Paliperidone

Paliperidone is a prescription medication used to treat Schizophrenia and Schizoaffective Disorder.

• Paliperidone is available under the following different brand names: Invega, Invega Sustenna, Invega Trinza, Invega Hafyera

Adult and pediatric dosage

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 (every 3rd month, Invega Trinza)

• 273mg
• 410mg
• 546mg
• 819mg

IM injectable suspension prefilled syringe (every 6th month, Invega Hafyera)

• 1,092mg/3.5mL
• 1,560mg/5mL

Schizophrenia

Adult dosage

Orally 

• 6 mg orally in the morning; may be titrated upward or downward in increments of 3 mg/day at intervals over 5 days; not to exceed 12 mg/day

IM, extended-release 1-month (Invega Sustenna)

• 234 mg in deltoid on treatment day 1, then 156 mg 1 week later (day 8)
• The recommended maintenance dose is 117 mg IM once monthly, although some patients may require lower or higher dosages (month dose range 39-234 mg)

IM, extended-release 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 every 3 months
  • Invega Sustenna 117 mg/month: Initiate Invega Trinza at 410 mg IM every 3 months
  • Invega Sustenna 156 mg/month: Initiate Invega Trinza at 546 mg IM every 3 months 
  • Invega Sustenna 234 mg/month: Initiate Invega Trinza at 819 mg IM every 3 months
• Conversion from 3-month IM injection to extended-release tablets
  • 273 mg IM (last 3 months to 24 weeks): 3 mg ER tab
  • 410 mg IM (last 3 months to 24 weeks): 3 mg ER tab; 6 mg if over 24 weeks
  • 546 mg IM (last 3 months to 18 weeks): 3 mg ER tab; 6 mg if 18-24 weeks; 9 mg if over 24 weeks
  • 819 mg IM (last 3 months to 18 weeks): 6 mg ER tab; 9 mg if 18-24 weeks; 12 mg if over 24 weeks

IM, extended-release 6-months (Invega Hafyera)

• Patients must be adequately treated with Invega Sustenna (1-month paliperidone) for at least 4 months OR with Invega Trinza (3-month paliperidone) for at least one 3-month cycle before initiating Invega Hafyera
• Conversion from monthly injection to 6-month injection
  • Initiate Invega Hafyera when the next Invega Sustenna dose is scheduled
  • Invega Sustenna 156 mg/month: Initiate Invega Hafyera at 1,092 mg IM every 6 months
  • Invega Sustenna 234 mg/month: Initiate Invega Hafyera at 1,560 mg IM every 6 months
  • There are no equivalent doses of Invega Hafyera for Invega Sustenna 39-mg, 78-mg, or 117-mg doses, which were not studied
• Conversion from 3-month injection to 6-month injection
  • Initial Invega Hafyera dose is based on the previous Invega Trinza
  • Initiate Invega Hafyera when the next Invega Trinza dose is scheduled
  • May administer Invega Hafyera dose up to 2 weeks before or after the next scheduled Invega Trinza
  • Invega Trinza 546 mg every 3 months: Initiate Invega Hafyera at 1,092 mg IM every 6 months
  • Invega Trinza 819 mg every 3 months: Initiate Invega Hafyera at 1,560 mg IM every 6 months
  • There are no equivalent doses of Invega Hafyera for Invega Trinza 273-mg or 410-mg doses, which were not studied
• Dosing interval and dosage adjustments
  • Following the initial dose, administer Invega Hafyera IM every 6 months
  • May adjust dosage every 6 months between 1,092 mg and 1,560 mg based on individual response and tolerability, if necessary
  • Owing to the potential longer duration to Invega Hafyera, the patient’s response to an adjusted dose may not be apparent for several months

Pediatric dosage

• Children younger than 12 years of age: Safety and efficacy not established
• Children 12 years or older, weighing less than 51 kg: 3 mg/day orally initially; may be increased if necessary in increments of 3 mg/day at intervals at day 5 or later; not to exceed 6 mg/day
• Children 12 years or older, weighing over 51 kg: 3 mg/day orally initially; may be increased if necessary in increments of 3 mg/day at intervals at day 5 or later; not to exceed 12 mg/day

Schizoaffective Disorder

Adult dosage

• Indicated for the schizoaffective disorder as monotherapy and as an adjunct to mood stabilizers or antidepressants
• 6 mg orally once daily in the morning (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 or 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 the deltoid or gluteal muscle; adjust dose based on tolerability and/or efficacy using available strengths; maintenance dose ranges between 78-234 mg once monthly

Pediatric dosage

• Children younger than 18 years of age: Safety and efficacy not established

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”.

Common side effects of Paliperidone include:

• drowsiness, 
• anxiety, 
• muscle stiffness, 
• tremors or shaking, 
• uncontrolled muscle movements, 
• the trouble with walking, balance, or speech, 
• weight gain, 
• upset stomach, 
• constipation, 
• fast heart rate, 
• stuffy nose, and 
• sore throat

Serious side effects of Paliperidone include:

• hives, 
• difficulty breathing, 
• swelling of the face, lips, tongue, or throat, 
• tremors or shaking in arms or legs, 
• uncontrolled muscle movements in the face (chewing, lip-smacking, frowning, tongue movement, blinking or eye movement), 
• any new or unusual muscle movements that cannot be controlled, 
• fast or pounding heartbeats, 
• fluttering in the chest, 
• shortness of breath, 
• sudden dizziness, 
• breast swelling (in men or women), 
• nipple discharge, 
• changes in menstrual periods, 
• impotence, 
• penis erection that is painful or lasts 4 hours or longer, 
• weight gain, 
• fever, 
• chills, 
• mouth sores, 
• skin sores, 
• sore throat, 
• cough, 
• increased thirst,
• increased urination, 
• hunger, 
• fruity breath odor, 
• very stiff (rigid) muscles, 
• high fever, and
• fainting

Rare side effects of Paliperidone include:

• none 

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them.  Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first

• Paliperidone has severe interactions with the following drugs:
  • goserelin
  • leuprolide
• Paliperidone has serious interactions with at least 74 other drugs.
• Paliperidone has moderate interactions with at least 372 other drugs.
• Paliperidone has minor interactions with the following drugs:
  • azithromycin
  • brimonidine
  • chasteberry
  • ethanol
  • eucalyptus
  • nefazodone
  • pazopanib
  • sage

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drugs interactions. Therefore, before using this drug, tell your doctor or pharmacist of all the drugs you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Contraindications

• Documented hypersensitivity to paliperidone or risperidone

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Paliperidone?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Paliperidone?”

Cautions

• Increased incidence of cerebrovascular adverse reactions (eg, stroke, transient ischemic attack, including fatalities) reported
• Neuroleptic malignant syndrome (NMS) reported in association with antipsychotic drugs; if NMS is suspected, discontinue treatment and provide symptomatic treatment and monitoring
• May induce orthostatic hypotension; use with caution in patients with known cardiovascular or cerebrovascular disease and patients predisposed to hypotension
• Motor instability, somnolence, and orthostatic hypotension reported, which may lead to falls and, consequently, fractures or other fall-related injuries; assess the 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
• Hyperprolactinemia reported; may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotropin secretion and gonadal steroidogenesis in female and male patients; galactorrhea, amenorrhea, gynecomastia, and impotence reported; long-standing hyperprolactinemia, when associated with hypogonadism, may lead to decreased bone density in both female and male subjects
• May cause CNS depression (somnolence, sedation, dizziness), which may impair abilities to perform tasks requiring mental alertness, including operating heavy machinery
• Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold
• Antipsychotic use has been associated with esophageal dysmotility and aspiration; use with caution in patients at risk of aspiration pneumonia
• Rare cases of priapism reported
• Use caution when prescribing to patients who will be experiencing conditions that may contribute to an elevation in core body temperature (eg, exercising strenuously, extreme heat exposure, concomitant medication with anticholinergic activity, dehydration)
• Avoid use in severe preexisting GI stenosis
• Rare cases of intraoperative floppy iris syndrome reported with risperidone in patients undergoing cataract surgery; paliperidone is the active metabolite of risperidone; use caution; benefits or risks of interrupting paliperidone or risperidone use before cataract surgery not established
• 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
• May increase risk of death in elderly patients with dementia-related psychosis
• Use caution in patients with a history of suicidal ideation or any form of psychotic illness; may increase the risk of suicide attempt
• Certain circumstances may increase the risk of the occurrence of Torsades de pointes and/or sudden death in association with the use of drugs that prolong the QTc interval, including bradycardia; hypokalemia or hypomagnesemia; concomitant use of other drugs that prolong the QTc interval; and presence of congenital prolongation of the QT interval
• The patient should see a healthcare provider or go to the nearest emergency room right away if the erection lasts more than 4 hr

Tardive dyskinesia

• Tardive dyskinesia may develop
• The risk of developing tardive dyskinesia and the likelihood that it will become irreversible appears to increase with the duration of treatment and cumulative dose; the syndrome may develop after relatively brief treatment periods or after discontinuing treatment
• May remit, partially or completely, if treatment is withdrawn; antipsychotic treatment may suppress (or partially suppress) signs and symptoms of the syndrome and thereby possibly mask the underlying process
• Reserve chronic antipsychotic treatment for patients who suffer from a chronic illness known to respond to antipsychotic drugs, and for whom alternatives are not available or appropriate
• In patients who require chronic treatment, use the lowest dose and the shortest duration of treatment producing a satisfactory clinical response; periodically reassess the need for continued treatment

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)
• Hyperglycemia and diabetes mellitus (DM), in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has also been reported
• Regularly monitor patients diagnosed with DM who started an atypical antipsychotic for worsening of glucose control
• Patients with risk factors for DM (eg, obesity, family history of diabetes) who are starting treatment should undergo fasting blood glucose testing upon initiation and periodically during treatment
• Monitor any patient treated with atypical antipsychotics for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness

Leukopenia, neutropenia, and agranulocytosis

• Leukopenia/neutropenia and agranulocytosis reported
• Possible risk factors for leukopenia/neutropenia include preexisting low white blood cell (WBC) count and a history of drug-induced leukopenia/neutropenia
• Monitor patients with clinically significant neutropenia for fever or other symptoms or signs of infection and treat promptly if such symptoms or signs occur
• If the history of clinically significant low WBC count or drug-induced leukopenia/neutropenia, monitor complete blood cell count (CBC) frequently during the first few months of therapy; discontinue if WBC decline more than 1000/ mm3 and continue monitoring WBC until recovery

Drug interaction overview

• The substrate of P-gp and CYP3A4
• Centrally-acting drugs and alcohol
  • Use with caution
  • Centrally-acting drugs and alcohol may modulate the CNS effects of paliperidone
• Drugs that cause orthostatic hypotension
  • Monitor orthostatic vital signs in patients who are vulnerable to hypertension
  • Drugs that induce orthostatic hypotension may enhance the orthostatic hypotensive effects of paliperidone
• Strong CYP3A4 and P-gp inducers (Invega Hafyera only)
  • Avoid coadministration of CYP3A4 and/or P-gp inducers
  • If a strong inducer is necessary, consider using paliperidone extended-release tablets
• Levodopa and other dopamine agonists
  • Monitor and manage appropriately
  • Paliperidone may antagonize the effect of levodopa and other dopamine agonists
• Drugs that prolong QT interval
  • Avoid coadministration with other drugs that are known to prolong QTc including Class 1A (eg, quinidine, procainamide) or Class III (eg, amiodarone, sotalol) antiarrhythmic medications, antipsychotic medications (eg, chlorpromazine, thioridazine), fluoroquinolones (eg, moxifloxacin), or any other class of medications known to prolong the QTc interval
  • Paliperidone may enhance the QT-prolonging effects of such drugs

Pregnancy and Lactation

• Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery
• Available data of pregnant females exposed to paliperidone have not 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 the 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 the breastfed infant or milk production
• Sedation, failure to thrive, jitteriness, and extrapyramidal symptoms (tremors and abnormal muscle movements) were 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)