ASENAPINE

brands

Class

• Neuroscience-based Nomenclature:dopamine, serotonin, norepinephrine receptor antagonist (DSN-RAn)
• Atypical antipsychotic (serotonin– dopamine antagonist; second-generation antipsychotics; also a mood stabilizer)

ASENAPINE commonly prescribed for

(Bold for FDA approved)

How ASENAPINE works

• Blocks dopamine 2 receptors, reducing positive symptoms of psychosis and stabilizing affective symptoms

• Blocks serotonin 2A receptors, causing enhancement of dopamine release in certain brain regions and thus reducing motor side effects and possibly improving cognitive and affective symptoms

• Interactions at a myriad of other neurotransmitter receptors may contribute to asenapine’s efficacy

• Serotonin 2C, serotonin 7, and alpha 2 antagonist properties may contribute to antidepressant actions

• Partial agonist at serotonin 1A receptors, which may be beneficial for mood, anxiety, and cognition in a number of disorders

How long until ASENAPINE works

• Psychotic symptoms can improve within 1 week, but it may take several weeks for full effect on behavior as well as on cognition

• Classically recommended to wait at least 4–6 weeks to determine efficacy of drug, but in practice some patients may require up to 16–20 weeks to show a good response, especially on negative or cognitive symptoms

Notable Side Effects

• Sedation, dizziness

• Oral hypoesthesia

• Application-site reactions (oral ulcers, blisters, peeling/sloughing, inflammation for sublingual; irritation, burning for transdermal)

• Akathisia

• May increase risk for diabetes and dyslipidemia

• Drug-induced parkinsonism

• Orthostatic hypotension

• Tardive dyskinesia (reduced risk compared to conventional antipsychotics)

• Risk of potentially irreversible, involuntary dyskinetic movements may increase with cumulative dose and treatment duration

Life Threatening Side Effects

• Type 1 hypersensitivity reactions (anaphylaxis, angioedema, low blood pressure, rapid heart rate, swollen tongue, difficulty breathing, wheezing, rash)

• Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients taking atypical antipsychotics

• As a class, antipsychotics are associated with an increased risk of death and cerebrovascular events in elderly patients with dementia; not approved for treatment of dementia-related psychosis

• Rare neuroleptic malignant syndrome may cause hyperpyrexia, muscle rigidity, delirium, and autonomic instability] with elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure

• Rare seizures

weight gain

not usual

sedation

common

What to do about ASENAPINE side effects

• Wait

• Wait

• Wait

• Anticholinergics may reduce drug-induced parkinsonism when present

• Beta blockers, benzodiazepines, or serotonin 2A antagonists (e.g., mirtazapine, cyproheptadine) may reduce akathisia

• Weight loss, exercise programs, and medical management for high BMIs, diabetes, dyslipidemia

• Metformin may help prevent or reverse antipsychotic-induced weight gain

• Switch to another atypical antipsychotic

usual dosage range

• Schizophrenia and bipolar mania (sublingual): 10–20 mg/day in 2 divided doses

• Schizophrenia (transdermal): 3.8 mg/24 hours

Dosage Forms

• Sublingual tablet 2.5 mg, 5 mg, 10 mg

• Transdermal system 3.8 mg/24 hours, 5.7 mg/24 hours, 7.6 mg/24 hours

long term use

• Should periodically reevaluate long-term usefulness in individual patients, but treatment may need to continue for many years

habit forming

• No

Renal Impairment

• Dose adjustment not generally necessary

Hepatic Impairment

• No dose adjustment necessary for mild to moderate impairment

• Contraindicated in patients with severe hepatic impairment

Cardiac Impairment

• Use in patients with cardiac impairment has not been studied, so use with caution because of risk of orthostatic hypotension

• Use with caution if patient is taking concomitant antihypertensive or alpha 1 antagonist

Elderly

• Some patients may tolerate lower doses better

• Although atypical antipsychotics are commonly used for behavioral disturbances in dementia, no agent has been approved for treatment of elderly patients with behavioral symptoms of dementia such as agitation

• Elderly patients with dementia-related psychosis treated with atypical antipsychotics are at an increased risk of death compared to placebo, and also have an increased risk of cerebrovascular events

• Consider pimavanserin for dementia-related psychosis or Parkinson’s disease psychosis instead of an atypical antipsychotic

Children and Adolescents

• Sublingual: approved to treat acute manic/ mixed episodes of bipolar I disorder in children ages 10 and older

• Transdermal asenapine is approved only in adults

• Efficacy for schizophrenia was not demonstrated in an 8-week, placebocontrolled, double-blind trial in adolescent patients ages 12 to 17 years

• Children and adolescents using asenapine may need to be monitored more often than adults and may tolerate lower doses better

Pregnancy

• Controlled studies have not been conducted in pregnant women

• There is a risk of abnormal muscle movements and withdrawal symptoms in newborns whose mothers took an antipsychotic during the third trimester; symptoms may include agitation, abnormally increased or decreased muscle tone, tremor, sleepiness, severe difficulty breathing, and difficulty feeding

• In animal studies, asenapine increased post-implantation loss and decreased pup weight and survival at doses similar to or less than recommended clinical doses; there was no increase in the incidence of structural abnormalities

• Psychotic symptoms may worsen during pregnancy and some form of treatment may be necessary

Breast Feeding

• Some drug is present in breast milk

• Recommended either to discontinue drug or formula feed

• Infants of women who choose to breast feed while on asenapine should be monitored for possible adverse effects