Vutrisiran (Monograph)

Brand name: Amvuttra
Drug class: Other Miscellaneous Therapeutic Agents

Medically reviewed by Drugs.com on Aug 10, 2025. Written by ASHP.

Introduction

Small interfering RNA (siRNA) that targets transthyretin (TTR) messenger RNA (mRNA); a TTR silencer.

Uses for Vutrisiran

Transthyretin-mediated Amyloidosis

Treatment of polyneuropathy in adults with hereditary transthyretin-mediated amyloidosis (ATTR).

Treatment of the cardiomyopathy of wild-type or hereditary ATTR in adults to reduce cardiovascular mortality, cardiovascular hospitalizations, and urgent heart failure visits.

Designated an orphan drug by FDA for use in ATTR.

Transthyretin-mediated amyloidosis can be inherited as an autosomal dominant trait caused by pathogenic variants/mutations in the TTR gene (ATTRv) or by deposition of wild-type TTR protein (ATTRwt). Selection of an appropriate disease-modifying therapy in patients with ATTR is based on the presence of cardiomyopathy and polyneuropathy and the distinction between ATTRv and ATTRwt amyloidosis.

The American Heart Association (AHA) states that TTR silencing therapy may be considered in patients with ATTRv and polyneuropathy.

Vutrisiran Dosage and Administration

General

Premedication and Prophylaxis

Patients administered vutrisiran should receive supplementation of vitamin A at the recommended daily allowance.

Administration

Sub-Q Administration

Administer by sub-Q injection only; should be administered by a clinician.

Commercially available as a single-dose 1-mL prefilled syringe containing 25 mg vutrisiran per 0.5 mL of solution.

If stored cold, allow vutrisiran prefilled syringes to warm to room temperature for 30 minutes prior to administration.

Visually inspect vutrisiran injection prior to administration and do not use if the solution is discolored, cloudy, or contains particulate matter.

Administer vutrisiran sub-Q into abdomen (except for 5-cm area around the navel), thigh, or upper arm. Avoid scar tissue or areas that are red, inflamed, or swollen.

If a dose is missed, administer dose as soon as possible. Resume dosing every 3 months from most recently administered dose.

Dosage

Dosage of vutrisiran sodium is expressed in terms of vutrisiran.

Adults

Transthyretin-mediated Amyloidosis

Polyneuropathy or Cardiomyopathy

Sub-Q Injection

25 mg once every 3 months.

Special Populations

Hepatic Impairment

Mild (total bilirubin ≤ULN and AST >ULN, or total bilirubin >1 to 1.5 times ULN and any AST) or moderate (total bilirubin >1.5 to 3 x ULN and any AST) hepatic impairment: No dosage adjustment necessary.

Renal Impairment

Mild or moderate renal impairment (eGFR 30 to <90 mL/min per 1.73 m²): No dosage adjustment necessary.

Geriatric Patients

No dosage adjustment necessary in patients ≥65 years of age.

Cautions for Vutrisiran

Contraindications

None.

Warnings/Precautions

Reduced Vitamin A Concentrations

Vutrisiran reduces serum vitamin A concentrations.

Patients should receive supplementation with the recommended daily allowance (RDA) of vitamin A. Manufacturer states that dosages exceeding the RDA should not be administered in an attempt to achieve normal serum vitamin A concentrations since serum concentrations are not reflective of total vitamin A concentrations in the body.

Refer patients who develop ocular symptoms suggestive of vitamin A deficiency (e.g., night blindness) to an ophthalmologist.

Immunogenicity

Anti-drug antibodies reported. Available data too limited to permit definitive conclusions regarding the effects of anti-drug antibody development.

Specific Populations

Pregnancy

No adequate data regarding use of vutrisiran in pregnant women.

In animal studies, fetal developmental toxicity (i.e., increased embryofetal mortality, decreased fetal body weight) observed when given sub-Q to pregnant rats at dosages associated with maternal toxicity.

Vutrisiran causes a decrease in vitamin A concentrations; vitamin A supplementation advised in patients receiving the drug. Vitamin A is essential for normal embryofetal development; however, excessive vitamin A concentrations associated with adverse developmental effects. Effects on fetus of a reduction in maternal serum TTR or of vitamin A supplementation unknown.

Lactation

Not known whether vutrisiran is distributed into milk, affects milk production, or affects the breast-fed infant.

Consider benefits of breast-feeding along with importance of vutrisiran to the woman and any potential adverse effects on the breast-fed infant from drug or underlying maternal condition.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

In HELIOS-A, 38% of patients receiving vutrisiran were ≥65 years of age, and 6% of patients were ≥75 years of age. In HELIOS-B, 92% of patients were ≥65 years of age, including 62% ≥75 years of age. No overall differences in safety or effectiveness observed between these patients and younger patients. No dosage adjustment required in geriatric patients.

Hepatic Impairment

No dosage adjustment recommended in patients with mild (total bilirubin ≤ULN and AST >ULN, or total bilirubin >1 to 1.5 times ULN and any AST) or moderate (total bilirubin >1.5 to 3 x ULN and any AST) hepatic impairment. Not studied in patients with severe hepatic impairment or those who have received a prior liver transplant.

Renal Impairment

No dosage adjustment recommended in patients with mild or moderate renal impairment (eGFR ≥30 to <90 mL/minute per 1.73 m²). Not studied in patients with severe renal impairment or end-stage renal disease.

Common Adverse Effects

Adverse effects (≥5%): Pain in extremity, arthralgia, dyspnea, decreased vitamin A concentrations.

Drug Interactions

No clinical drug interactions studies to date.

Based on in vitro studies, vutrisiran is not a substrate or inhibitor of cytochrome P-450 (CYP) isoenzymes. Drug interactions with substrates of CYP isoenzymes or drug transporters not expected.

Vutrisiran Pharmacokinetics

Absorption

Bioavailability

Peak concentrations showed dose-proportional increase while AUC increased in slightly more than dose-proportional manner following single sub-Q doses of 5–300 mg (0.2–12 times the recommended dose).

No accumulation of vutrisiran observed in plasma after repeated doses once every 3 months.

Median time to peak concentrations: 4 hours.

Onset

Following a single 25-mg dose, maximum TTR reduction reached at 6 weeks.

Duration

Following a single 25-mg dose, TTR reduction maintained for 90 days.

Distribution

Extent

Distributes primarily to liver following sub-Q administration.

Not known whether vutrisiran is distributed into milk.

Plasma Protein Binding

Approximately 80%. Concentration-dependent; decreases with increasing vutrisiran concentrations (from 78% at 0.5 mcg/mL to 19% at 50 mcg/mL).

Elimination

Metabolism

Metabolized by endo- and exonucleases to short nucleotide fragments of varying sizes within the liver. Circulating metabolites of vutrisiran have not been detected in plasma.

Elimination Route

Approximately 19.4% excreted as unchanged drug in urine at recommended dose of 25 mg.

Half-life

Median elimination half-life: 5.2 hours.

Special Populations

No clinically important differences in vutrisiran pharmacokinetics observed based on age, sex, race, mild or moderate renal impairment (eGFR ≥30 to <90 mL/minute per 1.73 m²), or mild or moderate hepatic impairment

Not studied in patients with severe renal impairment, end-stage renal disease, severe hepatic impairment, or prior liver transplant.

Stability

Storage

Parenteral

Injection

2–30°C in original carton; do not freeze.

Actions

Chemically modified, double-stranded, siRNA-N-acetylgalactosamine (GalNAc) conjugate.
Vutrisiran siRNA is directed to the liver (primary site of TTR synthesis) by conjugation to a triantennary GalNAc ligand that binds to the asialoglycoprotein receptor expressed on surface of hepatocytes.
Vutrisiran-mediated degradation of mutant and wild-type TTR mRNA through RNA interference results in a reduction of serum TTR protein and TTR protein deposits in tissues.
Reduces serum TTR concentrations by approximately 83% from baseline.

Advice to Patients

Advise patients that vutrisiran causes a decrease in serum vitamin A concentrations and instruct them to take the recommended daily allowance of vitamin A.
Advise patients to contact their healthcare provider if they experience ocular symptoms suggestive of vitamin A deficiency (e.g., night blindness). Refer patients to an ophthalmologist if they develop these symptoms.
Stress importance of patients informing clinicians if they are or plan to become pregnant or plan to breast-feed. Advise pregnant women and females of reproductive potential of the potential risk to a fetus, including that vutrisiran treatment leads to a decrease in serum vitamin A concentrations; vitamin A is essential for normal embryofetal development.
Stress importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary and herbal supplements, as well as any concomitant illnesses.
Inform 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.