erectile dysfunction (IM: ≤1%)

Hepatic: Increased serum ALT (adolescents and adults: <2%), increased serum AST (adolescents and adults: <2%)

Hypersensitivity: Anaphylaxis (adolescents and adults: <2%)

Local: Injection site reaction (IM: 3% to 10%), erythema at injection site (IM: ≤2%), swelling at injection site (IM: ≤2%)

Neuromuscular & skeletal: Dyskinesia (adolescents and adults: 2% to 9%), myalgia (1% to 4%), weakness (adolescents and adults: ≤4%), back pain (3%), tongue paralysis (oral, adolescents: 3%), limb pain (adolescents and adults: ≤3%), muscle rigidity (IM: 2%), arthralgia (adolescents and adults: <2%)

Ophthalmic: Blurred vision (adolescents and adults: 3%), abnormal eye movements (adolescents and adults: <2%; includes eye rolling)

Respiratory: Upper respiratory tract infection (2% to 10%), nasopharyngitis (adolescents and adults: 2% to 5%), cough (2% to 3%), rhinitis (oral: 1% to 3%), epistaxis (oral, adolescents: 2%), pharyngolaryngeal pain (oral: 1% to 2%), nasal congestion (adolescents and adults: <2%)

Frequency not defined:

Cardiovascular: Cerebrovascular accident (IM), ECG abnormality (IM), hypotension (oral), ischemia (oral), left bundle branch block (oral), peripheral edema (oral), postural orthostatic tachycardia (IM), transient ischemic attacks (oral)

Central nervous system: Abnormal gait (oral; parkinsonian gait), cogwheel rigidity (IM), drooling, hypertonia (IM), orthostatic dizziness (IM), psychomotor agitation (IM), restlessness (IM), seizure, tonic-clonic seizures (oral), trismus (oral), vertigo (IM)

Dermatologic: Fixed drug eruption (IM), papular rash (oral), urticaria (IM)

Endocrine & metabolic: Menstrual disease (IM)

Gastrointestinal: Abdominal pain (oral), hyperinsulinism (IM), oromandibular dystonia (IM)

Genitourinary: Breast engorgement (oral), breast hypertrophy (IM), breast swelling (IM), ejaculatory disorder (IM), mastalgia, nipple discharge (IM), sexual disorder (IM)

Hypersensitivity: Hypersensitivity (IM)

Neuromuscular & skeletal: Bradykinesia (IM), joint stiffness (IM), muscle spasm (IM), muscle twitching (IM), musculoskeletal pain (oral), neck stiffness (IM), torticollis (oral)

Ophthalmic: Oculogyric crisis (IM)

Respiratory: Aspiration pneumonia

<1%, postmarketing, and/or case reports: Agranulocytosis, angioedema, antiemetic effect, diabetes mellitus, intestinal obstruction (includes small intestine), leukopenia, motor dysfunction, neuroleptic malignant syndrome, neutropenia, priapism, prolonged QT interval on ECG, sensory disturbance (sensory instability), somnambulism, syncope, tardive dyskinesia, thrombotic thrombocytopenic purpura, urinary incontinence, urinary retention

ALERT: U.S. Boxed Warning

Increased mortality in elderly patients with dementia-related psychosis:

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Paliperidone is not approved for the treatment of patients with dementia-related psychosis.

Warnings/Precautions

Concerns related to adverse effects:

• Altered cardiac conduction: May alter cardiac conduction and prolong the QTc interval; life-threatening arrhythmias have occurred with therapeutic doses of antipsychotics (Ray 2009). Risk may be increased by conditions or concomitant medications that cause bradycardia, hypokalemia, and/or hypomagnesemia. Avoid use in combination with QTc-prolonging drugs. Avoid use in patients with congenital long QT syndrome and in patients with history of cardiac arrhythmia.

• Antiemetic effects: May mask toxicity of other drugs or conditions (eg, intestinal obstruction, Reye syndrome, brain tumor) due to antiemetic effects.

• Blood dyscrasias: Leukopenia, neutropenia, and agranulocytosis (sometimes fatal) have been reported in clinical trials and postmarketing reports with antipsychotic use; presence of risk factors (eg, preexisting low WBC or ANC, history of drug-induced leuko-/neutropenia) should prompt periodic blood count assessment. Monitor patients with clinically significant neutropenia for a fever or other signs of infection, and discontinue therapy if absolute neutrophil count <1,000/mm3.

• Cerebrovascular effects: An increased incidence of cerebrovascular adverse effects (eg, transient ischemic attack, stroke), including fatalities, has been reported in placebo-controlled trials of risperidone (paliperidone is the primary active metabolite of risperidone) for the unapproved use in elderly patients with dementia-related psychosis.

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving).

• Dyslipidemia: Increased cholesterol and triglycerides and decreased HDL have been noted. Use with caution in patients with a preexisting abnormal lipid profile.

• Esophageal dysmotility/Aspiration: Antipsychotic use has been associated with esophageal dysmotility and aspiration; risk increases with age. Use with caution in patients at risk for aspiration pneumonia (eg, Alzheimer disease), particularly in patients >75 years of age (Herzig 2017; Maddalena 2004).

• Extrapyramidal symptoms: May cause extrapyramidal symptoms (EPS), including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia (risk of these reactions is generally much lower relative to typical/conventional antipsychotics; frequencies reported are similar to placebo). Risk of dystonia (and probably other EPS) may be greater with increased doses, use of conventional antipsychotics, males, and younger patients. Factors associated with greater vulnerability to tardive dyskinesia include older in age, female gender combined with postmenopausal status, Parkinson disease, pseudoparkinsonism symptoms, affective disorders (particularly major depressive disorder), concurrent medical diseases such as diabetes, previous brain damage, alcoholism, poor treatment response, and use of high doses of antipsychotics (APA [Lehman 2004]; Soares-Weiser 2007). Consider therapy discontinuation with signs/symptoms of tardive dyskinesia.

• Falls: May increase the risk for falls due to somnolence, orthostatic hypotension, and motor or sensory instability.

• Hyperglycemia: Atypical antipsychotics have been associated with development of hyperglycemia; in some cases, may be extreme and associated with ketoacidosis, hyperosmolar coma, or death. All patients should be monitored for symptoms of hyperglycemia (eg, polydipsia, polyuria, polyphagia, weakness). Use with caution in patients with diabetes (or risk factors) or other disorders of glucose regulation; monitor for worsening of glucose control. Patients with risk factors for diabetes (eg, obesity or family history) should have a baseline fasting blood sugar and periodically during treatment.

• Hyperprolactinemia: Use is associated with increased prolactin levels; clinical significance of hyperprolactinemia in patients with breast cancer or other prolactin-dependent tumors is unknown.

• Hypersensitivity: Hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported.

• Intraoperative floppy iris syndrome: Few case reports describe intraoperative floppy iris syndrome (IFIS) in patients receiving risperidone and undergoing cataract surgery (Ford 2011). IFIS has not been reported with paliperidone, but caution is advised because it is the active metabolite of risperidone. Prior to cataract surgery, evaluate for prior or current paliperidone or risperidone use. The benefits or risks of interrupting paliperidone or risperidone prior to surgery have not been established; clinicians are advised to proceed with surgery cautiously.

• Neuroleptic malignant syndrome: Use may be associated with neuroleptic malignant syndrome; monitor for mental status changes, fever, muscle rigidity, and/or autonomic instability (risk may be increased in patients with Parkinson disease or Lewy body dementia).

• Orthostatic hypotension: May cause orthostatic hypotension and syncope; use with caution in patients with known cardiovascular disease (heart failure, history of myocardial infarction or ischemia, conduction abnormalities), cerebrovascular disease, or conditions that predispose the patient to hypotension (dehydration, hypovolemia, and treatment with antihypertensive medications).

• Priapism: Rare cases of priapism have been reported.

• Suicidal ideation: The possibility of a suicide attempt is inherent in psychotic illness or bipolar disorder; use with caution in high-risk patients during initiation of therapy. Prescriptions should be written for the smallest quantity consistent with good patient care.

• Temperature regulation: Impaired core body temperature regulation may occur; use caution with strenuous exercise, heat exposure, dehydration, and concomitant medication possessing anticholinergic effects.

• Weight gain: Significant weight gain has been observed with antipsychotic therapy; incidence varies with product. Monitor waist circumference and body mass index.

Disease-related concerns:

• Dementia: [US Boxed Warning]: Elderly patients with dementia-related psychosis treated with antipsychotics are at an increased risk of death compared to placebo. Most deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Use with caution in patients with Lewy body dementia or Parkinson disease dementia due to greater risk of adverse effects, increased sensitivity to extrapyramidal effects, and association with irreversible cognitive decompensation or death. (APA [Reus 2016]). Paliperidone is not approved for the treatment of dementia-related psychosis.

• Renal impairment: Use with caution in patients with mild renal disease; dosage reduction is recommended. Not recommended in patients with moderate (IM route only) to severe impairment.

• Seizures: Use with caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications that may lower seizure threshold. Elderly patients may be at increased risk of seizures due to an increased prevalence of predisposing factors.

Dosage form specific issues:

• Extended-release tablet: Use is not recommended in patients with preexisting severe GI-narrowing disorders (nondeformable controlled-release formulation). Patients with upper GI tract alterations in transit time may have increased or decreased bioavailability of paliperidone. Formulation consists of drug within a nonabsorbable shell; following drug release/absorption, the shell is expelled in the stool.

Other warnings/precautions:

• Discontinuation of therapy: When discontinuing antipsychotic therapy, the American Psychiatric Association (APA), Canadian Psychiatric Association (CPA), and World Federation of Societies of Biological Psychiatry (WFSBP) guidelines recommend gradually tapering antipsychotics to avoid physical withdrawal symptoms, including anorexia, anxiety, diaphoresis, diarrhea, dizziness, dyskinesia, headache, myalgia, nausea, paresthesia, restlessness, tremulousness, and vomiting (APA [Lehman 2004]; CPA 2005; Lambert 2007; WFSBP [Hasan 2012]). The risk of withdrawal symptoms is highest following abrupt discontinuation of highly anticholinergic or dopaminergic antipsychotics (Cerovecki 2013). Additional factors such as duration of antipsychotic exposure, the indication for use, medication half-life, and risk for relapse should be considered. In schizophrenia, there is no reliable indicator to differentiate the minority who will not from the majority who will relapse with drug discontinuation. However, studies in which the medication of well-stabilized patients were discontinued indicate that 75% of patients relapse within 6 to 24 months. Indefinite maintenance antipsychotic medication is generally recommended, and especially for patients who have had multiple prior episodes or 2 episodes within 5 years (APA [Lehman 2004]).

Monitoring Parameters

Mental status; vital signs (as clinically indicated); blood pressure (baseline; repeat 3 months after antipsychotic initiation, then yearly); weight, height, BMI, waist circumference (baseline; repeat at 4, 8, and 12 weeks after initiating or changing therapy, then quarterly; consider switching to a different antipsychotic for a weight gain ≥5% of initial weight); CBC (as clinically indicated; monitor frequently during the first few months of therapy in patients with preexisting low WBC or history of drug-induced leukopenia/neutropenia); electrolytes, renal and liver function (annually and as clinically indicated); personal and family history of obesity, diabetes, dyslipidemia, hypertension, or cardiovascular disease (baseline; repeat annually); fasting plasma glucose level/HbA1c (baseline; repeat 3 months after starting antipsychotic, then yearly); fasting lipid panel (baseline; repeat 3 months after initiation of antipsychotic; if LDL level is normal repeat at 2- to 5-year intervals or more frequently if clinical indicated); changes in menstruation, libido, development of galactorrhea, erectile and ejaculatory function (at each visit for the first 12 weeks after the antipsychotic is initiated or until the dose is stable, then yearly); abnormal involuntary movements or parkinsonian signs (baseline; repeat weekly until dose stabilized for at least 2 weeks after introduction and for 2 weeks after any significant dose increase); tardive dyskinesia (every 12 months; high-risk patients every 6 months); ocular examination (yearly in patients >40 years; every 2 years in younger patients) (ADA 2004; APA [Lehman 2004]; Marder 2004); fall risk (baseline and periodically during treatment in patients with diseases or on medications that may also increase fall risk).

Reproductive Considerations

Paliperidone may cause hyperprolactinemia, which may cause a reversible decrease in fertility in females.

Pregnancy Considerations

Information specific to paliperidone in pregnancy is limited (Onken 2018; Özdemir 2015; Zamora Rodriguez 2017).

Antipsychotic use during the third trimester of pregnancy has a risk for extrapyramidal symptoms (EPS) and/or withdrawal symptoms in newborns following delivery. Symptoms in the newborn may include agitation, feeding disorder, hypertonia, hypotonia, respiratory distress, somnolence, and tremor. These effects may be self-limiting and allow recovery within hours or days with no specific treatment, or they may be severe requiring prolonged hospitalization.

The ACOG recommends that therapy during pregnancy be individualized; treatment with psychiatric medications during pregnancy should incorporate the clinical expertise of the mental health clinician, obstetrician, primary healthcare provider, and pediatrician. Safety data related to atypical antipsychotics during pregnancy is limited and routine use is not recommended. However, if a woman is inadvertently exposed to an atypical antipsychotic while pregnant, continuing therapy may be preferable to switching to a typical antipsychotic that the fetus has not yet been exposed to; consider risk:benefit (ACOG 2008).

Paliperidone is the active metabolite of risperidone; refer to Risperidone monograph for additional information.

Health care providers are encouraged to enroll women 18 to 45 years of age exposed to paliperidone during pregnancy in the Atypical Antipsychotics Pregnancy Registry (1-866-961-2388 or http://www.womensmentalhealth.org/pregnancyregistry).

Patient Education

What is this drug used for?

• It is used to treat schizophrenia.

• It is used to treat schizoaffective disorder.

• It may be given to you for other reasons. Talk with the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache

• Weight gain

• Constipation

• Fatigue

• Anxiety

• Nausea

• Vomiting

• Stuffy nose

• Sore throat

• Restlessness

• Loss of strength and energy

• Tablet shell in stool

• Injection site irritation

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Infection

• High blood sugar like confusion, feeling sleepy, more thirst, hunger, passing urine more often, flushing, fast breathing, or breath that smells like fruit

• Fast heartbeat

• Severe dizziness

• Passing out

• Abnormal heartbeat

• Behavioral changes

• Mood changes

• Tremors

• Trouble moving

• Rigidity

• Slow heartbeat

• Trouble swallowing

• Seizures

• Drooling

• Bruising

• Bleeding

• Involuntary eye movements

• Lack of sweating

• Enlarged breasts

• Sexual dysfunction

• Loss of sex drive

• Nipple discharge

• Breast pain

• No menstrual periods

• Erection that lasts more than 4 hours

• Neuroleptic malignant syndrome like fever, muscle cramps or stiffness, dizziness, very bad headache, confusion, change in thinking, fast heartbeat, abnormal heartbeat, or sweating a lot.

• Tardive dyskinesia like unable to control body movements; tongue, face, mouth, or jaw sticking out; mouth puckering; and puffing cheeks.

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Frequently Asked Questions