nedosiran

Therapeutic Classification: none assigned

Pharmacologic Classification: small interfering ribonucleic acid agents

Indications ⬆ ⬇

REMS

Primary hyperoxaluria type 1 in patients with relatively preserved kidney function (CCr ≥30 mL/min/1.73 m²).

Action ⬆ ⬇

A double-stranded small interfering RNA (siRNA), conjugated to N-acetyl-D-galactosamine residues that bind to asialoglycoprotein receptors, allowing delivery to hepatocytes. It ultimately interrupts formation of hepatic lactate dehydrogenase, which reduces the production of oxalate by the liver.

Therapeutic effects:

Reduction in urinary oxalate excretion.

Pharmacokinetics ⬆ ⬇

Absorption: Extent of absorption following SUBQ administration unknown.

Distribution: Extensively distributed to tissues.

Metabolism/Excretion: Metabolized by endonucleases and exonucleases to shorter oligonucleotides. 27% excreted unchanged in the urine.

Half-Life: 15 hr.

Time/Action Profile ⬆ ⬇

(↓ in urinary oxalate excretion)

ROUTE	ONSET	PEAK	DURATION
SUBQ	several days	4–5 mo	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

None.

Use Cautiously in:

Severe renal impairment;
Moderate or severe hepatic impairment;
OB: Safety not established in pregnancy;
Lactation: Safety not established in breastfeeding;
Pedi: Children <9 yr (safety and effectiveness not established).

Adv. Reactions/Side Effects ⬆ ⬇

Local: injection site reactions

Interactions ⬆ ⬇

Drug-drug:

None reported.

Route/Dosage ⬆ ⬇

SC (Adults and Children ≥12 yr and ≥50 kg): 160 mg once monthly.
SC (Adults and Children ≥12 yr and <50 kg): 128 mg once monthly.
SC (Children 9–11 yr and ≥50 kg): 160 mg once monthly.
SC (Children 9–11 yr and <50 kg): 3.3 mg/kg (max = 128 mg) once monthly.

Availability ⬆ ⬇

Solution for SUBQ injection: 80 mg/0.5 mL (vials); 128 mg/0.8 mL (prefilled syringes); 160 mg/mL (prefilled syringes)

Assessment ⬆ ⬇

Assess for injection site reactions (redness, pain, bruising, rash, dimples).
Monitor for signs and symptoms of urinary stone formation (severe back pain, hematuria, dysuria).

Lab Test Considerations:

Monitor for percentage change in 24-hr urine oxalate excretion.
Monitor BUN and serum creatinine.

Implementation ⬆ ⬇

SC: Administer monthly.
If refrigerated, allow syringe to warm to room temperature 30 min before use. Inspect prefilled syringe/vial for particulate matter and discoloration before injection. Liquid should be colorless to yellow and particle-free. If the solution is cloudy or contains particulate matter, do not use. Administer into SUBQ tissue in the abdomen (>2 inches from the navel) or the upper thigh at 45° angle. Do not inject into a vein or into scarred or bruised skin. Store refrigerated for a maximum of 28 days. Do not freeze. Store in original carton, away from direct heat and light.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient/caregiver. Advise patient to read Patient Information before starting therapy. If a dose is missed, administer as soon as possible. If dose is missed by >7 days, administer as soon as possible and resume monthly dosing from the most recently administered dose.
Advise patient/caregivers to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
Instruct patient/caregivers on the appropriate dose, timing of the dose, how and where to inject SUBQ, and what to do if a dose is missed.
Instruct patient/caregivers to monitor for injection site reactions and signs and symptoms of kidney stones. Notify health care professional if any occur.
Rep: Advise patients of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes ⬆ ⬇

Reduction in urinary oxalate excretion.

US Brand Names ⬆ ⬇

Code ⬆

NDC Code

0169- Novo Nordisk
- 0169-5306- RIVFLOZA
  - 0169-5306-10- 1 SYRINGE in 1 CARTON (0169-5306-10) / 1 mL in 1 SYRINGE

0169- Novo Nordisk
- 0169-5307- RIVFLOZA
  - 0169-5307-08- 1 SYRINGE in 1 CARTON (0169-5307-08) / .8 mL in 1 SYRINGE

0169- Novo Nordisk
- 0169-5308- RIVFLOZA
  - 0169-5308-01- 1 VIAL in 1 CARTON (0169-5308-01) / .5 mL in 1 VIAL

70251- Nitto Denko Avecia
- 70251-360-
  - 70251-360-01- 4000 g in 1 CONTAINER (70251-360-01)

section name header

Pronunciation ⬇

Classifications ⬆ ⬇