Version May 2024
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:
Clinical considerations: Paliperidone is a major, active metabolite of risperidone.
Schizophrenia and schizoaffective disorder:
Oral: Initial: 6 mg once daily; may adjust daily dose based on response and tolerability in increments of 3 mg every ≥5 days up to a maximum of 12 mg/day. Usual dosage range: 6 to 12 mg/day. Note: According to manufacturer's labeling, 3 mg/day may be effective for some patients (eg, those who do not tolerate 6 mg/day).
IM:
Note: Formulation contains paliperidone palmitate. Dosing in the US labeling is based on paliperidone palmitate; dosing in the Canadian labeling is based on paliperidone base (paliperidone palmitate 1 mg is equivalent to paliperidone base ~0.64 mg).
Monthly paliperidone (Invega Sustenna): Note: Before starting monthly IM paliperidone, establish tolerability with a test dose of oral paliperidone or oral risperidone. After initiating monthly IM paliperidone, overlap with oral antipsychotics is not necessary (Ref).
Initiation: 234 mg (150 mg as base) on treatment day 1 followed by 156 mg (100 mg as base) 1 week later, with both doses administered in the deltoid muscle. The second dose may be administered 4 days before or after the 1-week time point. Note: When converting from other long-acting injectable antipsychotics (at steady state), initiation doses are not required.
|
Time since first injection |
Instructions |
|---|---|
|
<4 weeks |
Administer 156 mg (100 mg as base) in the deltoid muscle as soon as possible, followed by 117 mg (75 mg as base) in either the deltoid or gluteal muscle 5 weeks after the first injection (regardless of when 156 mg dose was administered). Then begin monthly maintenance dose 4 weeks later. |
|
4 to 7 weeks |
Administer 156 mg (100 mg as base) in the deltoid muscle as soon as possible, followed by another 156 mg (100 mg as base) dose in the deltoid muscle 1 week later. Then begin monthly maintenance dose 4 weeks later. |
|
>7 weeks |
Reinitiate entire dose titration. |
Maintenance: Five weeks after the first initiation dose, begin a maintenance dose of 39 to 234 mg (25 to 150 mg as base) every month administered in either the deltoid or gluteal muscle. Maximum: 234 mg (150 mg as base)/month. See the “Dose Conversions That Attain Similar Steady-State Paliperidone Exposure During Maintenance Treatment” table to identify an appropriate maintenance dose based on previous oral paliperidone dose or risperidone dose. The monthly maintenance dose may be administered 7 days before or after the monthly time point.
|
Time since last injection |
Instructions |
|---|---|
|
4 to 6 weeks |
Administer the missed dose as soon as possible. Then resume usual monthly maintenance dose 4 weeks later. |
|
>6 weeks to 6 months |
Maintenance dose 39 to 156 mg (25 to 100 mg as base): Administer 2 maintenance doses in the deltoid muscle 1 week apart. Then resume usual monthly maintenance dose 4 weeks later. Maintenance dose 234 mg (150 mg as base): Administer 156 mg (100 mg as base) in the deltoid muscle as soon as possible, followed by another 156 mg (100 mg as base) in the deltoid muscle 1 week later. Then resume usual monthly maintenance dose 4 weeks later. |
|
>6 months |
Reinitiate entire dose titration. |
Dosage adjustments: Adjustments may be made monthly based on response and tolerability; the full effect from dose adjustments may not be apparent for several months.
3-month paliperidone (FDA-approved for schizophrenia only) (Invega Trinza): Note: 3-month IM paliperidone 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.
Conversion from monthly IM paliperidone to 3-month IM paliperidone : Initiate 3-month IM paliperidone when the next monthly IM paliperidone dose is scheduled. Base the 3-month dose on the previous monthly dose, using the “Dose Conversions That Attain Similar Steady-State Paliperidone Exposure During Maintenance Treatment” table. 3-month IM paliperidone may be administered up to 7 days before or after the next monthly dose is due. Following the initial injection, administer every 3 months. Maintenance injections may be administered up to 2 weeks before or after the 3-month time point.
|
Time since last injection |
Instructions |
|---|---|
|
3.5 to <4 months |
Administer the missed dose as soon as possible. Then resume usual maintenance dose 3 months later. |
|
4 to 9 months |
Maintenance dose 273 mg (175 mg as base): Administer 78 mg (50 mg as base) of monthly IM paliperidone (Invega Sustenna) into the deltoid muscle on days 1 and 8. One month following the second injection, administer 273 mg (175 mg as base) of 3-month IM paliperidone (Invega Trinza) into the deltoid or gluteal muscle and resume usual dosing at 3-month intervals. Maintenance dose 410 mg (263 mg as base): Administer 117 mg (75 mg as base) of monthly IM paliperidone (Invega Sustenna) into the deltoid muscle on days 1 and 8. One month following the second injection, administer 410 mg (263 mg as base) of 3-month IM paliperidone (Invega Trinza) into the deltoid or gluteal muscle and resume usual dosing at 3-month intervals. Maintenance dose 546 mg (350 mg as base): Administer 156 mg (100 mg as base) of monthly IM paliperidone (Invega Sustenna) into the deltoid muscle on days 1 and 8. One month following the second injection, administer 546 mg (350 mg as base) of 3-month IM paliperidone (Invega Trinza) into the deltoid or gluteal muscle and resume usual dosing at 3-month intervals. Maintenance dose 819 mg (525 mg as base): Administer 156 mg (100 mg as base) of monthly IM paliperidone (Invega Sustenna) into the deltoid muscle on days 1 and 8. One month following the second injection, administer 819 mg (525 mg as base) of 3-month IM paliperidone (Invega Trinza) into the deltoid or gluteal muscle and resume usual dosing at 3-month intervals. |
|
>9 months |
Reinitiate treatment with monthly IM paliperidone (Invega Sustenna). 3-month IM paliperidone (Invega Trinza) can be resumed after the patient has been adequately treated with monthly IM paliperidone for at least 4 months. |
Dosage adjustments: Incremental dose adjustment can be made every 3 months based on response and tolerability to achieve usual dose of 273 to 819 mg (175 to 525 mg as base); response to an adjusted dose may not be apparent for several months.
6-month paliperidone (FDA-approved for schizophrenia only) (Invega Hafyera): Note: 6-month IM paliperidone is to be used only after either 4 doses of monthly IM paliperidone (Invega Sustenna) or 1 dose of 3-month IM paliperidone (Invega Trinza). The dose immediately preceding the 6-month IM injection can either be a monthly IM injection or a 3-month IM injection.
Conversion from monthly IM paliperidone to 6-month IM paliperidone: Administer the same dose for the 2 monthly injection cycles immediately preceding the first 6-month IM injection. Initiate 6-month IM paliperidone when the next monthly IM paliperidone dose is scheduled. 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. 6-month IM paliperidone may be administered up to 1 week before or after the next monthly dose is due. Following the initial injection, administer every 6 months. Maintenance injections may be administered up to 2 weeks before or 3 weeks after the 6-month time point.
Conversion from 3-month IM paliperidone to 6-month IM paliperidone: Initiate 6-month IM paliperidone when the next 3-month IM paliperidone dose is scheduled. 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. 6-month IM paliperidone may be administered up to 2 weeks before or after the next 3-month dose is due. Following the initial injection, administer every 6 months. Maintenance injections may be administered up to 2 weeks before or 3 weeks after the 6-month time point.
|
Time since last injection |
Instructions |
|---|---|
|
6 months and 3 weeks to <8 months |
Maintenance dose 1,092 mg: Do not administer the missed dose. Administer 156 mg (100 mg as base) of monthly IM paliperidone (Invega Sustenna) into the deltoid muscle on day 1. One month after the day 1 injection, administer 1,092 mg of 6-month IM paliperidone (Invega Hafyera) into the gluteal muscle and resume usual dosing at 6-month intervals. Maintenance dose 1,560 mg: Do not administer the missed dose. Administer 234 mg (150 mg as base) of monthly IM paliperidone (Invega Sustenna) into the deltoid muscle on day 1. One month after the day 1 injection, administer 1,560 mg of 6-month IM paliperidone (Invega Hafyera) into the gluteal muscle 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 (100 mg as base) of monthly IM paliperidone (Invega Sustenna) into the deltoid muscle on days 1 and 8. One month after the day 8 injection, administer 1,092 mg of 6-month IM paliperidone (Invega Hafyera) into the gluteal muscle and resume usual dosing at 6-month intervals. Maintenance dose 1,560 mg: Do not administer the missed dose. Administer 156 mg (100 mg as base) of monthly IM paliperidone (Invega Sustenna) into the deltoid muscle on days 1 and 8. One month after the day 8 injection, administer 1,560 mg of 6-month IM paliperidone (Invega Hafyera) into the gluteal muscle 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. |
Dosage adjustments: Incremental dose adjustment can be made every 6 months based on response and tolerability to achieve usual dose of 1,092 to 1,560 mg; response to an adjusted dose may not be apparent for several months.
|
Paliperidone ER tablet |
Paliperidone palmitate monthly IM injection (Invega Sustenna) |
Paliperidone palmitate 3-month IM injection (Invega Trinza) |
Paliperidone palmitate 6-month IM injection (Invega Hafyera) |
Risperidone ER IM injection (Risperdal Consta) |
Risperidone tablet |
|---|---|---|---|---|---|
|
Converting from 3-month IM paliperidone to paliperidone ER tablets: Do not use above table to determine appropriate dose, which is based on injection dose and weeks since last administration. Refer to the “Conversion From 3-Month IM Paliperidone to Paliperidone ER Tablets” table to determine oral dose. Converting from 3-month IM paliperidone to monthly IM paliperidone: Initiate monthly IM paliperidone when the next 3-month IM paliperidone dose is scheduled. Base the monthly dose on the previous 3-month dose. Following the initial injection, administer once monthly. Converting from other oral antipsychotics to long-acting injectable paliperidone: There are no systematically collected data to address switching patients from other oral antipsychotics to IM paliperidone. Converting from other long-acting injectable antipsychotics (at steady state) to monthly IM paliperidone: Initiate monthly IM paliperidone in the place of the next scheduled injection and continue at monthly intervals. The 2 initiation doses are not required in these patients. | |||||
|
3 mg/day |
39 mg (25 mg as base) every month |
Has not been studied |
Has not been studied |
No information available |
1 mg/day |
|
78 mg (50 mg as base) every month |
273 mg (175 mg as base) every 3 months |
Has not been studied |
25 mg every 2 weeks |
2 mg/day | |
|
6 mg/day |
117 mg (75 mg as base) every month |
410 mg (263 mg as base) every 3 months |
Has not been studied |
37.5 mg every 2 weeks |
3 mg/day |
|
9 mg/day |
156 mg (100 mg as base) every month |
546 mg (350 mg as base) every 3 months |
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 |
819 mg (525 mg as base) every 3 months |
1,560 mg every 6 months |
No information available |
5 mg/day |
Conversion from 3-month IM paliperidone to paliperidone ER tablets: Initiate paliperidone ER tablets ≥3 months after the last dose of 3-month IM paliperidone. Base the once-daily ER tablet dose on the last 3-month injection dose and weeks since last administered, using the following table:
|
Weeks since last 3-month IM injection | |||
|---|---|---|---|
|
≥12 weeks to 18 weeks |
>18 weeks to 24 weeks |
>24 weeks | |
|
Last 3-month IM injection dose |
Daily dose of oral paliperidone ER tablet | ||
|
273 mg (175 mg as base) |
3 mg |
3 mg |
3 mg |
|
410 mg (263 mg as base) |
3 mg |
3 mg |
6 mg |
|
546 mg (350 mg as base) |
3 mg |
6 mg |
9 mg |
|
819 mg (525 mg as base) |
6 mg |
9 mg |
12 mg |
Discontinuation of therapy:
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). Based upon clinical experience, some experts generally prefer cross-titration and overlap approaches rather than abrupt change (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) |
3-month IM injection (Invega Trinza) |
6-month IM injection (Invega Hafyera) |
|---|---|---|---|---|
|
a Since there are limited data on the use of long-acting injectable formulations in patients with kidney impairment, use of oral paliperidone or other alternative therapeutic options has been suggested (Schoretsanitis 2018). | ||||
|
CrCl ≥90 mL/minute |
No dosage adjustment necessary. |
No dosage adjustment necessary. |
No dosage adjustment necessary. |
No dosage adjustment necessary. |
|
80 to <90 mL/minute |
No dosage adjustment necessary. |
No dosage adjustment necessary. |
No dosage adjustment necessary. |
Use not recommended. |
|
50 to <80 mL/minute |
Initial: 3 mg once daily; maximum: 6 mg once daily. |
Initiation: 156 mg (as palmitate) or 100 mg (as base) on treatment day 1, followed by 117 mg (as palmitate) or 75 mg (as base) 1 week later with both doses administered in the deltoid. Maintenance: Five weeks after the first initiation dose, begin a maintenance dose of 78 mg (as palmitate) or 50 mg (as base) every month administered in either the deltoid or gluteal muscle. The dose can be subsequently adjusted to 39 to 156 mg (25 to 100 mg as base) every month administered in either the deltoid or gluteal muscle.a Maximum: 156 mg (100 mg as base)/month. |
Adjust dosage and stabilize the patient using the monthly IM injection, then transition to the 3-month IM injection.a Note: Monthly IM paliperidone (Invega Sustenna) 78 mg (as palmitate) or 50 mg (as base) = 3-month IM paliperidone (Invega Trinza) 273 mg (as palmitate) or 175 mg (as base). |
Use not recommended. |
|
10 to <50 mL/minute |
Initial: 1.5 mg once daily; 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).
Refer to adult dosing; use with caution. Additional monitoring of renal function and orthostatic blood pressure may be warranted. 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 (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).
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%), 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, priapism
Hematologic & oncologic: Anemia
Hypersensitivity: Fixed drug eruption, hypersensitivity reaction
Nervous system: Cogwheel rigidity, depression, drooling, psychomotor agitation, restlessness, vertigo
Neuromuscular & skeletal: Joint stiffness, muscle spasm, muscle twitching
Respiratory: Tonsillitis
Postmarketing (any formulation):
Cardiovascular: ECG abnormality (Stroup 2018), orthostatic dizziness (Stroup 2018)
Dermatologic: Toxic epidermal necrolysis (injection) (Struye 2016)
Endocrine & metabolic: Diabetes mellitus (Sliwa 2014), hyperinsulinism (Omi 2016), hyponatremia (Solmi 2017) (menstrual disease (Savitz 2015, Seo 2020), SIADH (Mazhar 2020), weight loss (Seo 2020)
Gastrointestinal: Dysphagia (Crouse 2018), intestinal obstruction
Genitourinary: Breast hypertrophy (Savitz 2015), ejaculatory disorder (Savitz 2015), mastalgia (Gopal 2017, Savitz 2015), nipple discharge (Gopal 2017, Savitz 2015), sexual disorder (Harrington 2010, Mauri 2017), urinary incontinence (Karslıoǧlu 2016), urinary retention
Hematologic & oncologic: Agranulocytosis (Wakuda 2019), leukopenia (Kim 2011), neutropenia (Kim 2011), thrombotic thrombocytopenic purpura
Hypersensitivity: Angioedema (Papadopoulou 2017), nonimmune anaphylaxis (Perry 2012)
Nervous system: Abnormal sensory symptoms (sensory instability), catatonia (McKeown 2010), cerebrovascular accident (Solmi 2017), hypertonia (Seo 2020), hypothermia (Hirapara 2019), neuroleptic malignant syndrome (Nayak 2011), seizure (Stroup 2018), somnambulism, tic disorder (Hsieh 2014)
Neuromuscular & skeletal: Bradykinesia (Solmi 2017), tardive dyskinesia (Wei 2012)
Ophthalmic: Oculogyric crisis (Seo 2020)
Respiratory: Respiratory tract infection (Harrington 2010, Mauri 2017)
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:
• Renal impairment: Use with caution in patients with kidney disease; dosage adjustment recommendations vary based on formulation.
• Seizures: Use with caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications that may lower seizure threshold. Elderly patients may be at increased risk of seizures due to an increased prevalence of predisposing factors.
Dosage form specific issues:
• Extended-release tablet: Use is not recommended in patients with preexisting severe GI-narrowing disorders (nondeformable controlled-release formulation). Patients with upper GI tract alterations in transit time may have increased or decreased bioavailability of paliperidone. Formulation consists of drug within a nonabsorbable shell; following drug release/absorption, the shell is expelled in the stool.
Other warnings/precautions:
• Discontinuation of therapy: When discontinuing antipsychotic therapy, 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]:
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 (Invega Hafyera Intramuscular)
1092MG/3.5ML (per mL): $4,552.42
1560 mg/5 mL (per mL): $4,779.94
Suspension Prefilled Syringe (Invega Sustenna Intramuscular)
39 mg/0.25 mL (per 0.25 mL): $669.58
78 mg/0.5 mL (per 0.5 mL): $1,339.21
117 mg/0.75 mL (per 0.75 mL): $2,008.85
156 mg/mL (per mL): $2,678.57
234 mg/1.5 mL (per mL): $2,678.49
Suspension Prefilled Syringe (Invega Trinza Intramuscular)
273MG/0.88ML (per 0.88 mL): $4,017.62
410MG/1.32ML (per mL): $4,565.55
546MG/1.75ML (per mL): $4,591.82
819MG/2.63ML (per mL): $4,582.99
Tablet, 24-hour (Invega Oral)
3 mg (per each): $14.71
6 mg (per each): $14.71
9 mg (per each): $22.07
Tablet, 24-hour (Paliperidone ER Oral)
1.5 mg (per each): $14.67 - $30.60
3 mg (per each): $14.67 - $30.60
6 mg (per each): $14.67 - $30.60
9 mg (per each): $22.00 - $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.
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, 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.
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 (Invega Sustenna): Prior to injection, shake syringe for at least 10 seconds to ensure a homogenous suspension. Administer using only the needles that are provided in the kit. The 2 initial injections should be administered in the deltoid muscle using a 11/2 inch, 22-gauge needle for patients ≥90 kg, and a 1 inch, 23-gauge needle for patients <90 kg. The 2 initial deltoid intramuscular injections help attain therapeutic concentrations rapidly. Alternate deltoid injections (right and left deltoid muscle). The second dose may be administered 4 days before or after the weekly time point. Monthly maintenance doses can be administered in either the deltoid or gluteal muscle. Administer injections in the gluteal muscle using a 11/2 inch, 22-gauge needle (regardless of patient weight) in the upper-outer quadrant of the gluteal area. Alternate gluteal injections (right and left gluteal muscle).
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: Treatment of schizophrenia.
Schizoaffective disorder (oral and monthly IM paliperidone): Treatment of schizoaffective disorder as monotherapy and as an adjunct to mood stabilizers or antidepressants.
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/ABCB1 (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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Agents With Seizure Threshold Lowering Potential: May enhance the adverse/toxic effect of Paliperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Amifampridine: Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. Risk C: Monitor therapy
Amisulpride (Oral): May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk of neuroleptic malignant syndrome or increased QTc interval may be increased. Risk C: Monitor therapy
Amisulpride (Oral): Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Amisulpride (Oral). Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Anti-Parkinson Agents (Dopamine Agonist): Antipsychotic Agents (Second Generation [Atypical]) may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Management: Consider avoiding atypical antipsychotic use in patients with Parkinson disease. If an atypical antipsychotic is necessary, consider using clozapine, quetiapine, or ziprasidone at lower initial doses, or a non-dopamine antagonist (eg, pimavanserin). Risk D: Consider therapy modification
ARIPiprazole: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of ARIPiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
ARIPiprazole Lauroxil: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of ARIPiprazole Lauroxil. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Asenapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Asenapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Benperidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Benperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Brexpiprazole: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Brexpiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromopride: May enhance the adverse/toxic effect of Antipsychotic Agents. Risk X: Avoid combination
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification
BuPROPion: May enhance the neuroexcitatory and/or seizure-potentiating effect of Agents With Seizure Threshold Lowering Potential. Risk C: Monitor therapy
Cabergoline: May diminish the therapeutic effect of Antipsychotic Agents. Risk X: Avoid combination
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Cariprazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Cariprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
ChlorproMAZINE: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of ChlorproMAZINE. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Clothiapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Clothiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
CloZAPine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
Daridorexant: May enhance the CNS depressant effect 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 enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk for akathisia, parkinsonism, or neuroleptic malignant syndrome may be increased. Risk C: Monitor therapy
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect 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
Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Donepezil: May enhance the neurotoxic (central) effect of Antipsychotic Agents. Risk C: Monitor therapy
Doxylamine: CNS Depressants may enhance the CNS depressant effect of Doxylamine. Risk C: Monitor therapy
DroPERidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification
Flupentixol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Flupentixol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
FluPHENAZine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of FluPHENAZine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Galantamine: May enhance the neurotoxic (central) effect of Antipsychotic Agents. Risk C: Monitor therapy
Guanethidine: Antipsychotic Agents may diminish the therapeutic effect of Guanethidine. Risk C: Monitor therapy
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy
Haloperidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Haloperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Huperzine A: May enhance the neurotoxic (central) effect of Antipsychotic Agents. Risk C: Monitor therapy
HydrOXYzine: May enhance the CNS depressant effect 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 enhance the adverse/toxic effect of Iloperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Inducers of CYP3A4 (Strong) and P-glycoprotein: May decrease the serum concentration of Paliperidone. Management: Monitor for reduced paliperidone effects when combined with strong inducers of both CYP3A4 and P-gp. Avoid use of these inducers with extended-release injectable paliperidone and instead manage patients with paliperidone extended-release tablets. Risk C: Monitor therapy
Iohexol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification
Iomeprol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification
Iopamidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification
Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification
Levoketoconazole: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect 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 therapy
Lithium: May enhance the neurotoxic effect of Antipsychotic Agents. Lithium may decrease the serum concentration of Antipsychotic Agents. Specifically noted with chlorpromazine. Risk C: Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Loxapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Loxapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Lumateperone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Lumateperone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Lurasidone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Lurasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Mequitazine: Antipsychotic Agents may enhance the arrhythmogenic effect of Mequitazine. Management: Consider alternatives to one of these agents when possible. While this combination is not specifically contraindicated, mequitazine labeling describes this combination as discouraged. Risk D: Consider therapy modification
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification
Metoclopramide: May enhance the adverse/toxic effect of Antipsychotic Agents. Risk X: Avoid combination
MetyroSINE: May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk for extrapyramidal symptoms and excessive sedation may be increased. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Molindone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Molindone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
OLANZapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of OLANZapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Periciazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Periciazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Perphenazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Perphenazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Pimozide: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Pimozide. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Pipamperone [INT]: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Pipamperone [INT]. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Piribedil: Antipsychotic Agents may diminish the therapeutic effect of Piribedil. Piribedil may diminish the therapeutic effect of Antipsychotic Agents. Management: Use of piribedil with antiemetic neuroleptics is contraindicated, and use with antipsychotic neuroleptics, except for clozapine, is not recommended. Risk X: Avoid combination
Polyethylene Glycol-Electrolyte Solution: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Polyethylene Glycol-Electrolyte Solution. Specifically, the risk of seizure may be increased. Risk C: Monitor therapy
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Prochlorperazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Prochlorperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Promazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Promazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QUEtiapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of QUEtiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Quinagolide: Antipsychotic Agents may diminish the therapeutic effect of Quinagolide. Risk C: Monitor therapy
RisperiDONE: May enhance the adverse/toxic effect of Paliperidone. Management: Additive paliperidone exposure is expected with this combination. Consider using an alternative combination when possible. Risk D: Consider therapy modification
Rivastigmine: May enhance the neurotoxic (central) effect of Antipsychotic Agents. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect 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
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Serotonergic Agents (High Risk): May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy
Sertindole: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Sertindole. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect 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 therapy
St John's Wort: May decrease the serum concentration of Paliperidone. Management: Monitor for reduced paliperidone effects when combined St. John's wort. Avoid use of St. John's wort with extended-release injectable paliperidone and instead manage patients with paliperidone extended-release tablets. Risk C: Monitor therapy
Sulpiride: Antipsychotic Agents may enhance the adverse/toxic effect of Sulpiride. Risk X: Avoid combination
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Tetrabenazine: May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk for NMS and extrapyramidal symptoms may be increased. Risk C: Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Thioridazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Thioridazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Thiothixene: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Thiothixene. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Trifluoperazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Trifluoperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Triptorelin: Hyperprolactinemic Agents may diminish the therapeutic effect of Triptorelin. Risk X: Avoid combination
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Valproate Products: May increase the serum concentration of Paliperidone. Risk C: Monitor therapy
Ziprasidone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Ziprasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification
Zuclopenthixol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Zuclopenthixol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Zuranolone: May enhance the CNS depressant effect 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
Paliperidone may cause hyperprolactinemia, which may cause a reversible decrease in fertility in females.
Information specific to paliperidone in pregnancy is limited (Onken 2018; Özdemir 2015; Zamora Rodriguez 2017).
Antipsychotic use during the third trimester of pregnancy has a risk for extrapyramidal symptoms (EPS) and/or withdrawal symptoms in newborns following delivery. Symptoms in the newborn may include agitation, feeding disorder, hypertonia, hypotonia, respiratory distress, somnolence, and tremor. These effects may be self-limiting and allow recovery within hours or days with no specific treatment, or they may be severe requiring prolonged hospitalization.
The ACOG recommends that therapy during pregnancy be individualized; treatment with psychiatric medications during pregnancy should incorporate the clinical expertise of the mental health clinician, obstetrician, primary healthcare provider, and pediatrician. Safety data related to atypical antipsychotics during pregnancy is limited and routine use is not recommended. However, if a woman is inadvertently exposed to an atypical antipsychotic while pregnant, continuing therapy may be preferable to switching to a typical antipsychotic that the fetus has not yet been exposed to; consider risk:benefit (ACOG 2008).
Paliperidone is the active metabolite of risperidone; refer to Risperidone monograph for additional information.
Health care providers are encouraged to enroll women 18 to 45 years of age exposed to paliperidone during pregnancy in the Atypical Antipsychotics Pregnancy Registry (1-866-961-2388 or http://womensmentalhealth.org/research/pregnancyregistry/).
Paliperidone is present in breast milk.
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.
|
Frequency of Antipsychotic Monitoringa,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. | ||
|
b ADA 2004; APA [Keepers 2020]; De Hert 2011; Gugger 2011; manufacturer's labeling. | ||
|
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 |
12 weeks after initiation and dose change; annually |
Check more frequently than annually if abnormal. Follow diabetes guidelines. |
|
Lipid panel |
12 weeks after initiation and dose change; 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: IM: Slow release (Monthly: Begins on day 1 and continues up to 126 days; 3- and 6-month: Begins on day 1 and continues up to 18 months).
Distribution: Vd: Oral: 487 L; Monthly 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).
Monthly IM (following a single-dose administration): Range: 25 to 49 days.
3-month IM: Deltoid injection range: 84 to 95 days; Gluteal injection range: 118 to 139 days.
6-month IM (following a single-dose administration): Gluteal injection range: 148 to 159 days.
Time to peak, plasma: Oral: ~24 hours; Monthly 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 monthly IM absorption observed in women.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
