0.8 ML nedosiran 160 MG/ML Prefilled Syringe [Rivfloza]

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 )

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. Table 1: RIVFLOZA Dose Regimen in Adults and Pediatric Patients (2 years of age and older) 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 Missed Dose If a planned dose is missed, administer RIVFLOZA as soon as possible. If the planned dose is missed by more than 7 days, administer RIVFLOZA as soon as possible and resume monthly dosing from the most recently administered dose. 2.2 Administration Instructions Pre-filled syringe: A healthcare provider, caregiver, or patient 12 years of age and older may inject RIVFLOZA using the pre-filled syringe. In pediatric patients 2 to less than 12 years of age who weigh ≥39 kg, a healthcare provider or caregiver may inject RIVFLOZA using the pre-filled syringe. Vials: RIVFLOZA vials are intended for use under the guidance and supervision of a healthcare provider. Adult patients or caregivers may administer RIVFLOZA after proper training in preparing RIVFLOZA vials for administration, if a healthcare provider determines that it is appropriate, and with medical follow-up as necessary. Administer RIVFLOZA by subcutaneous injection to the abdomen (at least 2 inches from the navel) or the upper thigh. Do not inject into a vein or into scarred or bruised skin. Inspect visually for particulate matter and discoloration prior to injection. RIVFLOZA should be colorless-to-yellow and particle free. If the solution is cloudy or contains particulate matter, do not use. Instructions for delivering the dosage are provided in the Instructions for Use leaflets enclosed with the RIVFLOZA Pre-filled Syringe and single-dose vial. Discard the unused portion of the drug.

CONTRAINDICATIONS None. None. ( 4 )

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.