paliperidone

(redirected from paliperidone palmitate)

paliperidone

Invega

paliperidone palmitate

Invega Sustenna

Pharmacologic class: Benzisoxazole derivative

Therapeutic class: Antipsychotic

Pregnancy risk category C

FDA Box Warning

• Elderly patients with dementia-related psychosis are at increased risk for death. Over course of 10-week controlled trial, death rate in drug-treated patients was about 4.5%, compared to about 2.6% in placebo group. Although causes of death varied, most appeared to be cardiovascular or infectious. Don't give drug to patients with dementia-related psychosis.

Action

Unknown. In schizophrenia, therapeutic activity may be mediated through combination of central serotonin2-and dopamine2-receptor antagonism. Drug is a major active metabolite of risperidone.

Availability

Injection (paliperidone palmitate): 39 mg, 78 mg, 117 mg, 156 mg, 234 mg in prefilled syringes

Tablets (extended-release): 1.5 mg, 3 mg, 6 mg, 9 mg

Indications and dosages

Schizophrenia

Adults: 6 mg P.O. once daily. Some patients may benefit from daily dosages as high as 12 mg or as low as 3 mg. If indicated, increase in increments of 3 mg/day at intervals of more than 5 days. Or initially, 234 mg I.M. (paliperidone palmitate) on treatment day 1 and 156 mg I.M. 1 week later. Recommended monthly maintenance dose is 117 mg; some patients may benefit from lower or higher maintenance doses within recommended range of 39 to 234 mg. Adjustment of maintenance dosage may be made monthly. When making dosage adjustments, consider paliperidone palmitate's prolonged-release characteristics, as the full effect of the dosage adjustment may not be evident for several months.

Adolescents ages 12 to 17 weighing 51 kg (112 lb) or more: 3 mg P.O. daily; increase dosage, if necessary, only after clinical reassessment at increments of 3 mg/day at intervals of more than 5 days up to a maximum of 12 mg/day.

Adolescents ages 12 to 17 weighing less than 51 kg (112 lb): 3 mg P.O. daily; increase dosage, if necessary, only after clinical reassessment at increments of 3 mg/day at intervals of more than 5 days up to a maximum of 6 mg/day.

Schizoaffective disorder

Adults: 6 mg P.O. once daily. Some patients may benefit from dosages as high as 12 mg or as low as 3 mg. Maximum recommended dosage is 12 mg/day.

Dosage adjustment

• Renal impairment

Contraindications

• Hypersensitivity to drug, its components, or risperidone

Precautions

Use cautiously in:

• GI strictures (use should be avoided), cardiovascular or cerebrovascular disease, diabetes mellitus, Parkinson's disease, or conditions that raise body temperature (such as exercise, exposure to extreme heat, and concomitant anticholinergics use)

• increased risk of hypotension (as from dehydration, hypovolemia, or antihypertensives), aspiration pneumonia, or suicide attempt

• increased risk of metabolic changes (including hyperglycemia, dyslipidemia, weight gain)

• concurrent use of other drugs that are centrally acting or prolong the QT interval (use should be avoided)

• history of seizures or breast cancer

• elderly patients with dementia-related psychosis

• pregnant or breastfeeding patients

• children younger than age 18 (safety and efficacy not established).

Administration

• Give tablets in morning with or without food.

• Administer tablets whole. Ensure that patient doesn't chew, divide, or crush them.

Administer paliperidone palmitate by deep I.M. injection only as a single injection. Don't give in divided injections. Don't administer I.V. or subcutaneously.

For first and second I.M. doses, give in the deltoid muscle using 1½-inch 22G needle for patients 90 kg (198 lb) or more or 1-inch 23G needle for patients less than 90 kg. After the second dose, monthly maintenance doses may be given in either the deltoid or gluteal muscle. For gluteal injection, use 1½-inch 22G needle regardless of patient weight.

Adverse reactions

CNS: dizziness, headache, akathisia, tardive dyskinesia, dystonia, extrapyramidal disorder, hypertonia, parkinsonism, sedation, somnolence, tremor, anxiety, asthenia, fatigue, seizure, stroke (in elderly patients with dementia-related psychosis), neuroleptic malignant syndrome (NMS)

CV: first-degree atrioventricular block, bundle-branch block, sinus arrhythmia, tachycardia, hypertension, orthostatic hypotension, prolonged QT interval, abnormal T wave, palpitations

EENT: blurred vision

GI: upper abdominal pain, dyspepsia, nausea, antiemetic effect, esophageal dysmotility, salivary hypersecretion, dry mouth

GU: hyperprolactinemia

Hematologic: leukopenia, neutropenia, agranulocytosis

Musculoskeletal: back pain, extremity pain

Respiratory: cough, dyspnea, aspiration pneumonia

Other: fever, weight gain, possible drug tolerance or dependency

Interactions

Drug-drug. Antihypertensives: increased risk of hypotension Centrally acting drugs with sedative effect: increased sedation Class IA antiarrhythmics (such as procainamide, quinidine), Class III antiarrhythmics (such as amiodarone, sotalol), anti-infectives (such as gatifloxacin, moxifloxacin), other antipsychotics (such as chlorpromazine, thioridazine), other drugs that prolong the QT interval: increased risk of prolonged QT interval

Dopamine agonists (such as levodopa): antagonized effects of these drugs

Drug-diagnostic tests. Blood glucose, serum prolactin: increased levels Granulocytes, leukocytes, neutrophils: decreased counts

Drug-food. Any food: possibly increased paliperidone effects

Drug-behaviors. Alcohol use: increased sedation

Patient monitoring

• Closely monitor patient at risk for suicide attempts.

• Monitor patient with diabetes regularly for signs and symptoms of worsening glycemic control.

• Stay alert for orthostatic hypotension.

Monitor patient for signs and symptoms of NMS (extremely high fever, muscle rigidity, altered mental status, irregular pulse or blood pressure, tachycardia, diaphoresis, arrhythmias). Immediately discontinue drug and take appropriate measures if NMS occurs.

Closely monitor CBC with differential, especially during first few months of therapy; discontinue drug if severe neutropenia occurs.

• Consider discontinuing drug if tardive dyskinesia occurs.

• Watch for signs and symptoms of drug tolerance, dependency, and abuse.

Patient teaching

• Inform patient he may take drug with or without food.

• Teach patient to take tablets whole and not to chew, divide, or crush them.

• Inform patient that tablet shell doesn't dissolve and may look like a complete tablet in stool.

Instruct patient to immediately discontinue drug and report signs or symptoms of NMS (such as high fever, muscle rigidity, altered mental status, irregular pulse or blood pressure, fast heart rate, or excessive sweating).

• Instruct patient to report fever or other signs and symptoms of infection.

• Tell patient drug may cause temporary blood pressure decrease if he stands or sits up suddenly. Instruct him to rise slowly and carefully.

• Advise patient to take precautions against dehydration and overheating.

• Caution patient not to consume alcohol during therapy.

• Caution patient to avoid hazardous activities until drug's effects on concentration, coordination, vision, and alertness are known.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, and behaviors mentioned above.

paliperidone

(pa-li-per-i-done) ,

Invega

(trade name),

Invega Sustenna

(trade name)

Classification

Therapeutic: antipsychotics
Pharmacologic: benzisoxazoles
Pregnancy Category: C

Indications

Oral: Intramuscular: Acute and maintenance treatment of schizophrenia. Oral: Acute treatment of schizoaffective disorder (as monotherapy or as adjunct to mood stabilizers and/or antidepressants).

Action

May act by antagonizing dopamine and serotonin in the CNS. Paliperidone is the active metabolite of risperidone.

Therapeutic effects

Decreased manifestations of schizophrenia.
Decreased manifestations of schizoaffective disorder.

Pharmacokinetics

Absorption: 28% absorbed following oral administration, food ↑ absorption; slowly absorbed after IM administration (concentrations higher and more rapidly achieved with administration into deltoid muscle).
Distribution: Unknown.
Metabolism and Excretion: 59% excreted unchanged in urine; 32% excreted in urine as metabolites.
Half-life: 23 hr (PO); 25–49 days (IM).

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
POunknown24 hr24 hr
IMunknown13 days1 mo

Contraindications/Precautions

Contraindicated in: Hypersensitivity to paliperidone or risperidone;Concurrent use of drugs known to cause QTc prolongation (including quinidine, procainamide, sotalol, amiodarone, chlorpromazine, thioridazine, moxifloxacin);History of congenital QTc prolongation or other cardiac arrhythmias;Bradycardia, hypokalemia, hypomagnesemia (↑ risk of QTc prolongation);Pre-existing severe GI narrowing (due to nature of tablet formulation);CCr <50 mL/min (for IM); Lactation: Discontinue drug or bottle feed.
Use Cautiously in: Patients with Parkinson's disease or dementia with Lewy Bodies (↑ sensitivity to effects of antipsychotics);History of suicide attempt;Patients at risk for aspiration pneumonia;History of seizures;Conditions which may ↑ body temperature (strenuous exercise, exposure to extreme heat, concurrent anticholinergics or risk of dehydration);↓ GI transit time (may ↑ blood levels);May mask symptoms of some drug overdoses, intestinal obstruction, Reye's Syndrome or brain tumor (due to antiemetic effect);Diabetes mellitus;Severe hepatic impairment;Renal impairment (dose ↓ recommended if CCr <80 mL/min); Obstetric: Neonates at ↑ risk for extrapyramidal symptoms and withdrawal after delivery when exposed during the 3rd trimester; use only if maternal benefit outweighs fetal risk; Pediatric: Children <12 yr (safety not established); Geriatric: ↑ risk of mortality in elderly patients treated for dementia-related psychosis; consider age-related ↓ in renal function.

Adverse Reactions/Side Effects

Central nervous system

  • neuroleptic malignant syndrome (life-threatening)
  • suicidal thoughts (life-threatening)
  • drowsiness (most frequent)
  • extrapyramidal disorders (dose related) (most frequent)
  • headache (most frequent)
  • insomnia (most frequent)
  • anxiety
  • confusion
  • dizziness
  • dysarthria
  • fatigue
  • syncope
  • tardive dyskinesia
  • weakness

Ear, Eye, Nose, Throat

  • blurred vision

Respiratory

  • dyspnea (most frequent)
  • cough

Cardiovascular

  • palpitations (most frequent)
  • tachycardia (dose related) (most frequent)
  • bradycardia
  • orthostatic hypotension
  • QTc interval prolongation

Gastrointestinal

  • abdominal pain (most frequent)
  • dry mouth
  • dyspepsia
  • nausea
  • swollen tongue

Genitourinary

  • impotence
  • priapism

Endocrinologic

  • amenorrhea
  • dyslipidemia
  • galactorrhea
  • gynecomastia
  • hyperglycemia
  • weight gain

Hematologic

  • agranulocytosis (life-threatening)
  • leukopenia
  • neutropenia

Musculoskeletal

  • back pain
  • dystonia (dose related)

Neurologic

  • akathisia
  • dyskinesia
  • tremor (dose related)

Miscellaneous

  • fever

Interactions

Drug-Drug interaction

↑ risk of CNS depression with other CNS depressants including alcohol, antihistamines, sedative/hypnotics, or opioid analgesics.May antagonize the effects of levodopa or other dopamine agonists.↑ risk of orthostatic hypotension with antihypertensives, nitrates, or other agents that lower BP.Carbamazepine may ↓ levels/effects.

Route/Dosage

Schizophrenia

Oral (Adults) 6 mg once daily; may titrate by 3 mg/day at intervals of at least 5 days (range 3–12 mg/day).
Oral (Children 12–17 yr) 3 mg once daily; may titrate by 3 mg/day at intervals of at least 5 days (not to exceed 6 mg if <51 kg or 12 mg if ≥51 kg).
Intramuscular (Adults) 234 mg initially, then 156 mg one week later; continue with monthly maintenance dose of 117 mg (range of 39–234 mg based on efficacy and/or tolerability).

Renal Impairment

Oral (Adults) CCr 50–79 mL/min—3 mg/day initially; dose may be ↑ to maximum of 6 mg/day; CCr 10–<50 mL/min—1.5 mg/day initially; dose may be ↑ to maximum of 3 mg/day.

Renal Impairment

Intramuscular (Adults) CCr 50–79 mL/min—156 mg initially, then 117 mg one week later; continue with monthly maintenance dose of 78 mg; CCr <50 mL/min—Contraindicated.

Schizoaffective Disorder

Oral (Adults) 6 mg/day; may titrate by 3 mg/day at intervals of at least 4 days (range 3–12 mg/day).

Renal Impairment

Oral (Adults) CCr 50–79 mL/min—3 mg/day initially; dose may be ↑ to maximum of 6 mg/day; CCr 10–<50 mL/min—1.5 mg/day initially; dose may be ↑ to maximum of 3 mg/day.

Availability

Extended-release tablets (Invega): 1.5 mg, 3 mg, 6 mg, 9 mg
Intramuscular injection (Invega Sustenna): 39 mg, 78 mg, 117 mg, 156 mg, 234 mg

Nursing implications

Nursing assessment

  • Monitor patient’s mental status (orientation, mood, behavior) before and periodically during therapy. Monitor closely for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression, especially during early therapy. Restrict amount of drug available to patient.
  • Assess weight and BMI initially and throughout therapy.
  • Monitor BP (sitting, standing, lying down) and pulse before and periodically during therapy. May cause prolonged QT interval, tachycardia, and orthostatic hypotension.
  • Observe patient when administering medication to ensure that medication is actually swallowed and not hoarded or cheeked.
  • Monitor patient for onset of extrapyramidal side effects (akathisia—restlessness; dystonia—muscle spasms and twisting motions; or pseudoparkinsonism—mask-like face, rigidity, tremors, drooling, shuffling gait, dysphagia). Report these symptoms; reduction of dose or discontinuation of medication may be necessary.
  • Monitor for tardive dyskinesia (involuntary rhythmic movement of mouth, face, and extremities). Report immediately; may be irreversible.
  • Monitor for development of neuroleptic malignant syndrome (fever, respiratory distress, tachycardia, seizures, diaphoresis, hypertension or hypotension, pallor, tiredness). Discontinue paliperidone and notify health care professional immediately if these symptoms occur.
  • Monitor for symptoms related to hyperprolactinemia (menstrual abnormalities, galactorrhea, sexual dysfunction).
  • Lab Test Considerations: Monitor fasting blood glucose and cholesterol levels before and periodically during therapy.
    • Monitor serum prolactin prior to and periodically during therapy. May cause ↑ serum prolactin levels.
    • Monitor CBC frequently during initial months of therapy in patients with pre-existing or history of low WBC. May cause leukopenia, neutropenia, or agranulocytosis. Discontinue therapy if this occurs.

Potential Nursing Diagnoses

Risk for self-directed violence (Indications,  Adverse Reactions)
Disturbed sensory perception (specify: visual, auditory, kinesthetic, gustatory, tactile, olfactory) (Indications)

Implementation

  • Oral: Administer once daily in the morning without regard to food. Tablets should be swallowed whole; do not crush, break or chew.
  • Intramuscular: Administer initial and second doses in deltoid using a 1 1/2-inch, 22 gauge needle for patients ≥90 kg (≥200 lb) or 1-inch 23 gauge needle for patients <90 kg (<200 lb). Monthly maintenance doses can be administered in either deltoid or gluteal sites. For gluteal injection, use 1 1/2-inch, 22 gauge needle regardless of patient weight. To avoid missed dose, may give second dose 4 days before or after the 1-wk timepoint. Monthly doses may be given up to 7 days before or after the monthly timepoint. After 1st month, if missed dose is within 4 wk of scheduled dose, administer 2nd dose of 156 mg as soon as possible. Give 3rd dose of 117 mg in either deltoid or gluteal muscle 5 wk after first injection (regardless of timing of 2nd injection). Then return to normal monthly injections in either deltoid or gluteal muscle. If >4 wk and <7 wk since 1st injection, resume by administering 156 mg dose in deltoid as soon as possible, a second 156 mg dose in deltoid in 1 wk, followed by monthly doses in deltoid or gluteal sites. If > 7 months since scheduled dose, administer using initial dosing schedule. During regular monthly dose schedule, if <6 wks since last injection, administer previously stabilized dose as soon as possible, then monthly. If >6 wks since last injection, resume dose previously stabilized on, unless stabilized on 234 mg (then 1st two injections should be 156 mg). Administer 1 dose in deltoid as soon as possible, then another deltoid injection of same dose 1 wk later, then resume regular monthly schedule. If >6 months since last injection, administer using initial dosing schedule.

Patient/Family Teaching

  • Instruct patient to take medication as directed. Advise patient that appearance of tablets in stool is normal and not of concern.
  • Inform patient of the possibility of extrapyramidal symptoms. Instruct patient to report these symptoms immediately to health care professional.
  • Advise patient to change positions slowly to minimize orthostatic hypotension.
  • May cause drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
  • Advise patient and family to notify health care professional if thoughts about suicide or dying, attempts to commit suicide; new or worse depression; new or worse anxiety; feeling very agitated or restless; panic attacks; trouble sleeping; new or worse irritability; acting aggressive; being angry or violent; acting on dangerous impulses; an extreme increase in activity and talking, other unusual changes in behavior or mood occur.
  • Advise patient that extremes in temperature should also be avoided; this drug impairs body temperature regulation.
  • Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications and alcohol.
  • Advise patient to seek nutritional, weight, or medical management as needed for weight gain or cholesterol elevation.
  • Instruct patient to notify health care professional promptly if sore throat, fever, unusual bleeding or bruising, rash, tremors, menstrual abnormalities, galactorrhea, or sexual dysfunction occur.
  • Advise patient to notify health care professional of medication regimen before treatment or surgery.
  • Advise female patients to notify health care professional if pregnancy is planned or suspected, or if breast feeding or planning to breast feed.
  • Emphasize the importance of routine follow-up exams to monitor side effects and continued participation in psychotherapy to improve coping skills.

Evaluation/Desired Outcomes

  • Decrease in excited, manic behavior.
  • Decrease in positive symptoms (delusions, hallucinations) of schizophrenia.
  • Decrease in negative symptoms (social withdrawal, flat, blunted affect) of schizophrenia.

paliperidone

an antipsychotic.
indication This drug is used to treat schizophrenia.
contraindications Lactation, seizure disorders, AV block, QT prolongation, torsade de pointes, and known hypersensitivity to this drug or to risperidone prohibit its use. Geriatric patients should not use this drug.
adverse effects Adverse effects of this drug include dizziness, orthostatic hypotension, blurred vision, vomiting, and weight gain. Life-threatening side effects include seizures, neuroleptic malignant syndrome, tachycardia, heart failure, and QT prolongation. Common side effects include EPS, pseudoparkinsonism, akathisia, dystonia, tardive dyskinesia, drowsiness, insomnia, agitation, anxiety, headache, nausea, anorexia, and constipation.
Mentioned in ?
References in periodicals archive ?
She is receiving paliperidone palmitate, 234 mg every 4 weeks.
His treatment included 30 mg/day aripiprazole, 1000 mg/day valproic acid, 200 mg/day quetiapine, 4 mg/day biperiden, and 100 mg/month paliperidone palmitate.
Janssen Research & Development, a company that aims to discover and develop innovative medicines, has received Priority Review for new drug application for three-month atypical antipsychotic paliperidone palmitate to treat schizophrenia in adults, it was reported yesterday.
3 Paliperidone depot utilizes a paliperidone palmitate nanosuspension, a hydrophobic ester derivative of an active metabolite of risperidone, 9-hydroxyrisperidone.
Janssen's paliperidone palmitate and Lilly's olanzapine pamoate are headed for approval in the FDA review process, and it is expected that both agents will be available by the end of the year.
These new depot formulations will command premium pricing, and Decision Resources forecasts peak-year sales of at least $500 million in schizophrenia for aripiprazole depot and at least $1 billion in post-2021 peak-year sales for paliperidone palmitate three-month depot.
A 3-month paliperidone palmitate (PPM-3) extended-release injectable suspension was approved by the FDA in May 2015 for preventing relapse among patients with schizophrenia, under the brand name Invega Trinza (Table 1).
BERLIN -- Once-monthly intramuscular paliperidone palmitate significantly delayed the unwelcome real world consequences of schizophrenia--including contact with the criminal justice system as well as psychiatric hospitalization--compared with oral antipsychotics, in the randomized PRIDE study.
The technology allows for a ready-to- use, one-month duration, intramuscular injection formulation of paliperidone palmitate which can be administered by healthcare professionals.
XEPLION will be available in Europe in milligrams of paliperidone palmitate in dose strengths of 25, 50, 75, 100 and 150 mg.
43-45) Ongoing studies of LAIA use in FEP are comparing paliperidone palmitate with risperidone microspheres and other oral antipsychotics.