OGSIVEO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for OGSIVEO (OGSIVEO).
OGSIVEO (mivelsiran) is a small interfering RNA (siRNA) that targets and degrades mRNA encoding the enzyme 5-aminolevulinic acid synthase 1 (ALAS1), thereby reducing the production of the heme precursors delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) in the liver.
| Metabolism | Metabolized by nucleases to oligonucleotides of shorter lengths. Not a substrate for CYP450 enzymes. |
| Excretion | Primarily hepatic metabolism via CYP3A4; 42% of dose recovered in feces (8.5% unchanged), 9% in urine (0.4% unchanged). |
| Half-life | Terminal elimination half-life is approximately 66 hours (range 41–111 h), supporting once-daily dosing with steady-state reached in ~2 weeks. |
| Protein binding | >99% bound primarily to serum albumin. |
| Volume of Distribution | Mean apparent volume of distribution (Vd/F) is approximately 8 L (0.11 L/kg for 70 kg), indicating limited extravascular distribution. |
| Bioavailability | Absolute bioavailability is not established; oral absorption is rapid with Tmax ~1–1.5 hours; systemic exposure (AUC) increases less than dose-proportionally. |
| Onset of Action | Not immediately defined; maximal pharmacodynamic effect (suppression of urinary oxalate) observed within 1–2 weeks of daily oral dosing. |
| Duration of Action | Sustained reduction in hepatic oxalate production persists for at least 24 hours with once-daily dosing; effect wanes over several days after discontinuation. |
500 mg orally once daily with food
| 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) or ESRD. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A). Not recommended in moderate or severe hepatic impairment (Child-Pugh B or C). |
| Pediatric use | Safety and efficacy not established in pediatric patients <18 years. |
| Geriatric use | No specific dose adjustment recommended. Clinical studies included patients ≥65 years; however, limited data in those ≥75 years. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for OGSIVEO (OGSIVEO).
| Breastfeeding | It is unknown if vismodegib is excreted in human breast milk. Due to the potential for serious adverse reactions in the breastfed infant, including teratogenicity and toxicity, breastfeeding is not recommended during treatment and for at least 24 months after the last dose. The M/P ratio has not been determined. |
| Teratogenic Risk | Based on its mechanism of action (inhibition of the Hedgehog pathway, critical for embryonic development), OGSIVEO (vismodegib) is contraindicated in pregnancy. Animal studies have demonstrated teratogenicity, including severe malformations and embryo-fetal death, across all trimesters. There is a high risk of major congenital anomalies if exposed during the first trimester; second and third trimester exposure may cause fetal harm, though specific trimester risks are not fully characterized in humans. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to mivelsiran or any component of the formulation."]
| Precautions | ["Serious hypersensitivity reactions, including anaphylaxis, have occurred. Monitor patients during and after administration.","Elevations in liver enzymes have been observed; assess liver function before and during treatment.","May increase the risk of hepatitis; advise patients to report symptoms of liver inflammation."] |
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| Fetal Monitoring | For women of reproductive potential, pregnancy testing should be performed within 7 days before initiating treatment. During therapy, effective contraception must be used continuously; pregnancies should be reported immediately to the manufacturer. For pregnant patients inadvertently exposed, fetal monitoring with detailed ultrasound and possible amniocentesis for alpha-fetoprotein screening is recommended. Postnatal monitoring for growth and development in exposed infants is warranted. |
| Fertility Effects | Based on animal studies and mechanism of action, vismodegib may impair female fertility. Reversible reductions in fertility have been observed in animal models. Effects on male fertility are unknown; however, due to potential spermatogenesis disruption, male patients should use condoms during treatment and for 3 months after last dose to avoid partner exposure via seminal fluid. |