Dosing & Uses
Dosage Forms & Strengths
transdermal system
3.8mg/24hr
5.7mg/24hr
7.6mg/24hr
Schizophrenia
Atypical antipsychotic indicated for adults with schizophrenia
Apply 3.8 mg/24 hr patch initially; may increase dosage to 5.7 mg/24 hr or 7.6 mg/24 hr after 1 week
Dosage Modifications
Renal impairment
- Mild-to-severe (GFR 15-90 mL/min): No dosage adjustment necessary
- Patients on dialysis: Not studied
- Effect of renal function on the excretion of other metabolites has not been studied
Hepatic impairment
- Mild-to-moderate (Child-Pugh A or B): No dosage adjustment necessary
- Severe (Child-Pugh C): Contraindicated
Dosing Considerations
In a short-term, placebo-controlled trial, no suggestion of added benefit was found at a dosage of 7.6 mg/24 hr; there was an increase in certain adverse reactions
Safety of doses >7.6 mg/24 hr has not been evaluated in clinical studies
Based on AUC of asenapine, asenapine transdermal 3.8 mg/24 hr corresponds to 5 mg PO BID of sublingual (SL) asenapine and asenapine transdermal 7.6 mg/24 hr corresponds to 10 mg PO BID of SL asenapine
Safety and efficacy not established
Schizophrenia
Based on a pharmacokinetic study in elderly patients with asenapine SL, dosage adjustments are not recommended based on age alone
Exposure in elderly patients is 30-40% higher as compared with adults
Not indicated for dementia-related psychosis
May increase risk of mortality in elderly patients with dementia-related psychosis
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (4)
- fexinidazole
fexinidazole and asenapine transdermal both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to block potassium channels and/or prolong QT interval.
- levodopa inhaled
asenapine transdermal decreases effects of levodopa inhaled by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Atypical (2nd generation) antipsychotics inhibit dopamine D2 receptors in varying degrees (clozapine and quetiapine are lower risk). .
- metoclopramide intranasal
asenapine transdermal increases toxicity of metoclopramide intranasal by pharmacodynamic synergism. Avoid or Use Alternate Drug. Potential for additive effects, including increased frequency and severity of tardive dyskinesia, other extrapyramidal symptoms, and neuroleptic malignant syndrome.
- selinexor
selinexor, asenapine transdermal. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.
Monitor Closely (10)
- fenfluramine
asenapine transdermal decreases effects of fenfluramine by pharmacodynamic antagonism. Use Caution/Monitor. Potent serotonin receptor antagonists may decrease fenfluramine efficacy. If coadministered, monitor appropriately.
- fluvoxamine
fluvoxamine will increase the level or effect of asenapine transdermal by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Dose reduction may be necessary
- fostemsavir
asenapine transdermal and fostemsavir both increase QTc interval. Use Caution/Monitor. QTc prolongation reported with higher than recommended doses of fostemsavir.
- lasmiditan
lasmiditan, asenapine transdermal. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.
- lemborexant
lemborexant, asenapine transdermal. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.
- oliceridine
oliceridine, asenapine transdermal. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
- remimazolam
remimazolam, asenapine transdermal. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.
- sodium sulfate/?magnesium sulfate/potassium chloride
sodium sulfate/?magnesium sulfate/potassium chloride increases effects of asenapine transdermal by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of enhanced CNS depression when using higher dose of magnesium sulfate together with a CNS depressant.
- sodium sulfate/potassium sulfate/magnesium sulfate
sodium sulfate/potassium sulfate/magnesium sulfate increases effects of asenapine transdermal by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of enhanced CNS depression when using higher dose of magnesium sulfate together with a CNS depressant.
- voclosporin
voclosporin, asenapine transdermal. Either increases effects of the other by QTc interval. Use Caution/Monitor.
Minor (0)
Adverse Effects
>10%
Application site reactions (14-15%)
Extrapyramidal symptoms (8-13%)
1-10%
Headache (9%)
Increased weight (4-6%)
Constipation (4-5%)
Akathisia (4%)
Somnolence (3-4%)
Increased hepatic transaminases >3x ULN (1.6-3.1%)
Dyspepsia (1-3%)
Diarrhea (1-3%)
Blood glucose increased (1-3%)
Dystonia (1-3%)
Nasopharyngitis (1-3%)
Upper respiratory tract infection (1-3%)
Creatine kinase elevations ≥3 x ULN at any time (1.6-2.1%)
Hypertension (2%)
Vomiting (<2%)
Dry mouth (<2%)
Asthenia (<2%)
Myalgia (<2%)
Increased prolactin levels (1.3%)
<1%
Anemia
Temporary bundle-branch block
Accommodation disorder
Swollen tongue
Hyponatremia
Dysarthria
Thrombocytopenia
Postmarketing Reports
Choking
Warnings
Increased mortality and dementia-related psychosis
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death
Not approved for treatment of dementia-related psychosis
Contraindications
Severe hepatic impairment (Child-Pugh C)
Hypersensitivity to asenapine or any components of the transdermal system
Cautions
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death; in placebo-controlled trials, patients, especially those taking atypical antipsychotic drugs, showed an increased risk of death in treated patients (1.6-1.7x) compared with placebo patients
Neuroleptic malignant syndrome associated with use; monitor for symptoms; discontinue if suspected, and provide intensive symptomatic treatment and monitoring
In placebo-controlled trials in elderly subjects with dementia, patients randomized to risperidone, aripiprazole, and olanzapine had a higher incidence of stroke and transient ischemic attack, including fatal stroke
Not approved for treatment of dementia-related psychosis
Atypical antipsychotic drugs, including asenapine transdermal, have caused metabolic changes, including hyperglycemia, diabetes mellitus, dyslipidemia, and body weight gain
Hypersensitivity reactions have been observed
Atypical antipsychotics cause orthostatic hypotension and syncope; risk is greatest during initial dose titration and when increasing the dose
May cause somnolence, postural hypotension, motor instability, and sensory instability, which may lead to falls and, consequently, fractures or other injuries; complete fall risk assessments in 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 & Lactation
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 condition
Pregnancy 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.Pharmacology
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%)
Administration
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)
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Formulary
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