logo

SAPHRIS® (asenapine) sublingual tablets

DESCRIPTION CLINICAL PHARMACOLOGY INDICATIONS AND USAGE
CONTRAINDICATIONS PRECAUTIONS ADVERSE REACTIONS
DOSAGE AND ADMINISTRATION HOW SUPPLIED WARNINGS
PRESCRIBING HIGHLIGHTS:  Please see package insert for additional information and possible updates to ensure safe and effective use of this medication. The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material. Please read the disclaimer carefully BEFORE accessing or using this site. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.  
  < Antipsychotic agentsled  
[ Disclaimer ] <<Back [ New drug index ]

WARNINGS  top of page

WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in the drug-treated patients of between 1.6 to 1.7 times that seen in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. SAPHRIS® (asenapine) is not approved for the treatment of patients with dementia-related psychosis [see Warnings and Precautions].

(DESCRIPTION) top of page

Initial U.S. Approval: 2009
DESCRIPTION
SAPHRIS is a psychotropic agent that is available for sublingual administration. Asenapine belongs to the class dibenzo-oxepino pyrroles. The chemical designation is (3aRS,12bRS)-5-Chloro-2-methyl-2,3,3a,12b-tetrahydro-1Hdibenzo[2,3:6,7]oxepino[4,5-c]pyrrole (2Z)-2-butenedioate (1:1). Its molecular formula is C17H16ClNO•C4H4O4 and its molecular weight is 401.84 (free base: 285.8).

Asenapine is a white to off-white powder.

SAPHRIS is supplied for sublingual administration in tablets containing 5-mg or 10-mg asenapine; inactive ingredients include gelatin and mannitol.

SAPHRIS, black cherry flavor, is supplied for sublingual administration in tablets containing 5-mg or 10-mg asenapine; inactive ingredients include gelatin, mannitol, sucralose, and black cherry flavor.

CLINICAL PHARMACOLOGY: top of page

CLINICAL PHARMACOLOGY

Mechanism of Action
The mechanism of action of asenapine, as with other drugs having efficacy in schizophrenia and bipolar disorder, is unknown. It has been suggested that the efficacy of asenapine in schizophrenia is mediated through a combination of antagonist activity at D2 and 5-HT2A receptors.

INDICATIONS AND USAGE  top of page

INDICATIONS AND USAGE
Schizophrenia
SAPHRIS is indicated for the treatment of schizophrenia. The efficacy of SAPHRIS was established in two 6-week trials and one maintenance trial in adults.

Bipolar Disorder
Monotherapy: SAPHRIS is indicated for the acute treatment of manic or mixed episodes associated with bipolar I disorder. Efficacy was established in two 3-week monotherapy trials in adults.

Adjunctive Therapy: SAPHRIS is indicated as adjunctive therapy with either lithium or valproate for the acute treatment of manic or mixed episodes associated with bipolar I disorder. Efficacy was established in one 3-week adjunctive trial in adults

CONTRAINDICATIONS top of page

Known hypersensitivity to SAPHRIS (asenapine), or to any components in the formulation.

PRECAUTIONS top of page

WARNINGS AND PRECAUTIONS
  • Cerebrovascular Adverse Events: An increased incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack) has been seen in elderly patients with dementia-related psychoses treated with atypical antipsychotic drugs.
  • Neuroleptic Malignant Syndrome: Manage with immediate discontinuation and close monitoring.
  • Tardive Dyskinesia: Discontinue if clinically appropriate.
  • Hyperglycemia and Diabetes Mellitus: Monitor patients for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Monitor glucose regularly in patients with, and at risk for, diabetes.
  • Weight Gain: Patients should receive regular monitoring of weight.
  • Hypersensitivity Reactions: Hypersensitivity reactions, including anaphylaxis and angioedema, have been observed.
  • Orthostatic Hypotension and Syncope: Dizziness, tachycardia or bradycardia, and syncope may occur, especially early in treatment. Use with caution in patients with known cardiovascular or cerebrovascular disease, and in antipsychotic-naïve patients.
  • Leukopenia, Neutropenia, and Agranulocytosis have been reported with antipsychotics. Patients with a pre-existing low white blood cell count (WBC) or a history of leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and SAPHRIS should be discontinued at the first sign of a decline in WBC in the absence of other causative factors.
  • 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.
  • Seizures: Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold.
  • Potential for Cognitive and Motor Impairment: Use caution when operating machinery.
  • Suicide: The possibility of a suicide attempt is inherent in schizophrenia and bipolar disorder. Closely supervise high-risk patients.

ADVERSE REACTIONS top of page

ADVERSE REACTIONS
Commonly observed adverse reactions (incidence geq5% and at least twice that for placebo) were:

Schizophrenia: akathisia, oral hypoesthesia, and somnolence.
Bipolar Disorder (Monotherapy): somnolence, dizziness, extrapyramidal symptoms other than akathisia, and weight increased.
Bipolar Disorder (Adjunctive): somnolence and oral hypoesthesia.


To report SUSPECTED ADVERSE REACTIONS, contact Schering Corporation, a subsidiary of Merck & Co., Inc., at 1-800-526-4099 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DOSAGE AND ADMINISTRATION  top of page

DOSAGE AND ADMINISTRATION
  Starting Dose Recommended Dose Maximum Dose
Schizophrenia – acute treatment in adults 5 mg sublingually twice daily 5 mg sublingually twice daily 10 mg sublingually twice daily
Schizophrenia – maintenance treatment in adults 5 mg sublingually twice daily for one week 10 mg sublingually twice daily 10 mg sublingually twice daily
Bipolar mania – adults: monotherapy 10 mg sublingually twice daily 5–10 mg sublingually twice daily 10 mg sublingually twice daily
Bipolar mania – adults: as an adjunct to lithium or valproate 5 mg sublingually twice daily 5–10 mg sublingually twice daily 10 mg sublingually twice daily
Administration: 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.

Administration Instructions
SAPHRIS is a sublingual tablet. To ensure optimal absorption, patients should be instructed to place the tablet under the tongue and allow it to dissolve completely. The tablet will dissolve in saliva within seconds. SAPHRIS sublingual tablets should not be crushed, chewed, or swallowed. Patients should be instructed to not eat or drink for 10 minutes after administration .

Schizophrenia
Usual Dose for Acute Treatment in Adults: The recommended starting and target dose of SAPHRIS is 5 mg given twice daily. In short term controlled trials, there was no suggestion of added benefit with a 10 mg twice daily dose, but there was a clear increase in certain adverse reactions. The safety of doses above 10 mg twice daily has not been evaluated in clinical studies.


Maintenance Treatment: Efficacy was demonstrated with SAPHRIS in a maintenance trial in patients with schizophrenia. The starting dose in this study was 5 mg twice daily with an increase up to 10 mg twice daily after 1 week based on tolerability. While there is no body of evidence available to answer the question of how long the schizophrenic patient should remain on SAPHRIS, patients should be periodically reassessed to determine the need for maintenance treatment.


Bipolar Disorder
Usual Dose for Acute Treatment of Manic or Mixed Episodes Associated with Bipolar I Disorder in Adults:


Monotherapy: The recommended starting dose of SAPHRIS, and the dose maintained by 90% of the patients studied, is 10 mg twice daily. The dose can be decreased to 5 mg twice daily if warranted by adverse effects or based on individual tolerability.

In controlled monotherapy trials, the starting dose for SAPHRIS was 10 mg twice daily. On the second and subsequent days of the trials, the dose could be lowered to 5 mg twice daily, based on tolerability, but less than 10% of patients had their dose reduced. The safety of doses above 10 mg twice daily has not been evaluated in clinical trials.


Adjunctive Therapy: The recommended starting dose of SAPHRIS is 5 mg twice daily when administered as adjunctive therapy with either lithium or valproate. Depending on the clinical response and tolerability in the individual patient, the dose can be increased to 10 mg twice daily. The safety of doses above 10 mg twice daily as adjunctive therapy with lithium or valproate has not been evaluated in clinical trials.


Maintenance Treatment: While there is no body of evidence available to answer the question of how long the bipolar patient should remain on SAPHRIS, whether used as monotherapy or as adjunctive therapy with lithium or valproate, it is generally recommended that responding patients be continued beyond the acute response. If SAPHRIS is used for extended periods in bipolar disorder, the physician should periodically re-evaluate the long-term risks and benefits of the drug for the individual patient.


Dosage in Special Populations
In a study of subjects with hepatic impairment who were treated with a single dose of SAPHRIS 5 mg, there were increases in asenapine exposures (compared to subjects with normal hepatic function), that correlated with the degree of hepatic impairment. While the results indicated that no dosage adjustments are required in patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment, there was a 7-fold increase (on average) in asenapine concentrations in subjects with severe hepatic impairment (Child-Pugh C) compared to the concentrations of those in subjects with normal hepatic function. Therefore, SAPHRIS is not recommended in patients with severe hepatic impairment. Dosage adjustments are not routinely required on the basis of age, gender, race, or renal impairment status [see Use in Specific Populations and Clinical Pharmacology].


Switching from Other Antipsychotics
There are no systematically collected data to specifically address switching patients with schizophrenia or bipolar mania from other antipsychotics to SAPHRIS or concerning concomitant administration with other antipsychotics. While immediate discontinuation of the previous antipsychotic treatment may be acceptable for some patients with schizophrenia, more gradual discontinuation may be most appropriate for others. In all cases, the period of overlapping antipsychotic administration should be minimized

HOW SUPPLIED top of page

HOW SUPPLIED/STORAGE AND HANDLING
SAPHRIS (asenapine) sublingual tablets are supplied as:


5-mg Tablets
Round, white to off-white sublingual tablets, with "5" on one side.
Child-resistant packaging
Box of 60 6 blisters with 10 tablets NDC 0052-0118-06
Hospital Unit Dose
Box of 100 10 blisters with 10 tablets NDC 0052-0118-90

10-mg Tablets
Round, white to off-white sublingual tablets, with "10" on one side.
Child-resistant packaging
Box of 60 6 blisters with 10 tablets NDC 0052-0119-06
Hospital Unit Dose
Box of 100 10 blisters with 10 tablets NDC 0052-0119-90

5-mg Tablets, black cherry flavor
Round, white to off-white sublingual tablets, with "5" on one side within a circle.
Child-resistant packaging
Box of 60 6 blisters with 10 tablets NDC 0052-2139-03
Hospital Unit Dose
Box of 100 10 blisters with 10 tablets NDC 0052-2139-04

10-mg Tablets, black cherry flavor
Round, white to off-white sublingual tablets, with "10" on one side within a circle.
Child-resistant packaging
Box of 60 6 blisters with 10 tablets NDC 0052-2142-03
Hospital Unit Dose
Box of 100 10 blisters with 10 tablets NDC 0052-2142-04


Storage
Store at 15°–30°C (59°–86°F) [see USP Controlled Room Temperature].

REFERENCE

Package Insert data: 

Manufactured by: Catalent UK Swindon Zydis Ltd., Blagrove, Swindon, Wiltshire, SN5 8RU, UK
U.S. Patent Nos. 5,763,476 and 7,741,358.
Copyright © 2009, 2011 N.V. Organon, a subsidiary of Merck & Co., Inc. All rights reserved.
Rev. 10/11
51310040


PRINCIPAL DISPLAY PANEL - 5 mg Bottle Carton
Rx only
NDC 0052-0118-06
Saphris® 5 mg
(asenapine) sublingual tablets

Fragile: Do not push tablet through
tablet pack.
Do not crush tablet. Do not chew or
swallow tablet.
60 Tablets
more Career Center image description
Medical Calculators - A thru Z
Lab Values - A thru Z