ASENAPINE MALEATE
Clinical safety rating: safe
Animal studies have demonstrated safety
Asenapine is an atypical antipsychotic with high affinity for serotonin 5-HT2A, 5-HT2C, 5-HT1A, and dopamine D2 receptors. It also antagonizes alpha1/alpha2-adrenergic and histamine H1 receptors, with moderate affinity for D3 and D4 receptors. The therapeutic effect in schizophrenia and bipolar disorder is primarily mediated through combined 5-HT2A and D2 receptor antagonism.
| Metabolism | Asenapine undergoes extensive hepatic metabolism via direct glucuronidation (UGT1A4) and oxidative metabolism (CYP1A2). The primary metabolites are asenapine N-glucuronide and N-desmethylasenapine, which are inactive. CYP2D6 and CYP3A4 play minor roles. |
| Excretion | Approximately 50% of the dose is excreted renally, and 40% fecally. After oral administration, about 50% appears in urine (as unchanged drug and metabolites) and 40% in feces. |
| Half-life | Terminal elimination half-life is approximately 24 hours. Steady-state is achieved within 3 days. The half-life allows for twice-daily dosing. |
| Protein binding | Asenapine is highly protein bound (95%), primarily to alpha-1-acid glycoprotein and albumin. |
| Volume of Distribution | Volume of distribution is approximately 20-25 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Sublingual: 35% (due to first-pass metabolism). Transdermal: Approximately 50% relative to sublingual route. |
| Onset of Action | Sublingual: Onset of antipsychotic effect occurs within 1-2 hours. Transdermal: Onset is slower, with clinical effects typically seen after 2-4 hours. |
| Duration of Action | Duration of action is approximately 12 hours for sublingual and 24 hours for transdermal patch, supporting twice-daily and once-daily dosing respectively. |
| Molecular Weight | 401.49 |
Sublingual: 5-10 mg twice daily; initial dose 5 mg twice daily, max 10 mg twice daily.
| Dosage form | TABLET |
| Renal impairment | No specific adjustment for renal impairment based on GFR; use caution in severe impairment (CrCl <15 mL/min) due to limited data. |
| Liver impairment | Child-Pugh A or B: No adjustment required. Child-Pugh C: Not recommended due to lack of data. |
| Pediatric use | Adolescents (12-17 years): Sublingual, initial 5 mg twice daily, may increase to 10 mg twice daily after 1 week if needed. |
| Geriatric use | Initiate at 5 mg twice daily; consider lower doses due to potential decreased clearance and increased sensitivity to adverse effects. |
| 1st trimester | Limited data; risk of neural tube defects and other malformations based on animal studies. Use only if benefit outweighs risk. |
| 2nd trimester | Monitor fetal growth; risk of extrapyramidal symptoms and withdrawal in neonates. Consider dose adjustment due to physiological changes. |
| 3rd trimester | Risk of neonatal extrapyramidal symptoms, sedation, and withdrawal. Taper if possible before delivery. |
Clinical note
Strong CYP1A2 inhibitors like fluvoxamine increase asenapine levels Sublingual administration food and drink can decrease absorption May cause cerebrovascular events in elderly patients with dementia.
| Placental transfer | Crosses placenta; detected in fetal plasma at concentrations similar to maternal levels. |
| Breastfeeding | Excreted in breast milk in small amounts; monitor infant for sedation, extrapyramidal effects, and poor feeding. Benefit likely outweighs risk for many patients. |
■ FDA Black Box Warning
Asenapine is not approved for the treatment of dementia-related psychosis in elderly patients. Increased risk of cerebrovascular adverse events (e.g., stroke, transient ischemic attack) and death has been observed in this population.
| Common Effects | bipolar disorder |
| Serious Effects |
Hypersensitivity to asenapine or any excipientConcomitant use with strong CYP1A2 inhibitors (e.g., fluvoxamine)
| Precautions | Neuroleptic Malignant Syndrome (NMS), Tardive Dyskinesia, Hyperglycemia and Diabetes Mellitus, Hyperprolactinemia, Orthostatic Hypotension and Syncope, Falls, Leukopenia, Neutropenia, and Agranulocytosis, QT Interval Prolongation, Seizures, Potential for Cognitive and Motor Impairment, Dysphagia, Body Temperature Regulation Dysfunction |
| Food/Dietary |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Asenapine maleate is a pregnancy category C drug. Limited human data; animal studies show increased fetal mortality and reduced fetal weight at doses similar to human therapeutic doses. Risks cannot be ruled out. Use only if potential benefit outweighs risk. |
| Fetal Monitoring | Monitor for extrapyramidal symptoms, weight gain, glucose abnormalities, and blood pressure changes in mother. For neonate, observe for withdrawal symptoms (agitation, hypertonia, tremors) and extrapyramidal signs for at least 48 hours after delivery if used in third trimester. |
| Fertility Effects | May cause hyperprolactinemia, which can suppress hypothalamic-pituitary-gonadal axis, leading to menstrual irregularities, anovulation, and reduced fertility. Resolution occurs upon discontinuation. |
| Avoid grapefruit and grapefruit juice. Do not eat or drink for 10 minutes after sublingual administration to allow full absorption. Avoid alcohol; may worsen CNS depression and hypotension. |
| Clinical Pearls | Rapidly dissolving tablet (RDT) must not be pushed through foil; peel back. Avoid grapefruit juice. Monitor for orthostatic hypotension, especially during titration. QTc prolongation risk; avoid with other QTc-prolonging drugs. Eosinophilic pneumonia reported; monitor for dyspnea, fever. Use with caution in hepatic impairment (Child-Pugh B: reduce dose). |
| Patient Advice | Take asenapine exactly as prescribed; do not change dose or stop without talking to your doctor. · Place the tablet (RDT) under your tongue and allow it to dissolve completely; do not swallow whole or crush. · Avoid eating or drinking for 10 minutes after taking the tablet. · Do not push the RDT through the foil blister; peel back the foil to prevent damage. · Grapefruit and grapefruit juice may increase side effects; avoid these while on asenapine. · Rise slowly from sitting or lying down to prevent dizziness or fainting. · Contact your doctor immediately if you experience fever, cough, or difficulty breathing. · Avoid alcohol while taking this medication. · If you miss a dose, take it as soon as you remember; if it is near the time of the next dose, skip the missed dose and resume your regular schedule. Do not double the dose. · Keep this medication out of reach of children and store at room temperature away from moisture and heat. |