Version July 2025
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.
Dosage guidance:
Safety: Antipsychotics are not indicated for use in catatonia and may worsen psychosis and increase risk for neuroleptic malignant syndrome in patients with catatonia (Ref).
Clinical considerations: Consult a psychiatry specialist for all management decisions; select antipsychotic carefully based on patient preference, clinical characteristics, history, comorbidities, and adverse effect profile (Ref).
Bipolar disorder:
Acute mania or acute episodes with mixed features and maintenance treatment (alternative agent) (off-label use): Oral: Initial: 6 mg once daily; may adjust daily dose based on response and tolerability in increments of 3 mg every ≥2 days up to 12 mg/day. Usual dosage range: 6 to 12 mg/day (Ref).
Schizophrenia and schizoaffective disorder:
Note: For the management of schizophrenia, may be used as monotherapy. For the treatment of schizoaffective disorder, may be used as monotherapy or as an adjunct to mood stabilizers or antidepressants.
Oral: Initial: 6 mg once daily, or if this is a first episode of psychosis, consider initiating at a reduced dose (eg, 3 mg/day) because these patients will be more sensitive to adverse effects. May increase daily dose based on response and tolerability in increments of 3 mg no sooner than every 3 days; monitor for akathisia, orthostatic hypotension, parkinsonism, and sedation during titration. May reduce dose to 3 mg/day in patients who do not tolerate 6 mg/day. Maximum: 12 mg/day (Ref).
IM (palmitate ER long-acting injectable suspension):
Note: Formulations contain 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
Note: Establish tolerability using oral paliperidone, oral risperidone, or long-acting injectable risperidone prior to initiating long-acting IM palmitate.
Invega Sustenna:
Initial: IM:234 mg (150 mg as base) on treatment day 1 followed by 156 mg (100 mg as base) on treatment day 8. May administer the second dose between days 4 and 12 if needed. Initiate maintenance dosing 5 weeks after the first initiation dose.
|
Time since first injection |
Instructions |
|---|---|
|
<4 weeks |
Administer 156 mg (100 mg as base) as soon as possible, followed by 117 mg (75 mg as base) 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) as soon as possible, followed by another 156 mg (100 mg as base) dose 1 week later. Then begin monthly maintenance dose 4 weeks later. |
|
>7 weeks |
Reinitiate entire dose titration. |
Oral overlap: It is not necessary to continue oral paliperidone following the first long-acting IM palmitate injection (Ref).
Maintenance dose: IM: 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. Five weeks after the first initiation dose, begin a maintenance dose of 39 to 234 mg (25 to 150 mg as base) every month. May administer each maintenance dose 3 to 5 weeks after previous IM dose. Adjust maintenance dose and frequency based on response and tolerability; the full effect from a dose adjustment may not be apparent for several months. Maximum: 234 mg/month (150 mg/month as base).
|
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 |
Usual maintenance dose 39 to 156 mg (25 to 100 mg as base): Administer the usual maintenance dose as soon as possible, followed by another usual maintenance dose 1 week later, then resume usual monthly maintenance dose 4 weeks later. Maintenance dose 234 mg (150 mg as base): Administer 156 mg (100 mg as base) as soon as possible, followed by another 156 mg (100 mg as base) 1 week later, then resume usual monthly maintenance dose 4 weeks later. |
|
>6 months |
Reinitiate entire dose titration. |
Erzofri:
Initial: IM: 351 mg on treatment day 1. Initiate maintenance dosing 4 weeks after initial dose.
Oral overlap: Oral overlap with paliperidone is not necessary. Use caution if it is continued following the first IM injection.
Maintenance dose: IM: 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. Four weeks after the initial dose, begin a maintenance dose of 39 to 234 mg every month; the 39 mg dose has not been studied in patients with schizoaffective disorder. May administer each maintenance dose 3 to 5 weeks after previous IM dose. Adjust maintenance dose and frequency based on response and tolerability; the full effect from a dose adjustment may not be apparent for several months. Maximum: 234 mg/month.
|
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 |
Usual maintenance dose 39 to 156 mg: Administer the usual maintenance dose as soon as possible, followed by another usual maintenance dose 1 week later, then resume usual monthly maintenance dose 1 month later. Usual maintenance dose 234 mg: Administer 156 mg as soon as possible, followed by another 156 mg 1 week later, then resume usual monthly maintenance dose 1 month later. |
|
>6 months |
Administer 351 mg as soon as possible, then resume usual monthly maintenance dose 1 month later. |
3-month paliperidone (FDA-approved for schizophrenia only) (Invega Trinza):
Note: 3-month IM paliperidone (Invega Trinza) is to be used only after 4 doses of monthly IM paliperidone (Invega Sustenna). The last 2 doses of monthly IM paliperidone should be the same dosage strength before starting 3-month IM paliperidone.
Initial: 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. Administer the initial dose of 3-month IM paliperidone (Invega Trinza) when the next monthly IM paliperidone (Invega Sustenna) dose is scheduled (or between 3 and 5 weeks since last monthly IM dose). Initiate maintenance dosing 3 months after the initial 3-month IM dose.
Maintenance: Administer the same dose as the initial 3-month IM paliperidone (Invega Trinza) dose every 3 months, adjusting dose if needed based on response and tolerability. May administer each maintenance dose 10 to 14 weeks after previous IM dose. Every 3 months, adjust maintenance dose if needed based on response and tolerability to a 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. Maximum: 819 mg every 3 months (Ref).
|
Time since last injection |
Instructions |
|---|---|
|
>3.5 months but <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) as soon as possible (day 1) and again on day 8. One month following the day 8 injection, administer 273 mg (175 mg as base) of 3-month IM paliperidone (Invega Trinza) 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) as soon as possible (day 1) and again on day 8. One month following the day 8 injection, administer 410 mg (263 mg as base) of 3-month IM paliperidone (Invega Trinza) 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) as soon as possible (day 1) and again on day 8. One month following the day 8 injection, administer 546 mg (350 mg as base) of 3-month IM paliperidone (Invega Trinza) 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) as soon as possible (day 1) and again on day 8. One month following the day 8 injection, administer 819 mg (525 mg as base) of 3-month IM paliperidone (Invega Trinza) 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. |
6-month paliperidone (FDA-approved for schizophrenia only) (Invega Hafyera):
Converting from monthly IM paliperidone (Invega Sustenna) to 6-month IM paliperidone (Invega Hafyera):
Note: 6-month IM paliperidone (Invega Hafyera) may only be used after 4 doses of monthly IM paliperidone (Invega Sustenna). The last 2 doses of monthly IM paliperidone should be the same dosage strength before starting 6-month IM paliperidone.
Initial: Base the 6-month dose on the previous monthly dose, using the "Dose Conversions That Attain Similar Steady-State Paliperidone Exposure During Maintenance Treatment" table. Administer the initial dose of 6-month IM paliperidone (Invega Hafyera) when the next monthly IM paliperidone (Invega Sustenna) dose is scheduled (or between 3 and 5 weeks since last monthly IM dose). Initiate maintenance dosing 6 months after the initial 6-month IM dose.
Maintenance: Administer the same dose as the initial 6-month IM paliperidone (Invega Hafyera) dose every 6 months, adjusting dose if needed based on response and tolerability. May administer each maintenance dose 22 to 27 weeks after previous IM dose. Every 6 months, adjust maintenance dose if needed based on response and tolerability to a usual dose of 1,092 to 1,560 mg; response to an adjusted dose may not be apparent for several months. Maximum: 1,560 mg every 6 months (Ref).
Converting from 3-month IM paliperidone (Invega Trinza) to 6-month IM paliperidone (Invega Hafyera):
Initial: Administer the initial dose of 6-month IM paliperidone (Invega Hafyera) when the next 3-month IM paliperidone (Invega Trinza) dose is scheduled (or between 2.5 and 3.5 months since last 3-month IM paliperidone dose). Base the 6-month dose on the previous 3-month dose, using the "Dose Conversions That Attain Similar Steady-State Paliperidone Exposure During Maintenance Treatment" table. Initiate maintenance dosing 6 months after the initial 6-month IM dose.
Maintenance: Administer the same dose as the initial 6-month IM paliperidone (Invega Hafyera) dose every 6 months, adjusting dose if needed based on response and tolerability. May administer each maintenance dose 22 to 27 weeks after previous IM dose. Every 6 months, adjust maintenance dose if needed based on response and tolerability to a usual dose of 1,092 to 1,560 mg; response to an adjusted dose may not be apparent for several months. Maximum: 1,560 mg every 6 months (Ref).
|
Time since last injection |
Instructions |
|---|---|
|
>6 months and 3 weeks but <8 months |
Maintenance dose 1,092 mg: Do not administer the missed dose. Administer 156 mg of monthly IM paliperidone (Invega Sustenna) as soon as possible. One month later, administer 1,092 mg of 6-month IM paliperidone (Invega Hafyera) and resume usual dosing at 6-month intervals. Maintenance dose 1,560 mg: Do not administer the missed dose. Administer 234 mg of monthly IM paliperidone (Invega Sustenna) as soon as possible. One month later, administer 1,560 mg of 6-month IM paliperidone (Invega Hafyera) and resume usual dosing at 6-month intervals. |
|
8 to 11 months |
Maintenance dose 1,092 mg: Do not administer the missed dose. Administer 156 mg of monthly IM paliperidone (Invega Sustenna) as soon as possible (day 1) and again on day 8. One month after the day 8 injection, administer 1,092 mg of 6-month IM paliperidone (Invega Hafyera) and resume usual dosing at 6-month intervals. Maintenance dose 1,560 mg: Do not administer the missed dose. Administer 156 mg of monthly IM paliperidone (Invega Sustenna) as soon as possible (day 1) and again on day 8. One month after the day 8 injection, administer 1,560 mg of 6-month IM paliperidone (Invega Hafyera) and resume usual dosing at 6-month intervals. |
|
>11 months |
Reinitiate treatment with monthly IM paliperidone (Invega Sustenna). 6-month IM paliperidone (Invega Hafyera) can be resumed after the patient has been adequately treated with monthly IM paliperidone for at least 4 months. |
|
Paliperidone ER tablet |
Paliperidone palmitate monthly IM injection (Invega Sustenna) |
Paliperidone palmitate monthly IM Injection (Erzofri) |
Paliperidone palmitate 3-month IM injection (Invega Trinza) |
Paliperidone palmitate 6-month IM injection (Invega Hafyera) |
Risperidone ER IM injection (Risperdal Consta) |
Risperidone tablet |
|---|---|---|---|---|---|---|
|
a Do not use this table to convert from the 3-month IM paliperidone injection to oral paliperidone tablets or between the risperidone IM injection and oral risperidone tablets. See information below about converting between 3-month IM paliperidone injection to oral paliperidone tablets. See risperidone monograph for information about converting between the risperidone IM injection and oral risperidone. | ||||||
|
b Janssen 2024; Lauriello 2024; manufacturer's labeling. | ||||||
|
3 mg/day |
39 mg (25 mg as base) every month |
39 mg every month |
Has not been studied |
Has not been studied |
No information available |
1 mg/day |
|
78 mg (50 mg as base) every month |
78 mg every month |
273 mg (175 mg as base) every 3 months |
Has not been studied |
25 mg every 2 weeks |
2 mg/day | |
|
6 mg/day |
117 mg (75 mg as base) every month |
117 mg every month |
410 mg (263 mg as base) every 3 months |
Has not been studied |
37.5 mg every 2 weeks |
3 mg/day |
|
9 mg/day |
156 mg (100 mg as base) every month |
156 mg every month |
546 mg (350 mg as base) every 3 months |
1,092 mg every 6 months |
50 mg every 2 weeks |
4 mg/day |
|
12 mg/day |
234 mg (150 mg as base) every month |
234 mg every month |
819 mg (525 mg as base) every 3 months |
1,560 mg every 6 months |
No information available |
6 mg/day |
Converting from 3-month IM paliperidone (Invega Trinza) to monthly IM paliperidone (Invega Sustenna): 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 "Dose Conversions That Attain Similar Steady-State Paliperidone Exposure During Maintenance Treatment" table. Following the initial injection, administer once monthly.
Converting from other oral antipsychotics to long-acting injectable paliperidone (monthly, 3-month, or 6-month): There are no systematically collected data to address switching patients from other oral antipsychotics to Invega Sustenna. If initiating Erzofri in a patient on a stable oral antipsychotic dose, gradually taper the oral antipsychotic after the first Erzofri injection.
Converting from other long-acting injectable antipsychotics (at steady state) to monthly IM paliperidone:
Note: Establish tolerability with oral paliperidone or oral risperidone. This step is not necessary if converting from Risperdal Consta.
Invega Sustenna: When the next long-acting injection is due, initiate maintenance dosing of Invega Sustenna (usual dose range: 39 to 234 mg/month) and continue at monthly intervals. The initial 2 doses (ie, during the one-week initiation dosing regimen) of monthly IM paliperidone schedule are not required.
Erzofri: When the next long-acting injection is due, initiate maintenance dosing of Erzofri (usual dose range: 39 to 234 mg/month) and continue at monthly intervals.
Converting from 3-month IM paliperidone (Invega Trinza) to paliperidone ER tablets: Do not use "Dose Conversions That Attain Similar Steady-State Paliperidone Exposure During Maintenance Treatment" table to determine appropriate dose. Initiate paliperidone ER when the next 3-month IM paliperidone is due. Increase the dose of oral paliperidone ER over the next 24 weeks using the "Converting From 3-month IM Paliperidone (Invega Trinza) to Paliperidone ER Tablets" table (eg, if last 3-month IM dose was 546 mg/month, initiate oral paliperidone at 3 mg/day; after 6 weeks, increase oral paliperidone to 6 mg/day, followed by an increase to 9 mg/day after an additional 6 weeks).
|
Weeks since last 3-month IM injection | |||
|---|---|---|---|
|
12 to 18 weeks |
>18 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:
Oral : In the treatment of chronic psychiatric disease switching therapy rather than discontinuation is generally advised if side effects are intolerable or treatment is not effective. If patient insists on stopping treatment, gradual dose reduction (ie, over several weeks to months) is advised to detect a re-emergence of symptoms and to avoid withdrawal reactions (eg, agitation, alternating feelings of warmth and chill, anxiety, diaphoresis, dyskinesias, GI symptoms, insomnia, irritability, myalgia, paresthesia, psychosis, restlessness, rhinorrhea, tremor, vertigo) unless discontinuation is due to significant adverse effects. Monitor closely to allow for detection of prodromal symptoms of disease recurrence (Ref).
Long- acting injectable: Switching to other treatments is generally advised if side effects are intolerable or treatment is not effective. However, if a patient insists on stopping treatment, gradual dose reduction to avoid withdrawal reactions is generally not needed with long-acting injectable antipsychotics. The risk of withdrawal symptoms from discontinuation of long-acting injectables is low because the rate of drug elimination is slow. Monitor closely to allow for detection of prodromal symptoms of disease recurrence (Ref).
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 (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
|
CrCl |
Oral ER tablet |
Monthly IM injection (Invega Sustenna) |
Monthly IM injection (Erzofri) |
3-month IM injection (Invega Trinza) |
6-month IM injection (Invega Hafyera) | |
|---|---|---|---|---|---|---|
|
a Onwordi 2021; Schoretsanitis 2018; Schoretsanitis 2023. | ||||||
|
b Canadian labeling. | ||||||
|
c T’jollyn 2024. | ||||||
|
≥80 mL/minute |
No dosage adjustment necessary. |
No dosage adjustment necessary. |
No dosage adjustment necessary. |
No dosage adjustment necessary. |
No dosage adjustment necessary. | |
|
50 to <80 mL/minute |
Initial: 3 mg once daily; maximum: 6 mg once daily. |
Note: Long-acting preparations should be avoided in patients with changing kidney function, as they are difficult to safely titrate and dose requirements may acutely change. Additionally, there are limited data on the use of long-acting injectable paliperidone in patients with kidney impairment. Consider using a different antipsychotic.c | ||||
|
Initiation: 156 mg (100 mg as base) on treatment day 1, followed by 117 mg (75 mg as base) 1 week later. Maintenance: Five weeks after the first initiation dose, begin a maintenance dose of 78 mg (50 mg as base) every month. The dose can be subsequently adjusted to 39 to 156 mg (25 to 100 mg as base) every month. Maximum: 156 mg (100 mg as base) every month. |
Initiation: 234 mg on treatment day 1. Maintenance: One month after initial dose, begin a maintenance dose of 78 mg every month. The dose can be subsequently adjusted to 39 to 156 mg every month. Maximum: 156 mg every month. |
Initiation: Note: Patient should already be stabilized on monthly injections of at least 78 mg (50 mg as base) before transitioning to an equivalent dose of the every 3-month injection. Refer to "Dosage: Adult" for the “Dose Conversions That Attain Similar Steady-State Paliperidone Exposure During Maintenance Treatment” table and for timing of initial injections. Maintenance: Administer the same dose as the initial 3-month IM paliperidone (Invega Trinza) dose every 3 months, adjusting dose if needed based on response and tolerability. Maximum: 546 mg (350 mg as base) every 3 months.b |
Note: Patient should already be stabilized on monthly injections of 156 mg (100 as base) or every 3-month IM injections of 546 mg (350 mg as base) before transitioning to every 6-month injections. Initial/Maintenance: 1,092 mg every 6 months. Maximum: 1,092 mg every 6 months.c | |||
|
10 to <50 mL/minute |
Initial: 1.5 mg once daily or 3 mg every other day; maximum: 3 mg once daily. |
Use not recommended. | ||||
|
<10 mL/minute |
Use not recommended. | |||||
Hemodialysis, intermittent (thrice weekly): Not significantly dialyzable (Ref): Avoid use (Ref).
Peritoneal dialysis: Not likely to be significantly dialyzable (Ref): Avoid use (Ref).
CRRT: Avoid use (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): Avoid use (Ref).
Oral, IM (monthly, 3-month or 6-month):
Mild to moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.
Severe impairment: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Severe neutropenia (ANC <1,000/mm3): Discontinue treatment.
Note: Avoid for behavioral problems associated with dementia or delirium unless alternative nonpharmacologic therapies have failed and patient may harm self or others. If used, consider deprescribing attempts to assess continued need and/or lowest effective dose. Of note, use in certain indications (eg, schizophrenia) may be appropriate (Ref). Consult a psychiatry specialist for all management decisions (Ref).
Schizophrenia and schizoaffective disorder: Refer to adult dosing; use with caution. Dosages in the lower range of recommended adult dosing are generally sufficient with late-onset schizophrenia or psychosis. Titrate dosage slowly and monitor carefully (Ref).
(For additional information see "Paliperidone: Pediatric drug information")
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 (Ref).
Schizoaffective disorder:
Oral: Adolescents ≥18 years: Oral: Extended-release tablet: 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 at intervals of more than 4 days, up to a maximum daily dose: 12 mg/day.
Parenteral: Adolescents ≥18 years: IM: Due to complexity of product formulations, conversions of formulations, and schedule management, dosing for the monthly injection (Invega Sustenna) in adolescents ≥18 years of age is addressed in "Dosing: Adult."
Schizophrenia:
Oral:
Children ≥12 years and Adolescents <18 years: Oral: Extended-release tablet: 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: Oral: Extended-release tablet: 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: IM: Due to complexity of product formulations and variations in recommendations, dosing for the monthly injection (Invega Sustenna), 3-month injection (Invega Trinza), and 6-month injection (Invega Hafyera) in adolescents ≥18 years of age is addressed in "Dosing: Adult."
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosage adjustment for toxicity: Children ≥12 years and Adolescents: Severe neutropenia (ANC <1,000/mm3): Discontinue treatment.
Oral:
Children ≥12 years and Adolescents ≤17 years: There are no dosage adjustments provided in the manufacturer's labeling for pediatric patients ≤17 years; clearance is decreased in renal impairment; adjust dose according to renal function. In adolescents ≥18 years and adults, doses reductions are suggested.
Adolescents ≥18 years:
CrCl ≥80 mL/minute: No dosage adjustment necessary.
CrCl 50 to 79 mL/minute: Initial dose: 3 mg once daily; maximum dose: 6 mg once daily.
CrCl 10 to 49 mL/minute: Initial dose: 1.5 mg once daily; maximum dose: 3 mg once daily.
CrCl <10 mL/minute: Use not recommended (has not been studied).
IM: Adolescents ≥18 years: Due to complexity of product formulations and variations in recommendations, dosing for the monthly injection (Invega Sustenna), 3-month injection (Invega Trinza), and 6-month injection (Invega Hafyera) in adolescents ≥18 years of age is addressed in "Dosing: Altered Kidney Function: Adult."
Children ≥12 years and Adolescents: Oral, IM:
Mild to moderate: No dosage adjustment necessary.
Severe impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Potentially life-threatening angioedema has been reported very rarely following oral and IM paliperidone (Ref).
Mechanism: Unknown; immunologic and non-immunologic mechanisms have been proposed, including IgE-related hypersensitivity, kinin-dependent processes, or C1-esterase inhibition deficiencies (Ref). An excipient (eg, polysorbate, polyethylene glycol) contained in the paliperidone IM formulation may also be a possible allergen (Ref)
Onset: Varied; Oral: Onset occurred during the second week of oral therapy, but a few hours following dosage increase from the initial dose of 3 mg/day to 6 mg/day. IM: 17 to 60 days following IM administration (Ref).
Risk factors:
• Dose-dependency: Increased risk of angioedema with increased dose (Ref)
• Route of administration: Tolerance to oral paliperidone but development of angioedema with IM paliperidone has been described (Ref)
Antipsychotics are associated with dyslipidemia in adult and pediatric patients, which is a component of the metabolic syndrome observed with this pharmacologic class. Although data are inconsistent regarding paliperidone’s risk, the following events have been observed: Increased serum cholesterol, decreased HDL cholesterol, and/or increased serum triglycerides (Ref).
Mechanism: The mechanism is not entirely understood and is likely multifactorial (Ref).
Onset: Varied; metabolic alterations from antipsychotics can develop in as short as 3 months after initiation (Ref).
Risk factors:
• Children and adolescents may be at increased risk for increased serum triglycerides with second-generation antipsychotic use (data does not involve use of paliperidone) (Ref)
• A higher BMI (potential risk factor) is potentially associated with higher risk of metabolic-related adverse events (Ref)
• Schizophrenia (regardless of medication use) is associated with a higher rate of morbidity/mortality compared to the general population primarily due to cardiovascular disease (Ref)
• Specific antipsychotic: Paliperidone is usually considered to have a low risk for causing lipid abnormalities in adults, although data are inconsistent (Ref)
Paliperidone is frequently associated with extrapyramidal symptoms (EPS), also known as drug-induced movement disorders in adult and pediatric patients. Antipsychotics can cause 4 main EPS: Acute dystonia, drug-induced parkinsonism, akathisia, and dyskinesia (which includes tardive dyskinesia) (Ref). EPS presenting as dysphagia, esophageal dysmotility, or aspiration have also been reported with antipsychotics, which may not be recognized as EPS (Ref).
Mechanism: EPS: Dose-related; due to antagonism of dopaminergic D2 receptors in nigrostriatal pathways (Ref). Tardive dyskinesia: Time-related (delayed); results from chronic exposure to dopamine 2 receptor antagonists leading to up-regulation of these receptors over time (Ref).
Onset:
Antipsychotics in general:
Acute dystonia: Rapid; in the majority of cases, dystonia usually occurs within the first 5 days after initiating antipsychotic therapy (and even with the first dose, particularly in patients receiving parenteral antipsychotics) or a dosage increase (Ref).
Drug-induced parkinsonism: Varied; onset may be delayed from days to weeks, with 50% to 75% of cases occurring within 1 month and 90% within 3 months of antipsychotic initiation, a dosage increase, or a change in the medication regimen (such as adding another antipsychotic agent or discontinuing an anticholinergic medication) (Ref).
Akathisia: Varied; may begin within several days after antipsychotic initiation but usually increases with treatment duration, occurring within 1 month in up to 50% of cases and within 3 months in 90% of cases (Ref)
Tardive dyskinesia: Delayed; symptoms usually appear after 1 to 2 years of continuous exposure to a dopamine 2 receptor antagonist and almost never before 3 months with an insidious onset, evolving into a full syndrome over days and weeks, followed by symptom stabilization and then a chronic waxing and waning of symptoms (Ref).
Esophageal dysfunction (associated with EPS): Varied; ranges from weeks to months following initiation (Ref)
Risk factors:
EPS (in general):
• Prior history of EPS (Ref)
• Higher doses (Ref)
• Younger age (in general, children and adolescents are usually at higher risk for EPS compared to adults) (Ref)
• Specific antipsychotic: Paliperidone, the primary active metabolite of risperidone, is usually associated with a moderate to high propensity to cause EPS, similar to risperidone’s propensity (Ref). Some limited data suggests that switching from risperidone to paliperidone improved preexisting EPS (Ref). The once monthly paliperidone formulation has been associated with a lower incidence of EPS compared with oral paliperidone, and the 3-month paliperidone formulation has been found to have a similar incidence of EPS compared to the once monthly paliperidone in patients with schizophrenia (Ref)
Acute dystonia:
• Males (Ref)
• Young age (Ref)
Drug-induced parkinsonism:
• Females (Ref)
• Older patients (Ref)
Akathisia:
• Higher antipsychotic dosages (Ref)
• Polypharmacy (Ref)
• Mood disorders (Ref)
• Females (Ref)
• Older patients (Ref)
Tardive dyskinesia:
• Age >55 years (Ref)
• Cognitive impairment (Ref)
• Concomitant treatment with anticholinergic medications (Ref)
• Diabetes (Ref)
• Diagnosis of schizophrenia or affective disorders (Ref)
• Females (Ref)
• Greater total antipsychotic exposure (especially first-generation antipsychotics) (Ref)
• History of extrapyramidal symptoms (Ref)
• Substance misuse or dependence (Ref)
• Race (White or African descent). Note: Although early literature supported race as a potential risk factor for tardive dyskinesia (Ref), newer studies have challenged this assertion (Ref).
Esophageal dysfunction (associated with EPS):
• Certain comorbidities such as neurologic degenerative disease, dementia, stroke, Parkinson disease, or myasthenia gravis (Ref)
• Older adults >75 years of age (may be risk factor due to age-related muscle atrophy, cognitive impairment, reduced esophageal peristalsis) (Ref)
Leukopenia and neutropenia have been reported rarely with paliperidone (Ref). Agranulocytosis has also been reported very rarely in a patient receiving a combination of paliperidone and risperidone (Ref).
Mechanism: Unclear and poorly understood (Ref). In cases where paliperidone is combined with risperidone, dose-related toxicity has been suspected as paliperidone is a major active metabolite of risperidone (Ref).
Onset: Varied; in general, drug-induced neutropenia usually manifests after 1 or 2 weeks of exposure and agranulocytosis usually appears 3 to 4 weeks following initiation of therapy; however, the onset may be insidious (Ref).
Risk factors:
• Older adults (Ref)
• History of drug-induced leukopenia/neutropenia or low white blood cell count/absolute neutrophil count (Ref)
Antipsychotics are associated with hyperglycemia in adult and pediatric patients, to varying degrees, which is a component of the metabolic syndrome observed with this pharmacologic class. Although data are insufficient regarding paliperidone’s risk, the following events have been observed: Increased serum glucose (fasting), mild insulin resistance and hyperinsulinemia (Ref).
Mechanism: The mechanism is not entirely understood and is likely multifactorial (Ref).
Onset: Varied; new-onset diabetes has been observed within the first 3 months to a median onset of 3.9 years of atypical antipsychotic initiation (studies did not include paliperidone) (Ref).
Risk factors (in general):
• African American race (Ref)
• Males (Ref)
• Younger adults (Ref)
• Preexisting obesity, poor exercise habits, or other risk factors for diabetes, including family history of diabetes (Ref)
• Exposure to other agents that also increase the risk of hyperglycemia (Ref)
• Specific antipsychotic: Risk of hyperglycemia and/or new onset diabetes appears to be low to moderate with paliperidone, although data are insufficient (Ref).
Paliperidone commonly causes hyperprolactinemia/increased serum prolactin in adult and pediatric patients, which may lead to gynecomastia, galactorrhea not associated with childbirth, amenorrhea, sexual disorder, and infertility (Ref). Although long-term effects of elevated prolactin levels have not been fully evaluated, some studies have also suggested a possible association between hyperprolactinemia and an increased risk for breast and/or pituitary tumors and osteopenia/osteoporosis (Ref).
Mechanism: Dose-related and possibly time-related; antagonism of dopamine D2 receptors in the tuberoinfundibular dopaminergic pathway which causes disinhibition of prolactin release resulting in hyperprolactinemia (Ref).
Onset: Varied; onset is typically within a few weeks following initiation or dosage increase, but may also arise after long-term stable use following atypical antipsychotic use (paliperidone not specifically studied) (Ref)
Risk factors:
• Specific antipsychotic: Similar to risperidone, risperidone’s active metabolite, paliperidone (9-hydroxy-risperidone) is considered a prolactin-elevating antipsychotic with a high risk for hyperprolactinemia (Ref)
• Higher doses (Ref)
• Females (particularly those of reproductive age) (Ref)
• Children and adolescents (Ref)
Older adults with dementia-related psychosis treated with antipsychotics are at an increased risk of death compared to placebo. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature (Ref). In addition, an increased incidence of cerebrovascular effects (eg, cerebrovascular accident, transient ischemic attacks), including fatalities, have been reported in placebo-controlled risperidone trials in older adults with dementia-related psychosis in elderly patients with dementia) (Ref). No studies have been conducted with paliperidone, a metabolite of risperidone. Of note, paliperidone is not approved for the treatment of dementia-related psychosis.
Mechanism: Unknown; possible mechanisms include arrhythmia, cardiac arrest, and extrapyramidal effects that may increase the risk of falls, aspirations, and pneumonia (Ref).
Risk factors:
Antipsychotics in general:
• Higher antipsychotic dosage (Ref)
• Dementia-related psychosis (eg, Lewy body dementia, Parkinson disease dementia)
• Older adults
All antipsychotics have been associated with neuroleptic malignant syndrome (NMS), although the incidence is less with second-generation (atypical) antipsychotics compared to first-generation (typical) antipsychotics. There are case reports of NMS with paliperidone, with several associated with the use of paliperidone palmitate long-acting IM injection, although there is also a single case report in a patient switching between oral risperidone and oral paliperidone (Ref).
Mechanism: Non–dose-related; idiosyncratic. Believed to be due to a reduction in CNS dopaminergic tone, along with the dysregulation of autonomic nervous system activity (Ref).
Onset: Varied; in general, most patients develop NMS within 2 weeks of initiating an antipsychotic, and in some patients, prodromal symptoms emerge within hours of initiation; once the syndrome starts, the full syndrome usually develops in 3 to 5 days (Ref). However, there are many cases of NMS occurring months after stable antipsychotic therapy (Ref).
Risk factors:
Antipsychotics in general:
• Males (twice as likely to develop NMS compared to females) (Ref)
• Dehydration (Ref)
• High-dose antipsychotic treatment (Ref)
• Concomitant lithium or benzodiazepine (potential risk factors) (Ref)
• Catatonia (Ref)
• Polypharmacy (Ref)
• Pharmacokinetic interactions (Ref)
• IM administration (Ref)
• Rapid dosage escalation (Ref)
• Psychomotor agitation (Ref)
Orthostatic hypotension and accompanying dizziness, postural orthostatic tachycardia, and syncope may sometimes occur, particularly with rapid titration and/or in older adults (which may result in subsequent falling and fracture). (Ref). In addition, tachycardia is common with paliperidone (Ref).
Mechanism: Orthostatic hypotension from antipsychotics is attributed to alpha-1 receptor antagonism (Ref). Antipsychotics in patients with schizophrenia are also associated with dysfunction of the autonomic nervous system with a variety sympathetic and parasympathetic effects, resulting in heart rate variability (Ref). In addition to paliperidone’s alpha-1 receptor antagonism, it can also block presynaptic alpha-2 receptors causing disinhibited norepinephrine release and activation of cardiac sympathetic nerves. However, it can also block histamine-1 and cholinergic receptors (low affinity) resulting in cardiac vagus nerve excitation (Ref)
Onset: Rapid; in general, antipsychotic-induced orthostatic hypotension is most common during the initial dose titration but can also occur following subsequent dose increases.
Risk factors:
Antipsychotics in general:
• Known cardiovascular disease (history of myocardial infarction or ischemic heart disease, heart failure, or conduction abnormalities) or cerebrovascular disease
• Known predisposing conditions (eg, hypovolemia/dehydration)
• Concomitant medications that also cause or exacerbate orthostatic hypotension (eg, tricyclic antidepressants, antihypertensive medications)
• Older adults
• Rapid dose titration (Ref)
Paliperidone has been associated with prolonged QT interval on ECG, with a possible risk for torsades de pointes (TdP), predominately in patients with other TdP risk factors or receiving concomitant agents that can prolong the QTc interval and/or increase paliperidone concentrations (Ref). Of the antipsychotics, paliperidone appears to have a modest to moderate QTc-prolongation effect at therapeutic doses, however, there is limited and conflicting evidence, with some based on paliperidone being a metabolite of risperidone (Ref).
Mechanism: Dose-dependent; paliperidone prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium current, although other mechanisms might also be involved (Ref).
Risk factors:
Drug-induced QTc prolongation/TdP (in general):
• Females (Ref)
• Age >65 years (Ref)
• Structural heart disease (eg, history of myocardial infarction or heart failure with a reduced ejection fraction) (Ref)
• History of drug-induced TdP (Ref)
• Genetic defects of cardiac ion channels (Ref)
• Congenital long QT syndrome (Ref)
• Baseline QTc interval prolongation (eg, >500 msec) or lengthening of the QTc by ≥60 msec (Ref)
• Electrolyte disturbances (eg, hypokalemia, hypocalcemia, hypomagnesemia) (Ref)
• Bradycardia (Ref)
• Hepatic impairment (Ref)
• Kidney impairment (Ref)
• Coadministration of multiple medications (≥2) that prolong the QT interval or increase drug interactions that increase serum drug concentrations of QTc prolonging medications (Ref). Note: Paliperidone is a metabolite of risperidone and metabolism by CYP450 isoenzymes plays a limited role in its elimination.
• Substance use (Ref)
Antipsychotics have been associated with sexual disorders in both males and females. Antipsychotic treatment has been associated with effects on all phases of sexual activity (libido, arousal, and orgasm); however, many patients with schizophrenia experience more frequent sexual dysfunction, with or without antipsychotic treatment. The following adverse reactions have been observed with paliperidone: Decreased libido, erectile dysfunction, and abnormal orgasm (Ref). In addition, priapism has been reported with paliperidone (Ref).
Mechanism: Antipsychotic-induced sexual dysfunction has been attributed to many potential mechanisms, including dopamine receptor antagonism, dopamine D2 receptor antagonism in the infundibular dopaminergic pathway causing hyperprolactinemia, histamine receptor antagonism, cholinergic receptor antagonism, and alpha-adrenergic receptor antagonism (Ref). Of note, paliperidone is associated with a high propensity for hyperprolactinemia (Ref). Priapism is believed to be caused by alpha-1 adrenergic antagonism (Ref).
Risk factors:
• Hyperprolactinemia (although a correlation with sexual dysfunction has been observed, a relationship has not been confirmed) (Ref)
• Schizophrenia (the prevalence of antipsychotic-induced sexual dysfunction in patients with schizophrenia is high [~50% to 60% compared with 31% of men in the general population]) (Ref)
• Specific antipsychotic: Based on data with risperidone, paliperidone is likely to be associated with a high prevalence of sexual dysfunction (Ref)
Antipsychotics may impair the body’s ability to regulate core body temperature, which may cause a potentially life-threatening heat stroke during predisposing conditions, such as heat wave or strenuous exercise. There are also case reports of potentially life-threatening hypothermia associated with paliperidone use (Ref).
Mechanism: Non–dose-related; idiosyncratic. Exact mechanism is unknown; however, body temperature is regulated by the hypothalamus with involvement of the dopamine, serotonin, and norepinephrine neurotransmitters. D2 antagonism may cause an increase in body temperature, while 5-HT2A (serotonin) receptor antagonism may cause a decrease in body temperature. Of note, paliperidone has pronounced 5-HT2A receptor antagonism, with stronger affinity for 5-HT2A receptors than for D2 receptors. In addition, antagonism of peripheral alpha-adrenergic receptors has also been suggested as a factor in the hypothermic effect by inhibiting peripheral responses to cooling (vasoconstriction and shivering) (Ref)
Onset: Hypothermia: Varied; antipsychotic-induced hypothermia cases indicate a typical onset in the period shortly after initiation of therapy or a dosage increase (first 7 to 10 days) (Ref)
Risk factors:
Antipsychotics in general:
Heat stroke:
• Psychiatric illness (regardless of medication use) (Ref)
• Dehydration (Ref)
• Strenuous exercise (Ref)
• Heat exposure (Ref)
• Concomitant medications possessing anticholinergic effects (Ref)
Hypothermia:
• In general, predisposing risk factors include: Older adults, cerebrovascular accident, preexisting brain damage, hypothyroidism, malnutrition, shock, sepsis, adrenal insufficiency, diabetes, disability, burns, exfoliative dermatitis benzodiazepine use, alcohol intoxication, kidney or liver failure (Ref)
• Schizophrenia (regardless of antipsychotic use) (Ref)
Paliperidone is associated with significant weight gain (increase of ≥7% from baseline) in adult and pediatric patients, which is a component of the metabolic syndrome observed with this pharmacologic class (Ref).
Mechanism: Multiple proposed mechanisms, including actions at serotonin, dopamine, histamine, and muscarinic receptors, with differing effects explained by differing affinity of antipsychotics at these receptors (Ref).
Onset: Varied; antipsychotic-induced weight gain usually occurs rapidly in the initial period following initiation, then gradually decreases and flattens over several months with patients continuing to gain weight in the long term (Ref).
Risk factors:
Antipsychotics in general:
• Family history of obesity (Ref)
• Parental BMI (Ref)
• Children and adolescents (Ref)
• Rapid weight gain in the initial period: Younger age, lower baseline BMI, more robust response to antipsychotic, and increase in appetite; rapid weight gain of >5% in the first month has been observed as the best predictor for significant long-term weight gain (Ref)
• Duration of therapy (although weight gain plateaus, patients continue to gain weight over time) (Ref)
• Schizophrenia (regardless of medication) is associated with a higher prevalence of obesity compared to the general population due to components of the illness, such as negative symptoms, sedentary lifestyles, and unhealthy diets (Ref)
Paliperidone:
• Specific antipsychotic: Paliperidone is considered to have an intermediate/moderate propensity for causing weight gain; olanzapine and clozapine are associated with a high risk (Ref)
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 both the oral and IM formulations.
>10%:
Cardiovascular: Tachycardia (1% to 14%) (table 1)
|
Drug (Paliperidone) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Paliperidone) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
9% |
0% |
Adolescents |
6 mg once daily |
Extended-release tablets |
Schizophrenia |
45 |
51 |
|
6% |
0% |
Adolescents |
3 mg once daily |
Extended-release tablets |
Schizophrenia |
16 |
51 |
|
6% |
0% |
Adolescents |
12 mg once daily |
Extended-release tablets |
Schizophrenia |
35 |
51 |
|
3% |
2% |
Adults |
3 to 6 mg once-daily fixed-dose range |
Extended-release tablets |
Schizoaffective disorder |
108 |
202 |
|
2% |
2% |
Adults |
3 to 12 mg once-daily flexible dose |
Extended-release tablets |
Schizoaffective disorder |
214 |
202 |
|
1% |
2% |
Adults |
9 to 12 mg once-daily fixed-dose range |
Extended-release tablets |
Schizoaffective disorder |
98 |
202 |
|
14% |
7% |
Adults |
3 mg once daily |
Extended-release tablets |
Schizophrenia |
127 |
355 |
|
14% |
7% |
Adults |
12 mg once daily |
Extended-release tablets |
Schizophrenia |
242 |
355 |
|
12% |
7% |
Adults |
6 mg once daily |
Extended-release tablets |
Schizophrenia |
235 |
355 |
|
12% |
7% |
Adults |
9 mg once daily |
Extended-release tablets |
Schizophrenia |
246 |
355 |
Endocrine & metabolic: Decreased HDL cholesterol (IM: 10% to 16%; oral: 7% to 29%) (table 2), hyperglycemia (≤11%) (table 3), increased LDL cholesterol (IM: <1%; oral: 4% to 14%), increased serum cholesterol (≤11%) (table 4), increased serum prolactin (females: 30% to 51%; males: 35% to 56%) (table 5), increased serum triglycerides (1% to 13%) (table 6), weight gain (2% to 19%)
|
Drug (Paliperidone) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Paliperidone) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
29% |
14% |
Adolescents |
3 mg once daily |
Extended-release tablets |
Schizophrenia |
7 |
28 |
|
23% |
14% |
Adolescents |
12 mg once daily |
Extended-release tablets |
Schizophrenia |
22 |
28 |
|
13% |
14% |
Adolescents |
6 mg once daily |
Extended-release tablets |
Schizophrenia |
23 |
28 |
|
7% |
14% |
Adolescents |
1.5 mg once daily |
Extended-release tablets |
Schizophrenia |
30 |
28 |
|
29% |
22% |
Adults |
6 mg once daily |
Extended-release tablets |
Schizophrenia |
134 |
200 |
|
23% |
22% |
Adults |
9 mg once daily |
Extended-release tablets |
Schizophrenia |
137 |
200 |
|
20% |
22% |
Adults |
12 mg once daily |
Extended-release tablets |
Schizophrenia |
135 |
200 |
|
16% |
22% |
Adults |
3 mg once daily |
Extended-release tablets |
Schizophrenia |
80 |
200 |
|
16% |
14% |
Adults |
234/234 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
81 |
203 |
|
15% |
14% |
Adults |
39 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
61 |
203 |
|
14% |
14% |
Adults |
156 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
106 |
203 |
|
14% |
9% |
Adults |
N/A |
Every-three-month extended-release injectable suspension |
Schizophrenia |
148 |
127 |
|
14% |
N/A |
Adults |
N/A |
Every-three-month extended-release injectable suspension |
Schizophrenia |
194 |
N/A |
|
13% |
N/A |
Adults |
N/A |
Every-six-month extended-release injectable suspension |
Schizophrenia |
423 |
N/A |
|
13% |
14% |
Adults |
234/39 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
71 |
203 |
|
11% |
14% |
Adults |
234/156 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
76 |
203 |
|
10% |
14% |
Adults |
78 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
115 |
203 |
|
Drug (Paliperidone) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Paliperidone) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
11% |
3% |
Adolescents |
12 mg once daily |
Extended-release tablets |
Schizophrenia |
27 |
32 |
|
0% |
3% |
Adolescents |
1.5 mg once daily |
Extended-release tablets |
Schizophrenia |
34 |
32 |
|
0% |
3% |
Adolescents |
3 mg once daily |
Extended-release tablets |
Schizophrenia |
9 |
32 |
|
0% |
3% |
Adolescents |
6 mg once daily |
Extended-release tablets |
Schizophrenia |
20 |
32 |
|
7% |
5% |
Adults |
234/156 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
86 |
241 |
|
7% |
5% |
Adults |
234/234 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
76 |
241 |
|
6% |
5% |
Adults |
39 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
64 |
241 |
|
6% |
5% |
Adults |
78 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
173 |
241 |
|
5% |
5% |
Adults |
6 mg once daily |
Extended-release tablets |
Schizophrenia |
156 |
236 |
|
5% |
5% |
Adults |
9 mg once daily |
Extended-release tablets |
Schizophrenia |
187 |
236 |
|
4% |
N/A |
Adults |
N/A |
Every-six-month extended-release injectable suspension |
Schizophrenia |
423 |
N/A |
|
4% |
2% |
Adults |
N/A |
Every-three-month extended-release injectable suspension |
Schizophrenia |
148 |
128 |
|
4% |
5% |
Adults |
156 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
154 |
241 |
|
4% |
5% |
Adults |
12 mg once daily |
Extended-release tablets |
Schizophrenia |
157 |
236 |
|
3% |
N/A |
Adults |
N/A |
Every-three-month extended-release injectable suspension |
Schizophrenia |
195 |
N/A |
|
3% |
5% |
Adults |
234/39 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
79 |
241 |
|
3% |
5% |
Adults |
3 mg once daily |
Extended-release tablets |
Schizophrenia |
93 |
236 |
|
Drug (Paliperidone) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Paliperidone) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|---|---|
|
11% |
7% |
Adolescents |
12 mg once daily |
Extended-release tablets |
Schizophrenia |
19 |
27 |
<170 mg/dL to ≥200 mg/dL |
|
6% |
7% |
Adolescents |
6 mg once daily |
Extended-release tablets |
Schizophrenia |
18 |
27 |
<170 mg/dL to ≥200 mg/dL |
|
4% |
7% |
Adolescents |
1.5 mg once daily |
Extended-release tablets |
Schizophrenia |
26 |
27 |
<170 mg/dL to ≥200 mg/dL |
|
0% |
7% |
Adolescents |
3 mg once daily |
Extended-release tablets |
Schizophrenia |
6 |
27 |
<170 mg/dL to ≥200 mg/dL |
|
7% |
3% |
Adults |
234/234 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
84 |
222 |
<200 mg/dL to ≥240 mg/dL |
|
6% |
3% |
Adults |
6 mg once daily |
Extended-release tablets |
Schizophrenia |
125 |
194 |
<200 mg/dL to ≥240 mg/dL |
|
4% |
3% |
Adults |
9 mg once daily |
Extended-release tablets |
Schizophrenia |
147 |
194 |
<200 mg/dL to ≥240 mg/dL |
|
3% |
3% |
Adults |
3 mg once daily |
Extended-release tablets |
Schizophrenia |
71 |
194 |
<200 mg/dL to ≥240 mg/dL |
|
3% |
3% |
Adults |
12 mg once daily |
Extended-release tablets |
Schizophrenia |
130 |
194 |
<200 mg/dL to ≥240 mg/dL |
|
3% |
3% |
Adults |
234/156 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
65 |
222 |
<200 mg/dL to ≥240 mg/dL |
|
2% |
3% |
Adults |
39 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
51 |
222 |
<200 mg/dL to ≥240 mg/dL |
|
2% |
3% |
Adults |
78 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
147 |
222 |
<200 mg/dL to ≥240 mg/dL |
|
2% |
3% |
Adults |
156 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
141 |
222 |
<200 mg/dL to ≥240 mg/dL |
|
1% |
N/A |
Adults |
N/A |
Every-three-month extended-release injectable suspension |
Schizophrenia |
194 |
N/A |
<200 mg/dL to ≥240 mg/dL |
|
1% |
4% |
Adults |
N/A |
Every-three-month extended-release injectable suspension |
Schizophrenia |
148 |
128 |
<200 mg/dL to ≥240 mg/dL |
|
0.7% |
N/A |
Adults |
N/A |
Every-six-month extended-release injectable suspension |
Schizophrenia |
423 |
N/A |
<200 mg/dL to ≥240 mg/dL |
|
0% |
3% |
Adults |
234/39 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
69 |
222 |
<200 mg/dL to ≥240 mg/dL |
|
Drug (Paliperidone) |
Placebo |
Population |
Dosage Form |
Indication |
Comments |
|---|---|---|---|---|---|
|
44% |
25% |
Females |
Once-monthly extended-release injectable suspension |
Schizoaffective disorder |
>26.72 ng/mL |
|
51% |
43% |
Females |
Once-monthly extended-release injectable suspension |
Schizophrenia |
>30 ng/mL |
|
32% |
15% |
Females |
Every-three-month extended-release injectable suspension |
Schizophrenia |
>26.72 ng/mL |
|
30% |
N/A |
Females |
Every-three-month extended-release injectable suspension |
Schizophrenia |
>26.72 ng/mL |
|
29% |
N/A |
Females |
Every-six-month extended-release injectable suspension |
Schizophrenia |
>26.72 ng/mL |
|
56% |
23% |
Males |
Once-monthly extended-release injectable suspension |
Schizoaffective disorder |
>13.13 ng/mL |
|
52% |
29% |
Males |
Once-monthly extended-release injectable suspension |
Schizophrenia |
>18 ng/mL |
|
46% |
25% |
Males |
Every-three-month extended-release injectable suspension |
Schizophrenia |
>13.13 ng/mL |
|
36% |
N/A |
Males |
Every-three-month extended-release injectable suspension |
Schizophrenia |
>13.13 ng/mL |
|
35% |
N/A |
Males |
Every-six-month extended-release injectable suspension |
Schizophrenia |
>13.13 ng/mL |
|
Drug (Paliperidone) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Paliperidone) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
13% |
3% |
Adolescents |
3 mg once daily |
Extended-release tablets |
Schizophrenia |
8 |
34 |
|
8% |
3% |
Adolescents |
6 mg once daily |
Extended-release tablets |
Schizophrenia |
26 |
34 |
|
7% |
3% |
Adolescents |
12 mg once daily |
Extended-release tablets |
Schizophrenia |
28 |
34 |
|
5% |
3% |
Adolescents |
1.5 mg once daily |
Extended-release tablets |
Schizophrenia |
38 |
34 |
|
11% |
5% |
Adults |
3 mg once daily |
Extended-release tablets |
Schizophrenia |
82 |
208 |
|
11% |
4% |
Adults |
234/234 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
84 |
221 |
|
11% |
N/A |
Adults |
N/A |
Every-three-month extended-release injectable suspension |
Schizophrenia |
194 |
N/A |
|
9% |
5% |
Adults |
6 mg once daily |
Extended-release tablets |
Schizophrenia |
136 |
208 |
|
9% |
5% |
Adults |
9 mg once daily |
Extended-release tablets |
Schizophrenia |
150 |
208 |
|
9% |
4% |
Adults |
78 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
153 |
221 |
|
8% |
2% |
Adults |
N/A |
Every-three-month extended-release injectable suspension |
Schizophrenia |
148 |
128 |
|
7% |
4% |
Adults |
156 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
139 |
221 |
|
6% |
4% |
Adults |
39 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
49 |
221 |
|
5% |
N/A |
Adults |
N/A |
Every-six-month extended-release injectable suspension |
Schizophrenia |
423 |
N/A |
|
4% |
5% |
Adults |
12 mg once daily |
Extended-release tablets |
Schizophrenia |
139 |
208 |
|
4% |
4% |
Adults |
234/156 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
82 |
221 |
|
1% |
4% |
Adults |
234/39 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
79 |
221 |
Gastrointestinal: Vomiting (5% to 11%)
Local: Erythema at injection site (IM: ≤13%), induration at injection site (≤13%), injection-site reaction (IM: 3% to 11%; including pain at injection site), swelling at injection site (IM: ≤13%), tenderness at injection site (IM: 31%)
Nervous system: Akathisia (1% to 17%) (table 7), drowsiness (≤26%), dystonia (1% to 14%) (table 8), extrapyramidal reaction (IM: 2% to 12%; oral: 4% to 40%; including torticollis, trismus), headache (6% to 15%), parkinsonism (2% to 18%; including parkinsonian gait), tremor (IM: ≤1%; oral: 2% to 12%)
|
Drug (Paliperidone) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Paliperidone) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
17% |
0% |
Adolescents |
12 mg once daily |
Extended-release tablets |
Schizophrenia |
35 |
51 |
|
11% |
0% |
Adolescents |
6 mg once daily |
Extended-release tablets |
Schizophrenia |
45 |
51 |
|
6% |
0% |
Adolescents |
3 mg once daily |
Extended-release tablets |
Schizophrenia |
16 |
51 |
|
4% |
0% |
Adolescents |
1.5 mg once daily |
Extended-release tablets |
Schizophrenia |
54 |
51 |
|
6% |
4% |
Adults |
9 to 12 mg once-daily fixed-dose range |
Extended-release tablets |
Schizoaffective disorder |
98 |
202 |
|
6% |
4% |
Adults |
3 to 12 mg once-daily flexible dose |
Extended-release tablets |
Schizoaffective disorder |
214 |
202 |
|
4% |
4% |
Adults |
3 to 6 mg once-daily fixed-dose range |
Extended-release tablets |
Schizoaffective disorder |
108 |
202 |
|
10% |
4% |
Adults |
12 mg once daily |
Extended-release tablets |
Schizophrenia |
242 |
355 |
|
9% |
6% |
Adults |
12 mg once daily |
Extended-release tablets |
Schizophrenia |
242 |
355 |
|
8% |
4% |
Adults |
9 mg once daily |
Extended-release tablets |
Schizophrenia |
246 |
355 |
|
7% |
6% |
Adults |
9 mg once daily |
Extended-release tablets |
Schizophrenia |
246 |
355 |
|
6% |
5% |
Adults |
78 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
223 |
262 |
|
6% |
3% |
Adults |
234/234 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
163 |
510 |
|
6% |
6% |
Adults |
3 mg once daily |
Extended-release tablets |
Schizophrenia |
127 |
355 |
|
5% |
2% |
Adults |
N/A |
Every-three-month extended-release injectable suspension |
Schizophrenia |
160 |
145 |
|
5% |
5% |
Adults |
39 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
130 |
262 |
|
5% |
5% |
Adults |
156 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
228 |
262 |
|
5% |
3% |
Adults |
234/156 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
165 |
510 |
|
4% |
4% |
Adults |
3 mg once daily |
Extended-release tablets |
Schizophrenia |
127 |
355 |
|
4% |
1% |
Adults |
N/A |
Every-three-month extended-release injectable suspension |
Schizophrenia |
160 |
145 |
|
4% |
N/A |
Adults |
N/A |
Every-three-month extended-release injectable suspension |
Schizophrenia |
224 |
N/A |
|
4% |
N/A |
Adults |
N/A |
Every-six-month extended-release injectable suspension |
Schizophrenia |
478 |
N/A |
|
4% |
6% |
Adults |
6 mg once daily |
Extended-release tablets |
Schizophrenia |
235 |
355 |
|
3% |
N/A |
Adults |
N/A |
Every-six-month extended-release injectable suspension |
Schizophrenia |
478 |
N/A |
|
3% |
N/A |
Adults |
N/A |
Every-three-month extended-release injectable suspension |
Schizophrenia |
224 |
N/A |
|
3% |
4% |
Adults |
6 mg once daily |
Extended-release tablets |
Schizophrenia |
235 |
355 |
|
3% |
3% |
Adults |
156 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
312 |
510 |
|
2% |
3% |
Adults |
39 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
130 |
510 |
|
2% |
3% |
Adults |
78 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
302 |
510 |
|
1% |
3% |
Adults |
234/39 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
160 |
510 |
|
Drug (Paliperidone) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Paliperidone) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
14% |
0% |
Adolescents |
12 mg once daily |
Extended-release tablets |
Schizophrenia |
35 |
51 |
|
11% |
0% |
Adolescents |
6 mg once daily |
Extended-release tablets |
Schizophrenia |
45 |
51 |
|
2% |
0% |
Adolescents |
1.5 mg once daily |
Extended-release tablets |
Schizophrenia |
54 |
51 |
|
3% |
1% |
Adults |
9 to 12 mg once-daily fixed-dose range |
Extended-release tablets |
Schizoaffective disorder |
98 |
202 |
|
2% |
1% |
Adults |
3 to 6 mg once-daily fixed-dose range |
Extended-release tablets |
Schizoaffective disorder |
108 |
202 |
|
2% |
1% |
Adults |
3 to 12 mg once-daily flexible dose |
Extended-release tablets |
Schizoaffective disorder |
214 |
202 |
|
5% |
1% |
Adults |
9 mg once daily |
Extended-release tablets |
Schizophrenia |
246 |
355 |
|
5% |
1% |
Adults |
12 mg once daily |
Extended-release tablets |
Schizophrenia |
242 |
355 |
|
2% |
0% |
Adults |
156 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
228 |
262 |
|
1% |
N/A |
Adults |
N/A |
Every-six-month extended-release injectable suspension |
Schizophrenia |
478 |
N/A |
|
1% |
N/A |
Adults |
N/A |
Every-three-month extended-release injectable suspension |
Schizophrenia |
224 |
N/A |
|
1% |
1% |
Adults |
3 mg once daily |
Extended-release tablets |
Schizophrenia |
127 |
355 |
|
1% |
1% |
Adults |
6 mg once daily |
Extended-release tablets |
Schizophrenia |
235 |
355 |
|
1% |
0% |
Adults |
N/A |
Every-three-month extended-release injectable suspension |
Schizophrenia |
160 |
145 |
|
1% |
0% |
Adults |
39 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
130 |
262 |
|
1% |
0% |
Adults |
78 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
223 |
262 |
Neuromuscular & skeletal: Hyperkinetic muscle activity (IM: 4% to 5%; oral: 4% to 17%)
Respiratory: Upper respiratory tract infection (2% to 12%)
1% to 10%:
Cardiovascular: Bradycardia (<2%), bundle branch block (3%), edema (oral: <2%), first-degree atrioventricular block (2%), hypertension (2%), orthostatic hypotension (IM: <1%; oral: 2% to 4%), palpitations (<2%), sinoatrial nodal rhythm disorder (oral: ≤2%)
Dermatologic: Pruritus (<2%), skin rash (<2%)
Endocrine & metabolic: Amenorrhea (2% to 6%) (table 9), decreased libido (IM: 1%) (table 10), galactorrhea not associated with childbirth (1% to 4%) (table 11), gynecomastia (3%) (table 12), irregular menses (<2%)
|
Drug (Paliperidone) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Paliperidone) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
6% |
0% |
Adolescents |
3 mg once daily |
Extended-release tablets |
Schizophrenia |
16 |
51 |
|
4% |
2% |
Adults |
N/A |
Once-monthly extended-release injectable suspension |
Schizoaffective disorder |
N/A |
N/A |
|
2% |
0% |
Adults |
N/A |
Every-three-month extended-release injectable suspension |
Schizophrenia |
N/A |
N/A |
|
2% |
1% |
Adults |
N/A |
Extended-release injectable suspension |
Schizophrenia |
N/A |
N/A |
|
Drug (Paliperidone) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
|---|---|---|---|---|---|
|
1% |
0% |
Females |
N/A |
Once-monthly extended-release injectable suspension |
Schizoaffective disorder |
|
1% |
0% |
Males |
N/A |
Once-monthly extended-release injectable suspension |
Schizoaffective disorder |
|
Drug (Paliperidone) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Paliperidone) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
4% |
0% |
Adolescents |
6 mg once daily |
Extended-release tablets |
Schizophrenia |
45 |
51 |
|
4% |
1% |
Adults |
N/A |
Once-monthly extended-release injectable suspension |
Schizoaffective disorder |
N/A |
N/A |
|
1% |
0% |
Adults |
N/A |
Once-monthly extended-release injectable suspension |
Schizophrenia |
N/A |
N/A |
|
Drug (Paliperidone) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Paliperidone) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
3% |
0% |
Adolescents |
12 mg once daily |
Extended-release tablets |
Schizophrenia |
35 |
51 |
Gastrointestinal: Abdominal distress (≤4%), constipation (4% to 5%), decreased appetite (1% to 2%), diarrhea (IM: 2% to 3%), dyspepsia (5% to 6%), flatulence (<2%), increased appetite (2% to 3%), nausea (4% to 8%), sialorrhea (1% to 6%), stomach discomfort (2%), tongue paralysis (oral: 3%), upper abdominal pain (≤4%), xerostomia (2% to 3%)
Genitourinary: Breast tenderness (<2%), erectile dysfunction (IM: ≤1%) (table 13), retrograde ejaculation (oral: <2%), urinary tract infection (≤3%)
|
Drug (Paliperidone) |
Placebo |
Dosage Form |
Indication |
|---|---|---|---|
|
1% |
0% |
Extended-release injectable suspension |
Schizoaffective disorder |
|
0.9% |
0% |
Extended-release injectable suspension |
Schizophrenia |
Hepatic: Increased serum alanine aminotransferase (<2%), increased serum aspartate aminotransferase (<2%)
Hypersensitivity: Anaphylaxis (<2%), swollen tongue (3%)
Nervous system: Agitation (IM: 8% to 10%; oral: <2%), anxiety (3% to 9%), asthenia (≤4%), dizziness (1% to 6%) (table 14), dysarthria (1% to 4%), fatigue (2% to 4%), insomnia (≤3%), lethargy (3%), nightmares (≤2%), opisthotonus (oral: <2%), psychosis (3%), sedated state (≤7%), sleep disorder (oral: 2% to 3%)
|
Drug (Paliperidone) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Paliperidone) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
6% |
0% |
Adolescents |
3 mg once daily |
Extended-release tablets |
Schizophrenia |
16 |
51 |
|
3% |
0% |
Adolescents |
12 mg once daily |
Extended-release tablets |
Schizophrenia |
35 |
51 |
|
2% |
0% |
Adolescents |
1.5 mg once daily |
Extended-release tablets |
Schizophrenia |
54 |
51 |
|
2% |
0% |
Adolescents |
6 mg once daily |
Extended-release tablets |
Schizophrenia |
45 |
51 |
|
6% |
4% |
Adults |
3 mg once daily |
Extended-release tablets |
Schizophrenia |
127 |
355 |
|
6% |
1% |
Adults |
39 mg |
Extended-release injectable suspension |
Schizophrenia |
130 |
510 |
|
5% |
4% |
Adults |
6 mg once daily |
Extended-release tablets |
Schizophrenia |
235 |
355 |
|
5% |
4% |
Adults |
12 mg once daily |
Extended-release tablets |
Schizophrenia |
242 |
355 |
|
4% |
4% |
Adults |
9 mg once daily |
Extended-release tablets |
Schizophrenia |
246 |
355 |
|
4% |
1% |
Adults |
156 mg |
Extended-release injectable suspension |
Schizophrenia |
312 |
510 |
|
4% |
1% |
Adults |
234/156 mg |
Extended-release injectable suspension |
Schizophrenia |
165 |
510 |
|
2% |
1% |
Adults |
78 mg |
Extended-release injectable suspension |
Schizophrenia |
302 |
510 |
|
2% |
1% |
Adults |
234/234 mg |
Extended-release injectable suspension |
Schizophrenia |
163 |
510 |
|
1% |
1% |
Adults |
234/39 mg |
Extended-release injectable suspension |
Schizophrenia |
160 |
510 |
Neuromuscular & skeletal: Arthralgia (<2%), back pain (3%), dyskinesia (1% to 9%) (table 15), limb pain (≤3%), muscle rigidity (2%; including neck stiffness), musculoskeletal pain (3%), myalgia (1% to 4%)
|
Drug (Paliperidone) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Paliperidone) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
6% |
0% |
Adolescents |
3 mg once daily |
Extended-release tablets |
Schizophrenia |
16 |
51 |
|
6% |
0% |
Adolescents |
12 mg once daily |
Extended-release tablets |
Schizophrenia |
35 |
51 |
|
2% |
0% |
Adolescents |
1.5 mg once daily |
Extended-release tablets |
Schizophrenia |
54 |
51 |
|
2% |
0% |
Adolescents |
6 mg once daily |
Extended-release tablets |
Schizophrenia |
45 |
51 |
|
3% |
1% |
Adults |
3 to 6 mg once-daily fixed-dose range |
Extended-release tablets |
Schizoaffective disorder |
108 |
202 |
|
1% |
1% |
Adults |
9 to 12 mg once-daily fixed-dose range |
Extended-release tablets |
Schizoaffective disorder |
98 |
202 |
|
1% |
1% |
Adults |
3 to 12 mg once-daily flexible dose |
Extended-release tablets |
Schizoaffective disorder |
214 |
202 |
|
9% |
3% |
Adults |
12 mg once daily |
Extended-release tablets |
Schizophrenia |
242 |
355 |
|
8% |
3% |
Adults |
9 mg once daily |
Extended-release tablets |
Schizophrenia |
246 |
355 |
|
6% |
3% |
Adults |
78 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
223 |
262 |
|
5% |
3% |
Adults |
3 mg once daily |
Extended-release tablets |
Schizophrenia |
127 |
355 |
|
4% |
3% |
Adults |
39 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
130 |
262 |
|
4% |
3% |
Adults |
156 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
228 |
262 |
|
3% |
3% |
Adults |
6 mg once daily |
Extended-release tablets |
Schizophrenia |
235 |
355 |
|
3% |
3% |
Adults |
N/A |
Every-three-month extended-release injectable suspension |
Schizophrenia |
160 |
145 |
|
3% |
1% |
Adults |
78 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
223 |
262 |
|
2% |
N/A |
Adults |
N/A |
Every-six-month extended-release injectable suspension |
Schizophrenia |
478 |
N/A |
|
2% |
1% |
Adults |
39 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
130 |
262 |
|
1% |
N/A |
Adults |
N/A |
Every-six-month extended-release injectable suspension |
Schizophrenia |
478 |
N/A |
|
1% |
N/A |
Adults |
N/A |
Every-three-month extended-release injectable suspension |
Schizophrenia |
224 |
N/A |
|
1% |
N/A |
Adults |
N/A |
Every-three-month extended-release injectable suspension |
Schizophrenia |
224 |
N/A |
|
1% |
1% |
Adults |
N/A |
Every-three-month extended-release injectable suspension |
Schizophrenia |
160 |
145 |
|
1% |
1% |
Adults |
156 mg |
Once-monthly extended-release injectable suspension |
Schizophrenia |
228 |
262 |
Ophthalmic: Abnormal eye movements (<2%; includes eye rolling), blurred vision (3%)
Respiratory: Cough (2% to 3%), epistaxis (oral: 2%), nasal congestion (<2%), nasopharyngitis (2% to 5%), pharyngolaryngeal pain (oral: 1% to 2%), rhinitis (1% to 3%)
<1%: Cardiovascular: Prolonged QT interval on ECG, syncope (table 16)
|
Drug (Paliperidone) |
Placebo |
Dosage Form |
Indication |
Number of Patients (Paliperidone) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
0.8% |
0.3% |
Extended-release tablets |
Schizophrenia |
850 |
355 |
|
0.3% |
0% |
Once-monthly extended-release injectable suspension |
Schizophrenia |
1,293 |
510 |
Frequency not defined (any formulation):
Cardiovascular: Postural orthostatic tachycardia
Dermatologic: Urticaria
Gastrointestinal: Oromandibular dystonia
Genitourinary: Breast engorgement, breast swelling, cystitis
Hematologic & oncologic: Anemia
Hypersensitivity: Fixed drug eruption, hypersensitivity reaction
Nervous system: Cogwheel rigidity, depression, psychomotor agitation, restlessness, vertigo
Neuromuscular & skeletal: Joint stiffness, muscle spasm, muscle twitching
Respiratory: Tonsillitis
Miscellaneous: Fever
Postmarketing (any formulation):
Cardiovascular: ECG abnormality (Ref), orthostatic dizziness (Ref)
Dermatologic: Toxic epidermal necrolysis (injection) (Ref)
Endocrine & metabolic: Diabetes mellitus (Ref), hyperinsulinism (Ref), hyponatremia (Ref), menstrual disease (Ref), SIADH (Ref), weight loss (Ref)
Gastrointestinal: Dysphagia (Ref), intestinal obstruction (Ref)
Genitourinary: Breast hypertrophy (Ref), ejaculatory disorder (Ref), mastalgia (Ref), nipple discharge (Ref), priapism (Ref), sexual disorder (Ref), urinary incontinence (Ref), urinary retention
Hematologic & oncologic: Agranulocytosis (Ref), leukopenia (Ref), neutropenia (Ref), thrombotic thrombocytopenic purpura
Hypersensitivity: Angioedema (Ref), nonimmune anaphylaxis (Ref)
Nervous system: Abnormal sensory symptoms (sensory instability), catatonia (Ref), cerebrovascular accident (Ref), delirium (Ref), drooling (Ref), hypertonia (Ref), hypothermia (Ref), neuroleptic malignant syndrome (Ref), seizure (Ref), somnambulism, tic disorder (Ref)
Neuromuscular & skeletal: Bradykinesia (Ref), rhabdomyolysis (Ref), tardive dyskinesia (Ref)
Ophthalmic: Oculogyric crisis (Ref)
Respiratory: Pleural effusion (Ref), respiratory tract infection (Ref)
Hypersensitivity (anaphylaxis, angioedema) to paliperidone, risperidone, or any component of the formulation.
Concerns related to adverse effects:
• 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).
• Falls: May increase the risk for falls due to somnolence, orthostatic hypotension, and motor or sensory instability.
Disease-related concerns:
• Altered kidney function: Use with caution in patients with kidney disease; dosage adjustment recommendations vary based on formulation, and some formulations are not recommended in moderate to severe kidney function. Long-acting preparations should be avoided in patients with changing kidney function, as they are difficult to safely titrate and dose requirements may acutely change. Additionally, there are limited data on the use of long-acting injectable paliperidone in patients with kidney impairment. Consider using a different antipsychotic (T’jollyn 2024).
• Seizures: Use with caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcohol use disorder, 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, gradually taper antipsychotics to avoid physical withdrawal symptoms and rebound symptoms (APA [Keepers 2020]; WFSBP [Hasan 2012]). Withdrawal symptoms may include agitation, alternating feelings of warmth and cold, anxiety, diaphoresis, dyskinesia, GI symptoms, insomnia, irritability, myalgia, paresthesia, psychosis, restlessness, rhinorrhea, tremor and vertigo (Lambert 2007; Moncrieff 2020). The risk of withdrawal symptoms is highest following abrupt discontinuation of highly anticholinergic or dopaminergic antipsychotics (Cerovecki 2013). Patients with chronic symptoms, repeated relapses, and clear diagnostic features of schizophrenia are at risk for poor outcomes if medications are discontinued (APA [Keepers 2020]).
Risk of dystonia is increased with the use of high potency and higher doses of conventional antipsychotics and in males and younger patients; occurring in up to 18% of children.
Long-term usefulness of paliperidone should be periodically re-evaluated in patients receiving the drug for extended periods of time. Invega is an extended-release tablet based on the OROSA osmotic delivery system. Water from the GI tract enters through a semipermeable membrane coating the tablet, solubilizing the drug into a gelatinous form which, through hydrophilic expansion, is then expelled through laser-drilled holes in the coating.
Similar to adult experience, the American Academy of Child and Adolescent Psychiatry (AACAP) guidelines recommend gradually tapering antipsychotics to avoid withdrawal symptoms and minimize the risk of relapse (AACAP [McClellan 2007]).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Suspension, Intramuscular, as palmitate:
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]
Suspension Prefilled Syringe, Intramuscular, as palmitate [preservative free]:
Erzofri: 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); 351 mg/2.25 mL (2.25 mL) [contains polyethylene glycol (macrogol)]
Invega Hafyera: 1092 mg/3.5 mL (3.5 mL); 1560 mg/5 mL (5 mL) [contains polyethylene glycol (macrogol)]
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 (macrogol)]
Tablet Extended Release 24 Hour, Oral:
Invega: 1.5 mg [DSC], 3 mg, 6 mg, 9 mg
Generic: 1.5 mg, 3 mg, 6 mg, 9 mg
May be product dependent
Suspension Prefilled Syringe (Erzofri Intramuscular)
39 mg/0.25 mL (per 0.25 mL): $779.17
78 mg/0.5 mL (per 0.5 mL): $1,558.40
117 mg/0.75 mL (per 0.75 mL): $2,337.66
156 mg/mL (per mL): $3,116.99
234 mg/1.5 mL (per mL): $3,116.91
351MG/2.25ML (per mL): $3,116.88
Suspension Prefilled Syringe (Invega Hafyera Intramuscular)
1092MG/3.5ML (per mL): $4,894.95
1560 mg/5 mL (per mL): $5,139.58
Suspension Prefilled Syringe (Invega Sustenna Intramuscular)
39 mg/0.25 mL (per 0.25 mL): $713.77
78 mg/0.5 mL (per 0.5 mL): $1,427.62
117 mg/0.75 mL (per 0.75 mL): $2,141.46
156 mg/mL (per mL): $2,855.39
234 mg/1.5 mL (per mL): $2,855.32
Suspension Prefilled Syringe (Invega Trinza Intramuscular)
273MG/0.88ML (per 0.88 mL): $4,282.85
410MG/1.32ML (per mL): $4,866.95
546MG/1.75ML (per mL): $4,894.95
819MG/2.63ML (per mL): $4,885.53
Tablet, 24-hour (Invega Oral)
3 mg (per each): $15.01
6 mg (per each): $15.01
9 mg (per each): $22.51
Tablet, 24-hour (Paliperidone ER Oral)
1.5 mg (per each): $2.69 - $30.60
3 mg (per each): $2.69 - $30.60
6 mg (per each): $2.69 - $30.60
9 mg (per each): $3.97 - $45.89
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Suspension Prefilled Syringe, Intramuscular:
Invega Sustenna: 50 mg/0.5 mL (0.5 mL); 75 mg/0.75 mL (0.75 mL); 100 mg/mL (1 mL); 150 mg/1.5 mL (1.5 mL) [contains polyethylene glycol (macrogol)]
Invega Trinza: 175 mg/0.875 mL (0.875 mL); 263 mg/1.315 mL (1.315 mL); 350 mg/1.75 mL (1.75 mL); 525 mg/2.625 mL (2.625 mL) [contains polyethylene glycol (macrogol)]
Tablet Extended Release 24 Hour, Oral:
Invega: 3 mg, 6 mg, 9 mg
Generic: 3 mg [DSC], 6 mg
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.
Long-acting IM injection: Administer by IM route only as a single injection (do not divide); do not administer by any other route. Do not mix with any other product or diluent. Avoid inadvertent injection into vasculature.
Monthly paliperidone: 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.
Erzofri: Administer initial dose in the deltoid muscle; thereafter, administer monthly injections in either the deltoid or the gluteal muscle. For management of missed doses, administer doses separated by a week in the deltoid muscle. For IM deltoid injections, use a 1 inch, 23-gauge needle for patients who weigh <90 kg, and use a 11/2 inch, 22-gauge needle in patients who weigh ≥90 kg. For IM gluteal injections, use a 11/2 inch, 22-gauge needle in all patients, regardless of weight.
Invega Sustenna: 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).
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.
Six-month paliperidone (Invega Hafyera): Prior to injection, shake syringe with tip pointing up very fast for at least 15 seconds. Rest briefly, then shake again for 15 seconds to ensure a homogenous suspension. Inject within 5 minutes of shaking vigorously; resuspend by shaking for ≥30 seconds if >5 minutes pass before injection. Inject slowly (over ~30 seconds), deep into the 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, 3-month IM paliperidone, or other commercially available needles to reduce the risk of blockage. Administer using a 1½ inch, 20-gauge thin-wall needle, regardless of patient weight, in the upper-outer quadrant of the gluteal area; alternate injections between right and left gluteal muscle. In the event of an incompletely administered dose, do not reinject the dose remaining in the syringe and do not administer another dose.
Oral: Administer in the morning without regard to meals; swallow extended-release tablets whole with liquids; do not crush, chew, or divide.
IM: Administer 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 two 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): Should only be administered by a health care professional. Prior to injection, shake syringe with tip pointing up for 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.
Six-month paliperidone (Invega Hafyera): Prior to injection, shake syringe with tip pointing up very fast for at least 15 seconds. Rest briefly, then shake again for 15 seconds to ensure a homogenous suspension. Inject within 5 minutes of shaking vigorously; resuspend by shaking for ≥30 seconds if >5 minutes pass before injection. Inject slowly (over ~30 seconds), deep into the 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, 3-month IM paliperidone, or other commercially available needles to reduce the risk of blockage. Administer using the provided 11/2-inch, 20-gauge thin wall needle, regardless of patient weight, in the upper-outer quadrant of the gluteal area; alternate injections between right and left gluteal muscle. In the event of an incompletely administered dose, do not reinject the dose remaining in the syringe and do not administer another dose.
Schizophrenia and schizoaffective disorder: Treatment of schizophrenia as monotherapy, and treatment of schizoaffective disorder as monotherapy and as an adjunct to mood stabilizers or antidepressants.
Bipolar disorder
Invega may be confused with Intuniv
Beers Criteria: Antipsychotics are identified in the Beers Criteria as potentially inappropriate medications to be avoided in patients 65 years and older due to an increased risk of stroke and a greater rate of cognitive decline and mortality in patients with dementia. Evidence also suggests there may be an increased risk of mortality with use independent of dementia Avoid antipsychotics for behavioral problems associated with dementia or delirium unless alternative nonpharmacologic therapies have failed and patient may harm self or others. In addition, antipsychotics should be used with caution in older adults due to their potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; monitor sodium closely with initiation or dosage adjustments in older adults. Use of antipsychotics may be appropriate for labeled indications including schizophrenia, bipolar disorder, Parkinson disease psychosis, adjunctive therapy in major depressive disorder, or for short-term use as an antiemetic (Beers Criteria [AGS 2023]).
Substrate of CYP3A4 (Minor), P-glycoprotein (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Acrivastine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Agents With Seizure Threshold Lowering Potential: May increase adverse/toxic effects of Paliperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Alcohol (Ethyl): CNS Depressants may increase CNS depressant effects of Alcohol (Ethyl). Risk C: Monitor
Alizapride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Amifampridine: Agents With Seizure Threshold Lowering Potential may increase neuroexcitatory and/or seizure-potentiating effects of Amifampridine. Risk C: Monitor
Amisulpride (Oral): Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Amisulpride (Oral). Specifically, the risk of seizures may be increased. Risk C: Monitor
Amisulpride (Oral): May increase adverse/toxic effects of Antipsychotic Agents. Specifically, the risk of neuroleptic malignant syndrome or increased QTc interval may be increased. Risk C: Monitor
Amisulpride (Oral): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Anti-Parkinson Agents (Dopamine Agonist): Antipsychotic Agents (Second Generation [Atypical]) may decrease therapeutic effects 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). Risk D: Consider Therapy Modification
Antidiabetic Agents: Hyperglycemia-Associated Agents may decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor
ARIPiprazole Lauroxil: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ARIPiprazole Lauroxil. Specifically, the risk of seizures may be increased. Risk C: Monitor
ARIPiprazole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ARIPiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor
Articaine: May increase CNS depressant effects of CNS Depressants. Management: Consider reducing the dose of articaine if possible when used in patients who are also receiving CNS depressants. Monitor for excessive CNS depressant effects with any combined use. Risk D: Consider Therapy Modification
Asenapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Asenapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Azelastine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Benperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Benperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Benperidol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Benzgalantamine-Galantamine: May increase neurotoxic (central) effects of Antipsychotic Agents. Risk C: Monitor
Blonanserin: CNS Depressants may increase CNS depressant effects 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. Risk D: Consider Therapy Modification
Blood Pressure Lowering Agents: May increase hypotensive effects of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor
Bornaprine: May increase adverse/toxic effects of Antipsychotic Agents. Specifically, tardive dyskinesia symptoms may be potentiated. Risk C: Monitor
Brexanolone: CNS Depressants may increase CNS depressant effects of Brexanolone. Risk C: Monitor
Brexpiprazole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Brexpiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor
Brimonidine (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Bromopride: May increase adverse/toxic effects of Antipsychotic Agents. Risk X: Avoid
Bromperidol: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Buclizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Buprenorphine: CNS Depressants may increase CNS depressant effects 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. Risk D: Consider Therapy Modification
BuPROPion: May increase neuroexcitatory and/or seizure-potentiating effects of Agents With Seizure Threshold Lowering Potential. Risk C: Monitor
BusPIRone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Cabergoline: May decrease therapeutic effects of Antipsychotic Agents. Risk X: Avoid
Cannabinoid-Containing Products: CNS Depressants may increase CNS depressant effects of Cannabinoid-Containing Products. Risk C: Monitor
Cariprazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Cariprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Cetirizine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk D: Consider Therapy Modification
Chloral Hydrate/Chloral Betaine: CNS Depressants may increase CNS depressant effects of Chloral Hydrate/Chloral Betaine. Management: Consider alternatives to the use of chloral hydrate or chloral betaine and additional CNS depressants. If combined, consider a dose reduction of either agent and monitor closely for enhanced CNS depressive effects. Risk D: Consider Therapy Modification
Chlormethiazole: May increase CNS depressant effects 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. Risk D: Consider Therapy Modification
Chlorphenesin Carbamate: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
ChlorproMAZINE: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ChlorproMAZINE. Specifically, the risk of seizures may be increased. Risk C: Monitor
Clothiapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Clothiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
CloZAPine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of CloZAPine. Specifically, the risk of seizures may be increased. Risk C: Monitor
CNS Depressants: Paliperidone may increase CNS depressant effects of CNS Depressants. Risk C: Monitor
CYP3A4 Inducers (Moderate): May decrease serum concentration of Paliperidone. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of Paliperidone. Management: Avoid coadministration of extended-release injectable paliperidone and strong CYP3A4 inducers. If coadministration is required consider use of paliperidone extended-release tablets, monitor for reduced effects, and increase the dose as needed. Risk D: Consider Therapy Modification
Dantrolene: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Daridorexant: May increase CNS depressant effects of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification
Deutetrabenazine: May increase adverse/toxic effects of Antipsychotic Agents. Specifically, the risk for akathisia, parkinsonism, or neuroleptic malignant syndrome may be increased. Risk C: Monitor
DexmedeTOMIDine: CNS Depressants may increase CNS depressant effects of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider Therapy Modification
Dexmethylphenidate-Methylphenidate: Antipsychotic Agents may increase adverse/toxic effects of Dexmethylphenidate-Methylphenidate. Dexmethylphenidate-Methylphenidate may increase adverse/toxic effects of Antipsychotic Agents. Specifically, the risk of extrapyramidal symptoms may be increased when these agents are combined. Risk C: Monitor
Difelikefalin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Difenoxin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dihydralazine: CNS Depressants may increase hypotensive effects of Dihydralazine. Risk C: Monitor
Dimethindene (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Donepezil: May increase neurotoxic (central) effects of Antipsychotic Agents. Risk C: Monitor
Dothiepin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Doxylamine: CNS Depressants may increase CNS depressant effects of Doxylamine. Risk C: Monitor
DroPERidol: May increase CNS depressant effects of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider Therapy Modification
Emedastine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk C: Monitor
Entacapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Esketamine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Flunarizine: CNS Depressants may increase CNS depressant effects of Flunarizine. Risk X: Avoid
Flunitrazepam: CNS Depressants may increase CNS depressant effects 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. Risk D: Consider Therapy Modification
Flupentixol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Flupentixol. Specifically, the risk of seizures may be increased. Risk C: Monitor
FluPHENAZine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of FluPHENAZine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Guanethidine: Antipsychotic Agents may decrease therapeutic effects of Guanethidine. Risk C: Monitor
Haloperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Haloperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Avoid) may increase QTc-prolonging effects of Haloperidol. Risk C: Monitor
Huperzine A: May increase neurotoxic (central) effects of Antipsychotic Agents. Risk C: Monitor
HydrOXYzine: May increase CNS depressant effects of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider Therapy Modification
Iloperidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iloperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Iohexol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects 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 antiseizure drugs. Risk D: Consider Therapy Modification
Iomeprol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects 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 antiseizure drugs. Risk D: Consider Therapy Modification
Iopamidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects 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 antiseizure drugs. Risk D: Consider Therapy Modification
Ixabepilone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kava Kava: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ketotifen (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kratom: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Lemborexant: May increase CNS depressant effects 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. Risk D: Consider Therapy Modification
Levocetirizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Levoketoconazole: QT-prolonging Agents (Indeterminate Risk - Avoid) may increase QTc-prolonging effects of Levoketoconazole. 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. Risk C: Monitor
Lithium: May increase neurotoxic effects of Antipsychotic Agents. Lithium may decrease serum concentration of Antipsychotic Agents. Specifically noted with chlorpromazine. Risk C: Monitor
Lofepramine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lofexidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Loxapine: CNS Depressants may increase CNS depressant effects of Loxapine. Management: Consider reducing the dose of CNS depressants administered concomitantly with loxapine due to an increased risk of respiratory depression, sedation, hypotension, and syncope. Risk D: Consider Therapy Modification
Lumateperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Lumateperone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Lurasidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Lurasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Magnesium Sulfate: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Melitracen [INT]: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Mequitazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Metergoline: Antipsychotic Agents may decrease therapeutic effects of Metergoline. Metergoline may decrease therapeutic effects of Antipsychotic Agents. Risk C: Monitor
Metergoline: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Methotrimeprazine: CNS Depressants may increase CNS depressant effects of Methotrimeprazine. Methotrimeprazine may increase CNS depressant effects 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. Risk D: Consider Therapy Modification
Methoxyflurane: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Metoclopramide: May increase adverse/toxic effects of Antipsychotic Agents. Risk X: Avoid
MetyroSINE: CNS Depressants may increase sedative effects of MetyroSINE. Risk C: Monitor
MetyroSINE: May increase adverse/toxic effects of Antipsychotic Agents. Specifically, the risk for extrapyramidal symptoms and excessive sedation may be increased. Risk C: Monitor
Minocycline (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Molindone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Molindone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Moxonidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Nabilone: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Nalfurafine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Noscapine: CNS Depressants may increase adverse/toxic effects of Noscapine. Risk X: Avoid
OLANZapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of OLANZapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Olopatadine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Opicapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Opioid Agonists: CNS Depressants may increase CNS depressant effects 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. Risk D: Consider Therapy Modification
Opipramol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Orphenadrine: CNS Depressants may increase CNS depressant effects of Orphenadrine. Risk X: Avoid
Oxomemazine: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Oxybate Salt Products: CNS Depressants may increase CNS depressant effects 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 Risk D: Consider Therapy Modification
OxyCODONE: CNS Depressants may increase CNS depressant effects 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. Risk D: Consider Therapy Modification
P-glycoprotein/ABCB1 Inducers: May decrease serum concentration of Paliperidone. Management: Avoid coadministration of extended-release injectable paliperidone and P-gp inducers. If coadministration is required, consider use of paliperidone extended-release tablets, monitor for reduced paliperidone effects, and increase the dose as needed. Risk D: Consider Therapy Modification
Paraldehyde: CNS Depressants may increase CNS depressant effects of Paraldehyde. Risk X: Avoid
Perampanel: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Periciazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Periciazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Periciazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Perphenazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Perphenazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Pimozide: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Pimozide. Specifically, the risk of seizures may be increased. Risk C: Monitor
Pipamperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Pipamperone. Specifically, the risk of seizures may be increased. Risk X: Avoid
Piribedil: Antipsychotic Agents may decrease therapeutic effects of Piribedil. Piribedil may decrease therapeutic effects of Antipsychotic Agents. Management: Use of piribedil with antiemetic neuroleptics is contraindicated, and use with antipsychotic neuroleptics, except for clozapine, is not recommended. Risk X: Avoid
Pizotifen: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Polyethylene Glycol-Electrolyte Solution: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Polyethylene Glycol-Electrolyte Solution. Specifically, the risk of seizure may be increased. Risk C: Monitor
Procarbazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Prochlorperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Prochlorperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Promazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Promazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Avoid) may increase QTc-prolonging effects 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. Risk C: Monitor
QUEtiapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of QUEtiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Quinagolide: Antipsychotic Agents may decrease therapeutic effects of Quinagolide. Risk C: Monitor
Rilmenidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
RisperiDONE: May increase adverse/toxic effects of Paliperidone. Management: Additive paliperidone exposure is expected with this combination. Consider using an alternative combination when possible. Risk D: Consider Therapy Modification
Rivastigmine: May increase neurotoxic (central) effects of Antipsychotic Agents. Risk C: Monitor
Ropeginterferon Alfa-2b: CNS Depressants may increase adverse/toxic effects of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider Therapy Modification
Serotonergic Agents (High Risk): May increase adverse/toxic effects of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor
Sertindole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sertindole. Specifically, the risk of seizures may be increased. Risk C: Monitor
Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sodium Phosphates. Specifically, the risk of seizure or loss of consciousness may be increased in patients with significant sodium phosphate-induced fluid or electrolyte abnormalities. Risk C: Monitor
Sulpiride: Antipsychotic Agents may increase adverse/toxic effects of Sulpiride. Risk X: Avoid
Suvorexant: CNS Depressants may increase CNS depressant effects 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. Risk D: Consider Therapy Modification
Tetrabenazine: May increase adverse/toxic effects of Antipsychotic Agents. Specifically, the risk for NMS and extrapyramidal symptoms may be increased. Risk C: Monitor
Thalidomide: CNS Depressants may increase CNS depressant effects of Thalidomide. Risk X: Avoid
Thioridazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Thioridazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Thiothixene: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Thiothixene. Specifically, the risk of seizures may be increased. Risk C: Monitor
Trifluoperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Trifluoperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Trimeprazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Triptorelin: Hyperprolactinemic Agents may decrease therapeutic effects of Triptorelin. Risk X: Avoid
Valerian: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Valproic Acid and Derivatives: May increase serum concentration of Paliperidone. Risk C: Monitor
Ziprasidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Ziprasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Zolpidem: CNS Depressants may increase CNS depressant effects 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. Risk D: Consider Therapy Modification
Zuclopenthixol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Zuclopenthixol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Zuranolone: May increase CNS depressant effects of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider Therapy Modification
Evaluate pregnancy status and provide preconception counseling prior to initiating treatment in patients who could become pregnant (APA [Keepers 2020]; BAP [McAllister-Williams 2017]). Patients effectively treated may continue their current antipsychotic medication when planning a pregnancy unless contraindications exist (ACOG 2023; BAP [McAllister-Williams 2017]); the lowest effective dose and avoidance of polytherapy is recommended (BAP [Barnes 2020]; BAP [McAllister-Williams 2017]). Management of mental health conditions in patients who could become pregnant should be based on a shared decision-making process that considers the possibility of pregnancy during treatment and the risks of discontinuing antipsychotic therapy (ACOG 2023; BAP [McAllister-Williams 2017]).
Antipsychotic agents may be associated with sexual dysfunction. Some second generation (atypical) antipsychotics such as paliperidone may cause hyperprolactinemia, resulting in menstrual disorders or impaired spermatogenesis. Consider changing to a medication that is prolactin-sparing in patients with clinical symptoms. Contraception should be provided if pregnancy is not desired as unintended pregnancies may occur when changing to a prolactin-sparing medication (APA [Keepers 2020]; BAP [McAllister-Williams 2017]).
Paliperidone crosses the placenta (Binns 2017).
Outcome data following exposure to second generation (atypical) antipsychotics (SGAs) as a class do not show a significant increased risk of major congenital malformations (BAP [Barnes 2020]; Viguera 2021; Wang 2021); however, data specific to paliperidone during pregnancy are limited (Binns 2017; de Azevedo 2020; Iwata 2021; Liu 2023; Onken 2018; Özdemir 2015; Zamora Rodriguez 2017). Data related to the long-term effects of in utero antipsychotic exposure on infant neurodevelopment and behavior are limited (BAP [McAllister-Williams 2017]; Straub 2022; Swetlik 2024).
Antipsychotic use during the third trimester of pregnancy increases the risk for extrapyramidal symptoms and/or withdrawal symptoms in newborns following delivery (Viguera 2023). Symptoms in the newborn may include agitation, feeding disorder, hypertonia, hypotonia, respiratory distress, somnolence, and tremor. These effects may require prolonged hospitalization or resolve within hours or days without specific treatment. Tapering the dose late in pregnancy to reduce the risk of symptoms is not recommended (APA [Keepers 2020]).
Atypical antipsychotics are associated with metabolic changes and the risk varies by specific agent. Available studies that evaluated the risk of developing gestational diabetes mellitus (GDM) during antipsychotic therapy have conflicting results, possibly due to differences in study design (ACOG 2023; Uguz 2019). Pregnant patients with diabetes mellitus or GDM may continue antipsychotic treatment (ACOG 2023). Consider the metabolic risks of the specific antipsychotic if treatment is initiated for the first time during pregnancy (Heinonen 2022). Screening for GDM should continue as part of standard prenatal care; early screening is not needed due to psychiatric medication exposure (ACOG 2023; BAP [McAllister-Williams 2017]).
Untreated and undertreated mental health conditions are associated with adverse pregnancy outcomes (ACOG 2023). Adverse obstetric and neonatal outcomes are associated with schizophrenia; however, comparisons between treated and untreated pregnancies are limited (BAP [McAllister-Williams 2017]). Discontinuing effective medications during pregnancy increases the risk of symptom relapse (ACOG 2023).
Patients effectively treated for schizophrenia pre-pregnancy may use the same medication during pregnancy unless contraindications exist (ACOG 2023; APA [Keeper 2020]). SGAs are better tolerated and have fewer extrapyramidal adverse effects than first generation (typical) antipsychotics (ACOG 2023). Long-acting/depot preparations should not be initiated during pregnancy but may be continued when the risk of recurrence is high (BAP [Barnes 2020]).
Management of mental health conditions should be made as part of a shared decision-making process (ACOG 2023; BAP [McAllister-Williams 2017]). Treatment should not be withheld or discontinued based only on pregnancy status. When medications are used, the lowest effective dose of a single agent is recommended. Optimize dosing prior to changing a medication or adding additional agents whenever possible. Close monitoring for symptom improvement with a validated screening tool during pregnancy is recommended. Manage side effects as needed (ACOG 2023).
Data collection to monitor pregnancy and infant outcomes following exposure to psychiatric medications is ongoing. Encourage pregnant patients ≤45 years of age with a history of psychiatric illness to enroll in the National Pregnancy Registry for Psychiatric Mediations (1-866-961-2388 or https://womensmentalhealth.org/research/pregnancyregistry/).
Paliperidone is present in breast milk.
Paliperidone is the active metabolite of risperidone; paliperidone is present in breast milk following maternal use of risperidone. Refer to the Risperidone monograph for additional information.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother; monitor breastfed infants for excess sedation, extrapyramidal symptoms, failure to thrive, and jitteriness.
Consider sedative properties when initiating an antipsychotic medication for the first time postpartum (BAP [Barnes 2020]). Drowsiness, irritability, motor abnormalities, poor feeding, sedation, and slowed development have been reported in infants exposed to antipsychotics via breast milk. Monitor breastfed infants, especially those who are premature or of low birth weight, or when other sedative drugs are also prescribed (BAP [Barnes 2020]; BAP [McAllister-Williams 2017]).
|
Frequency of Antipsychotic Monitoring for Paliperidonea,b | ||
|---|---|---|
|
Monitoring parameter |
Frequency of monitoring |
Comments |
|
a For all monitoring parameters, it is appropriate for check at baseline and when clinically relevant (based on symptoms or suspected adverse reactions) in addition to the timeline. | ||
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b ADA 2004; APA [Keepers 2020]; De Hert 2011; Gugger 2011; manufacturer's labeling. | ||
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c Risk factors for extrapyramidal symptoms (EPS) include prior history of EPS, high doses of antipsychotics, young age (children and adolescents at higher risk than adults), and dopaminergic affinity of individual antipsychotic. | ||
|
d Risk factors for tardive dyskinesia include age >55 years; females; White or African ethnicity; presence of a mood disorder, intellectual disability, or CNS injury; and past or current EPS. | ||
|
Adherence |
Every visit |
|
|
Blood chemistries (electrolytes, renal function, liver function, TSH) |
Annually |
|
|
CBC |
As clinically indicated |
Check frequently during the first few months of therapy in patients with preexisting low WBC or history of drug-induced leukopenia/neutropenia |
|
Extrapyramidal symptoms |
Every visit; 4 weeks after initiation and dose change; annually. Use a formalized rating scale at least annually or every 6 months if high riskc |
|
|
Fall risk |
Every visit |
|
|
Fasting plasma glucose/HbA1c |
4 months after initiation; annually |
Check more frequently than annually if abnormal. Follow diabetes guidelines. |
|
Lipid panel |
4 months after initiation; annually |
Check more frequently than annually if abnormal. Follow lipid guidelines. |
|
Mental status and alertness |
Every visit |
|
|
Metabolic syndrome history |
Annually |
Evaluate for personal and family history of obesity, diabetes, dyslipidemia, hypertension, or cardiovascular disease |
|
Prolactin |
Ask about symptoms at every visit until dose is stable. Check prolactin level if symptoms are reported. |
Hyperprolactinemia symptoms: Changes in menstruation, libido, gynecomastia, development of galactorrhea, and erectile and ejaculatory function |
|
Tardive dyskinesia |
Every visit; annually. Use a formalized rating scale at least annually or every 6 months if high riskd |
|
|
Vital signs (BP, orthostatics, temperature, pulse, signs of infection) |
Every visit (at least weekly during first 3 to 4 weeks of treatment); 4 weeks after dose change. |
|
|
Weight/Height/BMI |
8 and 12 weeks after initiation and dose change; quarterly |
Consider monitoring waist circumference at baseline and annually, especially in patients with or at risk for metabolic syndrome. Consider changing antipsychotic if BMI increases by ≥1 unit. Some experts recommend checking weight and height at every visit. |
Timing of serum samples: Draw trough just before next dose (Hiemke 2018).
Therapeutic reference range: 20 to 60 ng/mL (SI: 47 to 141 nmol/L) (Hiemke 2018). Note: Dosing should be based on therapeutic response as opposed to serum concentrations, however therapeutic drug monitoring can be used to confirm adherence (APA [Keepers 2020]).
Laboratory alert level: 120 ng/mL (SI: 282 nmol/L) (Hiemke 2018).
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.
Note: Pharmacokinetic parameters in adolescent patients weighing >51 kg were similar to adults; an increased drug exposure (23%) was observed in adolescent patient weighing <51 kg compared to adults and was not considered clinically significant.
Onset of action: Oral: Initial effects may be observed within 1 to 2 weeks of treatment with continued improvements through 4 to 6 weeks (Agid 2003; Levine 2010).
Absorption: Long-acting injection:
Monthly:
Erzofri: IM: Begins on day 1 and continues up to 176 days.
Invega Sustenna: IM: Begins on day 1 and continues up to ~4 months.
3- and 6-month: IM: Begins on day 1 and continues up to 18 months.
Distribution: Vd:
Oral: 487 L.
Long-acting injection:
Monthly:
Erzofri: IM: 2,840 L.
Invega Sustenna: IM: 391 L.
3- and 6-month: IM: 1,960 L.
Protein binding: 74%.
Metabolism: Hepatic via CYP2D6 and 3A4 (limited role in elimination); minor metabolism (<10% each) via dealkylation, hydroxylation, dehydrogenation, and benzisoxazole scission.
Bioavailability: Oral: 28%.
Half-life elimination:
Oral: 23 hours; 24 to 51 hours with renal impairment (CrCl <80 mL/minute).
Long-acting injection:
Monthly:
Erzofri: IM (following a single-dose administration): ~27 days.
Invega Sustenna: 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.
6-month: IM (following a single-dose administration): Gluteal injection range: 148 to 159 days.
Time to peak, plasma:
Oral: ~24 hours.
Long-acting injection:
Monthly:
Erzofri: IM: 16 to 28 days.
Invega Sustenna: IM: 13 days.
3-month: IM: 30 to 33 days.
6-month: IM: 29 to 32 days.
Excretion: Urine (80%; 59% as unchanged drug); feces (11%).
Altered kidney function: Elimination of paliperidone decreased with decreasing estimated creatinine clearance.
Sex: Slower long-acting monthly injection absorption observed in females.
