Nedosiran Sodium (Monograph)

Brand name: Rivfloza
Drug class: Other Miscellaneous Therapeutic Agents

Medically reviewed by Drugs.com on Nov 10, 2024. Written by ASHP.

[Web]

Introduction

Small interfering RNA that targets LDH A.

Uses for Nedosiran Sodium

Primary Hyperoxaluria Type 1

Used to lower urinary oxalate levels in adults and pediatric patients ≥9 years of age with primary hyperoxaluria type 1 (PH1) and relatively preserved kidney function (e.g., eGFR ≥30 mL/minute per 1.73 m²).

Designated an orphan drug by FDA for treatment of PH1.

European guidelines on the management of primary hyperoxaluria generally recommend nedosiran and other RNA interfering agents as second-line treatment of PH1 in select patients following conservative management with hyperhydration, potassium citrate, and pyridoxine supplementation.

Nedosiran Sodium Dosage and Administration

Administration

Sub-Q Administration

Administered via sub-Q injection.

Commercially available in single-dose prefilled syringes or a single-dose vial that does not require reconstitution or dilution before administration.

Prefilled syringes can be administered by a healthcare professional, caregiver, or patient ≥12 years of age; a healthcare professional or caregiver may administer the prefilled syringes to patients 9–11 years of age weighing ≥50 kg.

Vials are intended for use under the supervision of a healthcare professional; a trained caregiver may administer doses from the vial to a pediatric patient if deemed appropriate.

Administer sub-Q into the abdomen or upper thigh; do notadminister into a vein or scarred or bruised skin. Following administration, discard any unused portion of the drug.

If a dose is missed, administer as soon as possible; if >7 days from planned dose have elapsed, resume monthly dosing from the time of the most recently administered dose.

Dosage

Available as nedosiran sodium; dosage expressed in terms of nedosiran.

Pediatric Patients

Primary Hyperoxaluria Type 1

Sub-Q

Recommended dosage based on age and actual body weight (see Table 1).

Not to exceed 128 mg

Adults

Primary Hyperoxaluria Type 1

Sub-Q

Recommended dosage based on actual body weight.

≥50 kg: 160 mg once monthly.

<50 kg: 128 mg once monthly.

Special Populations

Hepatic Impairment

Mild hepatic impairment (total bilirubin ≤ULN with AST >ULN or total bilirubin 1–1.5 times ULN with any AST): No dosage adjustment recommended.

Moderate or severe hepatic impairment (total bilirubin >1.5 times ULN with any AST): Not studied, no dosage recommendations at this time.

Renal Impairment

eGFR ≥30 mL/minute per 1.73 m²: No dosage adjustment recommended.

eGFR <30 mL/minute per 1.73 m²: Not studied, no dosage recommendations at this time.

Geriatric Patients

No dosage adjustment recommended.

Cautions for Nedosiran Sodium

Contraindications

• None.

Warnings/Precautions

Immunogenicity

In clinical studies of patients with primary hyperoxaluria type 1, treatment with nedosiran did not lead to induction or boosting of anti-drug antibodies (ADA). No patient developed treatment-emergent ADA.

Specific Populations

Pregnancy

Insufficient data available to assess risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes with use of nedosiran in pregnancy.

Lactation

Not known whether drug is distributed into human milk; effects on breast-fed infants or on production of milk also unknown. Consider developmental and health benefits of breastfeeding along with the mother's need for nedosiran and any potential adverse effects on the breast-fed child from the drug or underlying maternal condition.

Pediatric Use

Safety and efficacy established in pediatric patients ≥9 years of age.

Safety and efficacy not established in pediatric patients <9 years of age.

Geriatric Use

Clinical studies did not include patients ≥65 years of age to determine whether they respond differently from younger patients. Manufacturer does not recommend dosage adjustment in geriatric patients.

Hepatic Impairment

No clinically significant differences in nedosiran pharmacokinetics/pharmacodynamics in patients with mild hepatic impairment (defined as total bilirubin ≤ULN with AST >ULN or total bilirubin 1–1.5 times ULN with any AST); no dosage adjustment recommended in such patients.

Not studied in moderate or severe hepatic impairment (total bilirubin >1.5 times ULN with any AST).

Renal Impairment

No clinically significant differences in nedosiran pharmacokinetics/pharmacodynamics in patients with mild to moderate renal impairment (eGFR 30–89 mL/minute per 1.73 m²); no dosage adjustment recommended in such patients.

Not studied in severe renal impairment (eGFR <30 mL/minute per 1.73 m²).

Common Adverse Effects

Most common adverse reaction (≥20%): injection site reactions.

Drug Interactions

Not an inhibitor or inducer of CYP enzymes; not a substrate or inhibitor of drug efflux and uptake transporters.

Specific Drugs

Nedosiran Sodium Pharmacokinetics

Absorption

Bioavailability

Dose-proportional increases in plasma exposure following single sub-Q doses of 1.5–6 mg/kg.

Time-independent pharmacokinetics with multiple monthly doses of 160 mg, 128 mg, or 3.3 mg/kg (dose administered dependent on actual body weight and age).

Does not accumulate in plasma after repeated monthly administration.

Onset

Time to maximum concentration ranges from 2–12 hours, with a median of 6 hours.

Distribution

Extent

Not known whether nedosiran distributes into breast milk.

Plasma Protein Binding

85.6%.

Elimination

Metabolism

Conversion to oligonucleotides by endonucleases or exonucleases.

Elimination Route

Following administration, approximately 27% of dose excreted unchanged into the urine within 24 hours.

Half-life

15 hours.

Special Populations

No clinically significant differences in pharmacokinetics or pharmacodynamics observed based on age (9–73 years), sex, race, or ethnicity.

Stability

Storage

Parenteral

Injection, for subcutaneous use

Prefilled syringes and vials: Store in original container, away from light and direct heat, and refrigerate at 2–8°C until ready to use; do not freeze. If needed, may store in original container, away from light and direct heat, at room temperature (15–30°C) for a maximum of 28 days (4 weeks).

Actions

• Synthetic, double-stranded small interfering RNA conjugated to an N-acetyl D-galactosamine ligand; this ligand ensures delivery of the drug to hepatocytes.

• After sub-Q administration and delivery of the drug to the liver, nedosiran degrades LDH A messenger RNA via RNA interference, resulting in reduced levels of hepatic LDH A.

• Reduced LDH A in the liver decreases LDH enzyme activity, which in turn decreases conversion of glyoxylate to oxalate in the liver and reduces oxalate levels in urine and plasma.

Advice to Patients

• Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

• Instruct patients/caregivers on the appropriate dose of nedosiran to use, the timing of the dose, how and where to inject subcutaneously, and what to do if a dose is missed.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary and herbal supplements, as well as any concomitant illnesses.

• Advise patients to inform their clinician if they are or plan to become pregnant or plan to breast-feed.

• Advise patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Nedosiran is obtained through specialty pharmacy distributors. Contact the manufacturer or consult the nedosiran website ([Web] ) for specific availability information.

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