patients with diseases, conditions, or medications that could exacerbate these effects, when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy Leukopenia, neutropenia, and agranulocytosis reported with use; perform a CBC count during first few months of therapy; in such patients, consider discontinuation of therapy at first sign of clinically significant decline in WBC count 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) Can elevate prolactin levels, and elevation can persist during long-term 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 Use with caution in patients with a history of seizures or with conditions that potentially lower the seizure threshold; conditions that lower the seizure threshold may be more prevalent in patients ≥65 years Potential disruption of body temperature regulation Inherent suicide risk with population treated warrants close supervision when drug therapy is changed Dysphagia, esophageal dysmotility, and aspiration may occur Both the rate and extent of absorption are increased when heat is applied to application; avoid exposing patch to direct external heat sources (eg, hair dryers, heating pads, electric blankets, heated water beds) Local skin reactions, such as irritation, were reported Tardive dyskinesia Tardive dyskinesia may develop in patients treated with antipsychotic drugs, including asenapine transdermal Risk appears highest among elderly patients, especially elderly women, but it is not possible to predict which patients are likely to develop the syndrome Reserve long-term antipsychotic treatment for patients who have a chronic illness that is responsive to antipsychotic drugs, or in patients in whom effective alternative therapies are not available or appropriate In patients who do require long-term treatment, use lowest dose and shortest duration of treatment producing a satisfactory clinical response; periodically reassess if it needs to be continued If signs and symptoms of tardive dyskinesia appear, consider discontinuing treatment Drug interaction overview Asenapine is a CYP1A2 and UGT1A4 substrate; weak CYP2D6 inhibitor Coadministration of asenapine with a CYP1A2 inhibitor increases AUC and plasma levels of asenapine; reduce dose based on clinical response, if necessary Owing to its alpha1-adrenergic antagonism with potential for inducing hypotension, asenapine may enhance the effects of certain antihypertensive agents; monitor blood pressure and adjust dosage of antihypertensive drug accordingly 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]) Asenapine may enhance inhibitory effects of paroxetine on its own metabolism by CYP2D6; concomitant use with paroxetine increases paroxetine AUC and plasma levels; reduce paroxetine dose by half when used in combination with asenapine Pregnancy Studies have not been conducted in pregnant women No human data available informing the drug-associated risk Animal data In a pre-and post-natal study in rats, IV administration of asenapine at doses up to 0.7 times the MRHD of 10 mg of sublingual asenapine twice daily produced increases in postimplantation loss and early pup deaths, and decreases in subsequent pup survival and weight gain Doses were up to 1.1x the maximum recommended human dose (MRHD) of 12.8 mg transdermal asenapine daily. Advise pregnant women of the potential risk to a fetus Pregnancy exposure registry Monitors pregnancy outcomes in women exposed to atypical antipsychotics during pregnancy For more information contact the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-andresearch-programs/pregnancyregistry/ Clinical considerations Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs during the third trimester of pregnancy Symptoms have varied in severity Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization; monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately Lactation Studies have not been conducted to assess the presence of asenapine in human milk, the effects of asenapine on the breastfed infant, or the effects of asenapine on milk production Asenapine is excreted in rat milk Consider developmental and health benefits of breastfeeding along with the mother's clinical need for asenapine transdermal and any potential adverse effects on the breastfed infant from asenapine transdermal or from the underlying maternal conditionPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Mechanism of action is unknown Efficacy thought to be mediated via combined antagonist activity at dopamine D2 and serotonin type 2 (5-HT2) receptors Absorption Peak plasma time: 12-24 hr Steady-state plasma concentrations are achieved in ~72 hr after the first application Application of a heating pad on asenapine transdermal patch for 8 hr led to a faster absorption rate (median peak plasma time ~8 hr) as compared with no heating pad Distribution Protein bound: 95% (including albumin and alpha1-acid glycoprotein) Vd: 20-25 L/kg Metabolism Direct glucuronidation by UGT1A4 Oxidative metabolism predominantly by CYP1A2 Elimination Half-life: 30 hr Excretion: Urine (~50%); feces (40%) Transdermal Administration Transdermal use only Apply patch every 24 hr; do not wear longer than 24 hr Apply to clean, dry, and intact skin at the selected application sites: hip, abdomen, upper arm, or upper back area Wear only 1 patch at any time Apply to a different application site each time a new patch is applied Do not cut open the pouch until ready to apply; do not use if the individual pouch seal is broken or appears to be damaged Apply whole transdermal patch; do not cut If patch lifts at the edges, reattach by pressing firmly and smoothing down the edges of the patch If patch comes off completely, apply a new one After use, fold used patch so that the adhesive side sticks to itself and safely discard If irritation or a burning sensation occurs while wearing patch, remove and apply a new patch to a new application site Showering is permitted, but use during swimming or taking a bath has not been evaluated Do not apply external heat sources (eg, heating pad) over the patch Storage Store at room temperature 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF) No images available for this drug. No images available for this drug.A Patient Handout is not currently available for this monograph.Print FormularyPatient DiscountsAdding plans allows you to compare formulary status to other drugs in the same class.To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.Create Your List of PlansAdding plans allows you to:View the formulary and any restrictions for each plan.Manage and view all your plans together – even plans in different states.Compare formulary status to other drugs in the same class.Access your plan list on any device – mobile or desktop. The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information. View explanations for tiers and restrictions Tier Description 1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs. 2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs. 3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs. 4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. 5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. 6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. NC NOT COVERED – Drugs that are not covered by the plan. Code Definition PA Prior Authorization Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription. 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