Amvuttra (Vutrisiran)
RNA interference therapy for hereditary transthyretin amyloidosis (hATTR)
Quick Facts About Amvuttra
Key Takeaways About Amvuttra
- Targeted RNAi therapy: Amvuttra uses RNA interference to specifically reduce transthyretin (TTR) protein production in the liver, addressing the root cause of hATTR-amyloidosis
- Convenient quarterly dosing: Given as a single subcutaneous injection once every 3 months, which can be self-administered at home after training
- Vitamin A supplementation required: Because TTR carries vitamin A, patients must take daily vitamin A supplements during treatment
- Not for use in pregnancy: Women of childbearing potential must use effective contraception due to the risk of vitamin A deficiency to the fetus
- Proven clinical efficacy: The HELIOS-A trial demonstrated significant improvement in polyneuropathy symptoms and quality of life compared to placebo
What Is Amvuttra and What Is It Used For?
Amvuttra (vutrisiran) is an RNA interference (RNAi) medicine used to treat hereditary transthyretin-mediated amyloidosis (hATTR-amyloidosis) in adult patients with stage 1 or stage 2 polyneuropathy. It works by silencing the gene responsible for producing the misfolded transthyretin protein that causes disease.
The active substance in Amvuttra is vutrisiran, a small interfering RNA (siRNA) that targets transthyretin (TTR) messenger RNA in the liver. Transthyretin is a protein primarily produced by the liver that normally transports vitamin A (retinol) and thyroxine throughout the body. In patients with hATTR-amyloidosis, genetic mutations cause TTR to misfold and aggregate into insoluble amyloid fibrils.
These amyloid deposits accumulate in various tissues and organs, particularly the peripheral nerves and heart, leading to progressive polyneuropathy and cardiomyopathy. The condition, historically known in some regions as familial amyloid polyneuropathy (FAP), affects an estimated 50,000 people worldwide. Without treatment, hATTR-amyloidosis is a progressive and ultimately fatal disease, with a median survival of approximately 7 to 11 years from symptom onset.
Amvuttra belongs to a class of medicines called RNA interference therapeutics. It is conjugated with N-acetylgalactosamine (GalNAc), which enables targeted delivery to the liver via the asialoglycoprotein receptor. Once inside liver cells (hepatocytes), vutrisiran engages the RNA-induced silencing complex (RISC), which cleaves TTR mRNA. This prevents the production of both mutant and wild-type TTR protein, reducing the amount of TTR available to form amyloid deposits.
In clinical studies, Amvuttra achieved a mean reduction of approximately 83% in serum TTR levels by day 90. This sustained reduction in TTR production helps halt disease progression and, in many cases, leads to improvement in neurological function, quality of life, and nutritional status. Amvuttra is approved for use in adults only and was first authorized by the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) in 2022.
RNA interference (RNAi) is a natural biological process in which small RNA molecules silence the expression of specific genes. Amvuttra harnesses this mechanism by introducing a synthetic siRNA molecule that precisely targets the messenger RNA encoding TTR. By degrading TTR mRNA before it can be translated into protein, Amvuttra reduces the supply of the protein that forms harmful amyloid deposits. This approach treats the disease at its genetic source rather than merely managing symptoms.
What Should You Know Before Taking Amvuttra?
Before starting Amvuttra, your doctor will assess your medical history, current medications, and pregnancy status. Key considerations include allergies to the ingredients, vitamin A levels, liver function, and the need for effective contraception in women of childbearing potential.
Amvuttra is a prescription-only medicine that should be initiated and supervised by a physician experienced in the management of amyloidosis. Before prescribing Amvuttra, your healthcare provider will perform a thorough evaluation to ensure the medicine is appropriate for you. This includes confirming the diagnosis of hATTR-amyloidosis with polyneuropathy, assessing the stage of your disease, and reviewing your complete medical history.
Contraindications
Do not use Amvuttra if you have ever had a severe allergic reaction (hypersensitivity) to vutrisiran or any of the other ingredients in this medicine. The inactive ingredients include sodium dihydrogen phosphate dihydrate, disodium phosphate dihydrate, sodium chloride, and water for injections. If you are unsure whether you have had an allergic reaction to any of these components, consult your doctor or pharmacist before receiving treatment.
Warnings and Precautions
Reduced Vitamin A Levels
Amvuttra lowers the amount of vitamin A (retinol) in your blood because it reduces transthyretin, the protein that carries vitamin A. Your doctor will prescribe a daily vitamin A supplement at the recommended dietary allowance (approximately 2,500 IU per day). Do not exceed the recommended dose of vitamin A, as both excessively high and low levels can be harmful.
Signs and symptoms of vitamin A deficiency may include:
- Night blindness (difficulty seeing in dim light)
- Dry eyes or eye irritation
- Blurred or cloudy vision
- Dry, rough skin
If you notice any changes in your vision or develop eye problems while taking Amvuttra, contact your doctor promptly. Your doctor may refer you to an ophthalmologist (eye specialist) for further evaluation. Vitamin A levels may remain low for more than 12 months after the last dose of Amvuttra, so continued supplementation and monitoring may be necessary even after discontinuation.
Liver Function
Elevated liver enzymes, including alkaline phosphatase (ALP) and alanine aminotransferase (ALT), have been reported in patients receiving Amvuttra. Your doctor will monitor your liver function through regular blood tests before and during treatment. Inform your doctor if you have a history of liver disease or if you experience symptoms such as unusual fatigue, loss of appetite, nausea, yellowing of the skin or eyes (jaundice), or dark urine.
Pregnancy and Breastfeeding
Pregnancy
You should not use Amvuttra if you are pregnant. Both excessively high and low levels of vitamin A can harm the development of an unborn baby. Since Amvuttra reduces vitamin A levels, it poses a potential risk to fetal development.
Women of childbearing potential should:
- Have pregnancy excluded before starting treatment with Amvuttra
- Use effective contraception during treatment
- Inform their doctor immediately if they plan to become pregnant or if an unplanned pregnancy occurs
If you are planning to become pregnant, your doctor will advise you to stop Amvuttra and vitamin A supplementation and will check that your vitamin A levels have returned to normal before you attempt to conceive. If an unplanned pregnancy occurs, your doctor will stop Amvuttra. During the first trimester, your doctor may advise stopping vitamin A supplements. During the last two trimesters, vitamin A supplementation may be resumed if your levels have not yet normalized, due to increased risk of deficiency in late pregnancy.
Breastfeeding
It is not known whether vutrisiran passes into breast milk. Your doctor will weigh the potential benefits of treatment for you against the potential risks to your breastfed infant before making a recommendation.
Children and Adolescents
Amvuttra is not recommended for children and adolescents under 18 years of age. Safety and efficacy have not been established in this population.
Driving and Operating Machinery
Amvuttra is considered to have no or negligible effect on the ability to drive and use machines. However, your doctor will advise you whether your underlying condition permits safe driving and machine operation.
Amvuttra contains less than 1 mmol (23 mg) sodium per mL, meaning it is essentially sodium-free. This is relevant for patients on a controlled sodium diet.
How Does Amvuttra Interact with Other Drugs?
No formal drug interaction studies have identified clinically significant interactions between Amvuttra and other medicines. However, patients should inform their healthcare provider about all medications, supplements, and herbal products they are taking.
Vutrisiran is not metabolized by cytochrome P450 enzymes and is not a substrate, inhibitor, or inducer of major drug-metabolizing enzymes or transporters. Based on its pharmacological properties and mechanism of action, clinically significant drug-drug interactions are not expected. Nevertheless, it is important to inform your doctor, pharmacist, or nurse about all medicines you are currently taking, have recently taken, or plan to take.
Although Amvuttra does not have known direct drug interactions, there are important considerations when using it alongside other therapies:
| Medication/Supplement | Consideration | Recommendation |
|---|---|---|
| Vitamin A supplements | Amvuttra reduces vitamin A levels; supplementation is required | Take recommended daily allowance (~2,500 IU/day); do not exceed dose |
| Retinoid medications | Isotretinoin, acitretin, and other retinoids are vitamin A derivatives | Discuss with your doctor; dosage adjustment may be needed |
| Tafamidis (Vyndaqel) | TTR stabilizer with a different mechanism; combination not studied | Discuss with your doctor; usually not used together |
| Patisiran (Onpattro) | Another RNAi therapy targeting TTR; concurrent use is redundant | Should not be used together |
| Hepatotoxic drugs | Amvuttra may elevate liver enzymes; additive hepatic effects possible | Increased liver monitoring may be warranted |
Patients with hATTR-amyloidosis often take multiple medications to manage various aspects of their disease, including cardiac medications, pain management drugs, and gastrointestinal agents. While no specific interactions have been identified with Amvuttra, the complexity of the disease and its treatment necessitates careful coordination between all healthcare providers involved in your care.
Always carry an up-to-date list of all your medicines (prescription, over-the-counter, and supplements) and present it to every healthcare provider you visit. If a new medicine is started or an existing one is changed while you are on Amvuttra, inform both prescribers to ensure safe co-administration.
What Is the Correct Dosage of Amvuttra?
The recommended dose of Amvuttra is 25 mg administered as a single subcutaneous injection once every 3 months (quarterly). The injection can be self-administered by the patient or given by a caregiver after proper training from a healthcare professional.
Amvuttra is available as a 25 mg/0.5 mL solution in a pre-filled syringe designed for subcutaneous (under the skin) injection. Each pre-filled syringe is for single use only and delivers one complete dose. No dose adjustments are required based on body weight, age, sex, race, or renal impairment.
Adults
Standard Adult Dose
25 mg subcutaneously once every 3 months
The injection should be administered into one of the following sites:
- Abdomen (stomach area) — preferred site for self-injection
- Thigh — suitable for self-injection or caregiver administration
- Upper arm — only when administered by another person (caregiver or healthcare professional)
Rotate injection sites with each dose. Do not inject into areas where the skin is tender, bruised, red, hard, or has scars or stretch marks.
Before your first self-injection, a healthcare professional will demonstrate the correct technique for preparing and administering Amvuttra using the pre-filled syringe. Detailed instructions for use are included with each syringe. Your doctor or nurse will determine how long you need to continue treatment.
Children and Adolescents
Amvuttra is not approved for use in patients under 18 years of age. There are no dosage recommendations for this population.
Elderly Patients
No dose adjustment is required for elderly patients. Clinical trials included patients up to 80 years of age, and no clinically meaningful differences in safety or efficacy were observed between older and younger patients.
Missed Dose
If a dose is missed, Amvuttra should be given as soon as possible. Treatment should then be resumed on the quarterly schedule from the most recently administered dose. For example, if the scheduled dose was missed by two weeks, administer the injection immediately and schedule the next dose three months from this date.
Overdose
In the unlikely event that you administer more than the prescribed dose, contact your doctor or pharmacist immediately, even if you do not experience any symptoms. Based on the mechanism of action, an overdose could result in greater-than-intended suppression of TTR and vitamin A levels. Your healthcare team will monitor you for potential adverse effects and provide supportive care as needed.
Do not use the syringe if the packaging is damaged or shows signs of tampering. Do not use if the syringe has been dropped onto a hard surface. Do not touch the plunger rod until you are ready to inject. Do not remove the needle cap until immediately before injection. Never replace the needle cap after removal. The solution should appear clear and colourless to yellow. Do not use if the solution is cloudy, discoloured, or contains particles.
What Are the Side Effects of Amvuttra?
The most common side effects of Amvuttra are injection site reactions (redness, pain, itching, bruising, or warmth) and elevated liver enzymes. Most side effects are mild to moderate and typically resolve without specific treatment.
Like all medicines, Amvuttra can cause side effects, although not everyone experiences them. The safety of Amvuttra was evaluated in the HELIOS-A phase 3 clinical trial, which included 164 patients with hATTR-amyloidosis treated for up to 18 months. The overall safety profile was favourable, with most adverse events being mild or moderate in severity.
The side effect categories below follow standard medical frequency classifications:
Common Side Effects
May affect up to 1 in 10 people
- Injection site reactions: redness (erythema), pain, itching (pruritus), bruising, warmth, swelling, or discolouration at the injection site
- Elevated liver enzymes: increased alkaline phosphatase (ALP) and alanine aminotransferase (ALT) on blood tests
Other Reported Effects
Reported during clinical trials and post-marketing surveillance
- Arthralgia (joint pain)
- Dyspnoea (shortness of breath)
- Vitamin A deficiency symptoms (night blindness, dry eyes)
- Reduced serum vitamin A levels (expected pharmacological effect)
Rare but Important
May affect fewer than 1 in 1,000 people
- Severe allergic (anaphylactic) reactions — seek immediate medical attention if you experience facial swelling, difficulty breathing, or widespread rash
Injection site reactions are the most frequently reported side effect. They are generally mild, occur within 24 hours of injection, and typically resolve within a few days without treatment. To minimize discomfort, ensure the solution has reached room temperature before injecting, rotate injection sites, and use proper injection technique as instructed by your healthcare professional.
The reduction in vitamin A levels is an expected pharmacological effect of Amvuttra rather than a side effect. However, it can lead to clinical symptoms if supplementation is inadequate. Your doctor will monitor your vitamin A levels and adjust supplementation as needed.
Contact your doctor or seek emergency care if you experience signs of a severe allergic reaction such as swelling of the face, lips, tongue, or throat; difficulty breathing or swallowing; severe skin rash or hives; rapid heartbeat; or feeling faint. Although severe allergic reactions to Amvuttra are very rare, prompt treatment is essential.
Reporting side effects: Reporting suspected adverse reactions after a medicine is authorised helps ensure ongoing monitoring of its benefit-risk balance. Healthcare professionals and patients are encouraged to report any suspected side effects to their national regulatory authority (e.g., the EMA in Europe, the FDA in the United States, or the MHRA in the United Kingdom).
How Should You Store Amvuttra?
Store Amvuttra at or below 30°C (86°F). Do not freeze. Keep the medicine out of the sight and reach of children and do not use it after the expiry date printed on the packaging.
Proper storage of Amvuttra is essential to maintain the integrity and efficacy of the medicine. Follow these storage guidelines carefully:
- Temperature: Store at or below 30°C (86°F). The pre-filled syringe may be stored at room temperature within this range.
- Freezing: Do not freeze. If the syringe has been accidentally frozen, do not use it. Contact your pharmacist for a replacement.
- Light: Store in the original carton to protect from light until ready for use.
- Expiry date: Do not use after the expiry date printed on the label, tray lid, and carton after "EXP." The expiry date refers to the last day of that month.
- Inspection: Before use, visually inspect the solution. It should appear clear and colourless to yellow. Do not use if the solution is cloudy, discoloured, or contains visible particles.
- Children: Keep out of the sight and reach of children at all times.
- Disposal: Do not dispose of medicines in household waste or via wastewater. Ask your pharmacist how to properly dispose of used syringes and medicines you no longer need. These measures help protect the environment.
If you are travelling with Amvuttra, ensure it is kept within the recommended temperature range. Do not check the medicine in airline luggage, as cargo holds may reach freezing temperatures. Carry it in your hand luggage with appropriate documentation from your healthcare provider.
What Does Amvuttra Contain?
Each pre-filled syringe contains 25 mg of vutrisiran (as vutrisiran sodium) in 0.5 mL of solution, along with buffer salts, sodium chloride, and water for injections.
Active Ingredient
The active substance is vutrisiran. Each pre-filled syringe contains vutrisiran sodium equivalent to 25 mg vutrisiran in 0.5 mL of solution. Vutrisiran is a double-stranded small interfering RNA (siRNA) conjugated with a triantennary N-acetylgalactosamine (GalNAc) ligand that facilitates targeted delivery to hepatocytes (liver cells).
Inactive Ingredients (Excipients)
- Sodium dihydrogen phosphate dihydrate (buffer)
- Disodium phosphate dihydrate (buffer)
- Sodium chloride (tonicity agent)
- Water for injections (solvent)
Sodium hydroxide and phosphoric acid may be used to adjust the pH of the solution. The total sodium content is less than 1 mmol (23 mg) per syringe.
Appearance and Packaging
Amvuttra is a clear, colourless to yellow solution for injection. Each pack contains one single-use pre-filled syringe equipped with a needle shield. The syringe includes a passive needle guard that automatically covers the needle after injection to help prevent needlestick injuries.
The marketing authorisation holder is Alnylam Netherlands B.V., Antonio Vivaldistraat 150, 1083 HP Amsterdam, Netherlands.
Frequently Asked Questions About Amvuttra
Amvuttra (vutrisiran) is used to treat hereditary transthyretin-mediated amyloidosis (hATTR-amyloidosis) in adults with stage 1 or stage 2 polyneuropathy. This is a rare genetic condition where a misfolded protein called transthyretin accumulates as amyloid deposits in nerves, the heart, and other organs. Amvuttra works by using RNA interference to reduce the production of TTR protein in the liver, thereby slowing or halting disease progression.
Amvuttra is given as a subcutaneous injection (under the skin) once every 3 months. The injection can be administered in the abdomen, thigh, or upper arm (if given by someone else). After proper training from a healthcare professional, patients or their caregivers can self-administer the injection at home using the pre-filled syringe provided.
The most common side effects are injection site reactions, including redness, pain, itching, bruising, or warmth at the injection site. These are typically mild and resolve within a few days. Elevated liver enzymes (alkaline phosphatase and ALT) have also been observed in blood tests. Most side effects do not require specific treatment.
Yes. Amvuttra reduces the transthyretin protein that normally carries vitamin A in the blood, leading to lower vitamin A levels. Patients must take a daily vitamin A supplement as recommended by their doctor (typically about 2,500 IU per day). Do not exceed the recommended dose. Vitamin A levels may remain low for more than 12 months after the last dose of Amvuttra.
Yes. After receiving proper training from a healthcare professional, patients or their caregivers can administer Amvuttra at home. The medicine comes in a pre-filled syringe that is designed for easy self-injection. Detailed instructions for use are provided with each syringe. This allows the convenience of home treatment without the need for regular healthcare facility visits.
Both Amvuttra and patisiran (Onpattro) are RNAi therapies that target the same TTR mRNA. The main differences relate to administration: Amvuttra is given as a subcutaneous injection every 3 months and can be self-administered at home, while patisiran is given as an intravenous infusion every 3 weeks in a healthcare setting with premedication. Both achieve similar TTR reduction, but Amvuttra offers the advantage of less frequent dosing and home administration.
References
This article is based on the following evidence-based sources. All medical claims have been verified against peer-reviewed research and international guidelines.
- European Medicines Agency (EMA). Amvuttra (vutrisiran) – Summary of Product Characteristics. EMA/528428/2022. Available at: ema.europa.eu/en/medicines/human/EPAR/amvuttra
- U.S. Food and Drug Administration (FDA). Amvuttra (vutrisiran) – Prescribing Information. Approved June 2022. Reference ID: 4839856.
- Adams D, Tournev IL, Taylor MS, et al. Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial. Amyloid. 2023;30(1):18-26.
- Ando Y, Coelho T, Berk JL, et al. Guideline of transthyretin-related hereditary amyloidosis for clinicians. Orphanet Journal of Rare Diseases. 2013;8:31.
- Benson MD, Waddington-Cruz M, Berk JL, et al. Inotersen treatment for patients with hereditary transthyretin amyloidosis. New England Journal of Medicine. 2018;379(1):22-31.
- Adams D, Gonzalez-Duarte A, O'Riordan WD, et al. Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis. New England Journal of Medicine. 2018;379(1):11-21.
- Coelho T, Adams D, Conceicao I, et al. A phase II, open-label, extension study of long-term patisiran treatment in patients with hereditary transthyretin-mediated (hATTR) amyloidosis. Orphanet Journal of Rare Diseases. 2020;15:179.
- World Health Organization (WHO). WHO Model List of Essential Medicines. 23rd edition. 2023.
About the Medical Editorial Team
This article was written and reviewed by the iMedic Medical Editorial Team, comprising licensed physicians specializing in pharmacology, neurology, and internal medicine. All content is reviewed according to the GRADE evidence framework and follows international medical guidelines.
Medical Review Process
- Initial research and drafting by medical writers
- Clinical review by specialist physicians
- Evidence verification against EMA/FDA sources
- Regular updates based on new evidence
Quality Standards
- Evidence Level 1A (systematic reviews, RCTs)
- No commercial funding or sponsorship
- GRADE evidence framework
- WCAG 2.2 AAA accessibility compliance