established a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes Drug detected in plasma in adults up to 18 months after a single 3-month paliperidone injection; clinical significance administered before pregnancy or anytime during pregnancy is unknown Pregnancy exposure registry Monitors pregnancy outcomes in females exposed to atypical antipsychotics during pregnancy Register patients by contacting the National Pregnancy Registry for atypical antipsychotics at 1-866-961-2388 or online at http://womensmentalhealth.org/clinical-andresearch-programs/pregnancyregistry/ Clinical considerations There are risks to the mother associated with untreated schizophrenia and with exposure to antipsychotics during pregnancy Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs; monitor for extrapyramidal and/or withdrawal symptoms and manage appropriately 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 Sedation, failure to thrive, jitteriness, and extrapyramidal symptoms (tremors and abnormal muscle movements) reported in breastfed infants exposed to risperidone (parent compound of paliperidone) Monitor infants exposed to treatment through breast milk 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. Mechanism of Action Paliperidone palmitate is hydrolyzed to paliperidone, a major active metabolite of risperidone Mechanism of action of paliperidone is unclear However, its efficacy in the treatment of schizophrenia could be mediated through a combination of central dopamine D2 and serotonin 5HT2A receptor antagonism Absorption Bioavailability: 28% Peak plasma time PO: 24 hr Invega Sustenna: 13 days Invega Trinza: 30-33 days Invega Hafyera: 29-32 days; release profile and dosing regimen results in sustained concentrations over 6 months Distribution Protein bound: 74% (racemic paliperidone) Vd PO: 487 L Invega Sustenna: 391 L Invega Trinza and Hafyera: 1,960 L Metabolism Metabolized by CYP2D6 and CYP3A4 Elimination Excretion PO: Urine (80%), feces (11%) Half-life PO: 23 hr Invega Sustenna: 25-49 days Invega Trinza: 118-139 days Invega Hafyera: 148 days (1,092-mg dose); 159 days (1,560-mg dose) 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 Avoid alcohol during treatment IM Preparation Invega Sustenna or Trinza: Shake prefilled syringe vigorously for at least 15 seconds within 5 minutes before administration to ensure a homogeneous suspension Invega Hafyera: Shake syringe with the syringe tip cap pointing up VERY FAST for at least 15 seconds, rest briefly, then shake again for 15 seconds; do not divide dose into multiple injections IM administration Administer only by a healthcare professional Visually inspect syringe for foreign matter and discoloration prior to administration, whenever product and container permit Do not mix with any other product or diluent Avoid inadvertent injection into a blood vessel Administer dose in a single injection; do not administer the dose in divided injections Inject slowly, deep into the upper-outer quadrant of the gluteal muscle Future injections should be alternated between the two gluteal muscles 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 Invega Hafyera Do not use needles from Invega Sustenna or Trinza or other commercially-available needles to reduce the risk of blockage 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 Every 6-months IM administration Before initiating q6mo IM therapy, establish tolerability with once-monthly paliperidone for at least 4 months May administer Invega Hafyera dose up to 1 week before or after the next scheduled Invega Sustenna Ensure the 2 injection cycles preceding the switch should be the same dosage strength before starting Invega Hafyera Incomplete administration Proper shaking can reduce likelihood for an incomplete injection Storing carton in a horizontal orientation improves the ability to resuspend this highly concentrated product In the event of an incompletely administered dose, do not reinject the dose remaining in the syringe and do not administer another Invega Hafyera Closely monitor and treat with oral paliperidone supplementation as clinically appropriate until the next scheduled Invega Hafyera See prescribing information of the oral paliperidone product for the recommended dosage of these products Missed Doses Invega Sustenna Second dose To avoid a missed dose, may give 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 Third and subsequent doses To avoid a missed dose, may give 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 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 Invega Hafyera To avoid a missed dose, may give injection up to 2 weeks before or 3 weeks after scheduled 6-mo dose Missed dose >6 mo and 3 weeks to <8 mo since last injection Do not administer next Invega Hafyera dose Last dose 1,092 mg: Administer Invega Sustenna 156 mg IM into deltoid muscle on Day 1; 1 month after Day 1, administer Invega Hafyera 1,092 mg IM into gluteal muscle Last dose 1,560 mg: Administer Invega Sustenna 234 mg IM into deltoid muscle on Day 1; 1 month after Day 1, administer Invega Hafyera 1,560 mg IM into gluteal muscle Missed dose >8 mo to ≤11 mo since last injection Do not administer next Invega Hafyera dose Last dose 1,092 mg: Invega Sustenna 156 mg IM on Days 1 and 8, then Invega Hafyera 1,092 mg IM 1 month after Day 8 Last dose 1,560 mg: Invega Sustenna 156 mg IM on Days 1 and 8, then Invega Hafyera 1,560 mg IM 1 month after Day 8 Missed dose >11 mo since last injection Reinitiate treatment with Invega Sustenna as described in its prescribing information Resume Invega Hafyera after patient has been adequately treated with Invega Sustenna for at least 4 months Storage Tablets Store up to 25ºC (77ºF); excursions permitted to 15-30ºC (59-86ºF) Protect from moisture Keep out of reach of children IM Store at room temperature 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF) are permitted Do not mix with any other product or diluent Ship and store in a horizontal position; see arrows on product carton for proper orientation BRAND FORM. UNIT PRICE PILL IMAGE Invega oral- 1.5 mg tabletInvega oral- 9 mg tabletInvega oral- 6 mg tabletInvega oral- 3 mg tabletpaliperidone oral- 9 mg tabletpaliperidone oral- 1.5 mg tabletpaliperidone oral- 3 mg tabletpaliperidone oral- 3 mg tabletpaliperidone oral- 6 mg tabletpaliperidone oral- 3 mg tabletpaliperidone oral- 1.5 mg tabletpaliperidone oral- 9 mg tabletpaliperidone oral- 6 mg tabletpaliperidone oral- 3 mg tabletpaliperidone oral- 9 mg tabletpaliperidone oral- 1.5 mg tabletpaliperidone oral- 6 mg tabletpaliperidone oral- 1.5 mg tabletpaliperidone oral- 9 mg tabletpaliperidone oral- 6 mg tabletpaliperidone oral- 3 mg tabletpaliperidone oral- 1.5 mg tabletCopyright © 2010 First DataBank, Inc.Print Patient Educationpaliperidone oral PALIPERIDONE EXTENDED-RELEASE - ORAL (PAL-ee-PER-i-done) COMMON BRAND NAME(S): Invega WARNING: There may be a slightly increased risk of serious, possibly fatal side effects (such as stroke, heart failure, fast/irregular heartbeat, pneumonia) when this medication is used by older adults with dementia. This medication is not approved for the treatment of dementia-related behavior problems. Discuss the risks and benefits of this medication, as well as other effective and possibly safer treatments for dementia-related behavior problems, with the doctor.If you are using paliperidone in combination with other medication to treat depression, also carefully read the drug information for the other medication. USES: This medication is used to treat certain mental/mood disorders (such as schizophrenia, schizoaffective disorder). This medication can decrease hallucinations and help you to think more clearly and positively about yourself, feel less agitated, and take a more active part in everyday life.Paliperidone belongs to a class of drugs called atypical antipsychotics. It works by helping to restore the balance of certain natural substances in the brain. HOW TO USE: Take this medication by mouth with or without food as directed by your doctor, usually once daily. Swallow the tablets whole with liquid. Do not crush or chew the tablets. Doing so can release all of the drug at once, increasing the risk of side effects.The dosage is based on your age, medical condition, and response to treatment.Take this medication regularly to get the most benefit from it. To help you remember, take it at the same time each day. Keep taking this medication even if you feel well. Do not stop taking this medication without consulting your doctor.Tell your doctor if your condition lasts or gets worse. SIDE EFFECTS: Drowsiness, dizziness, lightheadedness, drooling, stomach/abdominal pain, weight gain, or tiredness may occur. If any of these effects last or get worse, tell your doctor promptly.Dizziness and lightheadedness can increase the risk of falling. Get up slowly when rising from