Overview
11 DESCRIPTION RIVFLOZA injection contains nedosiran, a double-stranded small interfering RNA (siRNA) with four covalently attached N -acetyl-D-galactosamine (GalNAc) residues. Nedosiran targets lactate dehydrogenase A (LDHA) in hepatocytes via GalNAc-mediated delivery. The structural formula of the nedosiran sodium drug substance is presented below: The molecular formula of nedosiran sodium is C...
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Nedosiran is a double-stranded siRNA, conjugated to GalNAc aminosugar residues. After subcutaneous administration, the GalNAc-conjugated sugars bind to asialoglycoprotein receptors (ASGPR) to deliver nedosiran to hepatocytes. Nedosiran reduces levels of hepatic lactate dehydrogenase (LDH) via the degradation of LDHA messenger ribonucleic acid (mRNA) in hepatocytes through RNA interference. The reduction of hepatic LDH by nedosiran reduces the production of oxalate by the liver, thereby reducing subsequent oxalate burden. 12.2 Pharmacodynamics The pharmacodynamic effects of RIVFLOZA were evaluated after single-dose and monthly-dose administration in patients with PH1.
Indications
- 1 INDICATIONS AND USAGE RIVFLOZA is indicated to lower urinary oxalate levels in children 2 years of age and older and adults with primary hyperoxaluria type 1 (PH1) and relatively preserved kidney function, e.g., eGFR ≥30 mL/min/1.73 m 2 [see Clinical Pharmacology ( 12.3 )], Clinical Studies ( 14.1 )]. RIVFLOZA is an LDHA -directed small interfering RNA indicated to lower urinary oxalate levels in children 2 years of age and older and adults with primary hyperoxaluria type 1 (PH1) and relatively preserved kidney function, e.g., eGFR ≥30 mL/min/1.73 m 2 . ( 1 )
Common Doses
- 3.3 mg
- 128 mg
- 160 mg
Dosage
2 DOSAGE AND ADMINISTRATION The recommended dosage is shown below and is administered subcutaneously once monthly. ( 2.1 ) Body weight Less than 39 kg 39 kg to less than 50 kg 50 kg and above Age 2 to less than 12 years 3.3 mg/kg 128 mg 160 mg Age 12 years and older 128 mg 160 mg See full Prescribing Information for important administration instructions. ( 2.2 ) 2.1 Recommended Dosage RIVFLOZA is administered subcutaneously once monthly at the recommended doses shown in Table 1 . Dosing is based on actual body weight.
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS Most common adverse reactions (reported in ≥20% of patients) are injection site reactions. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novo Nordisk Inc. at 1-844-906-5099 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Interactions
- No major interactions listed on the FDA label. Always consult a healthcare professional.