SPRX-3
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SPRX-3 (SPRX-3).
Selective sigma-2 receptor ligand; induces mitochondrial dysfunction and endoplasmic reticulum stress leading to apoptosis in cancer cells. Also modulates autophagy.
| Metabolism | Primarily hepatic via CYP3A4 and CYP2D6; minor renal excretion. |
| Excretion | Primarily renal (70% unchanged, 15% as glucuronide conjugate); biliary/fecal (10%); other (5%). |
| Half-life | Terminal elimination half-life: 12 ± 3 hours; requires dose adjustment in renal impairment (CrCl <30 mL/min). |
| Protein binding | 95% bound to serum albumin; minor binding to alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd: 2.5 L/kg (extensive tissue distribution, including CNS and adipose). |
| Bioavailability | Oral: 65% (first-pass effect); Sublingual: 80%; Intranasal: 75%. |
| Onset of Action | Oral: 30-45 minutes; Intravenous: 5-10 minutes. |
| Duration of Action | Oral: 8-12 hours; Intravenous: 6-8 hours (dose-dependent). |
Not established; investigational drug. No approved standard adult dose available.
| Dosage form | CAPSULE |
| Renal impairment | No data available; renal excretion unknown. Use caution in GFR <30 mL/min. |
| Liver impairment | No data available; contraindicated in Child-Pugh class C. Use caution in class A and B. |
| Pediatric use | Not established; safety and efficacy not studied in pediatric patients. |
| Geriatric use | No specific data; start at lower end of dosing range if standard dose becomes available. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SPRX-3 (SPRX-3).
| Breastfeeding | SPRX-3 is excreted in human milk with a milk-to-plasma ratio of 0.8. Due to potential for serious adverse reactions in nursing infants, including immunosuppression and growth impairment, breastfeeding is not recommended during treatment and for at least 7 days after last dose. |
| Teratogenic Risk | SPRX-3 is classified as Pregnancy Category X. Animal studies have demonstrated teratogenic effects including craniofacial defects and neural tube closure abnormalities at subtherapeutic doses. First trimester exposure carries a high risk of major congenital malformations. Second and third trimester exposure may cause fetal growth restriction and oligohydramnios. Contraindicated in pregnancy. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to active substance or excipients; severe hepatic impairment; concurrent use with strong CYP3A4 inducers.
| Precautions | Monitoring for hepatotoxicity required; may cause QT prolongation; embryofetal toxicity; avoid concomitant use with strong CYP3A4 inhibitors. |
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| Fetal Monitoring | Monitor maternal complete blood count, liver function tests, and renal function at baseline and monthly. Perform fetal ultrasound for growth, amniotic fluid volume every 4 weeks starting at 20 weeks gestation. If accidental exposure occurs in first trimester, offer prenatal diagnostic testing. |
| Fertility Effects | SPRX-3 has been associated with reversible oligospermia in males and menstrual irregularities including anovulation in females in clinical trials. Preclinical studies show impaired folliculogenesis and temporary infertility; effects are reversible upon discontinuation. |