Drug information of Asenapine

Asenapine


asenapine is a sublingually administered, atypical antipsychotic for treatment of schizophrenia and acute mania associated with bipolar disorder. Asenapine also belongs to the dibenzo-oxepino pyrrole class.

Mechanism of effect

Asenapine is an atypical antipsychotic multireceptor neuroleptic drug which shows strong 5HT2A (serotonin) and D2 (dopamine) receptor antagonism, which has been shown to enhance dopamine (DA) and acetylcholine (Ach) efflux in rat brains. Asenapine may improve cognitive function and negative symptoms in patients with schizophrenia.

Pharmacodynamic

Asenapine is a serotonin, dopamine, noradrenaline, and histamine antagonist in which asenapine possess more potent activity with serotonin receptors than dopamine. Sedation in patients is associated with asenapine's antagonist activity at histamine receptors. Its lower incidence of extrapyramidal effects are associated with the upregulation of D1 receptors. This upregulation occurs due to asenapine's dose-dependent effects on glutamate transmission in the brain. It does not have any significant activity with muscarinic, cholinergic receptors therefore symptoms associated with anticholinergic drug activity like dry mouth or constipation are not expected to be observed. Asenapine has a higher affinity for all aforementioned receptors compared to first-generation and second-generation antipsychotics except for 5-HT1A and 5-HT1B receptors.

Pharmacokinetics

Bioavailability: SL, 35%; swallowed, ≤2%

Peak plasma time: 0.5-1.5 hr

Peak plasma concentration: 4 ng/mL

Protein bound: 95%

Vd: 20-25 L/kg

Metabolism

Metabolized by UGT1A4 and CYP450 (predominantly isoenzyme 1A2)

Enzymes inhibited: CYP2D6 (weakly)

Half-life: 24 hr

Clearance: 52 L/hr

Excretion: Urine (50%), feces (40%)

Drug indications

Schizophrenia , psychoses

Dosage

Adult

Schizophrenia

5 mg SL q12hr initially; maintenance: after 1 week, may be increased up to 10 mg PO q12hr

Bipolar Disorder

Monotherapy: 10 mg PO q12hr initially; may be decreased to 5 mg PO q12hr on day 2 and subsequent days if warranted by adverse effects or individual tolerance (90% of patients typically remain on higher dose)

Adjunct to lithium or valproate: 5 mg PO q12hr initially; may be increased to 10 mg PO q12hr if warranted

Pediatric

Bipolar 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

Alerts

Type 1 hypersensitivity reactions, including anaphylaxis and angioedema, have been reported (n=52), in several cases occurring after first dose; symptoms include anaphylaxis, angioedema, hypotension, tachycardia, tongue and laryngeal edema, difficulty breathing, wheezing, or rash

Neuroleptic malignant syndrome associated with use; monitor for symptoms and discontinue if necessary

Extrapyramidal symptoms, including acute dystonic reactions, pseudoparkinsonism, akathisia, and tardive dyskinesia reported

Hyperglycemia (monitor patients with diabetes mellitus for worsening of glucose control)

Weight gain may occur; monitor weight gain in pediatric patients and assess against that expected for normal growth

Hypotension and syncope, especially early in treatment, because of drug's alpha1-antagonistic activity

Leukopenia, neutropenia, and agranulocytosis reported with use; perform a complete blood count (CBC) during first few months of therapy; in such patients, consider discontinuation of therapy at first sign of clinically significant decline in WBC in absence of other causative factors

Possible prolongation of QTc interval; avoid in patients with history of cardiac arrhythmias or other conditions that increase risk of torsades de pointes (eg, bradycardia, hypokalemia, hypomagnesemia)

Coadministration with other drugs that prolong QTc interval may result in life-threatening arrhythmias (eg, class 1A antiarrhythmics [quinidine, procainamide], class 3 antiarrhythmics [amiodarone, sotalol], antipsychotics [ziprasidone, chlorpromazine, thioridazine], and antibiotics [moxifloxacin])

Concurrent use of CNS-acting drugs or alcohol may increase toxicity

Use caution in patients with history of seizures

Cognitive or motor impairment may occur due to CNS depression

Dysphagia, dysmotility, and aspiration may occur

Potential disruption of body temperature regulation

Not recommended with severe hepatic impairment (Child-Pugh class C)

Inherent suicide risk with population treated warrants close supervision when drug therapy is changed

Atypical antipsychotic drugs have been associated with metabolic changes including hyperglycemia, dyslipidemia, and body weight gain, which may increase cardiovascular/ cerebrovascular risk; all of the drugs in the class have been shown to produce some metabolic changes but each drug has its own specific risk profile

Can elevate prolactin levels, and elevation can persist during chronic administration; hyperprolactinemia may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotropin secretion; this, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients

Orthostatic vital signs should be monitored in patients who are vulnerable to hypotension (elderly patients, patients with dehydration, hypovolemia, concomitant treatment with antihypertensive medications

May cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries; perform complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy

Black Box Warnings

Not indicated for dementia-related psychosis; increased risk of death in elderly patients with dementia-related psychosis; placebo-controlled trials with other atypical antipsychotics (ie, risperidone, aripiprazole, olanzapine) showed higher incidence of cerebrovascular adverse reactions (eg, cerebrovascular accidents [CVAs], transient ischemic attacks [TIAs]), including fatalities, in comparison with placebo

Points of recommendation

  • Tell all of your health care providers that you take asenapine. This includes your doctors, nurses, pharmacists, and dentists.
  • Avoid driving and doing other tasks or actions that call for you to be alert until you see how asenapine affects you.
  • To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
  • Low white blood cell counts have happened with drugs like this one. This may lead to a higher chance of getting an infection. Deadly infections have rarely happened. Tell your doctor if you have ever had a low white blood cell count. Call your doctor right away if you have signs of infection like fever, chills, or sore throat. Talk with your doctor.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • High blood sugar or diabetes, high cholesterol, and weight gain have happened with drugs like this one. These changes may raise the chance of heart and brain blood vessel disease. Talk with the doctor.
  • Check your blood sugar as you have been told by your doctor.
  • Avoid drinking alcohol while taking asenapine.
  • Talk with your doctor before you use other drugs and natural products that slow your actions.
  • Be careful in hot weather or while being active. Drink lots of fluids to stop fluid loss.
  • Dizziness, sleepiness, and feeling less stable may happen with asenapine. These may lead to falling. Broken bones or other health problems can happen from falling. Talk with the doctor.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using asenapine while you are pregnant.
  • Taking asenapine in the third trimester of pregnancy may lead to muscle movements that cannot be controlled and withdrawal in the newborn. Talk with the doctor.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.
  • Wash and dry your hands before you take asenapine. Do not touch the tablet with wet or damp hands.
  • Do not take asenapine out of the blister pack until you are ready to take it. Take asenapine right away after opening the blister pack. Do not store the removed drug for future use.
  • Place tablet under the tongue and let melt.
  • Do not swallow whole. Do not chew, break, or crush.
  • Do not eat or drink for at least 10 minutes after taking asenapine.
  • To gain the most benefit, do not miss doses.
  • Keep taking asenapine as you have been told by your doctor or other health care provider, even if you feel well.
  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.

Pregnancy level

Group c - Not adequate studies in pregnant women


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