Dosing & Uses
Dosage Forms & Strengths
tablet, extended release
- 1.5mg
- 3mg
- 6mg
- 9mg
IM injectable suspension prefilled syringe (once monthly, Invega Sustenna)
- 39mg
- 78mg
- 117mg
- 156mg
- 234mg
IM injectable suspension prefilled syringe (q3month, Invega Trinza)
- 273mg
- 410mg
- 546mg
- 819mg
Schizophrenia
PO
- 6 mg PO qAM; may be titrated upward or downward in increments of 3 mg/day at intervals ≥5 days; not to exceed 12 mg/day
IM, sustained-released 1-month (Invega Sustenna)
- 234 mg in deltoid on treatment day 1, then 156 mg 1 week later (day 8)
- Recommended maintenance dose is 117 mg IM once monthly, although some patients may require lower or higher dosages (monthly dose range 39-234 mg)
IM, sustained-released 3-months (Invega Trinza)
- Patients must be adequately treated with Invega Sustenna (1-month paliperidone) for at least 4 months before initiating Invega Trinza
- Dose initiation dependent on once-monthly Invega Sustenna dose
- Initiate Invega Trinza when the next 1-month paliperidone dose is scheduled with an Invega Trinza dose based on the previous 1-month injection dose (see below)
- Conversion from monthly injection to 3-month injection
- Invega Sustenna 78 mg/month: Initiate Invega Trinza at 273 mg IM q3mo
- Invega Sustenna 117 mg/month: Initiate Invega Trinza at 410 mg IM q3mo
- Invega Sustenna 156 mg/month: Initiate Invega Trinza at 546 mg IM q3mo
- Invega Sustenna 234 mg/month: Initiate Invega Trinza at 819 mg IM q3mo
- Conversoin from 3-month IM injection to extended-release tablets
- 273 mg IM (last 3 months to 24wk): 3 mg ER tab
- 410 mg IM (last 3 months to 24wk): 3 mg ER tab; 6 mg if >24wk
- 546 mg IM (last 3 months to 18 wk): 3 mg ER tab; 6 mg if 18-24 wk; 9 mg if >24 wk
- 819 mg IM (last 3 months to 18 wk): 6 mg ER tab; 9 mg if 18-24 wk; 12 mg if >24 wk
Schizoaffective Disorder
Indicated for schizoaffective disorder as monotherapy and as an adjunct to mood stabilizers or antidepressants
6 mg PO qDay in am (range 3-12 mg); titration may not be necessary; if exceeding 6 mg/day, increases of 3 mg/day recommended at intervals of 4 days of more; not to exceed 12 mg/day
IM (initial): 234 mg in deltoid on treatment day 1, then 156 mg 1 week later (day 8)
IM (maintenance): Administer once each month IM in deltoid or gluteal muscle; adjust dose based on tolerability and/or efficacy using available strengths; maintenance dose ranges between 78-234 mg once monthly
Dosing Modifications
Renal impairment, PO
- CrCl 50-79 mL/min: 3 mg/day initially; not to exceed 6 mg/day
- CrCl 10-49 mL/min: 1.5 mg/day initially; not to exceed 3 mg/day
- CrCl <10 mL/min: Not recommended
Renal impairment, IM
- Moderate-to-severe (CrCl <50 mL/min): Not recommended
- Mild (CrCl 50-79 mL/min)
- Invega Sustenna: 156 mg IM in deltoid on treatment day 1, then 117 mg 1 week later; maintenance: 78 mg IM monthly
- Invega Trinza: Adjust dosage and stabilize the patient using the 1-month paliperidone palmitate extended-release injectable suspension (Invega Sustenna), then transition to Invega Trinza
Dosage Forms & Strengths
tablet, extended-release
- 1.5mg
- 3mg
- 6mg
- 9mg
Schizophrenia
<12 years: Safety and efficacy not established
≥12 years (<51 kg): 3 mg/day PO initially; may be increased if necessary in increments of 3 mg/day at intervals ≥5 days; not to exceed 6 mg/day
≥12 years (≥51 kg): 3 mg/day PO initially; may be increased if necessary in increments of 3 mg/day at intervals ≥5 days; not to exceed 12 mg/day
Schizoaffective Disorder
<18 years: Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>10%
Akathisia
Somnolence
Insomnia
Parkinsonism
Tachycardia
Hyperprolactinemia
Others similar to placebo (eg, headache)
<10% (selected)
Cough
Dystonia
Extrapyramidal symptoms (EPS)
Orthostatic hypotension
QT prolongation
Sialorrhea
Priapism
Weight gain
Constipation
Indigestion
Amenorrhea
Galactorrhea
Nausea
Dyspepsia
Salivation
Xerostomia
Myalgia
Extremity pain
Nasopharyngitis
Postmarketing Reports
Angioedema, swollen tongue
Ileus
Thrombotic thrombocytopenic purpura
Urinary incontinence, urinary retention
Falls
Warnings
Black Box Warnings
Not approved for dementia-related psychosis; patients with dementia-related psychosis who are treated with antipsychotic drugs are at increased risk of death, as shown in short-term controlled trials; deaths in these trials appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature
Contraindications
Documented hypersensitivity to paliperidone or risperidone
Cautions
Avoid use in severe preexisting GI stenosis
Avoid overheating and dehydration, medications with anticholinergic side effects being taken concomitantly, and strenuous exercise; impaired core body temperature regulation may occur
Rare cases of priapism reported
Rare cases of intraoperative floppy iris syndrome reported with risperidone in patients undergoing cataract surgery; paliperidone is active metabolite of risperidone; use caution; benefits or risks of interrupting paliperidone or risperidone use prior to cataract surgery not established
If tardive dyskinesia develops discontinue drug if clinically appropriate
Hyperprolactinemia occurs and persists during long-term administration
Prolongs QT interval modestly; avoid use with drugs that also increase QT interval and in patients with risk factors for prolonged QT interval
Potential risk of neuroleptic malignant syndrome (NMS); manage with immediate discontinuation of drug and close monitoring
Risk of orthostatic hypotension; use with caution in patients with known cardiovascular or cerebrovascular disease and patients predisposed to hypotension
Increased incidence of cerebrovascular adverse reactions (e.g. stroke, transient ischemic attack, including fatalities) reported
Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold
Patients with Parkinson disease may be more sensitive to CNS and extrapyramidal effects
May mask toxicity of other drugs or conditions (eg, intestinal obstruction) due to antiemetic effects
FDA warning regarding off-label use for dementia in elderly
Leukopenia/neutropenia and agranulocytosis reported; possible risk factors for leukopenia/neutropenia include preexisting low white blood cell (WBC) count and history of drug-induced leukopenia/neutropenia
If history of clinically significant low WBC count or drug-induced leukopenia/neutropenia, monitor complete blood count (CBC) frequently during first few months of therapy; discontinue drug at first sign of clinically significant WBC decline <1000/μL in absence of other causative factors, and continue monitoring WBC until recovery
May cause CNS depression, which may impair abilities to perform tasks requiring mental alertness, including operating heavy machinery
Motor instability, somnolence, and orthostatic hypotension reported, which may lead to falls and, consequently, fractures or other fall-related injuries; assess risk of falls when initiating treatment and recurrently for patients receiving repeated doses, particularly the elderly, with diseases, conditions, or medications that could exacerbate these effects
Antipsychotic use has been associated with esophageal dysmotility and aspiration; use with caution in patients at risk of aspiration pneumonia; not for use in patients unable to swallow the tablet whole
Use caution in patients with history of suicidal ideation or any form of psychotic illnes; may increase risk of suicide attempt
Metabolic changes
- Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular or cerebrovascular risk (eg, hyperglycemia, dyslipidemia, hyperprolactinemia, body weight gain)
- In some cases, hyperglycemia concomitant with use of atypical antipsychotics has been associated with ketoacidosis, hyperosmolar coma, or death
Pregnancy & Lactation
Pregnancy
There are no adequate and well controlled studies in pregnant women; use of first generation antipsychotic drugs during last trimester of pregnancy associated with extrapyramidal symptoms in neonate; symptoms are usually self-limited; not known whether paliperidone, when taken near end of pregnancy, will lead to similar neonatal signs and symptoms; in animal reproduction studies, there were no increases in fetal abnormalities when pregnant rats and rabbits were treated during the period of organogenesis with up to 8 times the maximum recommended human dose of paliperidone (on a mg/m² basis); in rat reproduction studies with risperidone, which is extensively converted to paliperidone in rats and humans, there were increases in pup deaths seen at oral doses which are less than maximum recommended human dose of risperidone on a mg/m² basis
Infertility
- Based on pharmacologic action of paliperidone (D2 receptor antagonism), treatment may result in an increase in serum prolactin levels, which may lead to a reversible reduction in fertility in females of reproductive potential
Lactation
Limited data from published literature report presence of paliperidone in human breast milk; there is no information on effects on breastfed infant, or on milk production; however, there are reports of sedation, failure to thrive, jitteriness, and extrapyramidal symptoms (tremors and abnormal muscle movements) in breastfed infants exposed to paliperidone’s parent compound, risperidone; consider developmental and health benefits of breastfeeding along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from drug or from mother’s underlying condition
Infants exposed to treatment through breastmilk should be monitored for excess sedation, failure to thrive, jitteriness, and extrapyramidal symptoms (tremors and abnormal muscle movements)
Pregnancy Categories
A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA:Information not available.
Pharmacology
Mechanism of Action
Major metabolite of risperidone; improves negative symptoms of psychoses and reduces incidence of EPS
Has high affinity for serotonin type 2 (5-HT2) receptors; binds to dopamine D2 receptors with 20 times lower affinity than that for 5-HT2 receptors; antagonizes alpha1-adrenergic, alpha2-adrenergic, and histaminergic receptors; has moderate affinity for serotonin type 1 (5-HT1C, 5-HT1D, 5-HT1A) receptors; has weak affinity for dopamine D1 receptors; has no affinity for muscarinic, beta1-adrenergic, and beta2-adrenergic receptors
Absorption
Bioavailability: 28%
Peak plasma time: PO, 24 hr; IM, 13 days
Distribution
Protein bound: 74%
Vd: 390-487 L
Metabolism
Metabolized by CYP2D6 and CYP3A4
Elimination
Half-life: PO, 23 hr; IM, 25-49 days
Excretion: Urine (80%), feces (11%)
Administration
Oral administration
May be taken with or without food
Swallow tablet whole with liquids; do not chew, crush or divide
The tablet shell, along with insoluble core components, is eliminated from the body; patients should not be concerned if they occasionally notice in their stool, something that looks like a tablet
IM administration
Each IM injection must be administered only by a healthcare professional
Prior to administration, shake the prefilled syringe vigorously for at least 15 seconds within 5 minutes prior to administration to ensure a homogeneous suspension
Once monthly IM injection
- Before initiating once monthly IM therapy, establish PO tolerability with paliperidone or risperidone
- First 2 doses are injected into deltoid; maintenance doses may be injected into either deltoid or gluteal muscle
Every 3-months IM administration
- Before initiating q3mo IM therapy, establish tolerability with once-monthly paliperidone for at least 4 months
- Initiate Invega Trinza when the next 1-month paliperidone dose is scheduled with an Invega Trinza dose based on the previous 1-month injection dose (see Adult Dosing)
Needle length and gauge
- Deltoid injection: If patient ≥90 kg, use 1.5-in. 22-gauge needle; if patient <90 kg, use 1-in. 23-gauge needle
- Gluteal injection: Use 1.5-in. 22-gauge needle regardless of patient weight
Missed Doses
Invega Sustenna
- Second dose
- To avoid a missed dose, patients may be given the second dose 4 days before or after the one-week time point
- <4 wk since first injection: Administer second initiation dose of 156 mg IM in deltoid muscle as soon as possible, then administer a third injection of 117 mg IM (deltoid or gluteal) 5 weeks afterwards; thereafter resume regular monthly dosing
- 4-7 wk since first injection: Resume dose with 2 injections of 156 mg IM in deltoid muscle 1 week apart; thereafter, resume regular monthly dosing
- >7 wk since first injection: Restart with recommended initiation (see Adult Dosing)
- Third and subsequent doses
- To avoid a missed dose, patients may be give the injection 7 days before or after the monthly time point
- 4-6 wk since last injection: Resume regular monthly dosing as soon as possible at previous stabilized dose; followed in monthly injections
- >6 wk to 6 months since last injection: Resume same dose as previously stabilized, unless stabilized on 234 mg/month, then the first 2 injections should each be 156 mg given 1 wk apart; thereafter, resume previously stabilized dose 1 month later
- >6 months since last injection: Administer 234 mg IM in deltoid on Day 1, then 156 mg IM in deltoid on Day 8; thereafter, resume administration 1 month after Day 8 at the previously stabilized dose (deltoid or gluteal)
Invega Trinza
- If necessary, patients may be given the injection up to 2 weeks before or after the 3-month time point
- Missed dose >9 months since last injection: Must reinitiate with the 1-month paliperidone as previously described (see Adult Dosing)
- Missed dose 3.5-4 months since last injection: Administer the patient’s regular dose as soon as possible, then continue with the 3-month injection following this dose
- Missed dose 4-9 months since last injection: Do not administer the next dose, instead use reinitiation schedule
- Reinitiation schedule based on last dose of Invega Trinza
- Administer Invega Sustenna, 2 doses given 1 week apart into deltoid muscle (ie, Day 1 and Day 8), then administer Invega Trinza 1 month after Day 8 (in deltoid or gluteal muscle)
- Last dose 273 mg: Invega Sustenna 78 mg IM on Days 1 and 8, then Invega Trinza 273 mg IM 1 month after Day 8
- Last dose 410 mg: Invega Sustenna 117 mg IM on Days 1 and 8, then Invega Trinza 410 mg IM 1 month after Day 8
- Last dose 546 mg: Invega Sustenna 156 mg IM on Days 1 and 8, then Invega Trinza 546 mg IM 1 month after Day 8
- Last dose 819 mg: Invega Sustenna 156 mg IM on Days 1 and 8, then Invega Trinza 819 mg IM 1 month after Day 8
Storage
IM: Store at room temperature 20-25°C (68-77°F); excursions between 15-30°C (59-86°F) are permitted
Images
Patient Handout
Formulary
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