Trade Names:Saphris- Tablets, sublingual 5 mg- Tablets, sublingual 10 mg
Unknown. May control psychotic symptoms through antagonism of selected dopamine and serotonin receptors in the CNS.
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.
Rapidly distributed throughout the body. Vd is approximately 20 to 25 L/kg; 95% bound to plasma proteins.
In liver by glucuronidation and CYP-450–mediated oxidation.
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.
Pharmacokinetics are similar in patients with severe renal impairment compared with healthy patients.Hepatic Function Impairment
Severe hepatic impairment exposure was 7 times higher than in healthy patients.Elderly
Cl decreased, increasing exposure by 30% in elderly patients.Gender
No significant pharmacokinetic difference between genders was found.Race
No effect of race on asenapine concentrations was observed. Pharmacokinetic exposure was similar among white and Japanese patients.Smoking
Smoking had no effect on the pharmacokinetics of asenapine.
Acute treatment of schizophrenia; treatment of acute mixed or manic episodes associated with bipolar I disorder with or without psychotic features.
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.SchizophreniaAdults
PO 5 mg twice daily (safety of dosages more than 10 mg twice daily not evaluated).Hepatic Function ImpairmentAdults
For severe hepatic impairment (Child-Pugh Score C), use is not recommended.
Store at 59° to 86° F.
Coadministration may enhance CNS depression. Use with caution.Antiarrhythmics, class IA (eg, procainamide, quinidine) and class III (eg, amiodarone, sotalol), antibiotics (eg, gatifloxacin, moxifloxacin), antipsychotics (eg, chlorpromazine, thioridazine, ziprasidone)
Additive effects on QT interval prolongation may increase the risk of life-threatening arrhythmias, including torsades de pointes. Avoid this combination.Antihypertensive agents
Because of alpha-1 adrenergic antagonism by asenapine, the effect of certain antihypertensive agents may be enhanced.Carbamazepine, cimetidine
Asenapine plasma concentrations may be decreased; however, no adjustment in the asenapine dose is needed.Dextromethorphan
Plasma concentrations of dextromethorphan may be increased. Use with caution.Fluvoxamine
Asenapine plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Use with caution.Imipramine
Asenapine plasma concentrations may be increased; however, no adjustment in the asenapine dose is needed.Paroxetine
Asenapine plasma concentrations may be decreased, while paroxetine plasma concentrations may be increased. Use with caution.Valproate
Asenapine plasma concentrations may be increased slightly; however, no adjustment in the asenapine dose is needed.
None well documented.
Somnolence (24%); insomnia (16%); extrapyramidal symptoms, headache (12%); akathisia, dizziness (11%); anxiety, fatigue (4%); depression, irritability (2%).
Constipation, oral hypoesthesia, vomiting (7%); dyspepsia, increased appetite, salivary hypersecretion (4%); dry mouth, dysgeusia, stomach discomfort, toothache (3%).
Elevated triglycerides (15%); elevated total cholesterol (9%); elevated fasting glucose (7%); elevated prolactin levels, elevated transaminases (3%).
Weight increase (5%).
Arthralgia (3%); pain in extremity (2%).
WarningsIncreased mortality in elderly patients with dementia-related psychosis
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Over a course of a 10-week controlled trial, the rate of death in drug-treated patients was about 4.5% compared with 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either CV (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature.
Assess CBC frequently during the first few months of therapy; assess blood glucose for hyperglycemia, especially in diabetic patients. In patients receiving treatment for extended time, periodically reevaluate the long-term usefulness of continued therapy. Regularly monitor patient's weight.
Category C .
Safety and efficacy not established.
Not recommended in patients with severe hepatic impairment.
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 (eg, stroke, transient ischemic attack), including fatalities, may occur.
Caution patients about operating potentially hazardous machinery (eg, cars) until they know whether the drug impairs their ability. Advise patients to avoid alcohol.
Clinical experience is limited in patients with concomitant illnesses. Use with caution in patients with a recent history of MI or unstable heart disease.
Use with caution in patients at risk for aspiration pneumonia.
Agranulocytosis, leukopenia, and neutropenia have been reported.
Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, may occur.
Asenapine may elevate prolactin levels; however, there is no evidence of increased breast tumor risk.
NMS has occurred and is potentially fatal. Signs and symptoms are altered mental status, diaphoresis, hyperpyrexia, irregular BP, irregular pulse, muscle rigidity, and tachycardia.
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).
Use with caution in patients with a history of seizures or with conditions that lower the seizure threshold (eg, Alzheimer dementia).
Possible suicide attempts are inherent to schizophrenia and bipolar disorder. Closely supervise high-risk patients.
Syndrome of potentially irreversible, involuntary dyskinetic movements may develop. Prevalence is highest in elderly patients, especially women.
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.
Copyright © 2009 Wolters Kluwer Health.