It is an atypical antipsychotic drug called paliperidone (Invega). It is risperidone's active metabolite. Patients with schizophrenia and psychosis are treated with it.

Paliperidone Uses:

• Schizophrenia:

  • Treatment of schizophrenia

• Schizoaffective disorder (oral and monthly IM paliperidone):

  • Treatment of schizoaffective disorder

• Off Label Use of Paliperidone in Adults:

  • Delusional infestation (also called delusional parasitosis);
  • Psychosis/agitation associated with dementia

Paliperidone (Invega) Dose in Adults

Paliperidone (Invega) Dose in the treatment of Schizoaffective disorder:

• Oral:

  • Usual dose: 6 mg once daily (given in the morning in clinical trials); no need for titration, while some individuals may benefit from lower or higher dosages (range: 3 to 12 mg daily).
  • If more than 6 mg per day, it is advised to increase by 3 mg per day, up to a maximum of 12 mg per day, at intervals greater than 4 days.

• Injection:

  • Monthly IM:
  • Note:
    • Patients who have never taken oral paliperidone or oral or injectable risperidone should maintain their tolerance with a test dose of either drug before beginning monthly IM paliperidone.
    • When the preceding oral antipsychotic treatment has been successfully terminated,

• Initiation of therapy:

  • Initial:
    • On the first day of treatment, deliver 234 mg (as palmitate) or 150 mg (as the base), followed by 156 mg (as palmitate) OR 100 mg (as the base) one week later, both doses going into the deltoid muscle.
    • Four days before or after the weekly time point are acceptable window times for the second dose.
  • Maintenance:
    • A maintenance dose of 39 to 234 mg (as palmitate) OR 25 to 150 mg (as the base) is then started every month and is injected into either the deltoid or gluteal muscle. The maintenance dose is adjusted based on response and tolerance after the 1-week starting regimen (the 39 mg dose [as palmitate] was not studied in schizoaffective disorder trials).
    • Seven days before or after the monthly time point may be used to provide the maintenance dose.

Conversion from oral paliperidone to monthly IM paliperidone:

• Start the 1-week introduction regimen of monthly IM paliperidone as directed.
• Using the following conversion, patients who were previously stabilised on oral dosages can anticipate a similar steady-state exposure during maintenance treatment with monthly IM paliperidone.:
  • 12 mg of oral extended-release medication every day, followed by 234 mg or 150 mg of IM maintenance medication (as the base) monthly
  • 9 mg of oral extended-release medication every day, followed by either 100 mg or 156 mg of IM maintenance medication (as the base) monthly
  • 6 mg oral extended-release dose daily, followed by 117 mg (as palmitate) or 75 mg IM maintenance dose (as the base) monthly
  • Daily dose of 3 mg of oral extended-release medication, followed by an IM maintenance dose of 39–78 mg (as palmitate) or 25–50 mg

Conversion from other oral antipsychotics to monthly IM paliperidone:

• Moving patients from other oral antipsychotics to monthly IM paliperidone is not supported by reliable data.

switching to monthly IM paliperidone from other long-acting injectable antipsychotics (at steady-state):

• Start monthly IM paliperidone at the time of the subsequent planned injection and keep doing so every month.
• In these people, the two initial dosages are not necessary.

The following advice have been provided for moving from injectable risperidone (Risperdal Consta) to monthly IM paliperidone (Invega Sustenna Canadian product labelling).:

• Risperdal Consta dosage of 25 mg every two weeks, followed by a monthly 78 mg (as palmitate) or 50 mg (as the base) IM paliperidone maintenance dose.
• Risperdal 37.5 mg every two weeks for the duration, followed by an IM paliperidone maintenance dose of 117 mg (as palmitate) or 75 mg (as the base) per month.
• Risperdal Consta dosage of 50 mg every two weeks, followed by an IM maintenance dose of 156 mg (as palmitate) or 100 mg (base) per month of paliperidone.

Paliperidone (Invega) Dosage adjustments:

• Month-to-month changes are possible (full effect from adjustments may not be seen for several months)

• Missed second initiation dose:

  • If <4 weeks have passed since the first injection:
    • Deliver the missed dose of 156 mg (as palmitate) or 100 mg (as the base) into the deltoid as soon as you can. Five weeks after the first injection, regardless of when the second injection was given, administer a third dose of 117 mg (as palmitate) OR 75 mg (as the base) into the deltoid or gluteal muscle, and then resume regular monthly maintenance dosing.
  • If ≥4 weeks and ≤7 weeks have passed since the first injection:
    • As soon as feasible, provide a 156 mg (as palmitate) or 100 mg (as the base) dose into the deltoid. One week later, administer another 156 mg (as palmitate) OR 100 mg (as the base) dose into the deltoid, and then begin regular monthly maintenance dosing.
  • If >7 weeks have passed since the first injection:
    • The dose guidelines for the start of therapy must be followed when restarting therapy.

Paliperidone (Invega) Missed maintenance dose:

• If ≥4 weeks and ≤6 weeks have passed since the last monthly injection:
  • Continue therapy on a monthly basis and provide the missed dose as soon as you remember.
• If >6 weeks and ≤6 months have passed since the last monthly injection:
  • If the maintenance dose was <234 mg (as palmitate) or 150 mg (as the base):
    • As soon as feasible, administer the same dose that the patient was previously stabilised on in the deltoid, followed by a second equivalent dose in the deltoid one week later, before resuming the maintenance dose every month.
  • If the maintenance dose was 234 mg (as palmitate) or 150 mg (as the base):
    • As soon as feasible, administer a 156 mg (as palmitate) or 100 mg (as the base) dose into the deltoid. One week later, administer a second 156 mg (as palmitate) OR 100 mg (as the base) dose into the deltoid. Finally, restart the maintenance dose at monthly intervals.
• If >6 months have passed since the last monthly maintenance injection:
  • Following the dose recommendations for the start of therapy, therapy must be restarted.

Paliperidone (Invega) Dose in the treatment of Schizophrenia:

• Oral:

  • Usual dose: 6 mg once daily (administred first thing in the morning in clinical studies); titration is not necessary, while some individuals may benefit from lower or higher dosages (range: 3 to 12 mg daily).
  • If the dosage is more than 6 mg per day, it is advisable to raise it by 3 mg per day, up to a maximum of 12 mg per day, no more frequently than every 5 days.

• Injection: IM:

  • Monthly paliperidone (Invega Sustenna):
  • Note:
    • Patients who have never used oral paliperidone or oral or injectable risperidone should maintain tolerability with a test dose of either medication before beginning monthly IM paliperidone.
    • When starting a monthly IM paliperidone regimen, an older oral antipsychotic medication regimen can be gradually discontinued.
    • paliperidone palmitate (US labelling) or paliperidone base-based dosing (Canadian labeling).

  • Initiation of therapy:

    • Initial: 156 mg (as palmitate) or 100 mg (as the base) given in the deltoid muscle one week after the initial dose of 234 mg (as palmitate) or 150 mg (as the base) on the first day of treatment.
    • Four days before or after the weekly time point are acceptable window times for the second dose.

  • Maintenance:

    • A maintenance dose of 117 mg (as palmitate) or 75 mg (as the base) given in either the deltoid or gluteal muscle every month should be started after the one-week initial regimen.
    • Some people might profit from monthly maintenance dosages that are higher or lower (monthly maintenance dosage range: 39 to 234 mg [as palmitate] or 25 to 150 mg [as the base]).
    • It's possible to provide the monthly maintenance dose 7 days before or after the month

Conversion from oral paliperidone to IM paliperidone:

• Start IM treatment following the 1-week starting regimen as directed. Using the following conversion, patients who had previously stabilised on oral doses can anticipate a similar steady state exposure during maintenance treatment with IM medication.:
  • 12 mg of oral extended-release medication every day, followed by 234 mg of palmitate or 150 mg of base per month for maintenance.
  • 9 mg of oral extended-release medication daily, followed by 156 mg (as palmitate) or 100 mg (as the base) of monthly maintenance medication
  • 6 mg of oral extended-release medication daily, followed by 117 mg (as palmitate) or 75 mg (as the base) of IM maintenance medication each month
  • daily dose of 3 mg of oral extended-release medication, followed by an IM maintenance dose of 39–78 mg (as palmitate) or 25–50 mg

Conversion from other oral antipsychotics to IM paliperidone:

• Regarding the transition of patients from other oral antipsychotics to IM paliperidone, no comprehensive data have been gathered.

Switching to intramuscular paliperidone (IM) from other long-acting injectable antipsychotics (at steady-state):

• Start taking IM paliperidone in place of the next scheduled injection and keep doing so every month. In these people, the two beginning dosages are not necessary.

The following suggestions have been offered for moving from injectable risperidone (Risperdal Consta) to monthly IM paliperidone (Invega Sustenna Canadian product labeling):

• 25 mg of Risperdal Consta every two weeks, followed by an IM paliperidone maintenance dose of 50 mg (as the basis) every month
• Risperdal 37.5 mg every two weeks for the initial dose, followed by 75 mg (as the base) of IM paliperidone every month for maintenance.
• 50 mg of Risperdal Consta every two weeks, followed by 100 mg of IM paliperidone (as the basis) every month for maintenance.

Paliperidone (Invega) Dosage adjustments:

• Could be modified monthly (full effect from adjustments may not be seen for several months)

• Missed second initiation dose:

  • If <4 weeks have elapsed since the first injection:
    • The third dose of 117 mg (as palmitate) OR 75 mg (as the base) should be given in either the deltoid or gluteal muscle five weeks after giving the missed dose (156 mg [as palmitate] or 100 mg [as the base]) in the deltoid.
  • If ≥4 weeks and ≤7 weeks have passed since the first injection:
    • As soon as feasible, provide a 156 mg (as palmitate) or 100 mg (as the base) dose into the deltoid. One week later, administer another 156 mg (as palmitate) OR 100 mg (as the base) dose into the deltoid, and then begin regular monthly maintenance dosing.
    • If more than seven weeks have gone since the initial injection, therapy must be restarted following the dose guidelines for the start of therapy.

Missed maintenance dose:

• If ≥4 weeks and ≤6 weeks have passed since the last monthly injection:
  • Continue therapy on a monthly basis and provide the missed dose as soon as you remember.
• If >6 weeks and ≤6 months have passed since the last monthly injection:
  • If the maintenance dose was <234 mg (as palmitate) or <150 mg (as the base):
    • As soon as feasible, administer the same dose that the patient was previously stabilised on in the deltoid, followed by a second equivalent dose in the deltoid one week later, before resuming the maintenance dose every month.
  • If the maintenance dose was 234 mg (as palmitate) or 150 mg (as the base):
    • As soon as feasible, administer a 156 mg (as palmitate) or 100 mg (as the base) dose into the deltoid. One week later, administer a second 156 mg (as palmitate) OR 100 mg (as the base) dose into the deltoid. Finally, restart the maintenance dose at monthly intervals.
  • If >6 months have passed since the last monthly maintenance injection:
    • Following the dose recommendations for the start of therapy, therapy must be restarted.

Three-month paliperidone (Invega Trinza):

Note:

• Only after monthly IM paliperidone (Invega Sustenna) has been proven to be an effective treatment for at least 4 months should three-month IM paliperidone be used.
• Prior to beginning 3 month IM paliperidone, the past two monthly IM doses of paliperidone should be the same dosage strength.

Conversion from monthly injection to 3-month injection:

• When the next monthly IM paliperidone dose is planned, begin the 3-month IM paliperidone course.
• Utilize the comparable 3.5 times larger amount for the 3-month dose and base it on the prior monthly dose.
• Paliperidone for three months can be given IM up to seven days before or after the scheduled date of the following monthly dose.
• After the first shot, give it every three months.
• The injection can be administered to patients up to two weeks before or after the 3-month mark.
• It has not been researched how monthly IM paliperidone (Invega Sustenna), 39 mg (as palmitate), or 25 mg (as the base), can be converted to 3month IM paliperidone (Invega Trinza).
  • Monthly intramuscular paliperidone (Invega Sustenna) 78 mg or 50 mg = 3-month intramuscular paliperidone (Invega Trinza) 273 mg or 175 mg (as base)
  • 3-month IM paliperidone (Invega Trinza) 410 mg (as palmitate) or 263 mg = monthly IM paliperidone (Invega Sustenna) 117 mg (as palmitate) or 75 mg (as base) (as base)
  • Monthly intramuscular paliperidone (Invega Sustenna) 156 mg or 100 mg = 3-month intramuscular paliperidone (Invega Trinza) 546 mg or 350 mg (as base)
  • Monthly intramuscular paliperidone (Invega Sustenna) 234 mg or 150 mg = 3-month intramuscular paliperidone (Invega Trinza) 819 mg or 525 mg (as base)

Conversion from 3-month IM paliperidone to monthly IM paliperidone:

• When the next 3-month IM paliperidone dose is planned, start the monthly IM paliperidone.
• Utilize the equivalent of 3.5 times the lower amount for the monthly dose and base it on the prior 3-month dose. After the first shot, give it once a month.
• Invega Trinza, a 3-month IM paliperidone tablet, contains 273 mg of palmitate or 175 mg of base. Invega Sustenna, a monthly IM paliperidone tablet, contains 78 mg of palmitate or 50 mg of base (as base)
• Monthly IM paliperidone (Invega Sustenna) 117 mg (as palmitate) or 75 mg (3-month IM paliperidone, Invega Trinza), or 410 mg (as palmitate), or 263 mg (as base) (as base)
• Invega Trinza, a 3-month IM paliperidone tablet, has 546 mg of palmitate or 350 mg of base. Invega Sustenna, a monthly IM paliperidone tablet, contains 156 mg of palmitate or 100 mg of base (as base)

Conversion from 3-month IM paliperidone to paliperidone extended-release tablets:

• Start taking paliperidone extended release tablets three months after your previous IM dose.
• Depending on the once-daily extended-release tablet dosage on the most recent injectable dosage for a 3-month period and the number of weeks since the last administration. Use the conversion shown below.
• If the last 3-month IM paliperidone dose was:
  • 3 months to >24 weeks since the last dose = 3 mg paliperidone extended-release tablets (273 mg as palmitate or 175 mg as base).
  • 410 mg (as palmitate) or 263 mg (as the base):
    • Paliperidone extended-release tablets in the dosage range of 3 months to 24 weeks after the last dose are 3 mg; those in the range of >24 weeks are 6 mg.
  • 546 mg (as palmitate) or 350 mg (as the base):
    • Paliperidone extended-release tablets in the dosage range of 3 months to 18 weeks after the last dose are 3 mg; 6 weeks to 24 weeks after the last dose are 6 mg; and 24 weeks or more after the last dose are 9 mg.
  • 819 mg (as palmitate) or 525 mg (as the base):
    • Paliperidone extended-release tablets in the dosage range of 3 months to 18 weeks after the last dose are 6 mg; from 18 weeks to 24 weeks after the last dose, they are 9 mg; and from 24 weeks after the last dose, they are 12 mg.

Paliperidone (Invega) Dosage adjustments:

• Depending on response and tolerance, dosage modifications can be done every three months in increments between 273 and 819 mg (as palmitate) or 175 and 525 mg (as the base).
• The patient's response to a changed dose might not be obvious for several months due to the long-acting nature of the medication.
• Missed dose 3 1/2 months to 4 months since the last injection:
  • As soon as you can, provide the dose from the previous three months, then resume regular dosing.
• Missed dose 4 months to 9 months since the last injection:
  • Do not administer the next 3-month dose. If the last 3-month dose was:
    • 273 mg (as palmitate) or 175 mg (as the base):
      • Monthly IM paliperidone (Invega Sustenna) dosages of 78 mg (as palmitate) or 50 mg (as the base) should be injected into the deltoid muscle.
      • One week later, administer the same amount of monthly IM paliperidone (Invega Sustenna).
      • Give 273 mg (as palmitate) or 175 mg (as the base) of the 3-month IM paliperidone (Invega Trinza) into the deltoid or gluteal muscle one month following the second injection, and then resume regular dosage at 3-month intervals.
    • 410 mg (as palmitate) or 263 mg (as the base):
      • Monthly IM paliperidone (Invega Sustenna) doses of 117 mg (as palmitate) or 75 mg (as the base) should be injected into the deltoid muscle.
      • One week later, administer the same amount of monthly IM paliperidone (Invega Sustenna). Give 410 mg (as palmitate) or 263 mg (as the base) of 3-month IM paliperidone one month following the second injection.
    • 546 mg (as palmitate) or 350 mg (as base):
      • Monthly IM paliperidone (Invega Sustenna) doses of 156 mg (as palmitate) or 100 mg (as the base) should be injected into the deltoid muscle.
      • One week later, administer the same amount of monthly IM paliperidone (Invega Sustenna).
      • Apply 546 mg (as palmitate) or 350 mg (as the base) of the 3-month IM paliperidone (Invega Trinza) to the deltoid or gluteal muscle one month following the second injection, and then resume regular dosing at 3-month intervals.
    • 819 mg (as palmitate) or 525 mg (as base):
      • Monthly IM paliperidone (Invega Sustenna) doses of 156 mg (as palmitate) or 100 mg (as the base) should be injected into the deltoid muscle.
      • One week later, administer the same amount of monthly IM paliperidone (Invega Sustenna).
      • Give 819 mg (as palmitate) or 525 mg (as the base) of the 3-month IM paliperidone one month after the second injection.
    • Missed dose longer than 9 months since the last injection:
      • Resuming monthly IM paliperidone therapy (Invega Sustenna).
      • After the patient has received adequate care with monthly IM paliperidone for at least 4 months, three-month IM paliperidone can be resumed.

Paliperidone (Invega) Dose in the treatment of Delusional infestation (also called delusional parasitosis) (off-label):

• Oral:
  • Initial dose: 3 mg per day; dose adjustment up to 9 mg per day dependent on response and tolerance
  • Responses to therapy are frequently seen after two weeks, reaching their peak effect after four.
  • To more clearly identify the function of paliperidone in this scenario, more information could be required.

Paliperidone (Invega) Discontinuation of therapy:

• American Psychiatric Association (APA), Canadian Psychiatric Association (CPA), and World Federation of Societies of Biological Psychiatry (WFSBP) guidelines recommend gradually tapering antipsychotics to avoid withdrawal symptoms and minimize the risk of relapse.
• The risk for withdrawal symptoms may be highest with highly anticholinergic or dopaminergic antipsychotics.
• When stopping antipsychotic therapy in patients with schizophrenia, the CPA guidelines recommend a gradual taper over 6 to 24 months, and the APA guidelines recommend reducing the dose by 10% each month.
• Continuing anti-parkinsonism agents for a brief period after discontinuation may prevent withdrawal symptoms.
• When switching antipsychotics, 3 strategies have been suggested:
  • Cross-titration (gradually discontinuing the first antipsychotic while gradually increasing the new antipsychotic),
  • overlap and taper (maintaining the dose of the first antipsychotic while gradually increasing the new antipsychotic, then tapering the first antipsychotic), and
  • abrupt change (abruptly discontinuing the first antipsychotic and either increasing the new antipsychotic slowly or starting it at a treatment dose).
• Evidence supporting ideal switch strategies and taper rates is limited, and results are conflicting.

Paliperidone (Invega) Dose in Children

Paliperidone (Invega) Dose in the treatment of irritability associated with autistic disorder: Limited data available:

• Children ≥12 years and Adolescents: Oral:

  • Extended-release tablet:

    • The starting dose is 3 mg once day; the maximum daily dose is 12 mg/day; titrate in weekly increments of 3 mg/day until clinical response or intolerance.
    • Based on a dosage-based open-label experiment with 25 patients, the therapeutic response was recorded in 84% of patients at a mean final dose of 7.1 mg/day (mean age: 15.3 years; range: 12 to 21 years).

Paliperidone (Invega) Dose in the treatment of Schizoaffective disorder: Oral:

• Extended-release tablet:

  • Adolescents ≥18 years:

    • Usual dose: 6 mg once daily (administred first thing in the morning in clinical studies); titration is not necessary, while some individuals may benefit from lower or higher dosages (range: 3 to 12 mg daily).
    • If the daily dose is more than 6 mg, it is advised to raise it by 3 mg at intervals longer than 4 days, up to a maximum of 12 mg per day.

  • Parenteral: Adolescents ≥18 years:

    • Monthly paliperidone injection (Invega Sustenna): IM:
    • Note:
      • Patients who have never used oral paliperidone or oral or injectable risperidone should first establish their tolerance with a test dose of either drug before starting monthly IM paliperidone.
      • When monthly IM paliperidone treatment begins, the oral antipsychotic regimen can be gradually discontinued.

• Initiation of therapy (2-dose series):

  • First: 234 mg on the first day of treatment, followed by 156 mg one week later, both dosages going into the deltoid muscle.
  • Four days before or after the weekly time point are acceptable window times to give the second dose.

  • Missed second initiation dose:

    • Catch-up dosage is dependent on the amount of time that has gone since the first dose if the second dose's intended administration date of 1 week and 4 days is missed.

Time elapsed since the last first dose	Catch-up dose for therapy initiation
<4 weeks	The third dose of 117 mg should be given in either the deltoid or gluteal muscle 5 weeks following the initial injection (regardless of when the second injection was given), and then you can resume your regular monthly maintenance dosing.
≥4 weeks to ≤7 weeks	Give a 156 mg dose (in the deltoid) as soon as you can, then another 156 mg dose (in the deltoid) a week later. After that, start your regular monthly maintenance doses.
>7 weeks	Recommendations for dosage should be followed before starting therapy.

• Maintenance:

  • Five weeks following the first of the initial series of injections, the first maintenance injection should be given.
  • Start a maintenance dose of 78 to 234 mg (given once per month), adjusting the dosage in accordance with response and tolerance.
  • Seven days before or after the monthly time point may be used to provide the maintenance dose.

• Missed maintenance dose:

  • Depending on how long has passed since the last dose, see table:

Time elapsed since last monthly maintenance injection	Catch-up dose for therapy initiation
≥4 weeks to ≤6 weeks	Give the missed dose as soon as you remember, then keep your monthly therapy appointments.
>6 weeks to ≤6 months and dose <234 mg	As soon as feasible, administer the same dose that the patient was previously stabilised on in the deltoid. One week later, administer a second dose that is equivalent to it, and then resume maintenance dose at monthly intervals.
>6 weeks to ≤6 months and dose 234 mg	As soon as feasible, administer a 156 mg dose in the deltoid. One week later, administer a second 156 mg dose in the same location. Finally, resume monthly maintenance doses.
>6 month	Restart by adhering to the dose guidelines for starting therapy.

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

 

• Start the 1-week introduction regimen of monthly IM paliperidone as directed.
• Patients who had previously stabilised on oral dosages can anticipate comparable steady-state exposure when receiving monthly IM paliperidone using the conversion below:

Oral extended-release once-daily dose	Monthly maintenance IM dose (Invega Sustenna)
3 mg	39 to 78 mg
6 mg	117 mg
9 mg	156 mg
12 mg	234 mg

Conversion from other oral antipsychotics to monthly IM paliperidone:

• Regarding transitioning patients from different oral antipsychotics to monthly intramuscular paliperidone, no comprehensive data have been gathered in this area.

Switching from other long-acting injectable antipsychotics (at steady-state) to monthly IM paliperidone:

• Paliperidone may be injected into the gluteal or deltoid muscles on a monthly basis, starting in place of the next planned injection.
• In these people, the two initial dosages are not necessary.

• Dosage adjustments:

  • Monthly modifications are possible, but their full effects might not be felt for several months.

Paliperidone (Invega) Dose in the treatment of Schizophrenia:

• Oral: Extended-release tablet:

  • Children ≥12 and Adolescents <18 years:

    • 3 mg once daily; no need for titration if a dosage increase is required following a clinical evaluation, it may be done in 3 mg/day increments, at least once every five days;
    • The maximum daily dose is weight dependent:
      • Less than 51 kgs: 6 mg/day;
      • 51 kgs or more: 12 mg/day;
    • Note: Higher doses were not linked to better efficacy during teenage clinical studies, but rather an elevated risk of side effects.

  • Adolescents: ≥18 years:

    • Usual dosage is 6 mg once daily, delivered in the morning in clinical studies; titration is not necessary, while some individuals may benefit from lower or greater amounts (range: 3 to 12 mg daily).
    • If the dose is more than 6 mg per day, it is advised to raise it by 3 mg per day, up to a maximum of 12 mg per day, no more frequently than every 5 days.

• Parenteral Treatment:

  • Adolescents ≥18 years:

    • Monthly paliperidone injection (Invega Sustenna): IM:
    • Note:
      • Tolerability should be established with oral paliperidone or oral risperidone prior to initiating monthly IM medication; a test dose of oral paliperidone or risperidone may be necessary.
      • You can stop taking any previous oral antipsychotics when you begin IM therapy.

  • Initiation of therapy (2-dose series):

    • Initial:
      • Both doses were given in the deltoid muscle: 234 mg on the first day of treatment and 156 mg one week later.
      • Four days before or after the weekly time point are acceptable window times to give the second dose.
    • Missed second initiation dose:
      • Catch-up dosage is dependent on the amount of time that has gone since the first dose if the second dose's intended administration date of 1 week and 4 days is missed.

Time elapsed since last monthly maintenance injection	Catch-up dosing
≥4 weeks to ≤6 weeks	Give the missed dose as soon as you remember, then keep your monthly therapy appointments.
>6 weeks to ≤6 months and dose <234 mg	As soon as feasible, administer the same dose that the patient was previously stabilised on in the deltoid. One week later, administer a second dose that is equivalent to it, and then resume maintenance dose at monthly intervals.
>6 weeks to ≤6 months and dose 234 mg	As soon as feasible, administer a 156 mg dose in the deltoid. One week later, administer a second 156 mg dose in the same location. Finally, resume monthly maintenance doses.
>6 months	Restart by adhering to the dose guidelines for starting therapy.

Conversion from oral paliperidone to IM paliperidone monthly injection:

• Start IM treatment following the 1-week starting regimen as directed.
• When adopting the following conversion, patients who had previously stabilised on oral doses can anticipate a similar steady-state exposure during maintenance therapy with IM therapy:

Oral extended-release once-daily dose	Monthly maintenance IM dose (Invega Sustenna)
3 mg	39 to 78 mg
6 mg	117 mg
9 mg	156 mg
12 mg	234 mg

• Switching from other long-acting injectable antipsychotics to IM paliperidone:

  • Start taking IM paliperidone in place of the subsequent planned injection, then do so every month after that.
  • These patients do not require the 1-week start programme.

Paliperidone (Invega) Dosage adjustments:

• Month-to-month changes are possible (full effect from adjustments may not be seen for several months).
• Three-month paliperidone (Invega Trinza): IM:
• Note:
  • Only after monthly IM paliperidone (Invega Sustenna) has been proven to be an effective treatment for at least 4 months should 3-month IM paliperidone be used.
  • Before starting 3-month IM paliperidone, the final two doses of monthly IM paliperidone should be the same dosage strength.

Conversion from monthly injection and 3-month injection:

• Monthly to 3-month injections:
  • When the next monthly IM paliperidone dose is planned, begin the 3-month IM paliperidone course.
  • Utilize the comparable 3.5 times larger amount for the 3-month dose and base it on the previous monthly dose.
  • Paliperidone for three months can be given IM up to seven days before or after the scheduled date of the following monthly dose.
  • After the first shot, give it every three months.
  • The injection can be administered to patients up to two weeks before or after the 3-month mark.
• Three-month to monthly injections:
  • When the next 3-month IM paliperidone dose is scheduled, begin monthly IM paliperidone.
  • Utilize the comparable 3.5 times lower dose to base the monthly dose on the prior 3-month dose (see following table).
  • After the first injection, give once a month.

Monthly IM paliperidone dose (Invega Sustenna)	3-month paliperidone dose (Invega Trinza)
78 mg	273 mg
117 mg	410 mg
156 mg	546 mg
234 mg	819 mg
Note: Conversion from monthly IM paliperidone (Invega Sustenna) 39 mg to 3-month IM paliperidone (Invega Trinza) has not been studied.

Conversion from 3-month IM paliperidone to oral paliperidone extended-release tablets:

• Start taking paliperidone extended-release tablets at least three months following your last IM dosage of the medication.
• Calculate the dosage for the once-daily extended-release pill using the last injectable dose and the time since it was last given.
• Use the conversion shown below.

3-month paliperidone dose (Invega Trinza)	Time elapsed since last IM dose	Oral extended-release once-daily dose
273 mg	≥12 weeks	3 mg
410 mg	12 weeks to ≤24 weeks	3 mg
	>24 weeks	6 mg
546 mg	12 to ≤18 weeks	3 mg
	>18 to ≤24 weeks	6 mg
	>24 weeks	9 mg
819 mg	12 to ≤18 weeks	6 mg
	>18 to ≤24 weeks	9 mg
	>24 weeks	12 mg

• Paliperidone (Invega) Dosage adjustments:

  • Depending on response and tolerance, dosage modifications can be done every three months in increments between 273 and 819 mg.
  • The patient's response to an altered dose could not be noticeable for several months due to the medication's long half-life.
  • Missed doses:
    • Time since the last dose affects the dose and the interval; In some circumstances, the usage of the Invega Sustenna monthly dosage form may be required.

Time elapsed since last 3-month maintenance dose	Catch-up dosing
3.5 months to 4 months	As soon as feasible, administer the dosage from the previous three months, then carry on with regular doses.
4 months to 9 months and dose 273 mg	Inject 78 mg of the medication paliperidone (Invega Sustenna) once every month into the deltoid muscle. One week later, repeat the same monthly IM paliperidone (Invega Sustenna) dose. Give 273 mg of 3-month IM paliperidone (Invega Trinza) into the deltoid or gluteal muscle one month after the second injection. Then, resume regular dosage at 3-month intervals.
4 months to 9 months and dose 410 mg	Paliperidone (Invega Sustenna) at a dose of 117 mg per month should be injected into the deltoid muscle. One week later, repeat the same monthly IM paliperidone (Invega Sustenna) dose. Give 410 mg of 3-month IM paliperidone (Invega Trinza) into the deltoid or gluteal muscle one month after the second injection, then resume regular dosage at 3-month intervals.
4 months to 9 months and dose 546 mg	Paliperidone (Invega Sustenna) at a dose of 156 mg per month should be injected into the deltoid muscle. One week later, repeat the same monthly IM paliperidone (Invega Sustenna) dose. Give 546 mg of 3-month IM paliperidone (Invega Trinza) into the deltoid or gluteal muscle one month after the second injection, then resume regular dosage at 3-month intervals.
4 months to 9 months and dose 819 mg	Paliperidone (Invega Sustenna) at a dose of 156 mg per month should be injected into the deltoid muscle. One week later, repeat the same monthly IM paliperidone (Invega Sustenna) dose. In the deltoid or gluteal muscle, inject 819 mg of the 3-month paliperidone (Invega Trinza) one month after the second injection. Then, resume regular dosing at 3-month intervals.
>9 months	Recommence monthly IM paliperidone therapy (Invega Sustenna).

Paliperidone (Invega) Pregnancy Category: Not assigned

• There is not much information available on pregnancy paliperidone.
• There is a possibility of withdrawal symptoms and extrapyramidal symptoms in the third trimester if antipsychotics are used during pregnancy.
• The newborn can experience agitation, feeding disorders, hypotonia and respiratory distress as well as somnolence and tremor.
• These effects can be self-limiting, allowing recovery in hours or days with no treatment or severe enough to require prolonged hospitalization.
• ACOG recommends that treatment during pregnancy is individualized; treatment with psychotropic medications during pregnancy should include the clinical expertise of the primary healthcare provider, mental health clinician, and pediatrician.
• There are limited safety data regarding atypical antipsychotics during pregnancy. Routine use is not recommended.
• If a woman accidentally takes an antipsychotic during pregnancy, she may need to continue therapy.
• Paliperidone, which might produce a reversible decline in female fertility, may cause hyperprolactinemia.

Use of paliperidone while breastfeeding

• Breast milk contains paliperidone.
• According to the manufacturer breastfeeding during therapy is a decision that should be made after considering the risks to infants and the benefits to mothers.
• The severe sedation, extrapyramidal symptoms, failure to thrive, and jitteriness in nursing newborns should be watched carefully.

Paliperidone (Invega) Dose in Kidney Disease:

• Clearance is decreased in renal impairment; adjust the dose according to renal function:

• Oral Administration:

  • Mild impairment (CrCl 50 to 79 mL/minute):

    • Initial dose: 3 mg once daily;
    • The maximum dose: 6 mg once daily

  • Moderate to severe impairment (CrCl 10 to 49 mL/minute):

    • Initial dose: 1.5 mg once daily;
    • The maximum dose: 3 mg once daily

  • Severe impairment (CrCl <10 mL/minute):

    • Use not recommended (has not been studied).

• IM Administration:

  • Mild impairment (CrCl 50 to 79 mL/minute):

    • Monthly IM paliperidone (Invega Sustenna):
      • Beginning of treatment: 156 mg as palmitate or 100 mg as the base on the first day of treatment, followed by 117 mg as palmitate OR 75 mg as the base one week later, both doses injected in the deltoid, and then a maintenance dose of 78 mg as palmitate OR 50 mg as the base every month (administered in the deltoid or gluteal muscle)
    • Three-month IM paliperidone (Invega Trinza):
      • Using the monthly IM injection, adjust the dosage and stabilise the patient before switching to the three-month IM injection.
      • Note:
        • Monthly intramuscular paliperidone (Invega Sustenna) 78 mg or 50 mg = 3-month intramuscular paliperidone (Invega Trinza) 273 mg or 175 mg (as base).

  • Moderate to severe impairment (CrCl <50 mL/minute):

    • Use not recommended

Paliperidone (Invega) Dose in Liver Disease:

• Oral, IM (monthly, 3- month):
  • Mild to moderate impairment (Child-Pugh class A or B):
    • No change in dose is necessary.
  • Severe impairment:
    • There are no dosage modifications listed on the manufacturer's label (has not been studied).

---

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

Common Side Effects of Paliperidone (Invega):

• Cardiovascular:

  • Tachycardia

• Central Nervous System:

  • Drowsiness
  • Extrapyramidal Reaction
  • Akathisia
  • Headache
  • Parkinsonian-Like Syndrome
  • Dystonia

• Endocrine & Metabolic:

  • Increased Serum Prolactin
  • Decreased HDL Cholesterol
  • Increased LDL Cholesterol
  • Weight Gain
  • Increased Serum Triglycerides
  • Increased Serum Cholesterol
  • Hyperglycemia

• Gastrointestinal:

  • Vomiting

• Neuromuscular & Skeletal:

  • Hyperkinesia
  • Tremor

Less Common Side Effects Of Paliperidone (Invega):

• Cardiovascular:

  • Orthostatic Hypotension
  • Bundle Branch Block
  • First Degree Atrioventricular Block
  • Hypertension
  • Sinus Arrhythmia
  • Bradycardia
  • Edema
  • Palpitations

• Central Nervous System:

  • Agitation
  • Anxiety
  • Sedation
  • Dizziness
  • Dysarthria
  • Lethargy
  • Fatigue
  • Sleep Disorder
  • Nightmares
  • Insomnia
  • Opisthotonus

• Dermatologic:

  • Pruritus
  • Skin Rash

• Endocrine & Metabolic:

  • Amenorrhea
  • Galactorrhea
  • Gynecomastia
  • Decreased Libido

• Gastrointestinal:

  • Nausea
  • Dyspepsia
  • Sialorrhea
  • Constipation
  • Abdominal Distress
  • Upper Abdominal Pain
  • Diarrhea
  • Swollen Tongue
  • Increased Appetite
  • Toothache
  • Xerostomia
  • Stomach Discomfort
  • Decreased Appetite
  • Flatulence

• Genitourinary:

  • Urinary Tract Infection
  • Breast Tenderness
  • Irregular Menses
  • Retrograde Ejaculation
  • Erectile Dysfunction

• Hepatic:

  • Increased Serum ALT
  • Increased Serum AST

• Hypersensitivity:

  • Anaphylaxis

• Local:

  • Injection Site Reaction
  • Erythema At Injection Site
  • Swelling At Injection Site

• Neuromuscular & Skeletal:

  • Dyskinesia
  • Myalgia
  • Weakness
  • Back Pain
  • Tongue Paralysis
  • Limb Pain
  • Muscle Rigidity
  • Arthralgia

• Ophthalmic:

  • Blurred Vision
  • Abnormal Eye Movements

• Respiratory:

  • Upper Respiratory Tract Infection
  • Nasopharyngitis
  • Cough
  • Rhinitis
  • Epistaxis
  • Pharyngolaryngeal Pain
  • Nasal Congestion

Uncommon Side effects of Paliperidone (Invega) Frequency Not Defined:

• Cardiovascular:

  • Cerebrovascular Accident (IM)
  • ECG Abnormality (IM)
  • Hypotension (Oral)
  • Ischemia (Oral)
  • Left Bundle Branch Block (Oral)
  • Peripheral Edema (Oral)
  • Postural Orthostatic Tachycardia (IM)
  • Transient Ischemic Attacks (Oral)

• Central Nervous System:

  • Abnormal Gait (Oral; Parkinsonian Gait)
  • Cogwheel Rigidity (IM)
  • Drooling
  • Hypertonia (IM)
  • Orthostatic Dizziness (IM)
  • Psychomotor Agitation (IM)
  • Restlessness (IM)
  • Seizure
  • Tonic-Clonic Seizures (Oral)
  • Trismus (Oral)
  • Vertigo (IM)

• Dermatologic:

  • Fixed Drug Eruption (IM)
  • Papular Rash (Oral)
  • Urticaria (IM)

• Endocrine & Metabolic:

  • Menstrual Disease (IM)

• Gastrointestinal:

  • Abdominal Pain (Oral)
  • Hyperinsulinism (IM)
  • Oromandibular Dystonia (IM)

• Genitourinary:

  • Breast Engorgement (Oral)
  • Breast Hypertrophy (IM)
  • Breast Swelling (IM)
  • Ejaculatory Disorder (IM)
  • Mastalgia
  • Nipple Discharge (IM)
  • Sexual Disorder (IM)

• Hypersensitivity:

  • Hypersensitivity (IM)

• Neuromuscular & Skeletal:

  • Bradykinesia (IM)
  • Joint Stiffness (IM)
  • Muscle Spasm (IM)
  • Muscle Twitching (IM)
  • Musculoskeletal Pain (Oral)
  • Neck Stiffness (IM)
  • Torticollis (Oral)

• Ophthalmic:

  • Oculogyric Crisis (IM)

• Respiratory:

  • Aspiration Pneumonia

Contraindications to Paliperidone (Invega):

Hypersensitivity to paliperidone or risperidone or any component in the formulation

Warnings and precautions

• Modified cardiac conduction

  • Prolongs QTc interval and changes cardiac conduction. Antipsychotics taken at therapeutic levels have been linked to life-threatening arrhythmias.
  • The risk may be increased by concurrent medications or medical disorders that result in hypokalemia, bradycardia, and/or hypomagnesemia.
  • Use with caution if taking QTc-prolonging medication.
  • Patients with past cardiac arrhythmia or those who have congenital long QT syndrome shouldn't use this drug.

• Anti-emetic effects

  • Antiemetic effects could conceal the dangers of other medications and health issues (eg, Reye syndrome or brain tumor).

• Blood dyscrasias

  • Leukopenia, neutropenia, and even deadly agranulocytosis have been seen in clinical trials and postmarketing reports following antipsychotic use.
  • Periodic blood count assessments should be done if there are any risk factors, such as low WBC or an ANC or preexisting history of drug-induced neutropenia/ leukopenia.
  • Patients with clinically severe neutropenia should have their fever and other infection symptoms checked often. Stop therapy if the absolute neutrophil count reaches 1,000/mm3.

• Effects on the cerebrovascular system:

  • Paliperidone, the main active metabolite, was examined in placebo-controlled studies of risperidone in older patients with dementia-related psychosis. There was an increase in cerebrovascular adverse events (eg, stroke, transient ischemic attacks, stroke).

• Depression in the CNS:

  • CNS depression can lead to mental or physical impairments. Patients should be cautious about driving, operating machinery, and other tasks that require mental alertness.

• Dyslipidemia

  • There have been increases in cholesterol and triglycerides, and decreased HDL.
  • Patients with an abnormal lipid profile should be cautious.

• Aspiration and Esophageal Dysmotility:

  • Antipsychotic use has been linked to esophageal dysmotility, aspiration, and increased risk with age.
  • Patients at high risk of aspiration pneumonia (eg Alzheimer's disease) should be treated with caution, especially patients over 75 years old.

• Extrapyramidal symptoms

  • Extrapyramidal symptoms (EPS) may occur, including pseudo-parkinsonism and acute dystonic reactions. These reactions are generally less common than those caused by conventional antipsychotics. Frequency reports are comparable to placebo.
  • Higher doses of antipsychotics and use of antipsychotics for men, younger patients, and males may increase the risk of dystonia.
  • There are several factors that increase the vulnerability to tardive dyskinesia, including older age, female gender, postmenopausal status and Parkinson disease symptoms.
  • Stop treating tardive dyskinesia symptoms and signs.

• Falls

  • May increase the chance of falling due to somnolence and orthostatic hypotension.
  • Patients with certain diseases or medications that can increase fall risk should have their fall risk assessed at baseline and again periodically throughout treatment.

• Hyperglycemia

  • Hyperglycemia can be caused by antipsychotics that are not typical. In some cases, this may lead to hyperglycemia, hyperosmolar compa or even death.
  • Hyperglycemia symptoms (eg, weakness, polydipsia or polyuria) should be checked on all patients.
  • Patients with diabetes (or risk factors for it) should be cautious. Monitor for any changes in glucose control.
  • Patients who are at high risk for developing diabetes (such as those who are obese or have a family history) should have a baseline fasting sugar level and be routinely checked throughout treatment.

• Hyperprolactinemia

  • Higher prolactin levels are related to it. Hyperprolactinemia in patients with breast cancer or other prolactin-dependent malignancies may have clinical importance, however this is unknown at this time.

• Hypersensitivity

  • There have been reports of allergic responses, such as anaphylactic shock or angioedema.

• Intraoperative floppy-iris syndrome:

  • Intraoperative floppy iris (IFIS) is uncommon in people who have taken risperidone or undergone cataract surgery.
  • Paliperidone has not been associated with IFIS, however you should exercise caution because it is a risperidone active metabolite.
  • Before you undergo cataract surgery, make sure to check for any previous risperidone or paliperidone use.

• Neuroleptic malignant Syndrome:

  • This medication may cause neuroleptic malignant symptoms.
  • Monitor for changes in mental status, fever, rigidity of the muscles, and/or instability.
  • It is unknown whether stopping paliperidone and risperidone before surgery has any advantages or disadvantages.

• Orthostatic hypotension

  • Patients with Lewy body dementia, Parkinson's disease, or Parkinson's may be more vulnerable.

• Priapism

  • There were a few isolated reports of priapism.

• Suicidal thoughts:

  • Psychotic illness and bipolar disorder can lead to suicide attempts. It is important to be cautious when starting therapy for high-risk patients.
  • Good patient care requires that prescriptions be limited to the minimum amount.

• Temperature regulation

  • It is possible to have impaired core body temperature regulation. Avoid heat exposure, strenuous exercise and any anticholinergic medication.

• Weight loss:

  • Antipsychotic therapy has led to significant weight gain; incidences vary from product to product.
  • You should monitor your waist circumference, and body mass index.

• Dementia: [US Boxed Warning]

  • Antipsychotics have a higher death rate than placebo for dementia-related psychosis in the elderly.
  • The majority of deaths were either from cardiovascular disease (eg heart failure, sudden death, etc.) or infectious diseases (eg pneumonia).
  • Patients with Parkinson's disease or Lewy body dementia should be cautious.
  • An increased susceptibility to extrapyramidal effects, a higher chance of severe responses, and a link to death or irreversible cognitive deterioration are all present.
  • The use of paliperidone to treat psychosis brought on by dementia is not authorised.

• Renal impairment

  • Patients with mild renal disease should be cautious; a reduction in dosage is advised.
  • Patients with severe (IM route only), or moderate dysfunction are not recommended.

• Seizures

  • Patients at high risk of seizures should be treated with caution, especially those who have had seizures in the past, are brain damaged, suffered from head trauma or have been drinking, and/or are receiving concurrent treatment with medication that could lower their seizure threshold.
  • Due to the increased prevalence of predisposing factors, elderly patients could be more at risk for seizures.

Paliperidone: Drug Interaction

Risk Factor C (Monitor therapy)
Acetylcholinesterase Inhibitors (Central)	May enhance the neurotoxic (central) effect of Antipsychotic Agents. Severe extrapyramidal symptoms have occurred in some patients.
Alcohol (Ethyl)	CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl).
Alizapride	May enhance the CNS depressant effect of CNS Depressants.
Amifampridine	Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine.
Amphetamines	Antipsychotic Agents may diminish the stimulatory effect of Amphetamines.
Antidiabetic Agents	Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
Blood Pressure Lowering Agents	May enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]).
Brexanolone	CNS Depressants may enhance the CNS depressant effect of Brexanolone.
Brimonidine (Topical)	May enhance the CNS depressant effect of CNS Depressants.
BuPROPion	May enhance the neuroexcitatory and/or seizure-potentiating effect of Agents With Seizure Threshold Lowering Potential.
Cannabidiol	May enhance the CNS depressant effect of CNS Depressants.
Cannabis	May enhance the CNS depressant effect of CNS Depressants.
CarBAMazepine	May decrease the serum concentration of Paliperidone.
Chlorphenesin Carbamate	CNS depressants' harmful or toxic effects could be increased.
CNS Depressants	Other CNS depressants' harmful or toxic effects might be exacerbated.
Deutetrabenazine	Could intensify the negative or hazardous effects of antipsychotic drugs. Particularly, there may be a higher chance of developing akathisia, parkinsonism, or neuroleptic malignant syndrome.
Dimethindene (Topical)	CNS depressants may have an enhanced CNS depressant impact.
Doxylamine	CNS depressants may have an enhanced CNS depressant impact. Management: The producer of the pregnancy-safe drug Diclegis (doxylamine/pyridoxine) particularly advises against combining it with other CNS depressants.
Dronabinol	CNS depressants may have an enhanced CNS depressant impact.
Erdafitinib	May increase the serum concentration of P-glycoprotein/ABCB1 Substrates.
Esketamine	May enhance the CNS depressant effect of CNS Depressants.
Guanethidine	Guanethidine's therapeutic impact may be diminished by antipsychotic medications.
Haloperidol	The QTcprolonging action of haloperidol may be enhanced by QT-prolonging agents (Indeterminate Risk - Avoid).
HydrOXYzine	CNS depressants may have an enhanced CNS depressant impact.
Kava Kava	CNS depressants' harmful or toxic effects could be increased.
Lithium	Antipsychotic Agents' neurotoxic effects might be amplified. Lithium may lower the level of antipsychotic agents in the blood. Particularly relevant with chlorpromazine.
Lofexidine	CNS depressants may have an enhanced CNS depressant impact. Management: Separate drug interaction monographs go into further detail about the medications indicated as exceptions to this book.
Lumacaftor	May lower the level of P-glycoprotein/ABCB1 Substrates in the serum. The serum concentration of P-glycoprotein/ABCB1 Substrates may rise when using lumacaftor.
Magnesium Sulfate	CNS depressants may have an enhanced CNS depressant impact.
Methylphenidate	Antipsychotic drugs may intensify methylphenidate's harmful or toxic effects.
MetyroSINE	Methylphenidate may make antipsychotic agents more harmful or poisonous.
MetyroSINE	The sedative effects of metyroSINE may be strengthened by CNS depressants.
Minocycline	Could intensify the negative or hazardous effects of antipsychotic drugs.
Mirtazapine	The CNS depressing action of mirtazapine may be enhanced by CNS depressants.
Nabilone	May enhance the CNS depressant effect of CNS Depressants.
P-glycoprotein/ABCB1 Inhibitors	May increase the serum concentration of Pglycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of pglycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.).
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.
Quinagolide	Antipsychotic Agents may diminish the therapeutic effect of Quinagolide.
Ranolazine	May increase the serum concentration of P-glycoprotein/ABCB1 Substrates.
Rufinamide	May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced.
Selective Serotonin Reuptake Inhibitors	CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced.
Serotonin Modulators	May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Exceptions: Nicergoline.
Tetrabenazine	May enhance the adverse/toxic effect of Antipsychotic Agents.
Tetrahydrocannabinol	May enhance the CNS depressant effect of CNS Depressants.
Tetrahydrocannabinol and Cannabidiol	May enhance the CNS depressant effect of CNS Depressants.
Trimeprazine	May enhance the CNS depressant effect of CNS Depressants.
Valproate Products	May increase the serum concentration of Paliperidone.
Risk Factor D (Consider therapy modification)
Anti-Parkinson Agents (Dopamine Agonist)	The therapeutic benefit of second-generation [atypical] antipsychotic agents may be reduced (Dopamine Agonist). When possible, alternative antipsychotic medications should be used with Parkinson disease patients. If an atypical antipsychotic is required, clozapine or quetiapine may provide the lowest risk of interactions.
Blonanserin	CNS Depressants may enhance the CNS depressant effect of Blonanserin.
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.
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.
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. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs.
Flunitrazepam	CNS Depressants may enhance the CNS depressant effect of Flunitrazepam.
HYDROcodone	CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone 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.
Inducers of CYP3A4 (Strong) and P-glycoprotein	May lower the level of paliperidone in the serum. Management: If at all possible, refrain from combining inducers of both CYP3A4 and P-glycoprotein throughout the 3-month dosage interval with the 3-month extended-release injectable suspension (Invega Trinza). When combining medications, think about selecting pills with an extended release.
Iohexol	The negative/toxic effects of iohexol may be amplified by substances with the potential to lower seizure thresholds. More specifically, there may be a higher chance of seizures. Treatment: Stop using medications 48 hours before using intrathecal iohexol that could lower the seizure threshold. To restart using such agents, give the treatment at least 24 hours. Prophylactic anticonvulsants may be used in nonelective surgeries.
Iomeprol	The negative/toxic effect of Iomeprol may be increased by substances with the potential to lower seizure thresholds. More specifically, there may be a higher chance of seizures. Treatment: Stop using medications 48 hours before using intrathecal iomeprol if they could lower the seizure threshold. To restart using such agents, give the treatment at least 24 hours. Prophylactic anticonvulsants may be used in nonelective surgeries.
Iopamidol	The negative/toxic effects of iopamidol may be increased by substances with the potential to lower seizure thresholds. More specifically, there may be a higher chance of seizures. Treatment: 48 hours before using intrathecal iopamidol, stop using any medications that could lower the seizure threshold. To restart using such agents, give the treatment at least 24 hours. Prophylactic anticonvulsants may be used in nonelective surgeries.
Itraconazole	May increase Paliperidone's ability to extend QTc. The metabolism of paliperidone may be slowed down by itraconazole.
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.
Methotrimeprazine	CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established.
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.
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.
Perampanel	May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination.
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.
Sodium Oxybate	CNS depressants may have an enhanced CNS depressant impact. Management: Take into account substitutes for combined use. Reduce the doses of one or more medications when simultaneous use is necessary. It is not advised to use sodium oxybate with alcoholic beverages or hypnotic sedatives.
St John's Wort	May lower the level of paliperidone in the serum. Management: If at all possible, refrain from combining inducers of both CYP3A4 and P-glycoprotein throughout the 3-month dosage interval with the 3-month extended-release injectable suspension (Invega Trinza). When combining medications, think about selecting pills with an extended release.
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.
Tapentadol	May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol 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.
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 Factor X (Avoid combination)
Amisulpride	Antipsychotic Agents may enhance the adverse/toxic effect of Amisulpride. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.
Azelastine (Nasal)	CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal).
Bromopride	May enhance the adverse/toxic effect of Antipsychotic Agents.
Bromperidol	May enhance the CNS depressant effect of CNS Depressants.
Metoclopramide	May enhance the adverse/toxic effect of Antipsychotic Agents.
Orphenadrine	CNS Depressants may enhance the CNS depressant effect of Orphenadrine.
Oxomemazine	May enhance the CNS depressant effect of CNS Depressants.
Paraldehyde	CNS Depressants may enhance the CNS depressant effect of Paraldehyde.
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.
Sulpiride	Antipsychotic Agents may enhance the adverse/toxic effect of Sulpiride.
Thalidomide	CNS Depressants may enhance the CNS depressant effect of Thalidomide.

Monitoring Parameters:

• Mental status
• vital signs (as clinically indicated)
• blood pressure 
• weight, height, BMI, waist circumference
• CBC 
• electrolytes
• renal and liver function 
• family history of obesity, diabetes, dyslipidemia, hypertension, or cardiovascular disease 
• fasting plasma glucose level/HbA 
• fasting lipid panel 
• changes in menstruation, libido, development of galactorrhea, erectile and ejaculatory function 
• Abnormal involuntary movements or parkinsonian signs 
• Tardive dyskinesia 
• Ocular examination

How to administer Paliperidone?

Oral:

• You can take it with or without food.
• Always swallow whole and combine extended-release tablets with liquids.
• Do not chew, split, or crush

Injection of IM:

• Only give one dose using the IM method (do NOT divide).
• Use only this technique for administration.
• Avoid injecting accidentally into the vasculature.

Monthly paliperidone, Invega Sustenna

• Mix it with other products or diluents.
• Before injecting, shake the syringe.Minimum 10 secondsTo ensure homogeneous suspension
• Use only the included needles to administer the medication.
• For patients who weigh more than 90 kg, the 2 initial injections should take place using a 1 1/2-inch, 22-gauge needle. Patients weighing less then 90 kgs need a 1 1/4-inch, 23-gauge tip.
• To quickly reach therapeutic concentrations, two initial intramuscular deltoid injections are needed.
• Deltoid injections in lieu of (right or left deltoid muscles).
• The fourth dose may be given four days before or four days after the weekly interval.
• You can use the gluteal or deltoid muscles to deliver monthly maintenance doses.
• A 1 1/2-inch, 22-gauge needle should be used to inject the gluteal muscles.
• Alternate gluteal injections are possible (right gluteal muscle and left gluteal muscles).
• Seven days before the monthly maintenance dose can be taken,

Three-months of paliperidone, Invega Trinza

• Be sure to shake the syringe tip upward before administering. least 15 seconds To guarantee uniform suspension
• Shake vigorously for five minutes, then inject.
• Deeply inject the medicine into the gluteal or deltoid muscles while going slowly.
• Use only the thin wall needles that are provided.
• Use needles made from monthly IM Paliperidone and other commercially available materials to lessen the possibility of blocking.
• Reach the middle of the deltoid muscles with a 1 1/2-inch, 22-gauge thin wall needle for individuals who weigh more than 90 kg. For patients weighing less than 90 kg, a 1 inch, 22 gauge thin-wall tip is employed.
• Deltoid injections in lieu of (right or left deltoid muscles).
• Apply injections to the gluteal muscles with a 1 1/2-inch, 22-gauge thin-walled needle (regardless patient weight).
• Alternating injections into the gluteus (right gluteal muscle and left gluteal muscle).
• Do not provide the incorrectly administered dose through injection.
• Until the subsequent 3-month injection, monitor the patient and give oral supplements as prescribed by a doctor.

Mechanism of action of Paliperidone (Invega):

• A benzisoxazole antipsychotic, paliperidone is the main active metabolite of risperidone.
• It's thought that it is a combination of central serotonergic, dopaminergic antagonism.
• Serotonin antagonism is a classic neuroleptic mechanism that improves psychoses by reducing the number of extrapyramidal side effect.
• Similar to risperidone, paliperidone has a high affinity for the a1, a2, D2, H1, and 5-HT-2A receptors and a low affinity for muscarinic receptors.
• Paliperidone has a three- to five-fold lower affinity for 5-HT-1A or 5-HT-1D and a nearly 10-fold lower affinity for 5-HT-2A and 5-HT-2A receptors compared to risperidone.

Notice:

• Teenagers who weighed more than 51 kg had pharmacokinetic characteristics that were similar to those of adults.
• Teenagers weighing less than 51 kg (23%) had a greater drug exposure rate than adults. This wasn't clinically significant, though.

Absorption: IM:

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

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 dysfunction (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

Time to peak plasma:

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

Excretion:

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

International Brand Names of Paliperidone:

• Invega
• Invega Sustenna
• Invega Trinza
• Inveda
• Inveda Sustenna
• Invega
• Invega SR
• Invega Sustenna
• Invega Trinza
• Keplioon
• Trevicta
• Xeplion

Paliperidone Brand Names in Pakistan:

No Brands Available in Pakistan.