Version May 2024
Primary hyperoxaluria type 1: Note: Dose based on actual body weight.
Children ≥9 to <12 years:
<50 kg: SUBQ: 3.3 mg/kg once monthly; round dose to nearest 0.1 mL; maximum dose: 128 mg/dose.
≥50 kg: SUBQ: 160 mg once monthly.
Children ≥12 years and Adolescents:
<50 kg: SUBQ: 128 mg once monthly.
≥50 kg: SUBQ: 160 mg once monthly.
Altered Kidney Function:
Children ≥9 years and Adolescents:
eGFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR <30 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Children ≥9 years and Adolescents:
Mild impairment (ie, total bilirubin = ULN and AST > ULN or total bilirubin >1 to 1.5 × ULN and any AST): No dosage adjustment necessary.
Moderate to severe impairment (ie, total bilirubin >1.5 × ULN with any AST): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
(For additional information see "Nedosiran: Drug information")
Primary hyperoxaluria type 1: Note: Dose based on actual body weight.
<50 kg: SUBQ: 128 mg once monthly.
≥50 kg: SUBQ: 160 mg once monthly.
Missed dose: If dose missed, administer as soon as possible. If the dose is missed by >7 days, administer as soon as possible and resume monthly dosing schedule based on most recently administered dose.
eGFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR <30 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer’s labeling; nedosiran pharmacokinetics may be altered in patients with impaired kidney function (Ref).
Hemodialysis: No dosage adjustment necessary (Ref).
Child-Turcotte-Pugh A: No dosage adjustment necessary.
Child-Turcotte-Pugh B and C: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in children, adolescents, and adults.
>10%: Local: Injection-site reaction (including bruising at injection site, erythema at injection site, pain at injection site, rash at injection site)
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• Injection-site reactions: Injection-site reactions, including erythema, pain, bruising, and rash, may occur; most reactions are mild in intensity.
Rivfloza: FDA approved October 2023; availability anticipated in 2024.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Subcutaneous, as sodium [preservative free]:
Rivfloza: 80 mg/0.5 mL (0.5 mL)
Solution Prefilled Syringe, Subcutaneous, as sodium [preservative free]:
Rivfloza: 128 mg/0.8 mL (0.8 mL); 160 mg/mL (1 mL)
No
SUBQ: If refrigerated, allow syringe or vial to warm to room temperature for 30 minutes prior to use. Administer SUBQ into the abdomen (avoiding the 2-inch area around the navel) or upper thigh. Inject at a 45° angle into pinched skin. Do not inject into veins or areas where the skin is scarred or bruised. Solution should be colorless to yellow and particle free; do not use if cloudy or contains particulate matter. Gently and slowly push plunger rod as far as it will go to inject the full dose.
Prefilled syringe:
Children ≥9 to <12 years and weight ≥50 kg: Dose should be administered by health care professional or trained caregiver.
Children ≥12 years and Adolescents: Dose may be administered by health care professional, trained caregiver, or patient.
Vial: 80 mg/0.5 mL: Note: Round dose to nearest 0.1 mL. Intended for single use only; does not contain a preservative; discard unused portion. If you see large bubbles, tap the side of the syringe to move the bubbles to the top and gently push air back into vial. Ensure appropriate dose is in syringe after clearing bubbles.
Dose ≤0.5 mL: Withdraw appropriate dose into one syringe.
Dose ≥0.6 mL: Withdraw appropriate dose into two syringes (maximum volume = 0.5 mL/syringe) and administer into two different locations (eg, if injecting into abdomen, inject into two different areas of abdomen).
Missed dose: If dose missed, administer as soon as possible. If the dose is missed by >7 days, administer as soon as possible and resume monthly dosing schedule based on the most recently administered dose.
SUBQ: Administer by a health care professional, caregiver, or patient if ≥12 years of age. If refrigerated, allow syringe to warm to room temperature for 30 minutes prior to use. May inject into the abdomen (avoiding the 2-inch area around the navel) or upper thigh. Do not inject into veins or areas where the skin is scarred or bruised. Clean planned injection site and uncap needle. Inject at a 45° angle into pinched skin. Push plunger rod as far as it will go to inject the full dose.
Store intact vials and prefilled syringes between 2°C to 8°C (36°F to 46°F). Can be stored, if needed, at 15°C to 30°C (59°F to 86°F) for a maximum of 28 days (4 weeks). Do not freeze. Store in original carton, away from direct heat and light.
To lower urinary oxalate levels in patients with primary hyperoxaluria type 1 and relatively preserved kidney function (eg, eGFR ≥30 mL/minute/1.73 m2) (FDA approved in ages ≥9 years and adults).
None known.
There are no known significant interactions.
Adverse events were not observed in animal reproduction studies except with dosing that also caused maternal toxicity.
Kidney function, heart rate (tachycardia/tachyarrhythmia), signs and symptoms of urinary stone formation, injection-site reactions (Baum 2023).
Nedosiran is a double-stranded siRNA, conjugated to GalNAc aminosugar residues that bind to asialoglycoprotein receptors allowing delivery to hepatocytes. Nedosiran interrupts intracellular messenger ribonucleic acids (mRNAs), thereby interrupting formation of hepatic lactate dehydrogenase, which reduces the production of oxalate by the liver.
Note: At the recommended doses, pharmacokinetic exposure of nedosiran in pediatric patients ≥9 years is similar to adult patients.
Onset: 30 days after first SUBQ dose.
Duration: No accumulation in the plasma after repeated monthly dosing.
Distribution: Vd: 126 L.
Protein binding: 85.6%.
Metabolism: By endo- and exonucleases to shorter oligonucleotides.
Half-life elimination: 15 hours.
Time to peak: Median: 6 hours; range: 2 to 12 hours.
Excretion: Urine: ~27% as unchanged drug.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
