RIVFLOZA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for RIVFLOZA (RIVFLOZA).
Rivfloza (nedosiran) is a synthetic, double-stranded small interfering RNA (siRNA) that targets hepatic lactate dehydrogenase A (LDHA) mRNA. By binding to LDHA mRNA with high specificity, it triggers RNA interference (RNAi)-mediated degradation of the transcript, thereby reducing LDHA enzyme levels. This inhibition decreases hepatic oxalate production, which is overproduced in primary hyperoxaluria type 1 (PH1) due to a deficiency in alanine-glyoxylate aminotransferase (AGT). Lowering oxalate levels reduces urinary oxalate excretion and deposition.
| Metabolism | Nedosiran is metabolized by endo- and exonucleases to smaller oligonucleotides of varying lengths. |
| Excretion | Primarily biliary/fecal (approx. 80% as unchanged drug in feces); renal excretion accounts for <5% of the dose. |
| Half-life | Terminal elimination half-life is approximately 24 hours (range 20-30 hours), supporting once-daily dosing. |
| Protein binding | >99% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Approximately 0.6 L/kg, indicating limited extravascular distribution (mainly confined to plasma and extracellular fluid). |
| Bioavailability | Oral: Approximately 12% (low due to extensive first-pass metabolism; increased with high-fat meal to about 20%). |
| Onset of Action | Oral: Clinical effect (reduction in liver fat and fibrosis biomarkers) observed within 4-8 weeks. |
| Duration of Action | Approximately 24 hours; consistent therapeutic effect maintained with once-daily dosing. |
0.5 mg/kg intravenously over 10 minutes once weekly.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for renal impairment, including end-stage renal disease on dialysis. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B); not studied in severe impairment (Child-Pugh C). |
| Pediatric use | 0.5 mg/kg intravenously over 10 minutes once weekly; no dose adjustment needed for children aged ≥12 years or weight ≥45 kg. |
| Geriatric use | No specific dose adjustment recommended; use with caution due to higher prevalence of hepatic dysfunction. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for RIVFLOZA (RIVFLOZA).
| Breastfeeding | No data on vutrisiran in human milk; animal studies show excretion in rat milk. M/P ratio unknown. Caution advised; consider developmental risks of RNAi drugs and benefits of breastfeeding. |
| Teratogenic Risk | RIVFLOZA (vutrisiran) is an RNAi therapeutic targeting transthyretin. No human pregnancy data; animal studies show no teratogenicity at exposures up to 32 times human AUC. Risk cannot be excluded; use only if benefit outweighs potential fetal risk across all trimesters. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
["History of hypersensitivity to nedosiran or any component of the formulation."]
| Precautions | ["Hypersensitivity reactions including anaphylaxis have occurred; monitor during administration.","Elevated liver transaminases (ALT/AST) have been reported; monitor liver function periodically.","Risk of vitamin B6 deficiency due to potential interference with pyridoxine metabolism; monitor B6 levels and supplement if needed.","Not recommended in patients with severe renal impairment (eGFR < 30 mL/min/1.73 m²) or end-stage renal disease (ESRD) due to lack of data."] |
Loading safety data…
| Monitor liver function tests (ALT, AST, bilirubin) monthly during pregnancy. Assess vitamin A levels due to possible interference with retinol-binding protein; supplement if deficient. Ultrasound monitoring for fetal growth and anatomy per standard obstetrical care. |
| Fertility Effects | No human fertility studies; animal studies show no impairment of male or female fertility at exposures up to 32 times human AUC. Theoretical risk due to off-target effects on germ cell gene expression unknown. |