Asenapine (Saphris, Secuado)
SGA • Last reviewed 2025-09-26
General information
Asenapine is an atypical second-generation antipsychotic available as sublingual tablets (Saphris) and a once-daily transdermal patch (Secuado). It is approved for schizophrenia and for acute manic or mixed episodes of bipolar I disorder as monotherapy or adjunctive therapy with lithium or valproate. Because of extensive first-pass metabolism, the sublingual formulation must not be swallowed; patients should avoid food or drink for 10 minutes after each dose.
Sublingual dosing starts at 5 mg twice daily with response typically at 5–10 mg twice daily. The transdermal patch delivers 3.8, 5.7, or 7.6 mg/24 h; titrate weekly based on tolerability and response. Asenapine’s receptor affinity profile produces lower weight gain compared with olanzapine but can still cause modest metabolic change.
Common adverse effects include oral hypoesthesia, somnolence, dizziness, akathisia, and modest prolactin elevation. Severe hepatic impairment markedly increases exposure and is a contraindication.
Transdermal asenapine delivers continuous exposure and can benefit patients who struggle with twice-daily sublingual dosing, though it may cause mild application-site pruritus.
Dosing & administration
Schizophrenia (sublingual): initiate 5 mg twice daily; may increase to 10 mg twice daily after ≥3 days.
Bipolar I manic/mixed episodes: start 10 mg twice daily on day 1, then continue 5–10 mg twice daily depending on response.
Transdermal patch: start 3.8 mg/24 h once daily; titrate to 5.7 mg/24 h or 7.6 mg/24 h at ≥1-week intervals.
Avoid food or drink for 10 minutes after sublingual dosing; rotate patch sites daily.
Reduce dose when co-administered with strong CYP1A2 inhibitors (fluvoxamine, ciprofloxacin).
Dose considerations
- Strong CYP1A2 inhibitors
- Reduce dose and monitor for sedation/EPS.
- Moderate hepatic impairment
- Use lower end of range with close monitoring.
- Severe hepatic impairment
- Contraindicated.
Mechanism of action
Asenapine antagonizes dopamine D2/D3 and serotonin 5-HT2A/2C receptors, providing antipsychotic efficacy with relatively low EPS risk.
Histamine H1 and adrenergic α1 antagonism contributes to sedation and orthostasis, while minimal muscarinic affinity limits anticholinergic burden.
- High 5-HT2A antagonism (Ki ~0.06 nM) exceeding D2 affinity.
- D3/D4 receptor blockade may benefit negative symptoms.
- Negligible muscarinic receptor affinity.
Metabolism & pharmacokinetics
Sublingual bioavailability ~35% with Tmax 0.5–1.5 h; transdermal Tmax 12–24 h.
Metabolized mainly via UGT1A4 glucuronidation and CYP1A2 oxidation; minor CYP2D6/CYP3A4 pathways. Half-life ~24 h (sublingual) to 30 h (transdermal).
Smoking has minimal effect; severe hepatic impairment increases exposure. ~95% protein bound.
Drug interactions
Strong CYP1A2 inhibitors (fluvoxamine, ciprofloxacin) increase levels; reduce dose.
Strong CYP1A2 inducers (rifampin, carbamazepine) may reduce efficacy; avoid or monitor.
CNS depressants increase sedation and orthostasis.
QT-prolonging agents should be used cautiously.
| Mechanism | Agents / factors | Management |
|---|---|---|
| CYP1A2 inhibition | Fluvoxamine | Reduce asenapine dose |
| CYP1A2 induction | Carbamazepine | Avoid or monitor for relapse |
| Additive CNS depression | Benzodiazepines, alcohol | Counsel patients |
Monitoring & safety checks
Baseline, 3 months, annually • Monitor metabolic changes
Orthostatic blood pressure
Baseline and dose changes • α1 antagonism
EPS assessment
Each visit • Detect akathisia
Hepatic function
Baseline • Avoid severe impairment
Educate on sublingual administration technique.
Inspect transdermal sites for dermatitis.
Discontinuation guidance
Taper over 1–2 weeks to limit relapse and cholinergic rebound.
Consider cross-titration if switching antipsychotics.
Adverse effects
Common: oral hypoesthesia, somnolence, dizziness, akathisia.
Serious: hypersensitivity reactions, QT prolongation.
References
- Saphris (asenapine) — Prescribing Information — FDA/Merck (2023)
- Secuado (asenapine transdermal system) — FDA/Noven (2023)
- Asenapine clinical review — Neuropsychiatric Disease and Treatment (2013) DOI: 10.2147/NDT.S32996
Educational use only — verify details in current prescribing information and authoritative clinical guidelines before making prescribing decisions.