Schedule H1

Sublingual; Transdermal (patch — NOT AVAILABLE in India)

• Sublingual tablets: 5 mg, 10 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Schizophrenia (Adults)

Phase Dose

Starting dose 5 mg sublingually twice daily

Titration May increase to 10 mg twice daily after 1 week based on clinical response and tolerability

Usual maintenance dose 5–10 mg sublingually twice daily

Maximum dose 10 mg twice daily (20 mg/day)

Clinical Notes:

• Tablet must be placed under tongue and allowed to dissolve completely

• Patient must not eat or drink for at least 10 minutes after administration

• Swallowing the tablet substantially reduces bioavailability (oral bioavailability <2%)

• Not interchangeable with other antipsychotics on a milligram-to-milligram basis

1. Acute Manic or Mixed Episodes Associated with Bipolar-I Disorder (Adults)

Phase Dose

Starting dose 10 mg sublingually twice daily

Titration Reduce to 5 mg twice daily if 10 mg dose is not tolerated

Usual maintenance dose 5–10 mg sublingually twice daily

Maximum dose 10 mg twice daily (20 mg/day)

Clinical Notes:

• Efficacy should be evaluated within 3 weeks of initiation

• May be used as monotherapy or adjunctive to lithium or valproate

• Reassess periodically to determine continued need for treatment

Secondary Indications – Adults (Off-label)

Indication Dose Notes

Maintenance therapy in Bipolar-I Disorder (OFF-LABEL) 5–10 mg sublingually twice daily Specialist only; extrapolated from acute efficacy data and international observational studies; reassess need every 3–6 months

Adjunctive treatment in Treatment-Resistant Depression (OFF-LABEL) 5 mg sublingually twice daily Specialist only; limited evidence from small RCTs; not first-line

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Not approved for paediatric use in India.

No Indian regulatory approval exists for use below 18 years of age.

Secondary Indications – Paediatric (Off-label)

Indication Age Dose Notes

Bipolar I Disorder – Manic/Mixed Episodes (OFF-LABEL) 10–17 years 2.5 mg sublingually twice daily initially; may increase to 5–10 mg twice daily after 3 days based on tolerability US FDA approved; NOT sanctioned in India; use only under child psychiatry specialist supervision in exceptional circumstances

Safety Notes:

• Minimum age: Avoid below 10 years; no safety data exists

• Not recommended below 18 years in routine Indian clinical practice

• If used off-label, closely monitor for:

• Extrapyramidal symptoms

• Excessive sedation

• Weight gain and metabolic changes (glucose, lipids)

• Suicidal ideation

Not significantly removed by dialysis.

• Periodic liver function monitoring recommended with prolonged use

• Severe hepatic impairment (Child-Pugh class C)

• Known hypersensitivity to asenapine or any excipient

• History of angioedema associated with asenapine use

• Patients unable to comply with sublingual administration technique (e.g., severe cognitive impairment, swallowing reflex issues)

• History of QT prolongation or concurrent use of QT-prolonging medications

• Pre-existing cardiovascular disease, cerebrovascular disease, or conditions predisposing to hypotension

• Parkinson's disease or Lewy body dementia (risk of worsening motor symptoms)

• History of seizures or conditions lowering seizure threshold

• Risk factors for metabolic syndrome (obesity, diabetes, dyslipidaemia)

• Elderly patients with dementia-related psychosis (increased mortality risk — boxed warning)

• Conditions predisposing to aspiration pneumonia

• History of leucopenia or drug-induced neutropenia

Parameter Recommendation

Risk category Not formally classified in India; limited human data

Overall safety Use only if potential benefit justifies potential fetal risk

Preferred alternatives Haloperidol, olanzapine (more safety data available in pregnancy)

When to use Severe psychiatric illness where treatment cannot be deferred; requires specialist psychiatric input

Monitoring Neonates exposed during third trimester: monitor for extrapyramidal symptoms, withdrawal signs, respiratory distress, feeding difficulties

Parameter Recommendation

Compatibility Not recommended during breastfeeding

Drug levels in milk Expected to be low due to high first-pass metabolism and poor oral bioavailability; however, no human lactation studies available

Preferred alternatives Olanzapine, quetiapine (more lactation safety data)

Infant monitoring If unavoidable use: monitor infant for sedation, poor feeding, irritability, and developmental milestones

Parameter Recommendation

Starting dose 5 mg sublingually twice daily

Titration Slow; increase only after 2 weeks if tolerated and clinically indicated

Maximum dose 10 mg twice daily

Special risks Orthostatic hypotension, excessive sedation, falls, cerebrovascular adverse events

Dementia-related psychosis Avoid — associated with increased risk of stroke and mortality; not approved for this indication

Interacting Drug/Class Effect Recommendation

Fluvoxamine (strong CYP1A2 inhibitor) Significantly increased asenapine plasma levels Avoid concomitant use or reduce asenapine dose substantially

Strong CYP2D6 inhibitors (paroxetine, fluoxetine, bupropion) Increased asenapine exposure Monitor closely for sedation, EPS; consider dose reduction

QT-prolonging drugs (fluoroquinolones, antiarrhythmics Class IA/III, certain antidepressants) Additive QT prolongation risk Avoid combination if possible; ECG monitoring essential

CNS depressants (benzodiazepines, opioids, alcohol) Enhanced sedation and respiratory depression Use with caution; start with lower doses

Interacting Drug/Class Effect Recommendation

Antihypertensives Additive hypotensive effect; risk of orthostatic hypotension Monitor BP, especially during initiation

Lithium, valproate No significant pharmacokinetic interaction; possible additive neurotoxicity Monitor for tremor, ataxia, confusion

Anticholinergic drugs Additive anticholinergic burden Use cautiously, especially in elderly; monitor for cognitive effects, constipation, urinary retention

Carbamazepine (CYP3A4 inducer) May reduce asenapine levels modestly Monitor clinical response; dose adjustment may be needed

• Somnolence/sedation

• Akathisia

• Oral hypoesthesia (numbness of mouth/tongue)

• Dizziness

• Dysgeusia (altered taste)

• Weight gain

• Increased appetite

• Dry mouth

• Fatigue

• Headache

• Constipation

Adverse Effect Clinical Action

Neuroleptic Malignant Syndrome Discontinue immediately; supportive care; specialist referral

QT prolongation / Torsades de Pointes Discontinue; ECG monitoring; correct electrolytes

Tardive dyskinesia Consider discontinuation; may be irreversible

Severe extrapyramidal symptoms Dose reduction or discontinuation; anticholinergic agents if needed

Seizures Discontinue; evaluate for precipitating factors

Angioedema / Anaphylaxis Discontinue permanently; emergency management

Agranulocytosis (rare) Discontinue; CBC monitoring; infection management

Severe hepatotoxicity Discontinue; LFT monitoring; specialist referral

Baseline (Before Initiation)

• Weight, BMI, waist circumference

• Fasting blood glucose, HbA1c

• Fasting lipid profile

• Blood pressure

• ECG (if cardiac risk factors or concurrent QT-prolonging drugs)

• Liver function tests

• Complete blood count

After Initiation / Dose Change

• Assess for EPS, akathisia, sedation: within 1–2 weeks

• Orthostatic blood pressure: during first week

• LFTs: at 4–6 weeks if hepatic risk factors

Long-term Monitoring

• Weight, glucose, lipids: every 3 months for first year, then every 6–12 months

• Tardive dyskinesia assessment: every 6 months

• ECG: annually if on long-term therapy or if cardiac risk factors present

• LFTs: periodically with prolonged use

Brand Name Manufacturer

Syxtene SL Sun Pharmaceutical

Asenapt Intas Pharmaceuticals

Asenta SL Torrent Pharmaceuticals

Asenap Mankind Pharma

• Not currently under NPPA price control (not in NLEM)

• Prices may vary between brands and retail outlets

1. Sublingual technique is critical — ensure patient understands that tablet must dissolve under tongue; swallowing dramatically reduces absorption and efficacy

1. 10-minute rule — no food or water for 10 minutes post-dose; counsel patients clearly on this

1. Oral numbness is common — warn patients about transient oral hypoesthesia; this often causes early non-adherence if not explained beforehand

1. Low prolactin impact — useful choice when prolactin elevation (galactorrhoea, amenorrhoea, sexual dysfunction) is problematic with other antipsychotics

1. Not suitable for PRN agitation — sublingual route and slow absorption make it unsuitable for acute agitation management

1. Metabolic profile intermediate — less weight gain than olanzapine or clozapine, but still requires metabolic monitoring

asenapine; schizophrenia; bipolar disorder; atypical antipsychotic; sublingual; second-generation antipsychotic; hepatic caution; QT prolongation; Schedule H1; psychiatry

RxIndia v0.3 — 12 Jun 2025

• CDSCO approved product information

• Indian Pharmacopoeia

• AIIMS Hospital Formulary

• API Textbook of Medicine

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• WHO ATC Classification

• Indian Psychiatric Society clinical practice recommendations

• US FDA label (used only for comparative off-label context and paediatric data)