IMPORTANT SAFETY INFORMATION AND INDICATIONS
IMPORTANT SAFETY INFORMATION
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. SAPHRIS is not approved for treatment of patients with dementia-related
Contraindications: SAPHRIS is contraindicated in patients with severe hepatic impairment (Child-Pugh C) or known hypersensitivity
to SAPHRIS or its formulation components. Reactions have included anaphylaxis and angioedema.
Cerebrovascular Adverse Events, Including Stroke: In clinical trials with antipsychotic drugs, elderly subjects with dementia had
a higher incidence of cerebrovascular adverse reactions, including fatalities vs placebo. SAPHRIS is not approved for the treatment of patients
with dementia-related psychosis.
Neuroleptic Malignant Syndrome (NMS): NMS, a potentially fatal symptom complex, has been reported with antipsychotics, including
SAPHRIS. NMS may cause hyperpyrexia, muscle rigidity, altered mental status, irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac
dysrhythmia. Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Management includes
immediate discontinuation of antipsychotics and other drugs not essential to concurrent therapy, intensive symptomatic treatment and monitoring, and
treatment of any concomitant serious medical problems.
Tardive Dyskinesia (TD): Risk of developing TD (a syndrome of potentially irreversible, involuntary dyskinetic movements) and the
likelihood it will become irreversible may increase as the duration of treatment and total cumulative dose of antipsychotic drugs given to the patient
increase. The syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses. Prescribe SAPHRIS in a manner
most likely to minimize TD. If signs and symptoms of TD appear, drug discontinuation should be considered.
Metabolic Changes: Atypical antipsychotics have been associated with metabolic changes that may increase cardiovascular/cerebrovascular risk:
Hyperglycemia and Diabetes Mellitus: Hyperglycemia, in some cases associated with ketoacidosis, hyperosmolar coma, or death, has
been reported in patients treated with atypical antipsychotics. Patients with risk factors for diabetes mellitus starting treatment with antipsychotics
should undergo fasting blood glucose testing at the beginning of and during treatment. Monitor any patient treated with antipsychotics for symptoms
of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop these symptoms during treatment should undergo fasting
blood glucose testing. In some cases, hyperglycemia resolved when the antipsychotic was discontinued; however, some patients required continuation
of anti-diabetic treatment despite discontinuation of the antipsychotic drug.
Dyslipidemia: Undesirable alterations in lipids have been observed in patients treated with atypical antipsychotics.
Weight Gain: Increases in weight have been observed with SAPHRIS. Monitor weight regularly in patients on SAPHRIS.
Hypersensitivity Reactions: Hypersensitivity reactions, including anaphylaxis, angioedema, hypotension, tachycardia, swollen tongue,
dyspnea, wheezing, and rash, have been observed in patients treated with SAPHRIS. In several cases, these reactions occurred after the first dose.
Orthostatic Hypotension, Syncope, and Other Hemodynamic Effects: SAPHRIS may induce orthostatic hypotension and syncope. Use SAPHRIS
with caution in patients with cardiovascular/cerebrovascular diseases, conditions which predispose to hypotension, and in the elderly. Use SAPHRIS
cautiously with other drugs that can induce hypotension, bradycardia, or respiratory or central nervous system depression. Monitor orthostatic vital
signs, and consider a dose reduction if hypotension occurs.
Leukopenia, Neutropenia, and Agranulocytosis: Leukopenia/neutropenia have been reported with antipsychotics, including SAPHRIS.
Agranulocytosis (including fatal cases) has been reported with other antipsychotics. Monitor complete blood count in patients with pre-existing low white
blood cell count (WBC)/absolute neutrophil count or history of drug-induced leukopenia/neutropenia. Discontinue SAPHRIS at the first sign of a clinically
significant decline in WBC and in severely neutropenic patients.
QT Prolongation: In an adult QT study, SAPHRIS was associated with increases in the QTc interval from 2 to 5 msec vs placebo. No SAPHRIS
patients had QTc increases of ≥60 msec or a QTc of ≥500 msec. Avoid SAPHRIS in combination with other drugs known to prolong QTc interval, in patients with
congenital prolongation of QT interval or a history of cardiac arrhythmias, and in circumstances that may increase occurrence of torsades de pointes and/or
sudden death in association with the use of drugs that prolong QTc interval.
Hyperprolactinemia: Like other drugs that antagonize dopamine D2 receptors, SAPHRIS can elevate prolactin levels and the elevation can
persist during chronic administration. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in patients receiving prolactin-elevating
Seizures: Use SAPHRIS with caution in patients with history of seizures or with conditions that lower the seizure threshold.
Potential for Cognitive and Motor Impairment: Somnolence was reported with SAPHRIS. Caution patients about performing activities requiring
mental alertness (eg, operating hazardous machinery or a motor vehicle).
Body Temperature Regulation: Appropriate care is advised when using SAPHRIS in patients who will experience conditions that increase body
temperature, eg, exercising strenuously, extreme heat, concomitant anticholinergics, or dehydration.
Suicide: The possibility of suicide attempt is inherent in psychotic illnesses and bipolar disorder. Close supervision of high-risk
patients should accompany drug therapy. Prescriptions should be written for the smallest quantity of tablets to reduce risk of overdose.
Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotics. Aspiration pneumonia is a common cause of
morbidity/mortality in elderly patients, in particular those with advanced Alzheimer’s dementia. SAPHRIS should not be used in patients at risk for
Drug Interactions: Monitor blood pressure and adjust antihypertensive drugs when taken with SAPHRIS. Based on clinical response,
SAPHRIS dose reduction may be necessary when used with strong CYP1A2 inhibitors (fluvoxamine). Reduce paroxetine (CYP2D6 substrate and inhibitor)
dose by half when taken with SAPHRIS.
Pregnancy: Advise patients to notify their healthcare provider of a known or suspected pregnancy. SAPHRIS may cause extrapyramidal
and/or withdrawal symptoms in neonates with third trimester exposure. Based on animal data, SAPHRIS may cause fetal harm. The National Pregnancy
Registry for Atypical Antipsychotics monitors pregnancy outcomes in women exposed to antipsychotics, including SAPHRIS, during pregnancy. For information,
contact 1-866-961-2388 or http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/.
Adverse Reactions: In clinical trials, commonly observed adverse reactions (≥5% and at least twice the rate of placebo) in adults
treated with SAPHRIS (5 and 10 mg BID) or pediatric patients (ages 10-17) treated with SAPHRIS (2.5, 5, and 10 mg BID) vs placebo were:
- Adult schizophrenia: akathisia (6% vs 3%), oral hypoesthesia (5% vs 1%), and somnolence (13% vs 7%)
- Adult bipolar I (monotherapy): somnolence (24% vs 6%), dizziness (11% vs 3%), extrapyramidal symptoms other than akathisia
(7% vs 2%), and increased weight (5% vs <1%)
- Adult bipolar I (adjunctive): somnolence (22% vs 10%) and oral hypoesthesia (5% vs 0%)
- Pediatric bipolar I (monotherapy): somnolence (49% vs 12%), dizziness (7% vs 3%), dysgeusia (6% vs 2%), oral paresthesia
(27% vs 4%), nausea (6% vs 3%), increased appetite (8% vs 2%), fatigue (9% vs 5%), and increased weight (3% vs 0%)
Postmarketing Experience: Application site reactions, primarily sublingual, have been reported (eg, oral ulcers, blisters,
peeling/sloughing, and inflammation). Choking has been reported, sometimes associated with oropharyngeal muscular dysfunction or hypoesthesia.
Indications and Usage
In bipolar I disorder:
SAPHRIS (asenapine) is indicated for the acute treatment of manic or mixed episodes of bipolar
I disorder as monotherapy in adults or pediatric patients (ages 10-17) or as adjunctive therapy
with either lithium or valproate in adults.
SAPHRIS is indicated for the acute and maintenance treatment of schizophrenia in adults.
Please also see the full Prescribing Information, including Boxed