Amvuttra

/ Medison

The recommended dose of Amvuttra is 25 mg administered via subcutaneous injection once every 3 months.
Vitamin A supplementation at approximately, but not exceeding, 2,500 IU to 3 ,000 IU vitamin A per day is advised for patients treated with Amvuttra.
See prescribing information for full details.

Treatment of hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) in adult patients with stage 1 or stage 2 polyneuropathy

Severe hypersensitivity (e.g., anaphylaxis) to the active substance or to any of the excipients.

Vitamin A deficiency
By reducing serum transthyretin (TTR) protein, Amvuttra treatment leads to a decrease in serum vitamin A (retinol) levels. Serum vitamin A levels may remain reduced for more than 12 months after the last dose of Amvuttra. Serum vitamin A levels below the lower limit of normal should be corrected and any ocular symptoms or signs due to vitamin A deficiency should be evaluated prior to initiation of treatment. Ophthalmological assessment is recommended if patients develop ocular symptoms suggestive of vitamin A deficiency, including reduced night vision or night blindness, persistent dry eyes, eye inflammation, corneal inflammation or ulceration, corneal thickening or corneal perforation.
During the first 60 days of pregnancy, both too high or too low vitamin A levels may be associated with an increased risk of foetal malformation. Therefore, pregnancy should be excluded before initiating Amvuttra and women of childbearing potential should practise effective contraception. In the event of an unplanned pregnancy, Amvuttra should be discontinued. No recommendation can be given whether to continue or discontinue vitamin A supplementation during the first trimester of an unplanned pregnancy. If vitamin A supplementation is continued, the daily dose should not exceed 3,000 IU per day, due to the lack of data supporting higher doses. Thereafter, vitamin A supplementation of 2,500 IU to 3,000 IU per day should be resumed in the second and third trimesters if serum vitamin A levels have not yet returned to normal, because of the increased risk of vitamin A deficiency in the third trimester.

Very common: Arthralgia, Pain in extremity.
Common: Dyspnoea, Injection site reaction, Blood alkaline phosphatase increased.
See prescribing information for full details.

No clinical interaction studies have been performed. Vutrisiran is not expected to cause interactions or to be affected by inhibitors or inducers of cytochrome P450 enzymes, or to modulate the activity of transporters. Therefore, vutrisiran is not expected to have clinically significant interactions with other medicinal products.

Women of childbearing potential: Treatment with Amvuttra reduces serum levels of vitamin A. Both too high or too low vitamin A levels may be associated with an increased risk of foetal malformation. Therefore, pregnancy should be excluded before initiation of treatment and women of childbearing potential should use effective contraception. If a woman intends to become pregnant, Amvuttra and vitamin A supplementation should be discontinued and serum vitamin A levels should be monitored and have returned to normal before conception is attempted. Serum vitamin A levels may remain reduced for more than 12 months after the last dose of treatment.
Pregnancy: There are no data on the use of Amvuttra in pregnant women. Due to the potential teratogenic risk arising from unbalanced vitamin A levels, Amvuttra should not be used during pregnancy. As a precautionary measure, vitamin A and thyroid stimulating hormone levels should be obtained early in pregnancy. Close monitoring of the foetus should be carried out, especially during the first trimester.
Lactation: It is unknown whether vutrisiran is excreted in human milk. There is insufficient information on the excretion of vutrisiran in animal milk.

In case of overdose, it is recommended that the patient be monitored as medically indicated for any signs or symptoms of adverse reactions and appropriate symptomatic treatment be instituted.