Asenapine

Severe (Child-Pugh Class C): Contraindicated.

Severe (Child-Pugh Class C) hepatic impairment.

Patient with risk factors for seizures or conditions that lower seizure threshold (e.g. Alzheimer's dementia); Parkinson's disease; history of cerebrovascular or CV disease (e.g. MI, heart failure, conduction abnormalities, ischaemic disease); risk factors for hypotension (e.g. dehydration and hypovolaemia); congenital long QT syndrome, history of cardiac arrhythmia; diabetes; risk factors for blood dyscrasias (e.g. pre-existing low WBC or history of drug-induced leucopenia or neutropenia); conditions that may elevate core body temperature (e.g. undergoing strenuous exercise, exposure to extreme heat, concomitant use of anticholinergic agents). Avoid abrupt withdrawal. Not approved for the treatment of elderly patients with dementia-related psychosis. Moderate hepatic impairment. Children and the elderly. Pregnancy and lactation.

Significant: CNS depression, dyslipidaemia, oesophageal dysmotility and aspiration, dysphagia; extrapyramidal symptoms (e.g. tardive dyskinesia, akathisia, hyperkinesia, dystonia, muscle rigidity, parkinsonism, tremor); increased risk of falls due to somnolence, orthostatic hypotension; syncope, QT interval prolongation, disruption of body temperature regulation; weight gain; leucopenia or neutropenia; seizures; hyperprolactinaemia.
Blood and lymphatic system disorders: Anaemia.
Eye disorders: Accommodation disorder.
Gastrointestinal disorders: Nausea, vomiting, abdominal pain, constipation, diarrhoea, dyspepsia, dysgeusia, oral mucosal lesions (e.g. ulcerations, blistering, inflammation), salivary hypersecretion.
General disorders and administration site conditions: Fatigue, fever, transdermal patch application site reactions (e.g. dermatitis, discolouration, discomfort, dryness, oedema, erythema, exfoliation, induration, irritation, pain, papules, pruritus).
Investigations: Increased ALT, AST, GGT.
Metabolism and nutrition disorders: Increased appetite, hyponatraemia.
Musculoskeletal and connective tissue disorders: Myalgia, restless legs syndrome.
Nervous system disorders: Dizziness, sedation, dysarthria, hypoaesthesia, paraesthesia.
Psychiatric disorders: Anxiety, altered mental status.
Renal and urinary disorders: Urinary retention.
Reproductive system and breast disorders: Sexual dysfunction, amenorrhoea.
Potentially Fatal: Neuroleptic Malignant Syndrome; ketoacidosis or hyperosmolar coma associated with extreme hyperglycaemia; serious hypersensitivity reactions (e.g. anaphylaxis, angioedema); blood dyscrasias (e.g. agranulocytosis).

SL: C

This drug may cause dizziness, somnolence, orthostatic hypotension, or extrapyramidal symptoms, if affected, do not drive, or operate machinery.

Monitor blood electrolytes levels, renal or liver function, TSH (annually); CBC (as clinically indicated); fasting plasma glucose or HbA_1c, lipid panel (12 weeks after initiation or dose change then annually thereafter); prolactin level (if with symptoms). Monitor mental status, adherence, and fall risk (every visit); vital signs such as blood pressure, temperature, pulse, orthostatics, or signs of infections (at least weekly during 1st 3-4 weeks of treatment and 4 weeks after dose change); BMI and waist circumference (8 and 12 weeks after initiation or dose change then quarterly); history of metabolic syndrome (annually). Assess for signs of extrapyramidal symptoms (using formalised rating scale at least annually or every 6 months for high risk); neuroleptic malignant syndrome (e.g. fever, muscle rigidity, autonomic instability); suicidal ideation.

Symptoms: Agitation, confusion, akathisia, orofacial dystonia, sedation, asymptomatic ECG findings (e.g. bradycardia, supraventricular complexes, intraventricular conduction delay), hypotension, circulatory collapse. Management: Symptomatic and supportive treatment. Maintain adequate airway, oxygenation, and ventilation. Monitor CV function for possible arrhythmias. Administer sympathomimetic agents (except epinephrine and dopamine), and IV fluids for hypotension and circulatory collapse. May give anticholinergic agents for severe extrapyramidal symptoms.

Enhanced QT prolongation effect with class 1A antiarrhythmics (e.g. quinidine, procainamide) or class 3 antiarrhythmics (e.g. amiodarone, sotalol), antipsychotics (e.g. ziprasidone, chlorpromazine, thioridazine), and antibiotics (e.g. gatifloxacin, moxifloxacin). Increased serum concentration with fluvoxamine, ciprofloxacin. May antagonise the effects of levodopa and dopamine agonists.

Reduced bioavailability with food and drink. May enhance the CNS effects of alcohol.

Description:
Mechanism of Action: Asenapine, a dibenzo-oxepino pyrrole derivative, is a 2nd generation or atypical antipsychotic. It has high affinity for various serotonin, and dopamine receptors, including adrenergic (α_1-2), and histamine (H₁ and H₂) receptors. It improves negative symptoms of psychotic disorders and decreases extrapyramidal side effects occurrence through its combined serotonin-dopamine antagonistic activity.
Pharmacokinetics:
Absorption: Rapidly absorbed in the sublingual, supralingual, and buccal mucosa. Bioavailability: 35% (sublingual). Reduced bioavailability with food and liquid (sublingual). Increased rate and extent of absorption with external heat source (transdermal). Time to peak plasma concentration: Within 0.5-1.5 hours (sublingual); 12-24 hours (transdermal).
Distribution: Undergoes rapid and extensive extravascular distribution. Volume of distribution: Approx 20-25 L/kg. Plasma protein binding: 95%, including albumin and α₁-acid glycoprotein.
Metabolism: Metabolised in the liver mainly via direct glucuronidation by UGT1A4 and via oxidation by CYP1A2 enzymes.
Excretion: Via urine (approx 50%); faeces (approx 40%). Terminal elimination half-life: Approx 24 hours (sublingual). Elimination half-life: Approx 30 hours (transdermal).

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 3036780, (R,R)-asenapine. https://pubchem.ncbi.nlm.nih.gov/compound/R_R_-asenapine. Accessed Nov. 21, 2023.

Store between 15-30°C. Protect from light and moisture (tab).

Thuốc chống loạn thần

N05AH05 - asenapine ; Belongs to the class of diazepines, oxazepines and thiazepines antipsychotics.

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Sycrest 5 mg Sublingual Tablets (Organon Pharma [UK] Limited). MHRA. https://products.mhra.gov.uk. Accessed 01/09/2023.