Amvuttra injection for hereditary and wild-type transthyretin amyloidosis

Amvuttra is an injectable medicine used to treat adults with specific forms of transthyretin-mediated amyloidosis, a rare disease caused by a buildup of abnormal protein deposits. It targets nerve damage in hereditary transthyretin-mediated amyloidosis and heart problems in both hereditary and wild-type forms to help reduce serious cardiovascular events.

Amvuttra is approved for use in adults for two main conditions:

• Treatment of the polyneuropathy (nerve damage) associated with hereditary transthyretin-mediated amyloidosis.
• Treatment of the cardiomyopathy (heart muscle disease) related to wild-type or hereditary transthyretin-mediated amyloidosis, with the aim of reducing cardiovascular mortality, hospitalizations due to heart problems, and urgent heart failure visits.

vutrisiran

Amvuttra contains vutrisiran, a small interfering RNA (siRNA) that specifically targets and reduces production of transthyretin, the abnormal protein responsible for amyloidosis. By decreasing transthyretin levels, it helps prevent further protein buildup that damages nerves and heart tissue.

The recommended dose of Amvuttra is 25 mg given by subcutaneous injection once every three months. The injection should be administered by a healthcare professional.

Injection Instructions:

1. If refrigerated, allow the prefilled syringe to reach room temperature for about 30 minutes before use.
2. Visually inspect the solution; it should be clear and colorless to yellow without particles. Do not use if cloudy or discolored.
3. Choose an injection site from the abdomen, thighs, or upper arms. Avoid the area within 5 cm of the navel, and avoid scarred, inflamed, or swollen areas. Clean the injection site.
4. Remove the needle cap without touching the needle. Do not recap the needle after use.
5. Pinch the skin and insert the needle at a 45° to 90° angle. Inject the entire medication dose by pushing the plunger fully, which activates the needle shield.
6. Dispose of the used syringe immediately in a sharps container.

Missed Dose: If a scheduled dose is missed, administer it as soon as possible and then resume dosing every three months from that date.

None.

Vitamin A supplementation is essential during Amvuttra treatment. Amvuttra reduces serum vitamin A levels, which may increase the risk of vitamin A deficiency. Patients should take the recommended daily allowance of vitamin A. Do not exceed the recommended vitamin A dose to try to normalize blood levels, as serum vitamin A does not reflect total body stores.

Refer patients to an ophthalmologist if they develop symptoms of vitamin A deficiency, such as night blindness.

The most commonly reported side effects (≥5%) include:

• Pain in extremities
• Joint pain (arthralgia)
• Shortness of breath (dyspnea)
• Decreased vitamin A levels

Injection site reactions occurred in about 4% of patients and included mild and transient bruising, redness, pain, itching, and warmth.

Serious adverse events reported in the polyneuropathy study included rare cases (1.6%) of atrioventricular (AV) heart block, including one complete AV block.

Pregnancy: There are no human data to assess risk during pregnancy. Amvuttra reduces serum vitamin A, essential for normal fetal development, and vitamin A supplementation is advised. Animal studies in rats showed developmental toxicity at high doses; no adverse effects were seen in rabbits. The potential effects of reduced maternal transthyretin or vitamin A supplementation on the fetus are unknown.

Lactation: It is unknown if vutrisiran is present in human milk or its effects on a breastfed infant. Decisions about breastfeeding should consider the clinical need for Amvuttra and potential risks to the infant.

Store the Amvuttra prefilled syringe refrigerated. Before injection, allow it to warm to room temperature for approximately 30 minutes without removing the syringe from its packaging.