Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Asenapine is not approved for the treatment of patients with dementia-related psychosis.
Agitation/aggression (severe, acute) associated with psychiatric disorders (eg, bipolar disorder, schizophrenia), substance intoxication, or other organic causes (alternative agent) (off-label use):
Note: Antipsychotics are appropriate when psychosis is suspected to be the primary cause of agitation/aggression. Other agents are used preferentially in some intoxications (eg, stimulants) or alcohol withdrawal. Depending on presentation, may combine with a benzodiazepine (CANMAT/ISBD [Yatham 2018]; WFSBP [Hasan 2012]; Wilson 2012).
Sublingual: 10 mg as a single dose (Pratts 2014).
Bipolar disorder:
Acute mania or episodes with mixed features:
Monotherapy: Sublingual: Initial: 5 to 10 mg twice daily; maximum dose: 10 mg twice daily.
Adjunctive therapy (with lithium or valproate): Sublingual: Initial: 5 mg twice daily; may increase to 10 mg twice daily based on response and tolerability; maximum dose: 10 mg twice daily.
Maintenance: Monotherapy: Sublingual: Continue with acute episode dose; decrease to 5 mg twice daily based on response and tolerability; maximum dose: 10 mg twice daily.
Schizophrenia:
Patch: Initial: Apply 3.8 mg per 24 hours patch once daily; may increase dose to 5.7 mg per 24 hours or 7.6 mg per 24 hours after 1 week based on response and tolerability.
Sublingual: Initial: 5 mg twice daily; may increase dose to 10 mg twice daily after 1 week based on response and tolerability; maximum dose: 10 mg twice daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Discontinuation of therapy: In the treatment of chronic psychiatric disease switching therapy rather than discontinuation is generally advised if side effects are intolerable or treatment is not effective. If patient insists on stopping treatment, gradual dose reduction (ie, over several weeks to months) is advised to detect a re-emergence of symptoms and to avoid withdrawal reactions (eg, agitation, alternating feelings of warmth and chill, anxiety, diaphoresis, dyskinesias, GI symptoms, insomnia, irritability, myalgia, paresthesia, psychosis, restlessness, rhinorrhea, tremor, vertigo) unless discontinuation is due to significant adverse effects. Monitor closely to allow for detection of prodromal symptoms of disease recurrence (APA [Keepers 2020]; Lambert 2007; Moncrieff 2020; Post 2020).
Switching antipsychotics: An optimal universal strategy for switching antipsychotic drugs has not been established. Strategies include: Cross-titration (gradually discontinuing the first antipsychotic while gradually increasing the new antipsychotic) and abrupt change (abruptly discontinuing the first antipsychotic and either increasing the new antipsychotic gradually or starting it at a treatment dose). In patients with schizophrenia at high risk of relapse, the current medication may be maintained at full dose as the new medication is increased (eg, overlap); once the new medication is at therapeutic dose, the first medication is gradually decreased and discontinued over 1 to 2 weeks (Cerovecki 2013; Remington 2005; Takeuchi 2017). Based upon clinical experience, some experts generally prefer cross-titration and overlap approaches rather than abrupt change (Stroup 2022).
No dosage adjustment necessary.
Mild-to-moderate hepatic impairment (Child-Pugh class A or B): No dosage adjustment necessary.
Severe hepatic impairment (Child-Pugh class C): Use is contraindicated.
(For additional information see "Asenapine: Pediatric drug information")
Bipolar disorder: Acute mania or episodes with mixed features ; monotherapy: Children ≥10 years and Adolescents ≤17 years: Sublingual: Initial: 2.5 mg twice daily; may titrate after 3 days to 5 mg twice daily, then after an additional 3 days to 10 mg twice daily based on tolerability; recommended daily dose range: 5 to 20 mg/day in 2 divided doses; maximum dose: 10 mg twice daily (20 mg/day).
Discontinuation of therapy: Similar to adult experience, the American Academy of Child and Adolescent Psychiatry (AACAP) guidelines recommend gradually tapering antipsychotics to avoid withdrawal symptoms (eg, insomnia, headache, GI symptoms) and minimize the risk of relapse unless discontinuation is due to significant adverse effects (AACAP [McClellan 2007]). In adults, decreasing the dose very gradually over weeks to months (eg, reducing the dose by 10% per month) with close monitoring is suggested to allow for detection of prodromal symptoms of disease recurrence (APA [Lehman 2004]; CPA 2005).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children ≥10 years and Adolescents:
Mild to severe impairment: No dosage adjustment necessary; asenapine exposure was similar to subjects with normal renal function; the effect of metabolite exposure with renal impairment has not been studied.
Dialysis: Has not been studied.
Children ≥10 years and Adolescents:
Mild to moderate hepatic impairment: No dosage adjustment necessary.
Severe hepatic impairment: Use is contraindicated.
Refer to adult dosing. Dosages in the lower range of recommended adult dosing are generally sufficient with late-onset schizophrenia and psychosis. Titrate dosage slowly and monitor carefully (Howard 2000).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Patch 24 Hour, Transdermal:
Secuado: 3.8 mg/24 hr (1 ea, 30 ea); 5.7 mg/24 hr (1 ea, 30 ea); 7.6 mg/24 hr (1 ea, 30 ea)
Tablet Sublingual, Sublingual:
Saphris: 2.5 mg, 5 mg, 10 mg [black cherry flavor]
Generic: 2.5 mg, 5 mg, 10 mg
May be product dependent
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet Sublingual, Sublingual:
Saphris: 5 mg, 10 mg
Sublingual: Sublingual tablets should be placed under the tongue and allowed to completely dissolve. Do not split, crush, chew, or swallow. Avoid eating or drinking for at least 10 minutes after administration.
Transdermal: Do not open pouch until ready to apply a patch. Apply 1 patch daily to clean, dry, intact skin of the upper arm, upper back, abdomen, or hip and leave on for only 24 hours. Wear only 1 patch at a time and do not use the same application site 2 times in a row. Do not cut patches. If application-site reaction (irritation, burning) occurs, remove patch and apply a new patch at a new application site. May shower while wearing patch but avoid swimming, bathing. Avoid placing external heat sources (eg, heating pad, hair dryer, electric blanket, heated water bed) on the patch. Discard by folding the used patch so that the adhesive side sticks to itself. See manufacturer's labeling for further administration instructions.
Sublingual: Tablets should be placed under the tongue and allowed to completely dissolve. Do not split, crush, chew, or swallow. Avoid eating or drinking for at least 10 minutes after administration.
Bipolar disorder (sublingual tablet only): Treatment of acute mania or episodes with mixed features associated with bipolar I disorder (as monotherapy in adult and pediatric patients ≥10 years of age or adjunctive treatment with lithium or valproate in adults) and maintenance treatment in adults (as monotherapy).
Schizophrenia (transdermal patch, sublingual tablet): Treatment of adults with schizophrenia.
Agitation/aggression (severe, acute) associated with psychiatric disorders (eg, bipolar disorder, schizophrenia), substance intoxication, or other organic causes
Beers Criteria: Antipsychotics are identified in the Beers Criteria as potentially inappropriate medications to be avoided in patients 65 years and older due to an increased risk of cerebrovascular accidents (stroke) and a greater rate of cognitive decline and mortality in patients with dementia. Antipsychotics may be appropriate for schizophrenia, bipolar disorder, other mental health conditions, or short-term use as antiemetic during chemotherapy but should be given in the lowest effective dose for the shortest duration possible. In addition, antipsychotics should be used with caution in older adults due to their potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; monitor sodium closely with initiation or dosage adjustments in older adults (Beers Criteria [AGS 2019]).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Actual frequency may be dependent upon dose and/or indication.
>10%:
Central nervous system: Drowsiness (children and adolescents: 46% to 53%; adults: 3% to 26%;), insomnia (adults: 15% to 16%; children and adolescents: 4%), akathisia (adults: 4% to 15%; children and adolescents: 1% to 2%), fatigue (4% to 14%), extrapyramidal reaction (adults: 8% to 13%; children and adolescents: 1% to 2%), headache (8% to 11%)
Endocrine & metabolic: Weight gain (adults: 1% to 22%; children and adolescents: 2% to 12%), increased serum triglycerides (adults: 3% to 18%; children and adolescents: 2% to 4%), increased serum glucose (adults: 3% to 16%; children and adolescents: 2%), decreased HDL cholesterol (6% to 15%), increased serum cholesterol (adults: 2% to 14%)
Gastrointestinal: Oral hypoesthesia (5% to 30%)
Local: Application site reaction (transdermal: 14% to 15%)
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (adults: 11%)
1% to 10%:
Cardiovascular: Hypertension (adults: 2% to 3%), tachycardia (1% to 3%), orthostatic hypotension (2%), syncope (≤1%)
Central nervous system: Dizziness (5% to 10%), bipolar mood disorder (exacerbation; adults: ≤8%), mania (adults: ≤8%), agitation (adults: 3% to 4%), suicidal ideation (children and adolescents: 3% to 4%), anxiety (adults: 3%), dystonia (1% to 3%), outbursts of anger (children and adolescents: 2%), drug-induced Parkinson's disease (children and adolescents: 1% to 2%), irritability (1% to 2%), disruption of body temperature regulation (≤1%)
Dermatologic: Skin rash (children and adolescents: 2%)
Endocrine & metabolic: Increased serum prolactin (2% to 3%), dehydration (children and adolescents: 2%), increased LDL cholesterol (1%)
Gastrointestinal: Increased appetite (2% to 10%), abdominal pain (children and adolescents: 9%; adults: 2% to 3%), dysgeusia (3% to 9%), constipation (adults: 3% to 7%), vomiting (3% to 7%), nausea (4% to 6%), sialorrhea (adults: ≤4%), diarrhea (3%), dyspepsia (adults: 3%), stomach discomfort (adults: 2% to 3%), toothache (adults: 2% to 3%), xerostomia (adults: 2% to 3%), hyperinsulinism (children and adolescents: 1% to 3%), glossalgia (children and adolescents: 2%)
Genitourinary: Dysmenorrhea (≤2%), galactorrhea not associated with childbirth (≤2%)
Hepatic: Increased serum transaminases (adults: 2% to 3%), increased serum alanine aminotransferase (1% to 3%), increased liver enzymes (2%), increased serum aspartate aminotransferase (children and adolescents: 2%)
Local: Application site erythema (transdermal: 9% to 10%), application-site pruritus (transdermal: 4% to 5%)
Neuromuscular & skeletal: Arthralgia (adults: 2%), muscle strain (children and adolescents: 2%), myalgia (1% to 2%), asthenia (<2%)
Respiratory: Nasopharyngitis (adults: 3% to 5%), oropharyngeal pain (children and adolescents: 3%), upper respiratory tract infection (3%), dyspnea (children and adolescents: 2%), nasal congestion (children and adolescents: 2%)
Miscellaneous: Fever (≤1%)
Frequency not defined:
Cardiovascular: Prolonged QT interval on ECG
Central nervous system: Altered mental status, falling, neuroleptic malignant syndrome, tardive dyskinesia
Gastrointestinal: Oral paresthesia, swollen tongue
<1%, postmarketing, and/or case reports: Accommodation disturbance, anaphylaxis, anemia, angioedema, application site irritation, blurred vision, bundle branch block (temporary), choking sensation, diabetes mellitus, diplopia, dysarthria, dyslipidemia, dysphagia, exfoliation of skin (sublingual: oral mucosal), gastroesophageal reflux disease, hyperpigmentation, hypersensitivity reaction, hyponatremia, hypotension, leukopenia, neutropenia, oral inflammation (sublingual), oral mucosal ulcer (sublingual), oropharyngeal blister (sublingual), seizure, skin photosensitivity, thrombocytopenia, urinary incontinence, wheezing
Severe hepatic impairment (Child-Pugh class C); hypersensitivity to asenapine or any component of the formulation (eg, anaphylaxis, angioedema, hypotension, tachycardia, swollen tongue, dyspnea, wheezing, rash)
Concerns related to adverse reactions:
• Blood dyscrasias: Leukopenia, neutropenia, and agranulocytosis (sometimes fatal) have been reported with antipsychotic use; presence of risk factors (eg, preexisting low WBC or history of drug-induced leuko/neutropenia) should have a complete blood count performed frequently during the first few months of therapy. Discontinue therapy at first signs of blood dyscrasias or if absolute neutrophil count <1,000/mm3.
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).
• Dyslipidemia: Has been reported with atypical antipsychotics; risk profile may differ between agents. Compared to other antipsychotics, the risk of dyslipidemia with asenapine is minimal to low (Solmi 2017).
• Esophageal dysmotility/aspiration: Antipsychotic use has been associated with esophageal dysmotility and aspiration; risk increases with age. Use with caution in patients at risk for aspiration pneumonia (eg, Alzheimer disease), particularly in patients >75 years (Herzig 2017; Maddalena 2004).
• Extrapyramidal symptoms: May cause extrapyramidal symptoms (EPS), including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia (risk of these reactions is generally much lower relative to typical/conventional antipsychotics; frequencies reported are similar to placebo). Risk of dystonia (and probably other EPS) may be greater with increased doses, use of conventional antipsychotics, males, and younger patients. Factors associated with greater vulnerability to tardive dyskinesia include older in age, female gender combined with postmenopausal status, Parkinson disease, pseudoparkinsonism symptoms, affective disorders (particularly major depressive disorder), concurrent medical diseases such as diabetes, previous brain damage, alcoholism, poor treatment response, and use of high doses of antipsychotics (APA [Keepers 2020]; Soares-Weiser 2007). Consider therapy discontinuation with signs/symptoms of tardive dyskinesia.
• Falls: May increase the risk for falls due to somnolence, orthostatic hypotension, and motor or sensory instability.
• Hyperglycemia: Atypical antipsychotics have been associated with development of hyperglycemia; in some cases, may be extreme and associated with ketoacidosis, hyperosmolar coma, or death. All patients should be monitored for symptoms of hyperglycemia (eg, polydipsia, polyuria, polyphagia, weakness). Use with caution in patients with diabetes or other disorders of glucose regulation; monitor for worsening of glucose control. Patients with risk factors for diabetes (eg, obesity, family history) should have a baseline fasting blood sugar and periodic assessment of glucose regulation. Compared to other antipsychotics, the risk of hyperglycemia with asenapine is minimal to low (Solmi 2017).
• Hypersensitivity: Anaphylaxis and hypersensitivity reactions (eg, angioedema, hypotension, tachycardia, swollen tongue, dyspnea, wheezing, rash) have been reported; some cases have occurred after a single dose.
• Hyperprolactinemia: May increase prolactin levels; clinical significance of hyperprolactinemia in patients with breast cancer or other prolactin-dependent tumors is unknown.
• Neuroleptic malignant syndrome: Use may be associated with neuroleptic malignant syndrome (NMS); monitor for mental status changes, fever, muscle rigidity, and/or autonomic instability. NMS can recur. Following recovery from NMS, reintroduction of drug therapy should be carefully considered; if an antipsychotic agent is resumed, monitor closely for NMS.
• Orthostatic hypotension: May cause orthostatic hypotension and syncope; use with caution in patients at risk of this effect (eg, concurrent medication use which may predispose to hypotension/bradycardia or presence of dehydration or hypovolemia) or in those who would not tolerate transient hypotensive episodes. Use caution with history of cerebrovascular or cardiovascular disease (myocardial infarction [MI], heart failure [HF], conduction abnormalities, or ischemic disease).
• QT prolongation: May result in QTc prolongation. Risk may be increased by conditions or concomitant medications which cause bradycardia, hypokalemia, and/or hypomagnesemia. Avoid use in combination with QTc-prolonging drugs and in patients with congenital long QT syndrome or patients with history of cardiac arrhythmia.
• Suicidal ideation: The possibility of a suicide attempt is inherent in psychotic illness or bipolar disorder; use with caution in high-risk patients during initiation of therapy. Prescriptions should be written for the smallest quantity consistent with good patient care.
• Temperature regulation: Antipsychotic use has been associated with impaired core body temperature regulation; caution with strenuous exercise, heat exposure, dehydration, and concomitant medication possessing anticholinergic effects (Kerwin 2004; Kwok 2005; Martinez 2002).
• Weight gain: Significant weight gain has been observed with antipsychotic therapy; incidence varies with product. Compared to other antipsychotics, the risk of weight gain with asenapine is low (Solmi 2017). Monitor waist circumference and BMI.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with cardiac disease, cerebrovascular disease, hemodynamic instability, prior MI, or ischemic heart disease.
• Dementia: [US Boxed Warning]: Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Most deaths appeared to be either cardiovascular (eg, HF, sudden death) or infectious (eg, pneumonia) in nature. Use with caution in patients with Lewy body dementia or Parkinson disease dementia due to greater risk of adverse effects, increased sensitivity to extrapyramidal effects, and association with irreversible cognitive decompensation or death (APA [Reus 2016]). Asenapine is not approved for the treatment of dementia-related psychosis.
• Hepatic impairment: Use is contraindicated in patients with severe hepatic impairment (Child-Pugh class C); increased drug concentrations may occur.
• Seizures: Use with caution in patients at risk of seizures or conditions that potentially lower the seizure threshold (eg, Alzheimer dementia). Elderly patients may be at increased risk of seizures due to an increased prevalence of predisposing factors.
Special populations:
• Older adult: Pharmacokinetic studies showed a decrease in clearance in older adults (65 to 85 years of age) with psychosis compared to younger adults; increased risk of adverse effects and orthostasis may occur.
• Pediatric: Pediatric patients may be more sensitive to dystonia with initial dosing and when the recommended dosing escalation schedule is not followed.
Dosage form specific issues:
• Transdermal patch: To properly dispose of transdermal patch, fold it over on itself and dispose of in trash. Avoid exposure of application site and surrounding area to direct external heat sources (eg, electric blankets, hair dryers, heated water beds, heating pads). Asenapine release from the patch increases with prolonged application of heat. Application-site reactions, including erythema, hyperpigmentation, and pruritus, have been observed with use; increased skin irritation may occur if patch is left in place for >24 hours or if same application site is used repeatedly.
Other warnings/precautions:
• Discontinuation of therapy: When discontinuing antipsychotic therapy, gradually taper antipsychotics to avoid withdrawal symptoms and rebound symptoms (APA [Keepers 2020]; WFSBP [Hasan 2012]). Withdrawal symptoms may include agitation, alternate feelings of warmth and cold, anxiety, diaphoresis, dyskinesia, insomnia, irritability, GI symptoms, myalgia, paresthesia, psychosis, restlessness, rhinorrhea, tremor, and vertigo (Lambert 2007; Moncrieff 2020). The risk of withdrawal symptoms is highest following abrupt discontinuation of highly anticholinergic or dopaminergic antipsychotics (Cerovecki 2013). Patients with chronic symptoms, repeated relapses, and clear diagnostic features of schizophrenia are at risk for poor outcomes if medications are discontinued (APA [Keepers 2020]).
Use with caution in children and adolescents; elevated prolactin levels have been observed; long-term effects on growth or sexual maturation have not been evaluated. Similar to adult experience, the American Academy of Child and Adolescent Psychiatry (AACAP) guidelines recommend gradually tapering antipsychotics to avoid withdrawal symptoms and minimize the risk of relapse (AACAP [McClellan 2007]).
Substrate of CYP1A2 (major), CYP2D6 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2D6 (weak)
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Acetylcholinesterase Inhibitors (Central): May enhance the neurotoxic (central) effect of Antipsychotic Agents. Severe extrapyramidal symptoms have occurred in some patients. Risk C: Monitor therapy
Agents With Seizure Threshold Lowering Potential: May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Amifampridine: Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. Risk C: Monitor therapy
Amisulpride (Oral): May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk of neuroleptic malignant syndrome or increased QTc interval may be increased. Risk C: Monitor therapy
Amphetamines: Antipsychotic Agents may enhance the adverse/toxic effect of Amphetamines. Antipsychotic Agents may diminish the stimulatory effect of Amphetamines. Risk C: Monitor therapy
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Anti-Parkinson Agents (Dopamine Agonist): Antipsychotic Agents (Second Generation [Atypical]) may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Management: Consider avoiding atypical antipsychotic use in patients with Parkinson disease. If an atypical antipsychotic is necessary, consider using clozapine, quetiapine, or ziprasidone at lower initial doses, or a non-dopamine antagonist (eg, pimavanserin). Risk D: Consider therapy modification
Antipsychotic Agents: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromopride: May enhance the adverse/toxic effect of Antipsychotic Agents. Risk X: Avoid combination
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification
BuPROPion: May enhance the neuroexcitatory and/or seizure-potentiating effect of Agents With Seizure Threshold Lowering Potential. Risk C: Monitor therapy
Cabergoline: May diminish the therapeutic effect of Antipsychotic Agents. Risk X: Avoid combination
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
Ciprofloxacin (Systemic): May increase the serum concentration of Asenapine. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
CYP1A2 Inhibitors (Strong): May increase the serum concentration of Asenapine. Risk C: Monitor therapy
Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Deutetrabenazine: May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk for akathisia, parkinsonism, or neuroleptic malignant syndrome may be increased. Risk C: Monitor therapy
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification
Dexmethylphenidate-Methylphenidate: Antipsychotic Agents may enhance the adverse/toxic effect of Dexmethylphenidate-Methylphenidate. Dexmethylphenidate-Methylphenidate may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk of extrapyramidal symptoms may be increased when these agents are combined. Risk C: Monitor therapy
Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Risk C: Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification
Guanethidine: Antipsychotic Agents may diminish the therapeutic effect of Guanethidine. Risk C: Monitor therapy
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification
Iohexol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification
Iomeprol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification
Iopamidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification
Levoketoconazole: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Levoketoconazole. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Lithium: May enhance the neurotoxic effect of Antipsychotic Agents. Lithium may decrease the serum concentration of Antipsychotic Agents. Specifically noted with chlorpromazine. Risk C: Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Mequitazine: Antipsychotic Agents may enhance the arrhythmogenic effect of Mequitazine. Management: Consider alternatives to one of these agents when possible. While this combination is not specifically contraindicated, mequitazine labeling describes this combination as discouraged. Risk D: Consider therapy modification
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification
Metoclopramide: May enhance the adverse/toxic effect of Antipsychotic Agents. Risk X: Avoid combination
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
MetyroSINE: May enhance the adverse/toxic effect of Antipsychotic Agents. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
PARoxetine: Asenapine may increase the serum concentration of PARoxetine. Management: Decrease the paroxetine dose by half when used concomitantly with asenapine. Monitor patients receiving this combination closely for signs and symptoms of increased paroxetine toxicity. Risk D: Consider therapy modification
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Piribedil: Antipsychotic Agents may diminish the therapeutic effect of Piribedil. Piribedil may diminish the therapeutic effect of Antipsychotic Agents. Management: Use of piribedil with antiemetic neuroleptics is contraindicated, and use with antipsychotic neuroleptics, except for clozapine, is not recommended. Risk X: Avoid combination
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Quinagolide: Antipsychotic Agents may diminish the therapeutic effect of Quinagolide. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Serotonergic Agents (High Risk): May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy
Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Sodium Phosphates. Specifically, the risk of seizure or loss of consciousness may be increased in patients with significant sodium phosphate-induced fluid or electrolyte abnormalities. Risk C: Monitor therapy
Sulpiride: Antipsychotic Agents may enhance the adverse/toxic effect of Sulpiride. Risk X: Avoid combination
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Tetrabenazine: May enhance the adverse/toxic effect of Antipsychotic Agents. Risk C: Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Thioridazine: CYP2D6 Inhibitors (Weak) may increase the serum concentration of Thioridazine. Management: Consider avoiding concomitant use of thioridazine and weak CYP2D6 inhibitors. If combined, monitor closely for QTc interval prolongation and arrhythmias. Some weak CYP2D6 inhibitors list use with thioridazine as a contraindication. Risk D: Consider therapy modification
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Triptorelin: Hyperprolactinemic Agents may diminish the therapeutic effect of Triptorelin. Risk X: Avoid combination
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification
Asenapine may cause hyperprolactinemia, which may decrease reproductive function in both males and females.
If treatment is needed in a woman planning a pregnancy, use of an agent other than asenapine is preferred (Larsen 2015).
Antipsychotic use during the third trimester of pregnancy has a risk for abnormal muscle movements (extrapyramidal symptoms) and/or withdrawal symptoms in newborns following delivery. Symptoms in the newborn may include agitation, feeding disorder, hypertonia, hypotonia, respiratory distress, somnolence, and tremor; these effects may be self-limiting or require hospitalization; monitoring of the neonate is recommended.
The American College of Obstetricians and Gynecologists (ACOG) recommends that therapy during pregnancy be individualized; treatment with psychiatric medications during pregnancy should incorporate the clinical expertise of the mental health clinician, obstetrician, primary health care provider, and pediatrician. Safety data related to atypical antipsychotics during pregnancy are limited and routine use is not recommended. However, if a woman is inadvertently exposed to an atypical antipsychotic while pregnant, continuing therapy may be preferable to switching to a typical antipsychotic that the fetus has not yet been exposed to; consider risk:benefit (ACOG 92 2008). If treatment is initiated during pregnancy, use of an agent other than asenapine is preferred (Larsen 2015).
Health care providers are encouraged to enroll women 18 to 45 years of age exposed to asenapine during pregnancy in the Atypical Antipsychotics Pregnancy Registry (1-866-961-2388 or http://www.womensmentalhealth.org/pregnancyregistry).
It is not known if asenapine is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
|
Frequency of Antipsychotic Monitoringa,b | ||
|---|---|---|
|
Monitoring parameter |
Frequency of monitoring |
Comments |
|
Adherence |
Every visit |
|
|
Blood chemistries (electrolytes, renal function, liver function, TSH) |
Annually |
|
|
CBC |
As clinically indicated |
Check frequently during the first few months of therapy in patients with preexisting low WBC or history of drug-induced leukopenia/neutropenia |
|
Extrapyramidal symptoms |
Every visit; 4 weeks after initiation and dose change; annually. Use a formalized rating scale at least annually or every 6 months if high riskc |
|
|
Fall risk |
Every visit |
|
|
Fasting plasma glucose/HbA1c |
12 weeks after initiation and dose change; annually |
Check more frequently than annually if abnormal. Follow diabetes guidelines. |
|
Lipid panel |
12 weeks after initiation and dose change; annually |
Check more frequently than annually if abnormal. Follow lipid guidelines. |
|
Mental status and alertness |
Every visit |
|
|
Metabolic syndrome history |
Annually |
Evaluate for personal and family history of obesity, diabetes, dyslipidemia, hypertension, or cardiovascular disease |
|
Prolactin |
Ask about symptoms at every visit until dose is stable. Check prolactin level if symptoms are reported. |
Hyperprolactinemia symptoms: Changes in menstruation, libido, gynecomastia, development of galactorrhea, and erectile and ejaculatory function |
|
Tardive dyskinesia |
Every visit; annually. Use a formalized rating scale at least annually or every 6 months if high riskd |
|
|
Vital signs (BP, orthostatics, temperature, pulse, signs of infection) |
Every visit (at least weekly during first 3 to 4 weeks of treatment); 4 weeks after dose change. |
|
|
Weight/Height/BMI |
8 and 12 weeks after initiation and dose change; quarterly |
Consider monitoring waist circumference at baseline and annually, especially in patients with or at risk for metabolic syndrome. Consider changing antipsychotic if BMI increases by ≥1 unit. Some experts recommend checking weight and height at every visit. |
|
a For all monitoring parameters, it is appropriate for check at baseline and when clinically relevant (based on symptoms or suspected ADRs) in addition to the timeline. b ADA 2004; APA [Keepers 2020]; de Hert 2011; Gugger 2011; manufacturer’s labeling. c Risk factors for extrapyramidal symptoms (EPS) include prior history of EPS, high doses of antipsychotics, young age (children and adolescents at higher risk than adults), and dopaminergic affinity of individual antipsychotic. d Risk factors for tardive dyskinesia include age >55 years; females; White or African ethnicity; presence of a mood disorder, intellectual disability, or CNS injury; and past or current EPS. | ||
Timing of serum samples: Draw trough just before next dose (Hiemke 2018).
Therapeutic reference range: 1 to 5 ng/mL (SI: 3.5 to 17.5 nmol/L) (Hiemke 2018). Note: Dosing should be based on therapeutic response as opposed to serum concentrations; however, therapeutic drug monitoring can be used to confirm adherence (APA [Keepers 2020]).
Laboratory alert level: 10 ng/mL (SI: 35 nmol/L) (Hiemke 2018).
Asenapine is a dibenzo-oxepino pyrrole atypical antipsychotic with mixed serotonin-dopamine antagonist activity. It exhibits high affinity for 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT5-7, D1-4, H1 and, alpha1- and alpha2-adrenergic receptors; moderate affinity for H2 receptors. Asenapine has no significant affinity for muscarinic receptors. The binding affinity to the D2 receptor is 19 times lower than the 5-HT2A affinity (Weber 2009). The addition of serotonin antagonism to dopamine antagonism (classic neuroleptic mechanism) is thought to improve negative symptoms of psychoses and reduce the incidence of extrapyramidal side effects as compared to typical antipsychotics (Huttunen 1995).
Onset of effect: Sublingual:
Agitation: Initial effects within 15 minutes (Pratts 2014).
Bipolar disorder, acute mania: Initial effects may be observed within days of treatment with continued improvements over 1 to 2 weeks (Goikolea 2013; Tohen 2000; Welten 2016).
Schizophrenia: Initial effects may be observed within 1 to 2 weeks of treatment with continued improvements through 4 to 6 weeks (Agid 2003; Levine 2010).
Absorption: Sublingual: Rapid; Transdermal: External heat source (eg, heating pad) applied to patch increases rate and extent of absorption.
Distribution: Vd: ~20 to 25 L/kg.
Protein binding: 95% (including albumin and α1-acid glycoprotein).
Metabolism: Hepatic via CYP1A2 oxidation and UGT1A4 glucuronidation.
Bioavailability: Sublingual: 35%; decreased if swallowed (<2%); decreased if administered with food or liquid.
Half-life elimination: Sublingual: Terminal: ~24 hours; Transdermal: ~30 hours.
Time to peak, plasma: Sublingual: 0.5 to 1.5 hours; Transdermal: 12 to 24 hours.
Excretion: Urine (~50%); feces (~40%).
Hepatic function impairment: Severe hepatic impairment (Child-Pugh class C) exposure was 7 times higher than in healthy patients.
Older adult: Clearance is decreased, increasing exposure by 30% to 40%.
Patch, 24-hour (Secuado Transdermal)
3.8 mg/24 hrs (per each): $50.88
5.7 mg/24 hrs (per each): $50.88
7.6 mg/24 hrs (per each): $50.88
Sublingual (Asenapine Maleate Sublingual)
2.5 mg (per each): $21.60 - $21.61
5 mg (per each): $21.61 - $22.52
10 mg (per each): $21.61 - $22.52
Sublingual (Saphris Sublingual)
2.5 mg (per each): $24.02
5 mg (per each): $24.01
10 mg (per each): $24.02
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
