SAPHRIS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SAPHRIS (SAPHRIS).
Asenapine is an atypical antipsychotic with high affinity for serotonin 5-HT2A, 5-HT2C, 5-HT6, and 5-HT7 receptors; dopamine D2, D3, and D4 receptors; and alpha2-adrenergic receptors. It also has moderate affinity for histamine H1 and alpha1-adrenergic receptors, and low affinity for muscarinic M1 receptors.
| Metabolism | Primarily metabolized by direct glucuronidation via UGT1A4 and to a lesser extent by oxidative metabolism via CYP1A2. Also a minor substrate of CYP3A4 and CYP2D6. |
| Excretion | After oral administration, approximately 50% of the dose is excreted in urine (mostly as metabolites, <1% unchanged) and 40% in feces (mostly as metabolites). |
| Half-life | Terminal elimination half-life is 30-40 hours, supporting once-daily dosing. |
| Protein binding | Approximately 95% bound to serum proteins, primarily albumin and alpha1-acid glycoprotein. |
| Volume of Distribution | 97 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Sublingual: absolute bioavailability approximately 30%. |
| Onset of Action | Sublingual: peak plasma concentration at 0.5-2 hours; clinical effect (antipsychotic) may be seen within 1-2 weeks. |
| Duration of Action | Effective over 24 hours with once-daily dosing; steady state achieved in 5-7 days. |
| Molecular Weight | 401.5 |
5 mg sublingually twice daily, may increase to 10 mg twice daily based on tolerability and efficacy.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min); use with caution. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). In moderate hepatic impairment (Child-Pugh class B), reduce dose to 5 mg once daily. |
| Pediatric use | Not approved for use in pediatric patients (safety and efficacy not established). |
| Geriatric use | Elderly patients with dementia-related psychosis are at increased risk of death; SAPHRIS is not approved for this population. Use lowest effective dose (5 mg twice daily) and monitor for orthostatic hypotension and sedation. |
| 1st trimester | Limited data; not recommended unless clearly needed. Risk of extrapyramidal symptoms and/or withdrawal in neonates after third trimester exposure. |
| 2nd trimester | Limited data; not recommended unless clearly needed. |
| 3rd trimester | Use third trimester may cause extrapyramidal and/or withdrawal symptoms in neonates; avoid if possible. |
Clinical note
Comprehensive clinical and safety monograph for SAPHRIS (SAPHRIS).
| Placental transfer | Asenapine crosses the placenta; data from animal studies demonstrate passage. Human data limited but transfer is assumed based on molecular weight and lipophilicity. |
| Breastfeeding | Asenapine is excreted in human milk. Due to potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account importance of drug to mother. |
■ FDA Black Box Warning
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. SAPHRIS is not approved for the treatment of patients with dementia-related psychosis.
| Serious Effects |
Hypersensitivity to asenapine or any component
| Precautions | Cerebrovascular adverse events in elderly patients with dementia, Neuroleptic malignant syndrome, Tardive dyskinesia, Metabolic changes (hyperglycemia, dyslipidemia, weight gain), Leukopenia, neutropenia, agranulocytosis, Orthostatic hypotension and syncope, Seizures, Potential for cognitive and motor impairment, QT prolongation, Hyperprolactinemia |
| Food/Dietary | Avoid food or drink for at least 10 minutes after sublingual administration to ensure complete absorption. Grapefruit juice may increase asenapine levels; avoid concurrent use. Alcohol can potentiate CNS depression; avoid alcohol intake. |
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| Lactation Rating | L4 - Possibly Hazardous |
| Teratogenic Risk | FDA Pregnancy Category C. Sublingual asenapine (SAPHRIS) is not recommended in pregnancy unless benefit outweighs risk. First trimester: No adequate human studies; animal studies show embryofetal toxicity (reduced fetal weight, delayed ossification) at doses 0.3-2 times MRHD. Second/third trimester: Neonates exposed to antipsychotics (including asenapine) during late pregnancy may experience extrapyramidal symptoms, sedation, or withdrawal after delivery; risk of neonatal jaundice? Limited data. |
| Fetal Monitoring | Monitor maternal weight gain, blood glucose (risk of hyperglycemia), and extrapyramidal symptoms. Fetal monitoring: standard prenatal care with anatomy scan; consider serial growth ultrasounds later in pregnancy. Neonatal monitoring for sedation, respiratory depression, and withdrawal symptoms (e.g., agitation, hypertonia) for at least 48 hours after delivery. |
| Fertility Effects | In animal studies, asenapine caused prolonged estrous cycles and reduced fertility at high doses (0.4-2.5 times MRHD). In humans, hyperprolactinemia may occur with antipsychotics, potentially causing menstrual irregularities, galactorrhea, or sexual dysfunction; however, asenapine has lower prolactin elevation than risperidone. Risk of reversible impairment of fertility in males (sperm count? No specific data for asenapine). |
| Clinical Pearls | Saphris (asenapine) is a sublingual tablet that must not be swallowed or crushed; instruct patients to place under the tongue and allow to dissolve completely. Absorption via oral mucosa is critical; food or water within 10 minutes can reduce bioavailability. Monitor for orthostatic hypotension, especially during dose titration. Due to risk of QT prolongation, avoid use with other QT-prolonging drugs and correct electrolyte abnormalities. Asenapine is associated with higher rates of oral hypoesthesia and dysgeusia compared to other antipsychotics. In elderly patients with dementia-related psychosis, increased risk of death; not approved for this population. |
| Patient Advice | Do not swallow, crush, or chew the tablet; place it under your tongue and let it dissolve completely. · Avoid eating or drinking anything for at least 10 minutes after taking the tablet. · Rise slowly from sitting or lying down to prevent dizziness or fainting. · Report any unusual tongue or mouth numbness, taste changes, or sores in the mouth. · This medication may cause drowsiness; do not drive or operate heavy machinery until you know how it affects you. · Avoid alcohol while taking this medication. · Contact your doctor immediately if you experience fast or irregular heartbeat, fainting, or seizures. · Do not stop taking this medication abruptly without consulting your doctor. |