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asenapine

Antipsychotic

Brands: Saphris, Secuado

Published 2025-12-22 · Last reviewed 2025-12-29 · 6 references

Content sourced from FDA labeling (DailyMed) and peer-reviewed literature.

Print sheet Review evidence

At a glance

Class: Antipsychotic·Typical dose: Schizophrenia (adults): initiate 5 mg sublingually twice daily; increase to 10 mg twice daily based on response; patch initiation 3.8 mg/24 h once daily with titration to 5.7–7.6 mg/24 h.·Half-life: Single-dose mean 24 h; Steady-state mean 24 h·LAI available: No

Class: Antipsychotic
Typical dose: Schizophrenia (adults): initiate 5 mg sublingually twice daily; increase to 10 mg twice daily based on response; patch initiation 3.8 mg/24 h once daily with titration to 5.7–7.6 mg/24 h.
Half-life: Single-dose mean 24 h; Steady-state mean 24 h
LAI available: No

Quick answers

What is asenapine?: Asenapine (brand Saphris sublingual tablets; Secuado transdermal system) is a second-generation (atypical) antipsychotic formulated to avoid extensive first-pass metabolism and provide rapid absorption.
What is Saphris?: Saphris is a brand name for asenapine (other brands: Secuado).
What is Saphris (asenapine) used for?: Label indications include: Schizophrenia (sublingual tablet); Schizophrenia (transdermal patch); Acute manic/mixed episodes in bipolar I disorder (adults); Acute manic/mixed episodes in bipolar I disorder (pediatrics ≥10).
What drug class is Saphris (asenapine)?: Atypical Antipsychotic.
What is the mechanism of action of Saphris (asenapine)?: Second-generation antipsychotic with antagonism at dopamine D2/D3 and serotonin 5-HT2A receptors; also blocks H1 and α1 receptors.
What strengths does Saphris (asenapine) come in?: Sublingual tablets: 2.5 mg, 5 mg, 10 mg (taken twice daily; must dissolve under the tongue).
Is Saphris (asenapine) a controlled substance?: No — it is not scheduled as a controlled substance under U.S. federal law.
What is Saphris (asenapine) dosing for schizophrenia?: Schizophrenia (adults): initiate 5 mg sublingually twice daily; increase to 10 mg twice daily based on response; patch initiation 3.8 mg/24 h once daily with titration to 5.7–7.6 mg/24 h.

General information

Asenapine (brand Saphris sublingual tablets; Secuado transdermal system) is a second-generation (atypical) antipsychotic formulated to avoid extensive first-pass metabolism and provide rapid absorption.

This profile focuses on its use in schizophrenia and bipolar I disorder; U.S. approvals include schizophrenia in adults (sublingual 2009, transdermal 2019) and acute manic or mixed episodes in adults and pediatric patients ≥10 years, as monotherapy or adjunct to lithium/valproate.

The compare view to weigh sedation, metabolic effects, and formulation logistics against alternative SGAs when tailoring adherence strategies.

Asenapine-focused evidence summaries can be reviewed alongside mood-stabiliser planning via the bipolar disorder hub or adherence workflows through the schizophrenia hub.

U.S. approvals

Schizophrenia (sublingual tablet) (2009)
Schizophrenia (transdermal patch) (2019)
Acute manic/mixed episodes in bipolar I disorder (adults) (2009)
Acute manic/mixed episodes in bipolar I disorder (pediatrics ≥10) (2015)

Formulations & strengths

Sublingual tablets: 2.5 mg, 5 mg, 10 mg (taken twice daily; must dissolve under the tongue).
Transdermal patch (Secuado): 3.8 mg/24 h, 5.7 mg/24 h, 7.6 mg/24 h applied once daily to rotating sites.

Generic availability

Sublingual tablets are available generically from several manufacturers since 2020 patent expiry.
The Secuado transdermal system remains brand-only in the United States as of 2025.

Sublingual tablets can cause oral numbness and require avoiding food or drink for 10 minutes after dosing. The patch can be helpful when swallowing is unreliable or when a patient declines LAIs, but cost and skin reactions can be limiting.

View labelExact

Mechanism of action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Asenapine exerts multi-receptor antagonism with high affinity for serotonergic and dopaminergic targets, stabilizing mesolimbic dopamine while modulating cortical serotonin pathways.

Strong 5-HT2A/5-HT2C antagonism coupled with D2/D3/D4 blockade underpins efficacy in psychosis and mania, while α1 and H1 antagonism explains orthostasis and sedation; minimal muscarinic activity keeps anticholinergic effects low.

Potent antagonist at serotonin 5-HT2A, 5-HT2C, 5-HT6, and 5-HT7 receptors.
High-affinity antagonist at dopamine D2, D3, and D4 receptors with moderately rapid dissociation.
Antagonist at adrenergic α1 and histamine H1 receptors.
Negligible muscarinic receptor binding.

Metabolism & pharmacokinetics

Sublingual bioavailability ≈35%; swallowing reduces exposure to <2%; Tmax 0.5–1 hour (sublingual) and 12–24 hours for the transdermal system.
Approximately 95% protein bound with large apparent distribution (~20–25 L/kg).
Metabolized hepatically via UGT1A4 and CYP1A2 (minor CYP2D6/CYP3A4 contributions); metabolites are largely inactive.
Terminal half-life ~24 hours after sublingual dosing; effective half-life for patch ~30 hours; smoking (CYP1A2 induction) may reduce exposure ~20%.
Excreted ~50% in feces and ~40% in urine predominantly as metabolites.

Dosing & administration

Schizophrenia (adults): initiate 5 mg sublingually twice daily; increase to 10 mg twice daily based on response; patch initiation 3.8 mg/24 h once daily with titration to 5.7–7.6 mg/24 h.
Bipolar I acute manic/mixed episodes (adults): start 10 mg sublingually twice daily on day 1, then 5–10 mg twice daily; adjunct dosing with lithium/valproate mirrors monotherapy.
Pediatric bipolar I (≥10 years): initiate 2.5 mg twice daily; titrate by 2.5–5 mg to a maximum 10 mg twice daily.
Therapeutic drug monitoring is not routinely recommended; serum levels have not correlated with efficacy.
Counsel sublingual users to avoid food or drink for 10 minutes after dosing; instruct patch users to rotate application sites and secure edges to maintain adhesion.

Adverse effects

FDA boxed warnings

Increased mortality in elderly patients with dementia-related psychosis (antipsychotic class warning).

Common side effects (≥10%)

Somnolence/sedation: Reported in ~13–24% of patients; leading reason for discontinuation.
Akathisia/restlessness: Occurs in ~10–12%, often within first 3 weeks.
Oral hypoesthesia/dysgeusia: Unique to sublingual formulation (7–15%); typically transient.
Weight gain: ≥7% weight gain in roughly 7–9% over 3–6 months.
Dizziness/orthostatic hypotension: Around 10%, more common during initial titration.
Extrapyramidal symptoms: Overall incidence ~10%, generally mild.

Other notable effects

Hypersensitivity reactions including rare anaphylaxis and angioedema—per labeling, discontinue permanently after such events.
QT prolongation is typically modest but monitor in patients with congenital long-QT syndrome or on QT-active combinations.
Hyperprolactinemia and dyslipidemia are infrequent but monitor if symptoms arise.
Contraindicated in severe hepatic impairment (Child-Pugh C) due to elevated exposure.

Interactions

Strong CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin) raise concentrations—monitor for sedation and EPS; dose reduction may be needed.
CYP1A2 inducers, including cigarette smoking and carbamazepine, lower exposure—monitor efficacy and adjust dose within labeling limits.
Potent enzyme inducers affecting UGT pathways (e.g., rifampin) can reduce levels; consider alternatives or monitor closely.
Additive CNS depression with benzodiazepines, opioids, alcohol, or antihistamines.
May antagonize effects of levodopa and dopamine agonists; avoid coadministration in Parkinson’s disease when possible.

Other useful information

Store sublingual tablets in original blister packaging; handle with dry hands and allow to dissolve fully under the tongue.
Oral numbness usually resolves within an hour; severe dysesthesia, swelling, or signs of hypersensitivity warrant urgent evaluation.
Rotate patch sites daily (upper arm, abdomen, hip, back) and inspect for erythema; mild application-site reactions occur in <10%.
Weight, fasting lipids, and glucose are typically monitored periodically despite relatively modest metabolic liability.
Changes in smoking status can alter plasma exposure through CYP1A2 induction or cessation; dosing may need reassessment when tobacco use changes.
Consider baseline and follow-up ECGs in patients with cardiac risk factors or concomitant QT-prolonging regimens.
The asenapine compare view, evidence feed, and printable counseling sheets via the asenapine print page can support longitudinal adherence discussions across visits.

References

Related hubs:Schizophrenia hub·Bipolar hub