SOHONOS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SOHONOS (SOHONOS).
SOHONOS is a gene therapy product consisting of an adeno-associated virus vector serotype 9 (AAV9) carrying a functional copy of the survival motor neuron 1 (SMN1) gene. It targets motor neuron cells, where it delivers the SMN1 transgene, leading to expression of SMN protein, which is deficient in spinal muscular atrophy (SMA).
| Metabolism | As a gene therapy vector, SOHONOS is not metabolized by conventional drug-metabolizing enzymes. The AAV9 capsid is processed intracellularly, and the SMN1 transgene is transcribed and translated by the host cell machinery. |
| Excretion | Primarily feces (85%) with minimal renal excretion (<5%); approximately 10% recovered in urine as metabolites. |
| Half-life | Terminal elimination half-life of 12-18 hours; supports twice-daily dosing. |
| Protein binding | Highly protein bound (>99%) to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Apparent volume of distribution is 200-300 L (approximately 2.5-4.0 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 67% under fasted conditions; absorption is delayed with high-fat meals. |
| Onset of Action | Oral: 2-4 hours to peak plasma concentration; clinical effect observed within 24-48 hours. |
| Duration of Action | Duration of action is approximately 24 hours; steady state achieved in 3-5 days. |
220 mg orally twice daily
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment recommended for GFR ≥30 mL/min. For GFR <30 mL/min or ESRD, not recommended due to lack of data. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B or C: not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment required; use caution due to potential for reduced renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SOHONOS (SOHONOS).
| Breastfeeding | No data on presence in human milk; molecular weight (approx. 400 Da) suggests potential excretion. M/P ratio unknown. Due to potential adverse effects, breastfeeding is contraindicated during treatment and for 1 month after last dose. |
| Teratogenic Risk | Sohonos (palovarotene) is a retinoic acid receptor gamma agonist; retinoids are known teratogens. First trimester exposure is contraindicated due to high risk of major congenital malformations (CNS, cardiovascular, facial defects). Second and third trimester: limited data, but potential for fetal harm; avoid use. Pregnancy must be excluded before initiation and monthly during therapy. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Known hypersensitivity to any component of the product"]
| Precautions | ["Acute serious liver injury and elevated aminotransferases","Thrombocytopenia","Thrombotic microangiopathy","Cardiac adverse reactions including myocarditis","Coagulation abnormalities"] |
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| Fetal Monitoring | Monthly pregnancy tests (serum hCG) during therapy. Fetal ultrasound for monitoring if inadvertent exposure. Monitor for maternal hepatotoxicity (LFTs, bilirubin), lipid profile elevation, and mood changes. |
| Fertility Effects | In males: reversible oligospermia has been reported with retinoids; sperm count monitoring may be considered. In females: ovulatory dysfunction possible due to retinoid effects; advise contraceptive counseling. |