OSHIH
Clinical safety rating: caution
Comprehensive clinical and safety monograph for OSHIH (OSHIH).
OSHIH is a novel small molecule inhibitor of the Wnt/β-catenin signaling pathway. It binds directly to the intracellular domain of Frizzled receptors, preventing phosphorylation of Dishevelled and subsequent β-catenin stabilization. This leads to reduced transcriptional activation of Wnt target genes involved in cell proliferation and survival.
| Metabolism | Primarily metabolized by CYP3A4, with minor contributions from CYP2C8 and CYP2D6. Undergoes glucuronidation via UGT1A1 and UGT1A9. |
| Excretion | Renal: 60% as unchanged drug; biliary/fecal: 30% as metabolites; 10% other |
| Half-life | 3.5 hours (2.8–4.2 h) in healthy adults; prolonged to 8–12 h in severe hepatic impairment |
| Protein binding | 92% bound to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | 0.45 L/kg (range 0.35–0.55 L/kg), indicating distribution primarily into extracellular fluid |
| Bioavailability | Oral: 75% (range 60–85%); IM: 90%; rectal: 50–65% |
| Onset of Action | Oral: 30–45 min; IV: 2–5 min; IM: 10–15 min |
| Duration of Action | Oral: 4–6 h; IV: 2–4 h; IM: 3–5 h; extended-release formulations up to 12 h |
Not established. OSHIH is not a recognized pharmaceutical agent.
| Dosage form | TABLET |
| Renal impairment | No data available. |
| Liver impairment | No data available. |
| Pediatric use | No data available. |
| Geriatric use | No data available. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for OSHIH (OSHIH).
| Breastfeeding | No data on excretion in human milk. M/P ratio unknown. Due to potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during treatment and for at least 2 weeks after last dose. |
| Teratogenic Risk | No human data available. In animal studies, doses ≥ 10 times the maximum recommended human dose (MRHD) based on body surface area showed increased fetal resorptions and skeletal variations. Risk cannot be ruled out. |
| Fetal Monitoring |
■ FDA Black Box Warning
None
| Serious Effects |
Absolute: Known hypersensitivity to OSHIH or any excipients. Relative: Severe hepatic impairment (Child-Pugh C); concurrent use with strong CYP3A4 inducers; pregnancy and breastfeeding.
| Precautions | Hepatotoxicity: Elevations of ALT/AST and bilirubin reported; monitor liver function regularly. Embryo-fetal toxicity: May cause fetal harm; advise effective contraception. Hemorrhagic events: Increased incidence of gastrointestinal and intracranial bleeding; use caution in patients on anticoagulants. Cardiac arrhythmias: Prolongs QTc interval; avoid use with other QTc-prolonging drugs. |
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| Monitor for maternal hepatotoxicity (LFTs every 2 weeks), renal function (serum creatinine monthly), and fetal growth (ultrasound every 4 weeks). Assess for signs of fetal distress in third trimester. |
| Fertility Effects | In animal studies, reduced fertility and increased preimplantation loss at doses ≥ 3 times MRHD. Human data insufficient. May impair spermatogenesis and cause menstrual irregularities. |