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.
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.
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
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.
• Renal impairment
• Hypersensitivity to drug, its components, or risperidone
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).
• 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.
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
Hematologic: leukopenia, neutropenia, agranulocytosis
Musculoskeletal: back pain, extremity pain
Respiratory: cough, dyspnea, aspiration pneumonia
Other: fever, weight gain, possible drug tolerance or dependency
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
• 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.
• 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.