INDICATION AND USES:
INVEGA® is an atypical antipsychotic agent indicated for Treatment of schizophrenia (1.1)
- Adults: Efficacy was established in three 6-week trials and one maintenance trial. (14.1)
- Adolescents (ages 12-17): Efficacy was established in one 6-week trial. (14.1)
Treatment of schizoaffective disorder as monotherapy and as an adjunct to mood stabilizers and/or antidepressants. (1.2)
- Efficacy was established in two 6-week trials in adult patients. (14.2)
DOSAGE AND ADMINISTRATION
| Initial Dose | Recommended Dose | Maximum Dose | ||
| Schizophrenia – adults (2.1) | 6 mg/day | 3 – 12 mg/day | 12 mg/day | |
| Schizophrenia- adolescents (2.1) |
Weight < 51kg | 3 mg/day | 3 – 6 mg/day | 6 mg/day |
| Weight > 51kg | 3 mg/day | 3 – 12 mg/day | 12 mg/day | |
| Schizoaffective disorder – adults (2.2) | 6 mg/day | 3 – 12 mg/day | 12 mg/day | |
Tablet should be swallowed whole and should not be chewed, divided, or crushed. (2.3)
SIDE EFFECTS:
Commonly observed adverse reactions (incidence ≥ 5% and at least twice that for placebo) were (6)
- Adults with schizophrenia: extrapyramidal symptoms, tachycardia, and akathisia.
- Adolescents with schizophrenia: somnolence, akathisia, tremor, dystonia, cogwheel rigidity, anxiety, weight increased, and tachycardia.
- Adults with schizoaffective disorder: extrapyramidal symptoms, somnolence, dyspepsia, constipation, weight increased, and nasopharyngitis.
CONTRAINDICATIONS:
Known hypersensitivity to paliperidone, risperidone, or to any excipients in INVEGA®. (4)
WARNINGS AND PRECAUTIONS:
- Cerebrovascular Adverse Reactions: 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. (5.2)
- Neuroleptic Malignant Syndrome: Manage with immediate discontinuation of drug and close monitoring. (5.3)
- QT Prolongation: Increase in QT interval, avoid use with drugs that also increase QT interval and in patients with risk factors for prolonged QT interval. (5.4)
- Tardive Dyskinesia: Discontinue drug if clinically appropriate. (5.5)
- Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/ cerebrovascular risk. These metabolic changes include hyperglycemia, dyslipidemia, and weight gain. (5.6)
- 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. (5.6)
- Dyslipidemia: Undesirable alterations have been observed in patients treated with atypical antipsychotics. (5.6)
DRUG INTERACTIONS:
- Centrally-acting drugs: Due to CNS effects, use caution in combination. Avoid alcohol. (7.1)
- Drugs that may cause orthostatic hypotension: An additive effect may be observed when co-administered with INVEGA®. (7.1)
- Strong CYP3A4/P-glycoprotein (P-gp) inducers: It may be necessary to increase the dose of INVEGA® when a strong inducer of both CYP3A4 and P-gp (e.g., carbamazepine) is co-administered. Conversely, on discontinuation of the strong inducer, it may be necessary to decrease the dose of INVEGA®. (7.2)
- Co-administration of divalproex sodium increased Cmax and AUC of paliperidone by approximately 50%. Adjust dose of INVEGA® if necessary based on clinical assessment. (7.2)
OVERDOSE:
While experience with paliperidone overdose is limited, among the few cases of overdose reported in pre-marketing trials, the highest estimated ingestion of INVEGA® was 405 mg. Observed signs and symptoms included extrapyramidal symptoms and gait unsteadiness. Other potential signs and symptoms include those resulting from an exaggeration of paliperidone’s known pharmacological effects, i.e., drowsiness and somnolence, tachycardia and hypotension, and QT prolongation. Torsade de pointes and ventricular fibrillation have been reported in a patient in the setting of overdose. Paliperidone is the major active metabolite of risperidone. Overdose experience reported with risperidone can be found in the OVERDOSAGE section of the risperidone package insert.
Management of Overdosage: 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. Consideration should be given to the extended-release nature of the product when assessing treatment needs and recovery. Multiple drug involvement should also be considered. 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.
- Uses
-
INDICATION AND USES:
INVEGA® is an atypical antipsychotic agent indicated for Treatment of schizophrenia (1.1)
- Adults: Efficacy was established in three 6-week trials and one maintenance trial. (14.1)
- Adolescents (ages 12-17): Efficacy was established in one 6-week trial. (14.1)
Treatment of schizoaffective disorder as monotherapy and as an adjunct to mood stabilizers and/or antidepressants. (1.2)
- Efficacy was established in two 6-week trials in adult patients. (14.2)
DOSAGE AND ADMINISTRATION
Initial Dose Recommended Dose Maximum Dose Schizophrenia – adults (2.1) 6 mg/day 3 – 12 mg/day 12 mg/day Schizophrenia-
adolescents (2.1)Weight < 51kg 3 mg/day 3 – 6 mg/day 6 mg/day Weight > 51kg 3 mg/day 3 – 12 mg/day 12 mg/day Schizoaffective disorder – adults (2.2) 6 mg/day 3 – 12 mg/day 12 mg/day Tablet should be swallowed whole and should not be chewed, divided, or crushed. (2.3)
- Side Effects
-
SIDE EFFECTS:
Commonly observed adverse reactions (incidence ≥ 5% and at least twice that for placebo) were (6)
- Adults with schizophrenia: extrapyramidal symptoms, tachycardia, and akathisia.
- Adolescents with schizophrenia: somnolence, akathisia, tremor, dystonia, cogwheel rigidity, anxiety, weight increased, and tachycardia.
- Adults with schizoaffective disorder: extrapyramidal symptoms, somnolence, dyspepsia, constipation, weight increased, and nasopharyngitis.
- Precautions
-
CONTRAINDICATIONS:
Known hypersensitivity to paliperidone, risperidone, or to any excipients in INVEGA®. (4)
WARNINGS AND PRECAUTIONS:
- Cerebrovascular Adverse Reactions: 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. (5.2)
- Neuroleptic Malignant Syndrome: Manage with immediate discontinuation of drug and close monitoring. (5.3)
- QT Prolongation: Increase in QT interval, avoid use with drugs that also increase QT interval and in patients with risk factors for prolonged QT interval. (5.4)
- Tardive Dyskinesia: Discontinue drug if clinically appropriate. (5.5)
- Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/ cerebrovascular risk. These metabolic changes include hyperglycemia, dyslipidemia, and weight gain. (5.6)
- 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. (5.6)
- Dyslipidemia: Undesirable alterations have been observed in patients treated with atypical antipsychotics. (5.6)
- Interactions
-
DRUG INTERACTIONS:
- Centrally-acting drugs: Due to CNS effects, use caution in combination. Avoid alcohol. (7.1)
- Drugs that may cause orthostatic hypotension: An additive effect may be observed when co-administered with INVEGA®. (7.1)
- Strong CYP3A4/P-glycoprotein (P-gp) inducers: It may be necessary to increase the dose of INVEGA® when a strong inducer of both CYP3A4 and P-gp (e.g., carbamazepine) is co-administered. Conversely, on discontinuation of the strong inducer, it may be necessary to decrease the dose of INVEGA®. (7.2)
- Co-administration of divalproex sodium increased Cmax and AUC of paliperidone by approximately 50%. Adjust dose of INVEGA® if necessary based on clinical assessment. (7.2)
- Overdose
-
OVERDOSE:
While experience with paliperidone overdose is limited, among the few cases of overdose reported in pre-marketing trials, the highest estimated ingestion of INVEGA® was 405 mg. Observed signs and symptoms included extrapyramidal symptoms and gait unsteadiness. Other potential signs and symptoms include those resulting from an exaggeration of paliperidone’s known pharmacological effects, i.e., drowsiness and somnolence, tachycardia and hypotension, and QT prolongation. Torsade de pointes and ventricular fibrillation have been reported in a patient in the setting of overdose. Paliperidone is the major active metabolite of risperidone. Overdose experience reported with risperidone can be found in the OVERDOSAGE section of the risperidone package insert.
Management of Overdosage: 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. Consideration should be given to the extended-release nature of the product when assessing treatment needs and recovery. Multiple drug involvement should also be considered. 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.