Drug information of Paliperidone

Paliperidone

Drug group:


Paliperidone is the primary active metabolite of risperidone. The mechanism of action is unknown but it is likely to act via a similar pathway to risperidone.

Mechanism of effect

The mechanism of action of paliperidone, as with other drugs having efficacy in schizophrenia, is unknown, but it has been proposed that the drug's therapeutic activity in schizophrenia is mediated through a combination of central dopamine Type 2 (D2) and serotonin Type 2 (5HT2A) receptor antagonism.

Pharmacodynamic

Paliperidone is also active as an antagonist at alpha 1 and alpha 2 adrenergic receptors and H1 histaminergic receptors, which may explain some of the other effects of the drug.

Pharmacokinetics

Bioavailability: 28%

Peak plasma time: PO, 24 hr; IM, 13 days

Protein bound: 74%

Vd: 390-487 L

Metabolism: Metabolized by CYP2D6 and CYP3A4

Half-life: PO, 23 hr; IM, 25-49 days

Excretion: Urine (80%), feces (11%)

Dosage

Adult

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

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

Pediatric

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

Drug contraindications

hypersensitivity to this drug

Alerts

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 illness; 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

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

Points of recommendation

Follow all directions on your prescription label and read all medication guides or instruction sheets. Use the medicine exactly as directed.

You may take paliperidone with or without food.

Swallow the tablet whole and do not crush, chew, or break it.

Your doctor will need to check your progress on a regular basis.

Store at room temperature away from moisture, heat, and light.

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

Get your prescription refilled before you run out of medicine completely.

 


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