siRNA targeting transthyretin (TTR) Pregnancy: US labelling §8.1: there are no available data on use in pregnant women to inform a drug-associated risk of adverse developmental outcomes. Treatment lowers serum vitamin A and vitamin A supplementation is advised; vitamin A is essential for normal embryofetal development but excessive levels are associated with adverse developmental effects, and the fetal effects of reduced maternal TTR and of vitamin A supplementation are unknown. In animal studies, subcutaneous vutrisiran in pregnant rats produced developmental toxicity (reduced fetal body weight and embryofetal mortality) at doses associated with maternal toxicity.

Vutrisiran

Brand names: Amvuttra

Vutrisiran is a subcutaneously administered small interfering RNA (siRNA) therapy used to treat hereditary transthyretin-mediated amyloidosis with polyneuropathy.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: 25 mg (25 mg/0.5 mL single-dose prefilled syringe)

Route: Subcutaneous injection only, administered by a healthcare professional, into the abdomen, thighs or upper arms (avoid the 5 cm area around the navel and any scarred, reddened, inflamed or swollen skin)

Frequency: Once every 3 months

No UK SPC (eMC) record was fetched in this bundle - figures are from the US prescribing information for AMVUTTRA (Alnylam, label date 2025-11-06); verify against the UK SPC before use. Indication in the fetched label is transthyretin-mediated amyloidosis (studied as hATTR polyneuropathy in HELIOS-A and ATTR cardiomyopathy in HELIOS-B). MISSED DOSE: administer as soon as possible, then resume dosing every 3 months from the most recently administered dose. VITAMIN A: treatment lowers serum vitamin A - supplement at the recommended daily allowance of vitamin A; do NOT give higher than the recommended daily allowance to try to normalise serum vitamin A levels, as serum levels do not reflect total body vitamin A. Refer patients to an ophthalmologist if ocular symptoms suggestive of vitamin A deficiency (e.g. night blindness) develop. PREPARATION: if stored cold, allow the syringe to reach room temperature for 30 minutes before use; inspect for discolouration or particulate matter (the solution should be clear and colourless to yellow); insert the needle at 45 to 90 degrees into pinched skin and push the plunger fully to activate the needle shield; do not recap; dispose of into a sharps container. GERIATRIC: no dose adjustment is required in patients 65 years of age and over. PAEDIATRIC: safety and effectiveness in paediatric patients have not been established - verify any under-18 use against a children's formulary.

Dose auto-extracted from US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

None - the US label section 4 Contraindications reads 'None'

Side effects

Pain in extremity (most common, at least 5%)
Arthralgia (most common, at least 5%)
Dyspnoea (most common, at least 5%)
Vitamin A decreased (most common, at least 5%)
Reduced serum vitamin A levels are a labelled warning - supplementation at the recommended daily allowance is advised

Clinical monograph

How it works

It is an RNA-interference agent that reduces hepatic production of both mutant and wild-type transthyretin, lowering the protein available to form amyloid deposits.

Prescribing in practice

Because transthyretin transports retinol, treatment lowers serum vitamin A, so vitamin A supplementation at the recommended daily allowance is advised and ophthalmic symptoms should be assessed.
It is given as a regular subcutaneous injection under specialist neurology or amyloidosis supervision.
Injection-site reactions can occur but are generally mild and transient.

Monitoring

Monitor neurological status and disease progression, and assess for symptoms of vitamin A deficiency such as visual disturbance.

Counselling the patient

Take vitamin A supplementation as advised and report any problems with night vision or dry eyes.
Injection-site reactions are usually mild and settle on their own.
Attend regular review appointments to monitor your condition.

Evidence & guidelines

Vutrisiran is supported by the HELIOS-A trial and is licensed for hereditary transthyretin amyloidosis with polyneuropathy.

Reference: NICE HST24; SmPC; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Drugs

Patisiran · siRNA targeting transthyretin (TTR)

Pathways