Usual Adult Dose for Schizophrenia

EXTENDED-RELEASE TABLETS:
6 mg orally once a day

• Dose range: 3 to 12 mg per day; dose increases may be made in increments of 3 mg per day and should occur at intervals of more than 5 days.
• Maximum dose: 12 mg/day

Comments:

• Initial dose titration is not required.
• Greater effects may be seen with higher doses, however this must be weighed against dose-related increases in adverse events.
• Doses above 6 mg per day have not been systematically studied for additional benefit.
• Efficacy was established with 3 trials using patients with schizophrenia for 6-weeks; efficacy in maintenance therapy was established with one adult trial.

1-MONTH EXTENDED-RELEASE INJECTABLE SUSPENSION:

• For patients who have never taken oral paliperidone or oral or injectable risperidone, tolerability should be established with oral paliperidone or oral risperidone prior to initiating treatment with paliperidone extended-release injectable suspension.
• Dosing in the US and Canada is the same; however, paliperidone extended-release injectable suspension is dosed as the salt (paliperidone palmitate) in the US and as the base (paliperidone) in Canada:

Paliperidone palmitate:

• Initial dose: 234 mg IM on day 1 followed by 156 mg IM one week later; administer IM into deltoid muscle
• Maintenance dose: 117 mg IM monthly; administer into deltoid or gluteal muscle
• Dose range: 39 to 234 mg based on patient tolerability and efficacy; dose adjustments may be made monthly, although full effect may not be evident for several months
• Maximum dose: 234 mg/month

Paliperidone (base):

• Initial dose: 150 mg IM on day 1 followed by 100 mg IM one week later; administer IM into deltoid muscle
• Maintenance dose: 75 mg IM monthly; administer into deltoid or gluteal muscle
• Dose range: 25 to 150 mg based on patient tolerability and efficacy; dose adjustments may be made monthly, although full effect may not be evident for several months

Comments:

• The dosing window for maintenance doses is 7 days before or after monthly time point.
• If a dose is missed during initial titration or maintenance dosing, see dosage adjustment section for guidance.

3-MONTH EXTENDED-RELEASE INJECTABLE SUSPENSION:

• Patients should be adequately treated for at least 4 months with the 1-month extended-release suspension prior to starting on the 3-month extended-release formulation.
• In order to establish a consistent maintenance dose, it is recommended that the last 2 doses of the 1-month extended-release suspension be of the same dosage strength.
• Initiate with the 3-month extended release injection when the next 1-month extended-release suspension dose is scheduled (up to 7-days before or after the monthly dose is scheduled).

Initial dose (based on the 1-month extended-release suspension dose):

• Initiate with 273 mg IM every 3 months if the last dose of the 1-month extended-release suspension was 78 mg
• Initiate with 410 mg IM every 3 months if the last dose of the 1-month extended-release suspension was 117 mg
• Initiate with 546 mg IM every 3 months if the last dose of the 1-month extended-release suspension was 156 mg
• Initiate with 819 mg IM every 3 months if the last dose of the 1-month extended-release suspension was 234 mg

Dose adjustments may be made every 3 months in increments within the range of 273 mg to 819 mg based on efficacy and tolerability; due to long-acting nature of the formulation, it may take several months for the patient's response to be apparent.

Comments:

• The initial dose will be 3.5-fold higher than monthly dose.
• The dosing window is 2 weeks before or after the 3-month time point.
• Missed doses should be avoided. If a dose is missed, see dosage adjustment section for guidance.
• Conversion from 39 mg IM once-monthly was not studied.
• If the needle becomes clogged during administration, the remaining dose should not be re-injected. Instead, the patient should be monitored and treated with oral supplementation until the next scheduled 3-month injection.

Use: For the treatment of schizophrenia

Usual Adult Dose for Schizoaffective Disorder

EXTENDED RELEASE TABLETS:
6 mg orally once a day

• Dose range: 3 to 12 mg per day; dose increases may be made in increments of 3 mg per day and should occur at intervals of more than 4 days.
• Maximum dose: 12 mg/day

Comments:

• Initial dose titration is not required.
• Greater effects may be seen with higher doses; however, this must be weighed against dose-related increases in adverse events.
• Doses above 6 mg per day have not been systematically studied for additional benefit.
• Efficacy was established with 2 trials using patients with schizoaffective disorder for 6 weeks.

1-MONTH EXTENDED-RELEASE INJECTABLE SUSPENSION:

• For patients who have never taken oral paliperidone or oral or injectable risperidone, tolerability should be established with oral paliperidone or oral risperidone prior to initiating treatment with paliperidone extended-release injectable suspension.
• Dosing in the US and Canada is the same; however, paliperidone extended-release injectable suspension is dosed as the salt (paliperidone palmitate) in the US and as the base (paliperidone) in Canada:

Paliperidone palmitate:

• Initial dose: 234 mg IM on day 1 followed by 156 mg IM one week later; administer IM into deltoid muscle
• Dose range: 78 to 234 mg based on patient tolerability and efficacy; dose adjustments may be made monthly, although full effect may not be evident for several months
• Maximum dose: 234 mg/month

Paliperidone (base):

• Initial dose: 150 mg IM on day 1 followed by 100 mg IM one week later; administer IM into deltoid muscle
• Dose range: 50 to 150 mg based on patient tolerability and efficacy; dose adjustments may be made monthly, although full effect may not be evident for several months

Comments:

• The dosing window for maintenance doses is 7 days before or after monthly time point.
• If a dose is missed during initial titration or maintenance dosing, see dosage adjustment section for guidance.

Use: Treatment of schizoaffective disorder as monotherapy and as an adjunct to mood stabilizers and/or antidepressants

Usual Pediatric Dose for Schizophrenia

EXTENDED-RELEASE TABLETS:
12 to 17 years old:

• Initial dose: 3 mg orally once a day
• Dose range: 3 to 12 mg per day; dose increases may be made in increments of 3 mg per day and should occur at intervals of more than 5 days.
• Maximum dose: 12 mg/day

Comments:

• Initial dose titration is not required.
• In the adolescent schizophrenia trials, higher doses (6 mg per day in patients weighing less than 51 kg; 12 mg per day in patients weighing 51 kg or more) did not demonstrate greater efficacy, while adverse events were dose-related.
• Efficacy was established with a 6-week trial in adolescent patients with schizophrenia.

Use: Treatment of schizophrenia

Renal Dose Adjustments

EXTENDED-RELEASE TABLETS:
Mild renal dysfunction (CrCl 50 mL/min to less than 80 mL/min): Initial dose: 3 mg orally once a day; may increase to a maximum of 6 mg orally once a day based on efficacy and tolerability.
Moderate to severe renal dysfunction (CrCl 10 mL/min to less than 50 mL/min): Initial dose: 1.5 mg orally once a day; may increase to a maximum of 3 mg orally once a day based on efficacy and tolerability.
CrCl less than 10 mL/min: Use not recommended

1-MONTH EXTENDED-RELEASE IM SUSPENSION:
Paliperidone palmitate:
Mild renal dysfunction (CrCl 50 to less than 80 mL/min):

• Initial dose: 156 mg IM on day 1 followed by 117 mg IM one week later; administer IM into deltoid muscle
• Maintenance dose: 78 mg IM monthly; administer IM into deltoid or gluteal muscle

Moderate to severe renal dysfunction (CrCl less than 50 mL/min): Use not recommended

Paliperidone base:
Mild renal dysfunction (CrCl 50 to less than 80 mL/min:

• Initial dose: 100 mg IM on day 1 followed by 75 mg IM one week later; administer IM into deltoid muscle
• Maintenance dose: 50 mg IM monthly, adjusted within the range of 25 to 100 mg based on individual efficacy and tolerability; administer IM into deltoid or gluteal muscle

Moderate to severe renal dysfunction (CrCl less than 50 mL/min): Use not recommended

3-MONTH EXTENDED-RELEASE IM SUSPENSION:
Mild renal dysfunction (CrCl 50 to less than 80 mL/min): Adjust dosage and stabilize patient using the 1-month extended-release suspension and then transition to 3-month suspension.
Moderate to severe renal dysfunction (CrCl less than 50 mL/min): Use not recommended

Liver Dose Adjustments

Mild to moderate hepatic impairment (Child-Pugh Class A and B): No dosage adjustments required
Severe hepatic impairment: Data not available

Dose Adjustments

Concomitant Administration with Strong CYP450 3A4/P-glycoprotein (P-gp) Inducers:
EXTENDED RELEASE TABLETS: May be necessary to increase the dose of paliperidone when coadministered with a strong inducer of both CYP450 3A4 and P-gp (e.g., carbamazepine, rifampin, St John's wort).
1-MONTH EXTENDED RELEASE IM SUSPENSION: Avoid use of strong CYP450 3A4/P-gp inducers and/or consider switching to oral extended-release tablets.
Paliperidone base and 3-MONTH EXTENDED-RELEASE IM SUSPENSION: When switching patients currently at steady-state on a long acting antipsychotic injection; initiate paliperidone extended-release injection at next scheduled injection; the 1-week initiation dosing regimen will not be necessary.

MISSED DOSES: 1-MONTH Extended-Release Suspension:

• Dosing window: Patients may receive second dose 4 days before or after the 1-week time point; third and subsequent doses may be given up to 7 days before or after monthly time point.

Missed INITIATION Doses:

• If second initiation dose is missed and it is less than 4 weeks since first injection: Administer 156 mg paliperidone palmitate OR 100 mg paliperidone base IM into deltoid muscle as soon as possible; maintenance dose should begin 5 weeks after the first injection.
• If second initiation dose is missed and it is 4 to 7 weeks from first injection: Administer 2 injections (156 mg paliperidone palmitate OR 100 mg paliperidone base), with the first as soon as possible and the second 1 week later, both IM into deltoid muscle, then resume normal monthly cycle.
• If second initiation dose is missed and it is more than 7 weeks from the first injection: Re-initiate initial dosing schedule.

Missed MAINTENANCE Doses:

• If less than 6 weeks have elapsed since last maintenance dose: Administer as soon as possible followed by injections at monthly intervals.
• If greater than 6 weeks but less than 6 months have elapsed since last monthly maintenance dose, and dose was less than 234 mg paliperidone palmitate OR 150 mg paliperidone base: Administer maintenance dose IM into deltoid muscle as soon as possible and repeat same dose IM into deltoid muscle 1 week later; then resume monthly dosing.
• If greater than 6 weeks but less than 6 months have elapsed since monthly maintenance dose of 234 mg paliperidone palmitate OR 150 mg paliperidone base: Administer 156 mg paliperidone palmitate OR 100 mg paliperidone base IM into deltoid muscle as soon as possible followed by the same dose IM into deltoid muscle one week later; then resume normal monthly cycle.
• If more than 6 months have elapsed since last maintenance injection: Re-initiate initial dosing schedule.

MISSED DOSES: 3-MONTH Extended-Release Suspension:
Dosing window: Up to 2 weeks before or after 3-month time point.

• If more than 3.5 months (up to but less than 4 months) have elapsed: Administer as soon as possible, then continue with the 3-month injections following this dose.
• If 4 months up to and including 9 months have elapsed: Re-initiation using the 1-month extended release suspension is necessary as follows:
• If the last dose of the 3-month suspension was 273 mg, give the 1-month extended release suspension at 78 mg IM into the deltoid muscle on Day 1 and Day 8, then 1 month after Day 8, resume 3-month extended-release suspension with 273 mg IM into deltoid or gluteal muscle
• If the last dose of the 3-month suspension was 410 mg, give the 1-month extended release suspension at 117 mg IM into the deltoid muscle on Day 1 and Day 8, then 1 month after Day 8, resume 3-month extended-release suspension with 410 mg IM into deltoid or gluteal muscle
• If the last dose of the 3-month suspension was 546 mg, give the 1-month extended release suspension at 156 mg IM into the deltoid muscle on Day 1 and Day 8, then 1 month after Day 8, resume 3-month extended-release suspension with 546 mg IM into deltoid or gluteal muscle
• If the last dose of the 3-month suspension was 819 mg, give the 1-month extended release suspension at 156 mg IM into the deltoid muscle on Day 1 and Day 8, then 1 month after Day 8, resume 3-month extended-release suspension with 819 mg IM into deltoid or gluteal muscle
• If more than 9 months have elapsed since last injection of the 3-month extended release suspension: Re-initiate with the 1-month extended release suspension; the 3-month extended-release suspension can be resumed after the patient has been adequately treated with the 1-month extended-release suspension for at least 4 months.

SWITCHING From 3-Month Extended-Release IM Suspension TO 1-Month Extended-Release IM Suspension:

• If the last dose of the 3-month extended-release suspension was 273 mg, after 3 months, switch to the 1-month extended-release suspension at 78 mg IM once a month
• If the last dose of the 3-month extended-release suspension was 410 mg, after 3 months, switch to the 1-month extended-release suspension at 117 mg IM once a month
• If the last dose of the 3-month extended-release suspension was 546 mg, after 3 months, switch to the 1-month extended-release suspension at 156 mg IM once a month
• If the last dose of the 3-month extended-release suspension was 819 mg, after 3 months, switch to the 1-month extended-release suspension at 234 mg IM once a month

SWITCHING From 3-Month Extended-Release IM Suspension TO Oral Paliperidone Extended-Release Tablets:

• If the last dose of the 3-month extended-release IM suspension was 273 mg, after 3 months start extended-release tablets at 3 mg orally once a day.
• If the last dose of the 3-month extended-release IM suspension was 410 mg, after 3 months start extended-release tablets at 3 mg orally once a day; at 24-weeks from last IM dose, increase oral dose to 6 mg once a day.
• If the last dose of the 3-month extended-release suspension was 546 mg, after 3 months start extended-release tablets at 3 mg orally once a day, at 18 weeks from last IM dose, increase oral dose to 6 mg orally once a day, at 24 weeks from last IM dose, increase oral dose to 9 mg orally once a day.
• If the last dose of the 3-month extended-release suspension was 819 mg, after 3 months start extended-release tablets at 6 mg orally once a day, at 18 weeks from last IM dose, increase oral dose to 9 mg orally once a day, at 24 weeks from last IM dose, increase oral dose to 12 mg orally once a day.

Precautions

US BOXED WARNINGS:
INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS:

• Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.
• Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients.
• Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group.
• Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature.
• Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality.
• The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear.
• This drug is not approved for the treatment of patients with dementia-related psychosis.

Safety and efficacy of the long-acting injection in patients younger than 18 years have not been established.

Safety and efficacy of paliperidone in patients younger than 12 years in the treatment of schizophrenia have not been established.

Safety and efficacy of paliperidone in patients younger than 18 years in the treatment of schizoaffective disorder have not been established.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration Advice:
Oral Extended Release Tablets:

• Swallow whole, do not chew, divide or crush.
• May take with or without food, however, it is best to always take with food or always without food; avoid alternating between the two.
• The tablet shell is eliminated from the body and patients should not be concerned if they see a tablet in their stool.

Extended-release injectable suspension:

• Should be administered by a health care professional by deep IM deltoid or gluteal injection using the appropriate enclosed safety needle; administer as a single injection.
• Inadvertent injection into a blood vessel should be avoided. Do not administer subcutaneously, intravascularly, or IV.
• Injections should be alternated between deltoid or gluteal muscles on the left and right sides of the body.
• The manufacturer product information should be consulted for the specific extended-release formulation; the 1-month and the 3-month formulations have formulation specific administration and preparation instructions.

Reconstitution/preparation techniques:
Extended-release injectable suspension:

• The syringe should be shaken for at least 15 second to homogenize the suspension.
• After shaking, the suspension should be injected within 5 minutes.

General:

• For patients who have missed a dose, see missed dose instructions in the dose adjustment section or consult manufacturer product information.
• Since paliperidone is the major active metabolite of risperidone, generally these agents should not be coadministered.
• Paliperidone palmitate is converted to paliperidone; this drug is a metabolite of risperidone.
• Controlled clinical trials assessing long-term use are not available; the physician who prescribes paliperidone for extended periods should periodically re-evaluate the long-term risks and benefits of the drug for the individual patient.
• No specific recommendations are available regarding switching from other antipsychotics or for the use of concomitant antipsychotics.
• This drug should not be used to manage acute agitation/severe psychotic states when immediate symptom control is needed.

Monitoring:

• Cardiovascular: Orthostatic vital signs in at-risk patients
• Hematologic: CBC frequently during the first few months in patients with preexisting low WBC and/or a prior history of drug-induced leukopenia or neutropenia
• Metabolic: Monitor for increases in blood sugar, weight, and lipids

Patient Advice:

• This drug may impair judgment, thinking, or motor skills; have patient avoid driving or operating machinery until adverse effects are determined.
• Advise patient to speak to physician or health care professional if pregnant, intend to become pregnant, or are breastfeeding.
• Advise patient that this drug may cause metabolic changes such as increases in blood sugar, body weight and lipids.
• Advise patients to avoid overheating and dehydration.
• Patients should be informed of the possibility of priapism, hyperprolactinemia, neuroleptic malignant syndrome, and tardive dyskinesia, and what to do if symptoms occur.

• Patients, families, and caregivers should be educated on the risks of suicidal thoughts and behaviors, as well as the risk of mania and hypomania; what to watch for and when to seek medical advice.
• This drug may impair judgment, thinking, or motor skills; have patient avoid driving or operating machinery until adverse effects are determined.
• Advise patient to speak to physician or health care professional if pregnant, intend to become pregnant, or are breastfeeding.
• Advise patient that this drug may cause metabolic changes such as increases in blood sugar, body weight and lipids.
• Patients should avoid overheating and dehydration.
• Patients should speak with their healthcare provider if they are taking, or plan to take any new prescription or over the counter medications because there is a potential for drug interactions; patients should be advised to avoid alcohol as it may make some side effects worse.

Frequently asked questions

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