Asenapine

Trade Names:Saphris- Tablets, sublingual 5 mg- Tablets, sublingual 10 mg

Pharmacology

Unknown. May control psychotic symptoms through antagonism of selected dopamine and serotonin receptors in the CNS.

Pharmacokinetics

Absorption

Rapidly absorbed sublingually. Absolute bioavailability is 35%, mean C _max was approximately 4 ng/mL, and T _max was 1 h after a 5 mg dose. Steady-state concentrations are reached within 3 days of twice-daily dosing. Food or water may decrease asenapine exposure.

Distribution

Rapidly distributed throughout the body. Vd is approximately 20 to 25 L/kg; 95% bound to plasma proteins.

Metabolism

In liver by glucuronidation and CYP-450–mediated oxidation.

Elimination

Elimination is 50% in urine and 40% in feces. The terminal half-life is approximately 24 h. Plasma Cl after IV administration is 52 L/h.

Special Populations

Pharmacokinetics are similar in patients with severe renal impairment compared with healthy patients.

Severe hepatic impairment exposure was 7 times higher than in healthy patients.

Cl decreased, increasing exposure by 30% in elderly patients.

No significant pharmacokinetic difference between genders was found.

No effect of race on asenapine concentrations was observed. Pharmacokinetic exposure was similar among white and Japanese patients.

Smoking had no effect on the pharmacokinetics of asenapine.

Indications and Usage

Acute treatment of schizophrenia; treatment of acute mixed or manic episodes associated with bipolar I disorder with or without psychotic features.

Contraindications

Standard considerations.

Dosage and Administration

PO Start with 10 mg twice daily (safety of higher dosages not evaluated). Dosage may be decreased to 5 mg twice daily if there are adverse effects.

PO 5 mg twice daily (safety of dosages more than 10 mg twice daily not evaluated).

For severe hepatic impairment (Child-Pugh Score C), use is not recommended.

General Advice

• Place tablet under the tongue and allow it to dissolve completely.
• Do not crush, chew, or swallow sublingual tablets.
• Patients should not eat or drink for 10 min after administration.

Storage/Stability

Store at 59° to 86° F.

Drug Interactions

Coadministration may enhance CNS depression. Use with caution.

Additive effects on QT interval prolongation may increase the risk of life-threatening arrhythmias, including torsades de pointes. Avoid this combination.

Because of alpha-1 adrenergic antagonism by asenapine, the effect of certain antihypertensive agents may be enhanced.

Asenapine plasma concentrations may be decreased; however, no adjustment in the asenapine dose is needed.

Plasma concentrations of dextromethorphan may be increased. Use with caution.

Asenapine plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Use with caution.

Asenapine plasma concentrations may be increased; however, no adjustment in the asenapine dose is needed.

Asenapine plasma concentrations may be decreased, while paroxetine plasma concentrations may be increased. Use with caution.

Asenapine plasma concentrations may be increased slightly; however, no adjustment in the asenapine dose is needed.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypertension (3%).

CNS

Somnolence (24%); insomnia (16%); extrapyramidal symptoms, headache (12%); akathisia, dizziness (11%); anxiety, fatigue (4%); depression, irritability (2%).

GI

Constipation, oral hypoesthesia, vomiting (7%); dyspepsia, increased appetite, salivary hypersecretion (4%); dry mouth, dysgeusia, stomach discomfort, toothache (3%).

Lab Tests

Elevated triglycerides (15%); elevated total cholesterol (9%); elevated fasting glucose (7%); elevated prolactin levels, elevated transaminases (3%).

Metabolic

Weight increase (5%).

Musculoskeletal

Arthralgia (3%); pain in extremity (2%).

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Hepatic Function

Not recommended in patients with severe hepatic impairment.

Body temperature regulation

Antipsychotics disrupt the ability to reduce core body temperature. Use with caution in patients who will experience conditions that may contribute to an elevation in core body temperature (eg, concomitant anticholinergic therapy, exposure to extreme heat, strenuous exercise, subject to dehydration).

Cerebrovascular adverse reactions

Cerebrovascular adverse reactions (eg, stroke, transient ischemic attack), including fatalities, may occur.

Cognitive and motor impairment

Caution patients about operating potentially hazardous machinery (eg, cars) until they know whether the drug impairs their ability. Advise patients to avoid alcohol.

Concomitant illness

Clinical experience is limited in patients with concomitant illnesses. Use with caution in patients with a recent history of MI or unstable heart disease.

Dysphagia

Use with caution in patients at risk for aspiration pneumonia.

Hematologic effects

Agranulocytosis, leukopenia, and neutropenia have been reported.

Hyperglycemia and diabetes mellitus

Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, may occur.

Hyperprolactinemia

Asenapine may elevate prolactin levels; however, there is no evidence of increased breast tumor risk.

NMS

NMS has occurred and is potentially fatal. Signs and symptoms are altered mental status, diaphoresis, hyperpyrexia, irregular BP, irregular pulse, muscle rigidity, and tachycardia.

Orthostatic hypotension

May occur. Most common during early treatment and in patients with CV disease, cerebrovascular disease, and conditions that predispose to hypotension (eg, dehydration, hypovolemia, treatment with antihypertensive agents).

Seizures

Use with caution in patients with a history of seizures or with conditions that lower the seizure threshold (eg, Alzheimer dementia).

Suicide

Possible suicide attempts are inherent to schizophrenia and bipolar disorder. Closely supervise high-risk patients.

Tardive dyskinesia

Syndrome of potentially irreversible, involuntary dyskinetic movements may develop. Prevalence is highest in elderly patients, especially women.

Weight gain

There is a potential for weight gain. In a 52-wk trial, approximately 14.7% of patients receiving asenapine gained at least 7% of their baseline weight.

Overdosage

Symptoms

Agitation, confusion.

Patient Information

• Instruct patient that sublingual tablets should be placed under the tongue and allowed to dissolve completely. Sublingual tablets should not be crushed, chewed, or swallowed.
• Advise patients not to eat or drink for 10 min after a dose is taken.
• Instruct patient not to stop taking asenapine when feeling better.
• Instruct patient with diabetes to monitor blood glucose more frequently when drug is started or dose is changed, and to inform health care provider of significant changes in readings.
• Advise patient to notify health care provider of the following: change in personality or mood, excessive drowsiness, involuntary body or facial movements, rapid pulse, swelling in the feet or ankles, weight gain.
• Advise patient to avoid strenuous activity in high temperature or humidity.
• Instruct patient to avoid alcoholic beverages and sedatives (eg, diazepam) while taking asenapine.
• Advise patient with preexisting low WBC or a history of drug-induced leukopenia/neutropenia that they should have their CBC monitored while taking this medicine.
• Inform patient of the risk of orthostatic hypotension. Symptoms may include feeling dizzy or light-headed upon standing, especially early in treatment, and also at times of reinitiating treatment or increases in dose.
• Advise patient taking antihypertensives to monitor BP at regular intervals.
• Advise patient that drug may impair judgment, thinking, or motor skills or cause drowsiness, and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.

Copyright © 2009 Wolters Kluwer Health.