Dosing and uses of Saphris (asenapine)
Adult dosage forms and strengths
sublingual tablet
- 2.5mg
- 5mg
- 10mg
Schizophrenia
5 mg SL q12hr initially; maintenance: after 1 week, may be increased up to 10 mg PO q12hr
Bipolar Disorder
Manic or mixed episodes associated with bipolar I disorder, either as monotherapy or as adjunct to lithium or valproate
Monotherapy: 10 mg PO q12hr initially; may be decreased to 5 mg PO q12hr on day 2 and subsequent days if warranted by adverse effects or individual tolerance (90% of patients typically remain on higher dose)
Adjunct to lithium or valproate: 5 mg PO q12hr initially; may be increased to 10 mg PO q12hr if warranted
If patient responds favorably, continue beyond initial acute phase (no recommendations at this time for duration of therapy)
Dosage modifications
Renal impairment
- Dose adjustment not necessary
Hepatic impairment
- Mild to moderate impairment (Child-Pugh class A or B): Dose adjustment not necessary
- Severe impairment (Child-Pugh class C): Contraindicated
Pediatric dosage forms and strengths
sublingual tablet
- 2.5mg
- 5mg
- 10mg
Bipolar Disorder
Indicated as monotherapy for acute treatment of manic or mixed episodes associated with bipolar I disorder
<10 years: Safety and efficacy not established
10-17 years: 2.5 SL q12hr initially; may increase to 5 mg SL q12hr after 3 days and to 10 mg SL q12hr after 3 additional days
Dosing Considerations
Pediatric patients are more sensitive to dystonia with initial dosing when recommended escalation schedule not followed
Safety and efficacy of doses >10 mg q12hr not established
Geriatric dosage forms and strengths
Not indicated for dementia-related psychosis, in view of increased risk of death as compared with placebo (see Black box warnings)
In elderly patients with psychosis, asenapine exposure (area under curve [AUC]) was on average 40% higher than in younger adults
Saphris (asenapine) adverse (side) effects
>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
Warnings
Black box warnings
Not indicated for dementia-related psychosis; increased risk of death in elderly patients with dementia-related psychosis; placebo-controlled trials with other atypical antipsychotics (ie, risperidone, aripiprazole, olanzapine) showed higher incidence of cerebrovascular adverse reactions (eg, cerebrovascular accidents [CVAs], transient ischemic attacks [TIAs]), including fatalities, in comparison with placebo
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
Extrapyramidal symptoms, including acute dystonic reactions, pseudoparkinsonism, akathisia, and tardive dyskinesia reported
Hyperglycemia (monitor patients with diabetes mellitus for worsening of glucose control)
Weight gain may occur; monitor weight gain in pediatric patients and assess against that expected for normal growth
Hypotension and syncope, especially early in treatment, because of drug's alpha1-antagonistic activity
Leukopenia, neutropenia, and agranulocytosis reported with use
Possible prolongation of QTc interval; avoid in patients with history of cardiac arrhythmias or other conditions that increase risk of torsades de pointes (eg, bradycardia, hypokalemia, hypomagnesemia)
Coadministration with other drugs that prolong QTc interval may result in life-threatening arrhythmias (eg, class 1A antiarrhythmics [quinidine, procainamide], class 3 antiarrhythmics [amiodarone, sotalol], antipsychotics [ziprasidone, chlorpromazine, thioridazine], and antibiotics [moxifloxacin])
Concurrent use of CNS-acting drugs or alcohol may increase toxicity
Use caution in patients with history of seizures
Cognitive or motor impairment may occur due to CNS depression
Dysphagia, dysmotility, and aspiration may occur
Potential disruption of body temperature regulation
Not recommended with severe hepatic impairment (Child-Pugh class C)
Inherent suicide risk with population treated warrants close supervision when drug therapy is changed
May increase prolactin levels; significance unknown
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
Pregnancy and lactation
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.
Pharmacology of Saphris (asenapine)
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%)
Administration
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
