paliperidone


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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.
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Dalteparin, darbepoetin, dasatinib, dexamethasone + neomycin sulphate + polymyxin B sulfate, epoetin beta, epoetin theta, epoetin zeta, erlotinib, estradiol + cyproterone, etoricoxib, everolimus, follitropin beta, formoterol + beclomethasone, fusidic + betamethasone, fusidic + hydrocortisone , goserelin, hydromorphone hydrochloride, ketorolac, levothyroxine + liothyronine, Linezolid, nadroparin, paliperidone palmitate, pazopanib, pegfilgrastim, piribedil, progesterone, prothipendyl, Reviparin, risperidone, sildenafil, sumatriptan, tinzaparin, tobramycin, tobramycin + dexamethasone, voriconazole.
1) Paliperidone Extended-Release Tablets is an atypical antipsychotic and is not approved for the treatment of patients with dementia-related psychosis.
org) is studying 10 drugs: aripiprazole (Ability), clozapine (Clozaril), iloperidone (Fanapt), paliperidone (Invega), lurasidone (Latuda), risperidone (Risperdal), asenapine (Saphris), quetiapine (Seroquel), ziprasidone (Geodon), and olanzapine (Zyprexa).
The Food and Drug Administration has approved the long-acting atypical antipsychotic Invega Trinza (3-month paliperidone palmitate) to treat schizophrenia, Janssen Pharmaceuticals has announced.
Paliperidone protects prefrontal cortical neurons from damages caused by MK-801 via Akt1/GSK3/S signaling pathway.
Antimanic agents with evidence for efficacy in acute mania include lithium, valproate, olanzapine, aripiprazole, quetiapine, risperidone, ziprasidone, paliperidone, haloperidol and to a lesser extent carbamazepine.
Aripiprazole (marketed as Abilify), Asenapine Maleate (marketed as Saphris), Clozapine (marketed as Clozaril), Iloperidone (marketed as Fanapt), Lurasidone (marketed as Latuda), Olanzapine (marketed as Zyprexa), Olanzapine/Fluoxetine (marketed as Symbyax), Paliperidone (marketed as Invega), Quetiapine (marketed as Seroquel), Risperidone (marketed as Risperdal) and Ziprasidone (marketed as Geodon) are the major atypical antipsychotic drugs marketed today.
He was sectioned under the Mental Health Act hours after the calls last February, and was forcibly injected chemical cosh Paliperidone - a powerful drug he now takes voluntarily.
Maher and her colleagues reviewed 2,066 articles published through May 2011 on the off-label use of aripiprazole, asenapine, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone.
3 Paliperidone depot utilizes a paliperidone palmitate nanosuspension, a hydrophobic ester derivative of an active metabolite of risperidone, 9-hydroxyrisperidone.
Drug Milligram equivalent to 20 Confidence mg of olanzapine (Zyprexa) Second generation antipsychotics Aripirazole (Abilify) 30 M Clozapine (Clozaril) 400 H Paliperidone (Invega) 9 M Quetiapine (Seroquel) 740 H Risperidone (Risperdal) 6 H First generation antipsychotics Haloperidol (Haldol) 10 H Perphenazine (Trilafon) 30 M Trifluoperazine (Stelazine) 20 M Key: H = high confidence level; M = moderate confidence level.
Paliperidone is a new molecular entity, which means this medication contains an active substance that has never before been approved for marketing in any form in the United States.