SPRX-105
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SPRX-105 (SPRX-105).
SPRX-105 is a dual dopamine D2 and serotonin 5-HT1A receptor partial agonist, functioning as a postsynaptic antagonist and presynaptic agonist at D2 receptors, and as a partial agonist at 5-HT1A receptors, modulating neurotransmitter release.
| Metabolism | Primarily metabolized by CYP3A4 and CYP2D6, with minor contributions from CYP1A2. |
| Excretion | Primarily renal (70-80% unchanged) with 15-20% biliary/fecal elimination. |
| Half-life | 12-15 hours in healthy adults; extended to 24-30 hours in renal impairment. |
| Protein binding | 92-95% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.8-1.2 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral: 65-75% due to first-pass metabolism. |
| Onset of Action | Oral: 30-60 minutes; IV: within 5-10 minutes. |
| Duration of Action | 8-12 hours for oral; 6-8 hours for IV; prolonged in hepatic impairment. |
SPRX-105 is administered orally at a dose of 50 mg once daily.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | For GFR 30-89 mL/min: no adjustment; GFR 15-29 mL/min: reduce dose to 25 mg once daily; GFR <15 mL/min: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose to 25 mg once daily; Child-Pugh C: contraindicated. |
| Pediatric use | Approved for ages 12 and older: 50 mg once daily. For children 6-11 years: 25 mg once daily based on weight ≥25 kg; weight <25 kg: 12.5 mg once daily. |
| Geriatric use | No dose adjustment required based on age alone; monitor renal function and adjust per renal guidelines. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SPRX-105 (SPRX-105).
| Breastfeeding | Not recommended during breastfeeding. M/P ratio unknown; drug likely excreted in human milk based on molecular weight and lipophilicity. Potential for infant toxicity. |
| Teratogenic Risk | First trimester: Limited data; no definitive human teratogenicity but animal studies show fetal abnormalities at supratherapeutic doses. Second/third trimester: Potential for fetal growth restriction and oligohydramnios due to placental hypoperfusion. Avoid in pregnancy unless benefit outweighs risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. SPRX-105 is not approved for the treatment of patients with dementia-related psychosis.
| Serious Effects |
Hypersensitivity to SPRX-105 or any components of the formulation; concomitant use with strong CYP3A4 inducers or inhibitors.
| Precautions | Increased mortality in elderly patients with dementia-related psychosis; cerebrovascular adverse events, including stroke; neuroleptic malignant syndrome; tardive dyskinesia; metabolic changes (hyperglycemia, dyslipidemia, weight gain); orthostatic hypotension and syncope; seizures; body temperature dysregulation; dysphagia. |
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| Monitor maternal blood pressure, renal function, and fetal growth via ultrasound every 4 weeks. Assess amniotic fluid volume. Perform nonstress test or biophysical profile weekly after 32 weeks. |
| Fertility Effects | Animal studies show reduced fertility and implantation in females at high doses. Human data insufficient; may impair ovarian function or spermatogenesis. Advise reproductive counseling prior to treatment. |