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    Active Ingredient
    Asenapine (as maleate) 5 mg, 10 mg

    Status in Israel

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Sublingual Tablet

    60 X 5 mg

    partial basket chart 8259 19949

    Sublingual Tablet

    60 X 10 mg

    partial basket chart 8260 19950

    Related information


    Usual Dose for Acute Treatment in Adults:
    The recommended starting and target dose is 5 mg given twice daily. In short term controlled trials, there was no suggestion of added benefit with a 10 mg twice daily dose, but there was a clear increase in certain adverse reactions. The safety of doses above 10 mg twice daily has not been evaluated in clinical studies.
    Maintenance Treatment: Efficacy was demonstrated with this product in a maintenance trial in patients with schizophrenia. The starting dose in this study was 5 mg twice daily with an increase up to 10 mg twice daily after 1 week based on tolerability. While there is no body of evidence available to answer the question of how long the schizophrenic patient should remain on this product, patients should be periodically reassessed to determine the need for maintenance treatment.
    Bipolar Disorder
    Usual Dose for Acute Treatment of Manic or Mixed Episodes Associated with Bipolar I Disorder in Adults:

    Monotherapy: The recommended starting dose, and the dose maintained by 90% of the patients studied, is 10 mg twice daily. The dose can be decreased to 5 mg twice daily if warranted by adverse effects or based on individual tolerability. In controlled monotherapy trials, the starting dose was 10 mg twice daily. On the second and subsequent days of the trials, the dose could be lowered to 5 mg twice daily, based on tolerability, but less than 10% of patients had their dose reduced. The safety of doses above 10 mg twice daily has not been evaluated in clinical trials.
    Adjunctive Therapy: The recommended starting dose is 5 mg twice daily when administered as adjunctive therapy with either lithium or valproate. Depending on the clinical response and tolerability in the individual patient, the dose can be increased to 10 mg twice daily. The safety of doses above 10 mg twice daily as adjunctive therapy with lithium or valproate has not been evaluated in clinical trials.
    Maintenance Treatment: While there is no body of evidence available to answer the question of how long the bipolar patient should remain on this product, whether used as monotherapy or as adjunctive therapy with lithium or valproate, it is generally recommended that responding patients be continued beyond the acute response. If this product is used for extended periods in bipolar disorder, the physician should periodically re-evaluate the long-term risks and benefits of the drug for the individual patient.
    Dosage in Special Populations: In a study of subjects with hepatic impairment who were treated with a single dose of 5 mg, there were increases in asenapine exposures (compared to subjects with normal hepatic function), that correlated with the degree of hepatic impairment. While the results indicated that no dosage adjustments are required in patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment, there was a 7-fold increase (on average) in asenapine concentrations in subjects with severe hepatic impairment (Child-Pugh C) compared to the concentrations of those in subjects with normal hepatic function. Therefore, this product is not recommended in patients with severe hepatic impairment. Dosage adjustments are not routinely required on the basis of age, gender, race, or renal impairment status.
    For full details see prescribing information.


    Treatment of schizophrenia in adults. Treatment of bipolar disorder: Monotherapy for the acute treatment of manic or mixed episodes associated with bipolar I disorder. Adjunctive therapy with either lithium or valproate for the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults.


    Hypersensitivity reactions, including anaphylaxis and angioedema, have been observed in patients treated with asenapine. Therefore, this product is contraindicated in patients with a known hypersensitivity to the product.

    Special Precautions

    INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS See full prescribing information for complete boxed warning. Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. this product is not approved for the treatment of patients with dementia-related psychosis.
    Cerebrovascular Adverse Events Including Stroke, In Elderly Patients with DementiaRelated Psychosis:
    In placebo-controlled trials with risperidone, aripiprazole, and olanzapine in elderly subjects with dementia, there was a higher incidence of cerebrovascular adverse reactions (cerebrovascular accidents and transient ischemic attacks) including fatalities compared to placebo-treated subjects. this product is not approved for the treatment of patients with dementia-related psychosis and is not recommended for use in this particular group of patients.
    Neuroleptic Malignant Syndrome: A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with administration of antipsychotic drugs, including this product. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. The diagnostic evaluation of patients with this syndrome is complicated. It is important to exclude cases where the clinical presentation includes both serious medical illness (e.g. pneumonia, systemic infection) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system pathology. The management of NMS should include: 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy; 2) intensive symptomatic treatment and medical monitoring; and 3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for NMS. If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. The patient should be carefully monitored, since recurrences of NMS have been reported.
    Tardive Dyskinesia: A syndrome of potentially irreversible, involuntary, dyskinetic movements can develop in patients treated with antipsychotic drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of antipsychotic treatment, which patients are likely to develop the syndrome. Whether antipsychotic drug products differ in their potential to cause Tardive Dyskinesia (TD) is unknown. The risk of developing TD and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic drugs administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses. There is no known treatment for established cases of TD, although the syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn. Antipsychotic treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown. Given these considerations, this product should be prescribed in a manner that is most likely to minimize the occurrence of TD. Chronic antipsychotic treatment should generally be reserved for patients who suffer from a chronic illness that (1) is known to respond to antipsychotic drugs, and (2) for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients who do require chronic treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically. The onset of extrapyramidal symptoms is a risk factor for tardive dyskinesia. If signs and symptoms of TD appear in a patient on this product, drug discontinuation should be considered. However, some patients may require treatment with this product despite the presence of the syndrome.
    For full details see prescribing information.

    Side Effects

    The most common adverse reactions (≥5% and at least twice the rate of placebo) reported with acute treatment in schizophrenia were akathisia, oral hypoesthesia, and somnolence. The safety profile of this product in the maintenance treatment of schizophrenia was similar to that seen with acute treatment. The most common adverse reactions (≥5% and at least twice the rate of placebo) reported with acute monotherapy treatment of manic or mixed episodes associated with bipolar I disorder were somnolence, dizziness, extrapyramidal symptoms other than akathisia, and weight increased and during the adjunctive therapy trial in bipolar disorder were somnolence and oral hypoesthesia. The information below is derived from a clinical trial database for this product consisting of over 4565 patients and/or normal subjects exposed to one or more sublingual doses of this product. A total of 1314 -treated patients were treated for at least 24 weeks and 785 this product-treated patients had at least 52 weeks of exposure at therapeutic doses. The stated frequencies of adverse reactions represent the proportion of individuals who experienced a treatment-emergent adverse event of the type listed. A reaction was considered treatment emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation. The figures in the tables and tabulations cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatment, uses, and investigators. The cited figures, however, do provide the prescriber with some basis for estimating the relative contribution of drug and nondrug factors to the adverse reaction incidence in the population studied.
    For full details see prescribig information.

    Drug interactions

    The risks of using this product in combination with other drugs have not been extensively evaluated. Given the primary CNS effects of this product, caution should be used when it is taken in combination with other centrally-acting drugs or alcohol. Because of its α1-adrenergic antagonism with potential for inducing hypotension, this product may enhance the effects of certain antihypertensive agents.
    Potential for Other Drugs to Affect this product: Asenapine is cleared primarily through direct glucuronidation by UGT1A4 and oxidative metabolism by cytochrome P450 isoenzymes (predominantly CYP1A2). The potential effects of inhibitors of several of these enzyme pathways on asenapine clearance were studied.
    For full details see prescribig information.

    Pregnancy and Lactation

    Pregnancy Pregnancy Category C: There are no adequate and well-controlled studies in pregnant women. In animal studies, asenapine increased post-implantation loss and decreased pup weight and survival at doses similar to or less than recommended clinical doses. In these studies there was no increase in the incidence of structural abnormalities caused by asenapine. Asenapine was not teratogenic in reproduction studies in rats and rabbits at intravenous doses up to 1.5 mg/kg in rats and 0.44 mg/kg in rabbits. These doses are 0.7 and 0.4 times, respectively, the maximum recommended human dose (MRHD) of 10 mg twice daily given sublingually on a mg/m2 basis. Plasma levels of asenapine were measured in the rabbit study, and the area under the curve (AUC) at the highest dose tested was 2 times that in humans receiving the MRHD. In a study in which rats were treated from day 6 of gestation through day 21 postpartum with intravenous doses of asenapine of 0.3, 0.9, and 1.5 mg/kg/day (0.15, 0.4, and 0.7 times the MRHD of 10 mg twice daily given sublingually on a mg/m2 basis), increases in post-implantation loss and early pup deaths were seen at all doses, and decreases in subsequent pup survival and weight gain were seen at the two higher doses. A cross-fostering study indicated that the decreases in pup survival were largely due to prenatal drug effects. Increases in post-implantation loss and decreases in pup weight and survival were also seen when pregnant rats were dosed orally with asenapine.
    Non-teratogenic Effects: Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in these neonates. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization. This product (asenapine) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
    Labor and Delivery: The effect on labor and delivery in humans is unknown.
    Nursing Mothers: Asenapine is excreted in milk of rats during lactation. It is not known whether asenapine or its metabolites are excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when administered to a nursing woman. It is recommended that women receiving this product should not breast feed.


    Human Experience: In pre-marketing clinical studies involving more than 3350 patients and/or healthy subjects, accidental or intentional acute overdose was identified in 3 patients. Among these few reported cases of overdose, the highest estimated ingestion was 400 mg. Reported adverse reactions at the highest dosage included agitation and confusion.
    Management of Overdose: There is no specific antidote to this product. The possibility of multiple drug involvement should be considered. An electrocardiogram should be obtained and management of overdose should concentrate on supportive therapy, maintaining an adequate airway, oxygenation and ventilation, and management of symptoms. Hypotension and circulatory collapse should be treated with appropriate measures, such as intravenous fluids and/or sympathomimetic agents (epinephrine and dopamine should not be used, since beta stimulation may worsen hypotension in the setting of this product-induced alpha blockade). In case of severe extrapyramidal symptoms, anticholinergic medication should be administered. Close medical supervision and monitoring should continue until the patient recovers.

    Merck Sharp & Dohme Corp., USA