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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SAPHRIS (SAPHRIS).
| Breastfeeding | Unknown if excreted in human breast milk; present in rat milk at 1.5 times maternal plasma levels. M/P ratio not established in humans. Use caution; if used, monitor infant for sedation, weight gain, or extrapyramidal symptoms. Consider alternative therapies, especially during breastfeeding of preterm or low-birth-weight infants. |
| 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. |
■ 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 components of the formulation"]
| 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"] |
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| 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). |