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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 psychosis.

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, angioedema, hypotension, tachycardia, swollen tongue, dyspnea, wheezing and rash.

Cerebrovascular Adverse Events, Including Stroke: In clinical trials with antipsychotic drugs, elderly subjects with dementia had a higher incidence of stroke (including fatal stroke) and transient ischemic attack 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. NMS may cause hyperpyrexia, muscle rigidity, delirium, and autonomic instability. If NMS is suspected, immediately discontinue SAPHRIS and provide intensive symptomatic treatment and monitoring.

Tardive Dyskinesia (TD): Risk of developing TD (a syndrome of potentially irreversible, involuntary dyskinetic movements) and the likelihood it will become irreversible increase as the duration of treatment and total cumulative dose of antipsychotic drugs, including SAPHRIS, given to the patient increase. The syndrome can develop, after relatively brief treatment periods, even at low doses, and may also occur after discontinuation of treatment. 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, including SAHPRIS, have caused metabolic changes, including the following:

  • Hyperglycemia and Diabetes Mellitus: Hyperglycemia, in some cases associated with ketoacidosis, hyperosmolar coma, or death, has been reported in patients treated with atypical antipsychotics. Hyperglycemia has been reported with SAPHRIS. Assess fasting plasma glucose before or soon after initiation of treatment, and monitor periodically during long-term treatment.
  • Dyslipidemia: Atypical antipsychotics cause adverse alterations in lipids have been observed in patients treated with atypical antipsychotics. Before or soon after initiation of antipsychotics, obtain a baseline fasting lipid profile and monitor periodically during treatment.
  • Weight Gain: Weight gain has been observed with atypical antipsychotics, including SAPHRIS. Monitor weight at baseline and frequently thereafter.

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 has caused orthostatic hypotension and syncope. Generally the risk is greatest during initial titration and when increasing the dose. Monitor orthostatic vital signs and monitor patients who are vulnerable to hypotension (elderly patients, patients with dehydration, hypovolemia, concomitant treatment with antihypertensive medications, patients with cardiovascular and/or cerebrovascular disease). Use SAPHRIS cautiously with other drugs that can cause hypotension, bradycardia, or respiratory or central nervous system depression. Monitor orthostatic vital signs, and consider a dose reduction if hypotension occurs.

Falls: SAPHRIS may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures, or other injuries. For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating antipsychotics and recurrently for patients on long-term therapy.

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) or absolute neutrophil count or history of drug-induced leukopenia or 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 compounds.

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.

Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotics. Dysphagia has been reported with SAPHRIS. Use SAPHRIS cautiously in patients at risk for dysphagia.

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, the most commonly observed adverse reactions 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: somnolence (13% vs 7%), akathisia (6% vs 3%), and oral hypoesthesia (5% vs 1%)
  • Adult bipolar I (monotherapy): somnolence (23% vs 5%), oral hypoesthesia (10% vs 1%), dizziness (8% vs 4%), extrapyramidal symptoms excluding akathisia (8% vs 4%), and akathisia (6% vs 2%)
  • Adult bipolar I (adjunctive): somnolence (22% vs 10%) and oral hypoesthesia (5% vs 0%)
  • Pediatric bipolar I (monotherapy): somnolence (49% vs 12%), oral hypoesthesia (27% vs 4%), fatigue (9% vs 5%), increased appetite (8% vs 2%), dizziness (7% vs 3%), dysgeusia (6% vs 2%), nausea (6% vs 3%), 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.

Please also see the full Prescribing Information, including Boxed Warning.