Saphris (asenapine maleate)

The sublingual tablets are available as asenapine maleate; the dosage is expressed in terms of asenapine. Based on the AUC of asenapine, the 3.8 mg/24 hours transdermal system corresponds to 5 mg twice daily of sublingual asenapine and the 7.6 mg/24 hours transdermal system corresponds to 10 mg twice daily of sublingual asenapine.

Asenapine maleate is commercially available as rapidly dissolving sublingual tablets containing 2.5 mg, 5 mg, or 10 mg of the drug; the oral bioavailability of the drug after sublingual administration is much higher than following oral administration. Asenapine is also commercially available as a transdermal system (patch) containing 3.8 mg/24 hours, 5.7 mg/24 hours, or 7.6 mg/24 hours.

Asenapine maleate tablets are administered sublingually twice daily. Patients should be instructed not to remove a sublingual tablet from the blister pack until just prior to administration. With dry hands, the blister pack should be pulled out of the case and the colored tab should be peeled back to expose the sublingual tablet; the tablet should not be pushed through the blister pack. The tablet should then be gently removed and placed under the tongue and allowed to dissolve completely; the tablet will dissolve in saliva within seconds. The blister pack should then be slid back into the case until it clicks. Patients should be instructed not to eat or drink for 10 minutes following administration of the sublingual tablets. The sublingual tablets should not be split, crushed, chewed, or swallowed. Refer to the prescribing information for full instructions for use of asenapine sublingual tablets. Store asenapine sublingual tablets at 20-25degreesC (excursions permitted between 15-30degreesC).

The asenapine transdermal system (patch) is applied once daily; each patch should be worn for 24 hours only. Instruct patients to wear only one patch at any time. The patch should be applied to clean, dry, and intact skin at the selected application site; application sites include the upper arm, upper back, abdomen, or hip. Change (rotate) application sites each time a new patch is applied. Do not cut open the pouch until ready to apply the patch; do not use the patch if the individual pouch seal is broken or damaged. Do not cut the asenapine patch. If the patch lifts at the edges, reattach it by pressing firmly and smoothing down the edges of the system. If the patch comes off completely, apply a new patch. To discard, fold the used patch so that the adhesive side sticks to itself and then place in the trash immediately. If irritation or a burning sensation occurs while wearing the patch, remove it and apply a new patch to a new application site. While showering is permitted, avoid swimming or bathing while wearing the patch. Do not apply external heat sources (e.g., heating pad) over the transdermal system; prolonged application of heat over the patch increases plasma concentrations of asenapine. Refer to the prescribing information for full instructions for use of the asenapine transdermal system. Store asenapine patches at 20-25degreesC (excursions permitted between 15-30degreesC). Do not store unpouched and keep out of reach of children.

No dosing information is available for this tab.

No dosing information is available for this tab.

Asenapine is cleared mainly through direct glucuronidation by uridine diphosphate-glucuronosyltransferase (UGT) enzyme 1A4 and oxidative metabolism by cytochrome P-450 (CYP) isoenzymes, principally by CYP1A2 and, to a lesser extent, by CYP3A4 and CYP2D6.

Asenapine is a weak inhibitor of CYP2D6; the drug does not induce CYP1A2 or CYP3A4.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*Severe hepatic impairment (Child-Pugh class C).

*Known hypersensitivity to asenapine or any component of the transdermal system. Anaphylaxis, angioedema, hypotension, tachycardia, swollen tongue, dyspnea, wheezing, and rash have been reported.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

Adverse effects occurring in 5% or more of adult patients receiving sublingual asenapine therapy for treatment of schizophrenia and at a frequency at least twice that reported with placebo in clinical trials include akathisia (including hyperkinesia), oral hypoesthesia, and somnolence (including sedation and hypersomnia).

Adverse effects occurring in 5% or more of adult patients receiving sublingual asenapine as monotherapy for bipolar I disorder and at a frequency at least twice that reported with placebo in clinical trials include somnolence, oral hypoesthesia, dizziness, extrapyramidal symptoms other than akathisia, and akathisia.

Adverse effects occurring in 5% or more of adult patients receiving sublingual asenapine as adjunctive therapy for bipolar I disorder and at a frequency at least twice that reported with placebo in clinical trials include somnolence and oral hypoesthesia.

Adverse effects occurring in 5% or more of pediatric patients receiving sublingual asenapine as monotherapy for bipolar I disorder and at a frequency at least twice that reported with placebo in clinical trials include somnolence , dizziness, dysgeusia, oral paresthesia, nausea, increased appetite, fatigue, and weight gain.

Adverse effects occurring in 5% or more of patients receiving transdermal asenapine therapy and at a frequency at least twice that reported with placebo in clinical trials include extrapyramidal disorder, application site reaction, and weight gain.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

No enhanced messaging available.

Safety and efficacy of sublingual asenapine in pediatric patients younger than 10 years of age have not been established.

Safety and efficacy of sublingual asenapine monotherapy for the management of bipolar I disorder in pediatric patients 10-17 years of age have been established in a double-blind, placebo-controlled trial of 3 weeks' duration. In a phase I study, pediatric patients 10-17 years of age appeared to be more sensitive to dystonia when the initial dosage titration schedule was not followed. Similar safety findings were reported in a long-term (50-week), open-label, uncontrolled safety trial in pediatric patients with bipolar I disorder treated with sublingual asenapine monotherapy. To reduce the risk of dystonia in pediatric patients, sublingual asenapine should be titrated according to the manufacturer's recommended dosing schedule. Safety and efficacy of sublingual asenapine as adjunctive therapy for the treatment of bipolar disorder have not been established in pediatric patients to date.

Efficacy of sublingual asenapine for the treatment of schizophrenia was not established in an 8-week, placebo-controlled, double-blind trial in adolescents 12-17 years of age receiving 2.5 or 5 mg of the drug twice daily. Clinically relevant adverse reactions in the pediatric schizophrenia trial were generally similar to those observed in the pediatric bipolar I and adult bipolar I and schizophrenia trials. No new major safety findings were reported in a 26-week, open-label, uncontrolled safety trial of sublingual asenapine monotherapy in pediatric patients with schizophrenia. Safety and efficacy of transdermal asenapine have not been established in pediatric patients.

Pharmacokinetics of sublingual asenapine in pediatric patients 10-17 years of age generally are similar to those observed in adults.

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to asenapine during pregnancy. For more information, clinicians may contact the National Pregnancy Registry for Atypical Antipsychotics at 866-961-2388 or visit https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregi stry/atypicalantipsychotic/.

Studies have not been conducted with asenapine in pregnant women. There are no available human data informing the drug-associated risk. Asenapine was not teratogenic in animal reproduction studies with IV administration to rats and rabbits during organogenesis at dosages 0.7 and 0.4 times, respectively, the maximum recommended human dosage (MRHD) of 10 mg sublingually twice daily and at dosages 1.1 and 0.66 times, respectively, the MRHD of 12.8 mg of transdermal asenapine daily. In a pre- and postnatal study in rats, IV administration of asenapine at dosages up to 0.7 times the MRHD produced increases in post-implantation loss and early pup deaths and decreases in subsequent pup survival and weight gain. These dosages are up to 1.1 times the MRHD of 12.8 mg transdermal asenapine daily. Advise pregnant women of the potential hazard to a fetus.

Neonates exposed to antipsychotic agents during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. Symptoms reported to date have included agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder. The symptoms have varied in severity; some neonates recovered within hours to days without specific treatment, while others have required prolonged hospitalization. Neonates should be monitored for extrapyramidal and/or withdrawal symptoms and managed appropriately if symptoms occur.

It is not known whether asenapine is distributed into milk in humans. The drug is distributed into milk in rats. The effects of asenapine on breast-fed infants and on milk production also are not known. The benefit of asenapine therapy to the woman as well as the benefits of breast-feeding to the infant should be weighed against the potential risk to the infant from exposure to the drug or from the underlying maternal condition.

Dosage adjustment is not required in geriatric patients based on age alone.

Clinical trials with asenapine in the treatment of schizophrenia and bipolar mania did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger adults. In premarketing clinical studies of sublingual asenapine, 1.1% of approximately 2250 asenapine-treated patients were 65 years of age and older. In the placebo-controlled trial of transdermal asenapine, 1.6% of approximately 614 patients were 65 years of age and older.

Asenapine exposure is 30-40% higher in geriatric patients compared with younger adult patients. Routine dosage adjustment of asenapine is not necessary based on age alone. However, multiple factors that may increase the pharmacodynamic response to asenapine, resulting in poorer tolerance and orthostasis, could be present in geriatric patients, and such patients should be monitored carefully during therapy.

Geriatric patients with dementia-related psychosis treated with asenapine are at an increased risk of death compared with those treated with placebo. In addition, an increased incidence of adverse cerebrovascular events (cerebrovascular accidents and transient ischemic attacks), including fatalities, has been observed in geriatric patients with dementia-related psychosis treated with certain atypical antipsychotic agents (aripiprazole, olanzapine, risperidone) in placebo-controlled studies. The manufacturers of sublingual and transdermal asenapine state that the drug is not approved for the treatment of patients with dementia-related psychosis .