0.5 ML lumasiran 189 MG/ML Injection [Oxlumo]

INDICATIONS AND USAGE OXLUMO is indicated for the treatment of primary hyperoxaluria type 1 (PH1) to lower urinary and plasma oxalate levels in pediatric and adult patients [see Clinical Pharmacology (12.1) , Clinical Studies (14.1 , 14.2 , 14.3) ] . OXLUMO is a HAO1 -directed small interfering ribonucleic acid (siRNA) indicated for the treatment of primary hyperoxaluria type 1 (PH1) to lower urinary and plasma oxalate levels in pediatric and adult patients. ( 1 )

DOSAGE AND ADMINISTRATION The recommended dose of OXLUMO by subcutaneous injection is based on body weight. ( 2.1 ) Body Weight Loading Dose Maintenance Dose less than 10 kg 6 mg/kg once monthly for 3 doses 3 mg/kg once monthly, beginning 1 month after the last loading dose 10 kg to less than 20 kg 6 mg/kg once monthly for 3 doses 6 mg/kg once every 3 months (quarterly), beginning 1 month after the last loading dose 20 kg and above 3 mg/kg once monthly for 3 doses 3 mg/kg once every 3 months (quarterly), beginning 1 month after the last loading dose See Full Prescribing Information for important preparation and administration instructions. ( 2.2 ) 2.1 Recommended Dosage The recommended dosing regimen of OXLUMO consists of loading doses (monthly for 3 doses) followed by maintenance doses (beginning 1 month after the last loading dose) administered subcutaneously as shown in Table 1. Dosing is based on actual body weight. Table 1. OXLUMO Weight-Based Dosing Regimen Body Weight Loading Dose Maintenance Dose Less than 10 kg 6 mg/kg once monthly for 3 doses 3 mg/kg once monthly, beginning 1 month after the last loading dose 10 kg to less than 20 kg 6 mg/kg once monthly for 3 doses 6 mg/kg once every 3 months (quarterly), beginning 1 month after the last loading dose 20 kg and above 3 mg/kg once monthly for 3 doses 3 mg/kg once every 3 months (quarterly), beginning 1 month after the last loading dose For Patients on Hemodialysis Administer OXLUMO after hemodialysis if administered on dialysis days. Missed Dose If a dose is delayed or missed, administer OXLUMO as soon as possible. Resume prescribed monthly or quarterly dosing, from the most recently administered dose. 2.2 Administration Instructions OXLUMO is intended for subcutaneous use and should be administered by a healthcare professional. Visually inspect the drug product solution. Do not use if it contains particulate matter or if it is cloudy or discolored. OXLUMO is a sterile, preservative-free, clear, colorless-to-yellow solution. It is supplied in a single-dose vial, as a ready-to-use solution that does not require additional reconstitution or dilution prior to administration. Use aseptic technique. Divide injection volumes greater than 1.5 mL equally into multiple syringes. For volumes less than 0.3 mL, a sterile 0.3-mL syringe is recommended. If using a 0.3 mL (30 unit) insulin syringe, 1-unit markings indicate 0.01 mL. Administer subcutaneous injection into the abdomen, thigh, or the side or back of the upper arms. Rotate injection sites. Do not inject into scar tissue or areas that are reddened, inflamed, or swollen. If injecting into the abdomen, avoid the area around the navel. If more than one injection is needed for a single dose of OXLUMO, the injection sites should be at least 2 cm apart. Discard unused portion of the drug.

CONTRAINDICATIONS None. None. ( 4 )

Mechanism of Action Lumasiran reduces levels of glycolate oxidase (GO) enzyme by targeting the hydroxyacid oxidase 1 ( HAO1 ) messenger ribonucleic acid (mRNA) in hepatocytes through RNA interference. Decreased GO enzyme levels reduce the amount of available glyoxylate, a substrate for oxalate production. As the GO enzyme is upstream of the deficient alanine: glyoxylate aminotransferase (AGT) enzyme that causes PH1, the mechanism of action of lumasiran is independent of the underlying AGXT gene mutation. OXLUMO is not expected to be effective in primary hyperoxaluria type 2 (PH2) or type 3 (PH3) because its mechanism of action does not affect the metabolic pathways causing hyperoxaluria in PH2 and PH3.