vutrisiran (Rx)

Brand and Other Names:Amvuttra
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injectable, solution

  • 25mg/0.5mL single-dose prefilled syringe

Polyneuropathy

Indicated for polyneuropathy associated with hereditary transthyretin-mediated amyloidosis (hATTR)

25 mg SC q3Months

Dosage Modifications

Renal impairment

  • Mild or moderate (eGFR ≥30 to <90 mL/min/1.73 m2): No dose adjustment recommended
  • Severe (eGFR <30 mL/min/1.73 m2) or ESRD: Not studied

Hepatic impairment

  • Mild (total bilirubin [TB] ≤1x ULN and AST >1x ULN, or TB 1-1.5 x ULN and any AST): No dose adjustment recommended
  • Moderate or severe: Not studied

Safety and efficacy not established

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Adverse Effects

>10%

Arthralgia (11%)

1-10%

Dyspnea (7%)

Vitamin A decreased (7%)

Injection site reactions (4%)

Atrioventricular heart block (1.6%)

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Warnings

Contraindications

None

Cautions

Vitamin A deficiency

  • Decreases serum vitamin A levels
  • Supplement vitamin A at recommended daily allowance (RDA)
  • Do not give higher doses than RDA to try to achieve normal serum vitamin A levels during treatment, as serum vitamin A levels do not reflect the total vitamin A in the body
  • Refer patients to an ophthalmologist if ocular symptoms suggestive of vitamin A deficiency (eg, night blindness) develop
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Pregnancy & Lactation

Pregnancy

Data regarding use in pregnant females are not available to inform of drug-associated risk of adverse developmental outcomes

Vutrisiran leads to decreased serum vitamin A levels, and vitamin A supplementation is advised

Vitamin A is essential for normal embryofetal development; however, excessive levels of vitamin A are associated with adverse developmental effects

Animal studies

  • SC administration to pregnant rats (up to 30 mg/kg/day) during organogenesis resulted in developmental toxicity (reduced fetal body weight and embryofetal mortality) at doses associated with maternal toxicity
  • SC administration (up to 20 mg/kg) to pregnant rats q6days throughout pregnancy and lactation resulted in no adverse developmental effects on the offspring

Lactation

Data are not available regarding presence in human milk, effects on breastfed infants, or effects on milk production

Consider developmental and health benefits of breastfeeding along with the mother’s clinical need for vutrisiran and any potential adverse effects on the breastfed infant from vutrisiran or from the underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

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Pharmacology

Mechanism of Action

Double-stranded small interfering ribonucleic acid (siRNA) conjugated with N-acetylgalactosamine (GalNAc) that causes degradation of mutant and wild-type transthyretin (TTR) mRNA through RNA interference, which results in reduced serum TTR protein and TTR protein deposits in tissues

Absorption

Peak plasma time: 4 hr

Distribution

Protein bound 80%

Vd: 10.1 L

Distributes primarily to liver after SC dosing

Metabolism

Metabolized by endo- and exonucleases to short nucleotide fragments of varying sizes within the liver

Elimination

Half-life: 5.2 hr

Clearance: 21.4 L/hr

Renal clearance: 4.5-5.7 L/hr

Excretion, 25-mg dose: 19.4% unchanged in urine

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Administration

SC Preparation

If stored cold, allow syringe to warm to room temperature for 30 minutes before use

Remove syringe from packaging by gripping syringe body; do not touch plunger rod until ready to inject

Visually inspect solution for discoloration and particulate matter; solution should appear clear and colorless to yellow

Discard if solution contains particulate matter, or appears cloudy or discolored

SC Administration

Administer SC by healthcare professional

Administer in abdomen, thighs, or upper arms

Avoid injecting the 5-cm area around the navel, scar tissue, or areas that are reddened, inflamed, or swollen

Pinch the cleaned skin and fully insert the needle into the pinched skin at a 45-90º angle

Push the plunger rod as far as it will go to administer the dose and activate the needle shield

Release the plunger rod to allow the needle shield to cover the needle; do not block the plunger rod movement

Once administered, immediately discard used syringe into a sharps container

Missed dose

  • Administer as soon as possible
  • Resume dosing q3Months from most recently administered dose

Storage

Store at 2-30ºC (36-86ºF) in original carton until ready for use; do not freeze

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Images

No images available for this drug.
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Patient Handout

A Patient Handout is not currently available for this monograph.
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Formulary

FormularyPatient Discounts

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The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL Quantity Limits
Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST Step Therapy
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR Other Restrictions
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.