paliperidone palmitate

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.

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.