Oxlumo
(lumasiran)Dosage & Administration
| 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 |
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Oxlumo Prescribing Information
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)].
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.
| 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.
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.
Injection: 94.5 mg/0.5 mL clear, colorless-to-yellow solution in a single-dose vial.
Pregnancy
Risk Summary
There are no available data with the use of OXLUMO in pregnant women to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.
No adverse effects on pregnancy or embryo-fetal development related to OXLUMO were observed in rats at 45 times and in rabbits at 90 times the maximum recommended human dose in women (see Data).
The estimated background risk of major birth defects and miscarriage in the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data
Animal Data
In an embryo-fetal development study in pregnant rats, lumasiran was administered subcutaneously at doses of 3, 10, and 30 mg/kg/day during organogenesis (gestational days 6-17). Administration of lumasiran resulted in no effects on embryo-fetal survival or fetal body weights and no lumasiran-related fetal malformations were observed. The 30 mg/kg/day dose in rats is 45 times the maximum recommended human dose (MRHD) for women of 3 mg/kg/month normalized to 0.1 mg/kg/day, based on body surface area. In an embryo-fetal development study in female rabbits, lumasiran was administered subcutaneously at doses of 3, 10, and 30 mg/kg/day during organogenesis (gestational days 7-19). There were decreases in maternal food consumption and decreases in maternal body weight gains at doses ≥3 mg/kg/day. There were no lumasiran-related fetal findings identified at doses up to 30 mg/kg/day (90 times the normalized MRHD based on body surface area).
In a postnatal development study, lumasiran administered subcutaneously to pregnant female rats on gestational days 7, 13, 19 and on lactation days 6, 12, and 18 through weaning at doses up to 50 mg/kg did not produce maternal toxicity or developmental effects in the offspring.
Lactation
Risk Summary
There are no data on the presence of OXLUMO in human milk, the effects on the breastfed child, or the effects of the drug on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for OXLUMO and any potential adverse effects on the breastfed child from OXLUMO or from the underlying maternal condition.
Pediatric Use
The safety and effectiveness of OXLUMO have been established in pediatric patients aged birth and older. Use of OXLUMO in these age groups is supported by evidence from an adequate and well controlled study of OXLUMO in pediatric patients 6 years or older and adults with PH1 (ILLUMINATE-A), a single-arm clinical study in pediatric patients less than 6 years of age with PH1 (ILLUMINATE-B), and a single-arm clinical study in pediatric and adult patients with PH1 who had advanced chronic kidney disease including patients on hemodialysis (ILLUMINATE-C) [see Adverse Reactions (6.1), Clinical Studies (14)].
Geriatric Use
Clinical studies of OXLUMO did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.
Hepatic Impairment
No dose adjustment is recommended for patients with mild [total bilirubin > upper limit of normal (ULN) to 1.5 × ULN or AST > ULN] or moderate hepatic impairment (total bilirubin > 1.5 to 3 × ULN with any AST). OXLUMO has not been studied in patients with severe hepatic impairment (total bilirubin > 3 × ULN with any AST) [see Clinical Pharmacology (12.3)].
Renal Impairment
No dose adjustment is necessary in patients with renal impairment including patients with kidney failure treated with hemodialysis [see Clinical Pharmacology (12.3)]. OXLUMO has not been studied in patients on peritoneal dialysis.
None.
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.
The safety of OXLUMO has been evaluated in a placebo-controlled trial and two single-arm clinical trials. Across these trials, 98 patients with PH1 have been treated with OXLUMO, including 71 pediatric patients and 15 patients on hemodialysis. Overall, 92 patients were treated for at least 6 months, 78 patients for at least 12 months, and 29 patients for at least 24 months.
In the randomized, placebo-controlled, double-blind study ILLUMINATE-A in pediatric and adult patients with PH1 aged 6 to 61 years, 26 patients received OXLUMO, and 13 patients received placebo. Of these, 25 patients received ≥5 months of treatment.
In two single-arm studies in patients with PH1, ILLUMINATE-B (patients <6 years of age) and ILLUMINATE-C (pediatric and adult patients with moderately or severely reduced GFR [eGFR ≤45 mL/min/1.73 m2 or pediatric patients <12 months of age with serum creatinine above the upper limit of normal for age] and patients with kidney failure on hemodialysis), the OXLUMO safety profile was similar to that seen in ILLUMINATE-A [see Clinical Studies (14)].
In placebo-controlled and open-label clinical studies the most common adverse reaction reported was injection site reaction. Injection site reactions included erythema, swelling, pain, hematoma, pruritus, and discoloration. These symptoms were generally mild and resolved within one day of the injection and did not lead to discontinuation of treatment.
| Adverse Reaction | OXLUMO N=26 N (%) | Placebo N=13 N (%) |
|---|---|---|
| ||
| Injection site reaction | 10 (38) | 0 (0) |
| Abdominal pain * | 4 (15) | 1 (8) |
Postmarketing Experience
The following additional adverse reaction has been reported during post-approval use. Because these events are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency.
Immune system disorder: Hypersensitivity