asenapine (Rx)

>10%

Somnolence (24%)

Headache (12%)

Dizziness (11%)

Pediatric patients

• Oral paraesthesia (27%)
• Somnolence (49%)

1-10%

Extrapyramidal symptoms (EPS) other than akathisia (7%)

Insomnia (6%)

Weight gain (5%)

Akathisia (4%)

Anxiety (4%)

Fatigue (4%)

Oral hypoesthesia (4%)

Dyspepsia (4%)

Dry mouth (3%)

Dysgeusia (3%)

Arthralgia (3%)

Toothache (3%)

Depression (2%)

Extremity pain (2%)

Pediatric patients

• Nausea (6%)
• Abdominal pain (6%)
• Fatigue (9%)
• Increased weight (3%)
• Hyperinsulinemia (2%)
• Increased appetite (8%)
• Headache (9%)
• Dizziness (7%)
• Dysgeusia (6%)
• Akathisia (2%)
• Insomnia (3%)
• Suicidal ideation (3%)
• Tachycardia (1%), Glossodynia (1%), Irritability (1%), Muscle pain (1%), Increased ALT (1%), Increased AST (1%), Dehydration (1%), Myalgia (1%), Parkinsonism (1%), Anger (1%), Dysmenorrhea (1%), Rash (1%), Nasal congestion (1%), Dyspnea (1%), Oropharyngeal pain (1%)

Postmarketing Reports

Sublingual administration: Application site reactions including oral ulcers, blisters, peeling/sloughing, and inflammation

Choking reported by patients, some of whom may have also experienced oropharyngeal muscular dysfunction or hypoesthesia

Falls

Contraindications

Known hypersensitivity

Severe hepatic impairment (Child-Pugh C)

Cautions

Type 1 hypersensitivity reactions, including anaphylaxis and angioedema, have been reported (n=52), in several cases occurring after first dose; symptoms include anaphylaxis, angioedema, hypotension, tachycardia, tongue and laryngeal edema, difficulty breathing, wheezing, or rash

Neuroleptic malignant syndrome associated with use; monitor for symptoms and discontinue if necessary

Hyperglycemia (monitor patients with diabetes mellitus for worsening of glucose control); assess fasting plasma glucose before or soon after initiation of antipsychotic medication, and monitor periodically during long-term treatment

Weight gain may occur; monitor weight at baseline and frequently thereafter; monitor weight in pediatric patients and assess against that expected for normal growth

Hypotension and syncope, especially during initial dose titration and when increasing dose; orthostatic vital signs should be monitored in patients who are vulnerable to hypotension (elderly patients, patients with dehydration, hypovolemia, concomitant treatment with antihypertensive medications, patients with known cardiovascular disease (history of myocardial infarction or ischemic heart disease, heart failure, or conduction abnormalities), and patients with cerebrovascular disease; monitoring of orthostatic vital signs should be considered in such patients, and dose reduction considered if hypotension occurs

Leukopenia, neutropenia, and agranulocytosis reported with use; perform a complete blood count (CBC) during first few months of therapy; in such patients, consider discontinuation of therapy at first sign of clinically significant decline in WBC in absence of other causative factors

Concurrent use of CNS-acting drugs or alcohol may increase toxicity

Use with caution in patients with a history of seizures or with conditions that potentially lower seizure threshold; conditions that lower seizure threshold may be more prevalent in patients 65 years or older

Cognitive or motor impairment may occur due to CNS depression; caution patients about operating hazardous machinery, including motor vehicles, until they are reasonably certain that therapy does not affect them adversely

Dysphagia, dysmotility, and aspiration may occur; use cautiously in patients at risk for aspiration

Potential disruption of body temperature regulation; strenuous exercise, exposure to extreme heat, dehydration, and anticholinergic medications may contribute to elevation in core body temperature; use with caution in patient who may experience these conditions

Not recommended with severe hepatic impairment (Child-Pugh class C)

Inherent suicide risk with population treated warrants close supervision when drug therapy is changed

Atypical antipsychotic drugs have been associated with metabolic changes including hyperglycemia, dyslipidemia, and body weight gain, which may increase cardiovascular/ cerebrovascular risk; all of the drugs in the class have been shown to produce some metabolic changes but each drug has its own specific risk profile

Monitor weight gain in pediatric patients and assess against that expected for normal growth

Can elevate prolactin levels, and elevation can persist during chronic administration; hyperprolactinemia may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotropin secretion; this, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients

Orthostatic vital signs should be monitored in patients who are vulnerable to hypotension (elderly patients, patients with dehydration, hypovolemia, concomitant treatment with antihypertensive medications

May cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries; perform complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy

Extrapyramidal symptoms, including acute dystonic reactions, pseudoparkinsonism, akathisia, and tardive dyskinesia reported

QT prolongation

• Based on clinical trials, therapy should be avoided in combination with other drugs known to prolong QTc including Class 1A antiarrhythmics (eg, quinidine, procainamide) or Class 3 antiarrhythmics (e.g., amiodarone, sotalol), antipsychotic medications (eg, ziprasidone, chlorpromazine, thioridazine), and antibiotics (eg, gatifloxacin, moxifloxacin)
• Treatment should also be avoided in patients with a history of cardiac arrhythmias and in other circumstances that may increase risk of occurrence of torsade de pointes and/or sudden death in association with use of drugs that prolong QTc interval, including bradycardia; hypokalemia or hypomagnesemia; and presence of congenital prolongation of QT interval

Tardive dyskinesia

• Risk of tardive dyskinesia and likelihood that it will become irreversible increase with duration of treatment and cumulative dose
• Syndrome can develop after a relatively brief treatment period, even at low doses; may also occur after discontinuation of treatment; prescribe in a manner most likely to reduce risk of tardive dyskinesia
• Chronic antipsychotic treatment should generally be reserved for patients who suffer from a chronic illness that is known to respond to antipsychotic drugs and for whom alternative, effective, but potentially less harmful treatments are not available or appropriate; some patients may require treatment despite presence of syndrome
• In patients who do require chronic treatment, use lowest dose and shortest duration of treatment producing a satisfactory clinical response; periodically reassess need for continued treatment

Pregnancy category: C

Neonates exposed to antipsychotic drugs during 3rd trimester of pregnancy are at risk for EPS or withdrawal symptoms after delivery; these complications vary in severity, with some being self-limited and others requiring ICU unit support and prolonged hospitalization

Lactation: Excretion in milk unknown; use with caution

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Mechanism of action unknown; efficacy thought to be mediated via combined antagonist activity at dopamine D2 and serotonin type 2 (5-HT2) receptors

Absorption

Bioavailability: SL, 35%; swallowed, ≤2%

Peak plasma time: 0.5-1.5 hr

Peak plasma concentration: 4 ng/mL

Distribution

Protein bound: 95%

Vd: 20-25 L/kg

Metabolism

Metabolized by UGT1A4 and CYP450 (predominantly isoenzyme 1A2)

Enzymes inhibited: CYP2D6 (weakly)

Elimination

Half-life: 24 hr

Clearance: 52 L/hr

Excretion: Urine (50%), feces (40%)

Instructions

Sublingual tablet; to allow optimal absorption, place under tongue and allow to dissolve completely (dissolves within seconds)

Do not chew, split, crush, or swallow sublingual tablet

Do not eat or drink for at least 10 minutes after administration