What is Lumasiran sodium (monograph)?
Introduction
Lumasiran sodium is a HAO1-directed small interfering ribonucleic acid (siRNA).
Uses for Lumasiran Sodium
Lumasiran sodium has the following uses:
Lumasiran sodium is indicated for the treatment of primary hyperoxaluria type 1 (PH1) to lower urinary oxalate levels in pediatric and adult patients.
Lumasiran Sodium Dosage and Administration
General
Lumasiran sodium is available in the following dosage form(s) and strength(s):
-
Injection: 94.5 mg/0.5 mL in a single-dose vial.
Dosage
It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:
Pediatric Patients
Dosage and Administration
-
The recommended dose of lumasiran sodium by subcutaneous injection is based on body weight.
|
Body Weight |
Loading Dose |
Maintenance Dose (begin 1 month after the last loading dose) |
|---|---|---|
|
less than 10 kg |
6 mg/kg once monthly for 3 doses |
3 mg/kg once monthly |
|
10 kg to less than 20 kg |
6 mg/kg once monthly for 3 doses |
6 mg/kg once every 3 months (quarterly) |
|
20 kg and above |
3 mg/kg once monthly for 3 doses |
3 mg/kg once every 3 months (quarterly) |
See Full Prescribing Information for important preparation and administration instructions.
Adults
Dosage and Administration
-
The recommended dose of lumasiran sodium by subcutaneous injection is based on body weight.
|
Body Weight |
Loading Dose |
Maintenance Dose (begin 1 month after the last loading dose) |
|---|---|---|
|
less than 10 kg |
6 mg/kg once monthly for 3 doses |
3 mg/kg once monthly |
|
10 kg to less than 20 kg |
6 mg/kg once monthly for 3 doses |
6 mg/kg once every 3 months (quarterly) |
|
20 kg and above |
3 mg/kg once monthly for 3 doses |
3 mg/kg once every 3 months (quarterly) |
See Full Prescribing Information for important preparation and administration instructions.
Warnings
Contraindications
-
None.
Warnings/Precautions
Specific Populations
Pregnancy
Risk Summary: There are no available data with the use of lumasiran sodium 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 lumasiran sodium were observed in rats at 45 times and in rabbits at 90 times the maximum recommended human dose in women.
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.
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, and 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
There are no data on the presence of lumasiran sodium 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 lumasiran sodium and any potential adverse effects on the breastfed child from lumasiran sodium or from the underlying maternal condition.
Pediatric Use
The safety and effectiveness of lumasiran sodium have been established in pediatric patients aged birth and older. Use of lumasiran sodium in these age groups is supported by evidence from an adequate and well controlled study of lumasiran sodium in children 6 years or older and adults with PH1 (ILLUMINATE-A), and a single-arm clinical study in children less than 6 years of age with PH1 (ILLUMINATE-B).
Geriatric Use
Clinical studies of lumasiran sodium 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 >1.5–3 × ULN with any AST). Lumasiran sodium has not been studied in patients with severe hepatic impairment (total bilirubin >3 × ULN with any AST).
Renal Impairment
No dose adjustment is necessary in patients with an estimated glomerular filtration rate (eGFR) of ≥30 mL/min/1.73 m2. Lumasiran sodium has not been studied in patients with an eGFR <30 mL/min/1.73 m2or patients on dialysis.
Common Adverse Effects
The most common adverse reaction (reported in ≥20% of patients) is injection site reactions.
How should I use Lumasiran sodium (monograph)
General
Lumasiran sodium is available in the following dosage form(s) and strength(s):
-
Injection: 94.5 mg/0.5 mL in a single-dose vial.
Dosage
It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:
Pediatric Patients
Dosage and Administration
-
The recommended dose of lumasiran sodium by subcutaneous injection is based on body weight.
|
Body Weight |
Loading Dose |
Maintenance Dose (begin 1 month after the last loading dose) |
|---|---|---|
|
less than 10 kg |
6 mg/kg once monthly for 3 doses |
3 mg/kg once monthly |
|
10 kg to less than 20 kg |
6 mg/kg once monthly for 3 doses |
6 mg/kg once every 3 months (quarterly) |
|
20 kg and above |
3 mg/kg once monthly for 3 doses |
3 mg/kg once every 3 months (quarterly) |
See Full Prescribing Information for important preparation and administration instructions.
Adults
Dosage and Administration
-
The recommended dose of lumasiran sodium by subcutaneous injection is based on body weight.
|
Body Weight |
Loading Dose |
Maintenance Dose (begin 1 month after the last loading dose) |
|---|---|---|
|
less than 10 kg |
6 mg/kg once monthly for 3 doses |
3 mg/kg once monthly |
|
10 kg to less than 20 kg |
6 mg/kg once monthly for 3 doses |
6 mg/kg once every 3 months (quarterly) |
|
20 kg and above |
3 mg/kg once monthly for 3 doses |
3 mg/kg once every 3 months (quarterly) |
See Full Prescribing Information for important preparation and administration instructions.