Atypical (Second-generation) Antipsychotic — Sublingual Pregnancy: Should not be used during pregnancy unless the clinical condition of the woman requires treatment with asenapine and only if the potential benefit outweighs the potential risk to the foetus — there are no adequate data in pregnant women; asenapine was not teratogenic in animal studies but maternal and embryo toxic effects were found. Newborn infants exposed to antipsychotics during the third trimester are at risk of extrapyramidal and/or withdrawal symptoms varying in severity and duration (agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress or feeding disorder have been reported) and should be monitored carefully. Breast-feeding should be discontinued during treatment. Fertility: no impairment observed in nonclinical studies.

Asenapine

Brand names: Sycrest

Asenapine is a second-generation (atypical) antipsychotic licensed for the treatment of moderate to severe manic episodes associated with bipolar disorder.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: Monotherapy: recommended starting dose 5 mg twice daily, increased to 10 mg twice daily based on individual clinical response and tolerability. Combination therapy: starting dose 5 mg twice daily, increased to 10 mg twice daily depending on clinical response and tolerability

Route: Sublingual

Frequency: Twice daily — one dose in the morning and one dose in the evening

Max: 10 mg twice daily is the highest dose stated in §4.2 (no separate numeric maximum is given in the SPC text retrieved)

Source: UK SPC (eMC) for Sycrest 10mg sublingual tablets, §4.2 (https://www.medicines.org.uk/emc/product/7737/smpc). METHOD OF ADMINISTRATION (critical to efficacy): do not remove the tablet from the blister until ready to take it; use dry hands when touching the tablet; do not push the tablet through the pack and do not cut or tear the pack — peel back the coloured tab and remove the tablet gently. Do not crush the tablet. To ensure optimal absorption the sublingual tablet should be placed under the tongue and allowed to dissolve completely; it will dissolve in saliva within seconds. Tablets should NOT be chewed or swallowed. Eating and drinking should be avoided for 10 minutes after administration. When used with other medicinal products, Sycrest should be taken last. Treatment is not advised in patients unable to comply with this method of administration, as the bioavailability of asenapine when swallowed is low (< 2% with an oral tablet formulation). ELDERLY: should be used with care; limited efficacy data in patients 65 years of age and older. HEPATIC IMPAIRMENT: no dose adjustment required in mild impairment; caution in moderate impairment (Child-Pugh B) as elevated plasma levels cannot be excluded in some patients; in severe impairment (Child-Pugh C) a 7-fold increase in exposure was observed and Sycrest is NOT recommended. PAEDIATRIC: a pharmacokinetic study and a short-term efficacy and safety study were performed in patients aged 10–17 years with manic or mixed episodes associated with bipolar I disorder, with long-term safety explored in a 50-week open-label extension, but 'no recommendation on a posology can be made' — no paediatric dose is stated in the UK SPC and none should be inferred. Paediatric patients appeared to be more sensitive to dystonia with initial dosing when a gradual up-titration schedule was not followed. Verify any under-18 use against a children's formulary. (For reference only, and NOT a UK-licensed regimen: the US label gives 2.5 mg sublingually twice daily as the starting dose for bipolar mania monotherapy in patients aged 10–17 years, range 2.5–10 mg twice daily.) §4.4 and §4.8 were truncated at the source-fetch limit and §4.5 was not retrieved in this bundle — verify the complete interactions section (interactions listed below are from the US label's drug-interaction table, as marked).

Dose adjustments

Renal

No dose adjustment is required for patients with renal impairment. There is no experience with asenapine in patients with severe renal impairment who have a creatinine clearance less than 15 mL/min.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Hypersensitivity to the active substance or to any of the excipients (UK SPC §4.3 — the only contraindication stated)
US label additionally contraindicates severe hepatic impairment (Child-Pugh C) and a history of hypersensitivity reactions to asenapine (which have included anaphylaxis, angioedema, hypotension, tachycardia, swollen tongue, dyspnoea, wheezing and rash); the UK SPC does not contraindicate but does not recommend severe hepatic impairment

Side effects

Very common: somnolence and anxiety (the most frequently reported adverse reactions in clinical trials)
Common: weight increased, increased appetite, dystonia, akathisia, dyskinesia, parkinsonism, sedation, dizziness, dysgeusia, oral hypoaesthesia, nausea, alanine aminotransferase increased, muscle rigidity, fatigue
Uncommon: sinus bradycardia, bundle branch block, ECG QT prolonged, sinus tachycardia, orthostatic hypotension, hypotension, syncope, seizure, extrapyramidal disorder, dysarthria, salivary hypersecretion, swollen tongue, dysphagia, glossodynia, oral paraesthesia, hyperglycaemia, sexual dysfunction, amenorrhoea, falls
Rare: neutropenia, allergic reactions, restless legs syndrome, pulmonary embolism, oral mucosal lesions (ulcerations, blistering and inflammation), gynaecomastia, galactorrhoea
Not known: neuroleptic malignant syndrome, rhabdomyolysis, neonatal drug withdrawal syndrome. Extrapyramidal symptoms occurred more often than with placebo (15.4% vs 11.0%), with a dose-response relationship for akathisia and an increasing trend for parkinsonism at higher doses

Interactions

Strong CYP1A2 inhibitors, e.g. fluvoxamine — asenapine is metabolised by CYP1A2; a full therapeutic dose of fluvoxamine is expected to cause a substantial increase in asenapine exposure and dosage reduction of asenapine based on clinical response may be necessary (US label §7.1)
CYP2D6 substrates and inhibitors, e.g. paroxetine — asenapine may enhance the inhibitory effects of paroxetine on its own metabolism; the US label advises reducing the paroxetine dose by half when used in combination (US label §7.1)
Antihypertensive drugs — because of its alpha-1-adrenergic antagonism with potential for inducing hypotension, asenapine may enhance the effects of certain antihypertensive agents; monitor blood pressure and adjust the antihypertensive dose accordingly (US label §7.1)
Other medicinal products thought to prolong the QT interval — caution is advised (UK SPC §4.4)

Clinical monograph

How it works

It acts as an antagonist at dopamine D2 and serotonin 5-HT2A receptors, with activity at a range of other serotonin, adrenergic, dopamine and histamine receptors.

Prescribing in practice

It must be given as a sublingual tablet and patients should avoid eating or drinking for a short period afterwards, as swallowing greatly reduces absorption; oral hypoaesthesia may occur.
Hypersensitivity reactions, including serious allergic reactions, have been reported and warrant immediate discontinuation.
As with other antipsychotics, it can prolong the QT interval and is associated with extrapyramidal effects, weight gain and metabolic changes.

Monitoring

Monitor weight, blood glucose, lipids and, where indicated, ECG, along with extrapyramidal symptoms.

Counselling the patient

Place the tablet under the tongue and let it dissolve; do not chew or swallow it.
Do not eat or drink for a short while after taking the tablet.
Report any rash, swelling or difficulty breathing immediately.

Evidence & guidelines

Efficacy in acute bipolar mania is supported by randomised controlled trials underpinning its UK licence.

Reference: NICE CG185 (Bipolar Disorder); Sycrest SPC; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways