INDICATION AND USES:
SAPHRIS is an atypical antipsychotic indicated for (1):
- Schizophrenia in adults
- Bipolar I disorder
- Acute monotherapy treatment of manic or mixed episodes, in adults and pediatric patients 10 to 17 years of age
- Adjunctive treatment to lithium or valproate in adults
- Maintenance monotherapy treatment in adults
DOSAGE AND ADMINISTRATION
| Starting Dose | Recommended Dose | Maximum Dose | |
| Schizophrenia – acute treatment in adults (2.2) | 5 mg sublingually twice daily | 5 mg sublingually twice daily | 10 mg sublingually twice daily |
| Schizophrenia – maintenance treatment in adults (2.2) | 5 mg sublingually twice daily | 5-10 mg sublingually twice daily | 10 mg sublingually twice daily |
| Bipolar mania – adults: acute and maintenance monotherapy (2.3) | 5-10 mg sublingually twice daily | 5-10 mg sublingually twice daily | 10 mg sublingually twice daily |
| Bipolar mania – pediatric patients (10 to 17 years): monotherapy (2.3) | 2.5 mg sublingually twice daily | 2.5-10 mg sublingually twice daily | 10 mg sublingually twice daily |
| Bipolar mania – adults as an adjunct to lithium or valproate (2.3) | 5 mg sublingually twice daily | 5-10 mg sublingually twice daily | 10 mg sublingually twice daily |
Do not swallow tablet. SAPHRIS sublingual tablets should be placed under the tongue and left to dissolve completely. The tablet will dissolve in saliva within seconds. Eating and drinking should be avoided for 10 minutes after administration. (2.1, 17)
SIDE EFFECTS:
The most commonly observed adverse reactions (incidence ≥5% and at least twice that for placebo) were (6.1):
- Schizophrenia Adults: akathisia, oral hypoesthesia, somnolence.
- Bipolar I Disorder Adults (Monotherapy): somnolence, oral hypoesthesia, dizziness, extrapyramidal symptoms (excluding akathisia) and akathisia.
- Bipolar I Disorder Pediatric Patients (Monotherapy): somnolence, dizziness, dysgeusia, oral paresthesia, nausea, increased appetite, fatigue, increased weight.
- Bipolar I Disorder Adults (Adjunctive): somnolence, oral hypoesthesia.
CONTRAINDICATIONS:
Severe hepatic impairment (Child-Pugh C). (8.7, 12.3)
Known hypersensitivity to SAPHRIS (asenapine), or to any components in the formulation. (4, 5.6, 17)
WARNINGS AND PRECAUTIONS:
- Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis: Increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack). (5.2)
- Neuroleptic Malignant Syndrome: Manage with immediate discontinuation and close monitoring. (5.3)
- Tardive Dyskinesia: Discontinue if clinically appropriate. (5.4)
- Metabolic Changes: Monitor for hyperglycemia/diabetes mellitus, dyslipidemia, and weight gain. (5.5)
- Orthostatic Hypotension: Monitor heart rate and blood pressure and warn patients with known cardiovascular or cerebrovascular disease, and risk of dehydration or syncope. (5.7)
- Leukopenia, Neutropenia, and Agranulocytosis: Perform complete blood counts (CBC) in patients with pre-existing low white blood cell count (WBC) or history of leukopenia or neutropenia. Consider discontinuing SAPHRIS if a clinically significant decline in WBC occurs in absence of other causative factors. (5.9)
- QT Prolongation: Increases in QT interval; avoid use with drugs that also increase the QT interval and in patients with risk factors for prolonged QT interval. (5.10)
- Seizures: Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold. (5.12)
- Potential for Cognitive and Motor Impairment: Use caution when operating machinery. (5.13)
DRUG INTERACTIONS:
- Antihypertensive Drugs: SAPHRIS may cause hypotension. (5.7, 7.1, 12.3)
- Paroxetine (CYP2D6 substrate and inhibitor): Reduce paroxetine by half when used in combination with SAPHRIS. (7.1, 12.3)
OVERDOSE:
In adult pre-marketing clinical studies involving more than 3350 patients and/or healthy subjects, accidental or intentional acute overdosage of SAPHRIS was identified in 3 patients. Among these few reported cases of overdose, the highest estimated ingestion of SAPHRIS was 400 mg. Reported adverse reactions at the highest dosage included agitation and confusion.
Management of Overdosage: There is no specific antidote to SAPHRIS. The possibility of multiple drug involvement should be considered. An electrocardiogram should be obtained and management of overdose should concentrate on supportive therapy, maintaining an adequate airway, oxygenation and ventilation, and management of symptoms. Consult with a Certified Poison Control Center for up-to-date guidance and advice on the management of overdosage (1-800-222-1222.) 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 SAPHRIS-induced alpha blockade). In case of severe extrapyramidal symptoms, anticholinergic medication should be administered. Close medical supervision and monitoring should continue until the patient recovers
- Uses
-
INDICATION AND USES:
SAPHRIS is an atypical antipsychotic indicated for (1):
- Schizophrenia in adults
- Bipolar I disorder
- Acute monotherapy treatment of manic or mixed episodes, in adults and pediatric patients 10 to 17 years of age
- Adjunctive treatment to lithium or valproate in adults
- Maintenance monotherapy treatment in adults
DOSAGE AND ADMINISTRATION
Starting Dose Recommended Dose Maximum Dose Schizophrenia – acute treatment in adults (2.2) 5 mg sublingually twice daily 5 mg sublingually twice daily 10 mg sublingually twice daily Schizophrenia – maintenance treatment in adults (2.2) 5 mg sublingually twice daily 5-10 mg sublingually twice daily 10 mg sublingually twice daily Bipolar mania – adults: acute and maintenance monotherapy (2.3) 5-10 mg sublingually twice daily 5-10 mg sublingually twice daily 10 mg sublingually twice daily Bipolar mania – pediatric patients (10 to 17 years): monotherapy (2.3) 2.5 mg sublingually twice daily 2.5-10 mg sublingually twice daily 10 mg sublingually twice daily Bipolar mania – adults as an adjunct to lithium or valproate (2.3) 5 mg sublingually twice daily 5-10 mg sublingually twice daily 10 mg sublingually twice daily Do not swallow tablet. SAPHRIS sublingual tablets should be placed under the tongue and left to dissolve completely. The tablet will dissolve in saliva within seconds. Eating and drinking should be avoided for 10 minutes after administration. (2.1, 17)
- Side Effects
-
SIDE EFFECTS:
The most commonly observed adverse reactions (incidence ≥5% and at least twice that for placebo) were (6.1):
- Schizophrenia Adults: akathisia, oral hypoesthesia, somnolence.
- Bipolar I Disorder Adults (Monotherapy): somnolence, oral hypoesthesia, dizziness, extrapyramidal symptoms (excluding akathisia) and akathisia.
- Bipolar I Disorder Pediatric Patients (Monotherapy): somnolence, dizziness, dysgeusia, oral paresthesia, nausea, increased appetite, fatigue, increased weight.
- Bipolar I Disorder Adults (Adjunctive): somnolence, oral hypoesthesia.
- Precautions
-
CONTRAINDICATIONS:
Severe hepatic impairment (Child-Pugh C). (8.7, 12.3)
Known hypersensitivity to SAPHRIS (asenapine), or to any components in the formulation. (4, 5.6, 17)
WARNINGS AND PRECAUTIONS:
- Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis: Increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack). (5.2)
- Neuroleptic Malignant Syndrome: Manage with immediate discontinuation and close monitoring. (5.3)
- Tardive Dyskinesia: Discontinue if clinically appropriate. (5.4)
- Metabolic Changes: Monitor for hyperglycemia/diabetes mellitus, dyslipidemia, and weight gain. (5.5)
- Orthostatic Hypotension: Monitor heart rate and blood pressure and warn patients with known cardiovascular or cerebrovascular disease, and risk of dehydration or syncope. (5.7)
- Leukopenia, Neutropenia, and Agranulocytosis: Perform complete blood counts (CBC) in patients with pre-existing low white blood cell count (WBC) or history of leukopenia or neutropenia. Consider discontinuing SAPHRIS if a clinically significant decline in WBC occurs in absence of other causative factors. (5.9)
- QT Prolongation: Increases in QT interval; avoid use with drugs that also increase the QT interval and in patients with risk factors for prolonged QT interval. (5.10)
- Seizures: Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold. (5.12)
- Potential for Cognitive and Motor Impairment: Use caution when operating machinery. (5.13)
- Interactions
-
DRUG INTERACTIONS:
- Antihypertensive Drugs: SAPHRIS may cause hypotension. (5.7, 7.1, 12.3)
- Paroxetine (CYP2D6 substrate and inhibitor): Reduce paroxetine by half when used in combination with SAPHRIS. (7.1, 12.3)
- Overdose
-
OVERDOSE:
In adult pre-marketing clinical studies involving more than 3350 patients and/or healthy subjects, accidental or intentional acute overdosage of SAPHRIS was identified in 3 patients. Among these few reported cases of overdose, the highest estimated ingestion of SAPHRIS was 400 mg. Reported adverse reactions at the highest dosage included agitation and confusion.
Management of Overdosage: There is no specific antidote to SAPHRIS. The possibility of multiple drug involvement should be considered. An electrocardiogram should be obtained and management of overdose should concentrate on supportive therapy, maintaining an adequate airway, oxygenation and ventilation, and management of symptoms. Consult with a Certified Poison Control Center for up-to-date guidance and advice on the management of overdosage (1-800-222-1222.) 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 SAPHRIS-induced alpha blockade). In case of severe extrapyramidal symptoms, anticholinergic medication should be administered. Close medical supervision and monitoring should continue until the patient recovers