Paliperidone

What is Paliperidone?

• Paliperidone (Invega) is an atypical antipsychotic agent used to treat schizophrenia and schizoaffective disorder.

Paliperidone

What are the uses of this medicine?

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Paliperidone (Invega) extended-release tablets are used:

• for the treatment of schizophrenia.
• for the treatment of schizoaffective disorder as monotherapy and an adjunct to mood stabilizers and/or antidepressant therapy.

How does this medicine work?

• Paliperidone is the major active metabolite of risperidone.
• The mechanism of action of paliperidone in schizophrenia is unclear.
• However, the drug's therapeutic effect in schizophrenia could be mediated through a combination of central dopamine Type 2 (D2) and serotonin Type 2 (5HT2A) receptor antagonism.

Who Should Not Use this medicine ?

This medicine cannot be used in patients with:

• with a known hypersensitivity to either paliperidone or risperidone, or to any of the excipients in the Invega.

What drug interactions can this medicine cause?

• Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Be sure to mention any of the following:

• antidepressants
• certain antibiotics such as erythromycin (E.E.S., E-Mycin, Erythrocin), gatifloxacin (Tequin) (not available in the United States), moxifloxacin (Avelox), and sparfloxacin (Zagam)
• certain antipsychotics such as chlopromazine (Sonazine, Thorazine), pimozide (Orap), risperidone (Risperdal) and thioridazine
• cisapride (Propulsid)
• levodopa (in Sinemet, in Stalevo)
• medications for anxiety, high blood pressure, or seizures
• medications for irregular heartbeat such as amiodarone (Cordarone), disopyramide (Norpace), dofetilide (Tikosyn)
• procainamide (Procanbid, Pronestyl), quinidine (Quinidex), and sotalol (Betapace, Betapace AF)
• sedatives
• sleeping pills
• tranquilizers

Is this medicine FDA approved?

• Oral formulations of paliperidone were approved for use in the United States in 2006 as treatment for schizophrenia and schizoaffective disorder, as extended release tablets of 1.5, 3, 6 and 9 mg under the brand name Invega.
• Subsequently, parenteral formulations of paliperidone palmitate were developed that could be administered every one or three months.
• These palmitate formulations are given intramuscularly in varying doses and are available under the brand names Invega Sustenna and Invega Trinzia.

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How should this medicine be used?

Recommended dosage:

For Schizophrenia:

In Adults:

• The recommended dose of Invega® (paliperidone) Extended-Release Tablets for the treatment of schizophrenia in adults is 6 mg administered once daily.
• When dose increases are indicated, increments of 3 mg/day are recommended.
• The maximum recommended dose is 12 mg/day.

In Adolescents (12–17 years of age):

• The recommended starting dose of Invega® (paliperidone) Extended-Release Tablets for the treatment of schizophrenia in adolescents 12–17 years of age is 3 mg administered once daily.
• Dose increases, if considered necessary, should be made only after clinical reassessment and should occur at increments of 3 mg/day at intervals of more than 5 days.

For Schizoaffective Disorder:

In Adults:

• The recommended dose of Invega® (paliperidone) Extended-Release Tablets for the treatment of schizoaffective disorder in adults is 6 mg administered once daily.
• Dose increases, if indicated, generally should occur at intervals of more than 4 days.
• When dose increases are indicated, increments of 3 mg/day are recommended.
• The maximum recommended dose is 12 mg/day.

Administration:

• Paliperidone comes as an extended-release tablet to take by mouth.
• Invega® can be taken with or without food.
• Invega® must be swallowed whole with the aid of liquids.
• Tablets should not be chewed, divided, or crushed.
• The medication is contained within a nonabsorbable shell designed to release the drug at a controlled rate.
• The tablet shell, along with insoluble core components, is eliminated from the body; patients should not be concerned if they occasionally notice in their stool something that looks like a tablet.
• Talk to your doctor about how you are feeling during your treatment.
• If your symptoms are still bothersome, your doctor may gradually increase your dose, not more often than once every 5 days.
• Paliperidone controls the symptoms of schizophrenia but does not cure the condition.
• Continue to take paliperidone even if you feel well.
• Do not stop taking paliperidone without talking to your doctor.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Extended-Release Tablets are intended for oral administration

This medicine is available in fallowing brand namesː

• Invega

What side effects can this medication cause?

The most common side effects of this medicine include:

In Adults with schizophrenia:

• extrapyramidal symptoms, tachycardia, and akathisia.

In Adolescents with schizophrenia:

• somnolence, akathisia, tremor, dystonia, cogwheel rigidity, anxiety, weight increased, and tachycardia.

In Adults with schizoaffective disorder:

• extrapyramidal symptoms, somnolence, dyspepsia, constipation, weight increased, and nasopharyngitis.

Less common, but serious side effects may include:

• Increased mortality in elderly patients with dementia-related psychosis
• Cerebrovascular adverse reactions, including stroke, in elderly patients with dementia-related psychosis
• Neuroleptic malignant syndrome
• QT prolongation
• Tardive dyskinesia
• Metabolic changes
• Hyperprolactinemia
• Potential for gastrointestinal obstruction
• Orthostatic hypotension and syncope
• Falls
• Leukopenia, neutropenia, and agranulocytosis
• Potential for cognitive and motor impairment
• Seizures
• Dysphagia
• Priapism
• Disruption of body temperature regulation

What special precautions should I follow?

• Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Invega® is not approved for use in patients with dementia-related psychosis.
• An increased incidence of cerebrovascular adverse reactions (e.g. stroke, transient ischemic attack, including fatalities) has been seen in elderly patients with dementia- related psychoses treated with atypical antipsychotics.
• Neuroleptic Malignant Syndrome (NMS), a potentially fatal symptom complex, has been reported in association with antipsychotic drugs, including paliperidone. If NMS is suspected, immediately discontinue Invega® and provide symptomatic treatment and monitoring.
• Paliperidone causes a modest increase in the corrected QT (QTc) interval. Avoid use with drugs that also increase QT interval and in patients with risk factors for prolonged QT interval.
• Tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements, may develop in patients treated with antipsychotic drugs. If signs and symptoms of tardive dyskinesia appear in a patient on Invega®, drug discontinuation should be considered. However, some patients may require treatment with Invega® despite the presence of the syndrome.
• Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/ cerebrovascular risk. These metabolic changes include hyperglycemia, dyslipidemia, and weight gain.
• Hyperglycemia and Diabetes Mellitus: Monitor patients for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Monitor glucose regularly in patients with diabetes or at risk for diabetes.
• Dyslipidemia: Undesirable alterations have been observed in patients treated with atypical antipsychotics.
• Weight Gain: Significant weight gain has been reported. Monitor weight gain.
• Like other drugs that antagonize dopamine D2 receptors, paliperidone elevates prolactin levels and the elevation persists during chronic administration. Prolactin elevations occur and persist during chronic administration.
• Because the Invega® tablet is non-deformable and does not appreciably change in shape in the gastrointestinal tract, Invega® should ordinarily not be administered to patients with pre-existing severe gastrointestinal narrowing.
• Paliperidone can induce orthostatic hypotension and syncope in some patients because of its alpha-blocking activity. Invega® should be used with caution in patients with known cardiovascular disease (e.g., heart failure, history of myocardial infarction or ischemia, conduction abnormalities), cerebrovascular disease, or conditions that predispose the patient to hypotension.
• Somnolence, postural hypotension, motor and sensory instability have been reported with the use of antipsychotics, including Invega®, which may lead to falls and, consequently, fractures or other fall-related injuries.
• Events of leukopenia/neutropenia have been reported temporally related to antipsychotic agents, including Invega. Monitor patients with clinically significant neutropenia for fever or other symptoms or signs of infection and treat promptly if such symptoms or signs occur. Discontinue Invega® in patients with severe neutropenia (absolute neutrophil count < 1000/mm3) and follow their WBC until recovery.
• Somnolence, sedation, and dizziness were reported as adverse reactions in subjects treated with Invega. Patients should be cautioned about performing activities requiring mental alertness, such as operating hazardous machinery or operating a motor vehicle, until they are reasonably certain that paliperidone therapy does not adversely affect them.
• Like other antipsychotic drugs, Invega® should be used cautiously in patients with a history of seizures or other conditions that potentially lower the seizure threshold. Conditions that lower the seizure threshold may be more prevalent in patients 65 years or older.
• Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Invega® and other antipsychotic drugs should be used cautiously in patients at risk for aspiration pneumonia.
• Drugs with alpha-adrenergic blocking effects have been reported to induce priapism. Severe priapism may require surgical intervention.
• Disruption of the body's ability to reduce core body temperature has been attributed to antipsychotic agents. Counsel patients on the importance of avoiding overheating and dehydration.
• Advise patients to avoid alcohol while taking Invega.
• Advise breastfeeding women using Invega® to monitor infants for somnolence, failure to thrive, jitteriness, and extrapyramidal symptoms (tremors and abnormal muscle movements) and to seek medical care if they notice these signs.
• Advise females of reproductive potential that Invega® may impair fertility due to an increase in serum prolactin levels. The effects on fertility are reversible.
• Paliperidone is associated with a low rate of serum aminotransferase elevations during therapy, but has not been linked to instances of clinically apparent acute liver injury.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• extrapyramidal symptoms
• gait unsteadiness
• drowsiness
• somnolence
• tachycardia
• hypotension
• QT prolongation
• Torsade de pointes
• ventricular fibrillation

Management of overdosage:

• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.
• There is no specific antidote to paliperidone, therefore, appropriate supportive measures should be instituted and close medical supervision and monitoring should continue until the patient recovers.
• In case of acute overdose, establish and maintain an airway and ensure adequate oxygenation and ventilation.
• Administration of activated charcoal together with a laxative should be considered.
• The possibility of obtundation, seizures, or dystonic reaction of the head and neck following overdose may create a risk of aspiration with induced emesis.
• Cardiovascular monitoring should commence immediately, including continuous electrocardiographic monitoring for possible arrhythmias.
• If antiarrhythmic therapy is administered, disopyramide, procainamide, and quinidine carry a theoretical hazard of additive QT-prolonging effects when administered in patients with an acute overdose of paliperidone.
• Similarly, the alpha-blocking properties of bretylium might be additive to those of paliperidone, resulting in problematic hypotension.
• Hypotension and circulatory collapse should be treated with appropriate measures, such as intravenous fluids and/or sympathomimetic agents (epinephrine and dopamine should not be used, since beta stimulation may worsen hypotension in the setting of paliperidone-induced alpha blockade).
• In cases of severe extrapyramidal symptoms, anticholinergic medication should be administered.

Can this medicine be used in pregnancy?

• Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery.
• Overall, available data from published epidemiologic studies of pregnant women exposed to paliperidone have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

Can this medicine be used in children?

• Safety and effectiveness of Invega® for the treatment of schizophrenia in patients < 12 years of age have not been established.
• Safety and effectiveness of Invega® for the treatment of schizoaffective disorder in patients < 18 years of age have not been studied.

What are the active and inactive ingredients in this medicine?

Active ingredient:

• paliperidone

Inactive ingredients:

• carnauba wax, cellulose acetate, hydroxyethyl cellulose, propylene glycol, polyethylene glycol, polyethylene oxides, povidone, sodium chloride, stearic acid, butylated hydroxytoluene, hypromellose, titanium dioxide, and iron oxides. The 3 mg tablets also contain lactose monohydrate and triacetin.

Who manufactures and distributes this medicine?

Manufactured for:

• Janssen Pharmaceuticals, Inc.
• Titusville, NJ

What should I know about storage and disposal of this medication?

• Store up to 25°C (77°F); excursions permitted to 15 – 30°C (59 – 86°F).
• Protect from moisture.
• Keep out of reach of children.

Antipsychotic agents

First Generation

• Phenothiazines
  • Chlorpromazine, Fluphenazine, Perphenazine, Prochlorperazine, Thioridazine, Trifluoperazine

• Other
  • Haloperidol, Lithium, Loxapine, Molindone, Pimozide

Second Generation (Atypicals)

• Aripiprazole, Asenapine, Brexpiprazole, Cariprazine, Clozapine, Iloperidone, Lurasidone, Olanzapine, Paliperidone, Pimavanserin, Quetiapine, Risperidone, Ziprasidone

• Dailymed label info on Paliperidone
• FDA Paliperidone

Paliperidone Resources
Latest articles Most recent articles Ongoing trials	Wikipedia

Paliperidone Resources
Latest articles Most recent articles Ongoing trials	Wikipedia