Asenapine

Indications

Asenapine is used for: Schizophrenia, Acute mixed or manic episodes in bipolar disorder

Adult Dose

Sublingual Schizophrenia Adult: Initially, 5 mg bid, may increase to 10 mg bid after 1 wk if tolerated. Sublingual Acute mixed or manic episodes in bipolar disorder Adult: As monotherapy or adjunct to lithium or valproate: Initially, 5 mg bid, may increase to 10 mg bid depending on clinical response and tolerability. Hepatic impairment Mild to moderate impairment (Child-Pugh class A or B): Dose adjustment not necessary Severe impairment (Child-Pugh class C): Contraindicated

Child Dose

Bipolar Disorder Indicated as monotherapy for acute treatment of manic or mixed episodes associated with bipolar I disorder <10 years: Safety and efficacy not established 10-17 years: 2.5 SL q12hr initially; may increase to 5 mg SL q12hr after 3 days and to 10 mg SL q12hr after 3 additional days

Renal Dose

Renal impairment Dose adjustment not necessary

Administration

Sublingual tablet; to allow optimal absorption, place under tongue and allow to dissolve completely (dissolves within seconds) Do not chew, split, crush, or swallow sublingual tablet Do not eat or drink for at least 10 minutes after administration

Contra Indications

Hypersensitivity to asenapine. Dementia-related psychosis. Severe (Child-Pugh Class C) hepatic impairment.

Precautions

Patient w/ history of seizure disorder, known CV disease (e.g. heart failure, MI or ischaemia, arrhythmia), cerebrovascular disease, dehydration, bradycardia, hypovolaemia, hypokalaemia, Parkinson’s disease, dementia w/ Lewy Bodies (DLB). Moderate (Child-Pugh Class B) hepatic impairment. Pregnancy and lactation.

Pregnancy-Lactation

Interactions

Increased plasma concentration w/ fluvoxamine. May enhance the effects of certain antihypertensive agents (due to its α1-adrenergic antagonism) and CNS depressants. May increase exposure of paroxetine. May antagonise the effects of levodopa and dopaminergics.

Adverse Effects

Side effects of Asenapine : Significant: Extrapyramidal symptoms (e.g. pseudoparkinsonism, dystonia, akathisia, tardive dyskinesia) seizure, syncope, orthostatic hypotension, QT prolongation, dysphagia, hyperprolactinaemia, leukopenia, neutropenia. Nervous: Somnolence, sedation, dizziness, oral hypoaesthesia, paraesthesia, speech disturbance, irritability, anxiety. CV: Tachycardia. GI: Constipation, nausea, dry mouth, glossodynia, hypersalivation, taste disturbance, swollen tongue. Genitourinary: Urinary retention. Endocrine: Galactorrhoea, gynaecomastia, amenorrhoea, impotence. Haematologic: Thrombocytopenia. Ophthalmologic: Blurred vision, mydriasis. Others: Fatigue. Potentially Fatal: Neuroleptic malignant syndrome (manifesting as hyperthermia, muscle rigidity, altered mental status, autonomic instability, elevated serum creatine phosphokinase levels, myoglobinuria, acute renal failure), agranulocytosis, hyperglycaemia (associated w/ ketoacidosis or hyperosmolar coma).

Mechanism of Action

Mechanism of action unknown; efficacy thought to be mediated via combined antagonist activity at dopamine D2 and serotonin type 2 (5-HT2) receptors