Amvuttra

Therapy should be initiated under the supervision of a physician knowledgeable in the management of amyloidosis. Treatment should be started as early as possible in the disease course to prevent the accumulation of disability. Posology The recommended dose of Amvuttra is 25 mg administered via subcutaneous injection once every 3 months.

4). The decision to continue treatment in those patients whose disease progresses to stage 3 polyneuropathy should be taken at the discretion of the physician based on the overall benefit and risk assessment. There is limited data with vutrisiran in patients with New York Heart Association (NYHA) Class IV and in patients who have both NYHA Class III and National Amyloidosis Centre (NAC) stage III.

However, if patients on vutrisiran progress to these stages, these data suggest that patients can remain on treatment. 3 Missed dose If a dose is missed, Amvuttra should be administered as soon as possible. Dosing should be resumed every 3 months, from the most recently administered dose.

2). 5 to 3 × ULN and any AST) hepatic impairment. 2). 73 m2). 2). Paediatric population The safety and efficacy of Amvuttra in children or adolescents < 18 years of age have not been established. No data are available. Method of administration Amvuttra is for subcutaneous use only.

Amvuttra may be administered by a healthcare professional, the patient, or a caregiver. Patients or caregivers may inject Amvuttra after guidance has been provided by a healthcare professional on proper subcutaneous injection technique.

This medicinal product is ready-to-use and for single-use only. Visually inspect the solution for particulate matter and discolouration. Do not use if discoloured or if particles are present. Prior to administration, if stored cold, the pre-filled syringe should be allowed to warm by leaving carton at room temperature for about 30 minutes.

• The subcutaneous injection should be administered into one of the following sites: the abdomen, thighs, or upper arms. If injected in the upper arm, the injection should be administered by a healthcare professional or a caregiver.

Amvuttra should not be injected into scar tissue or areas that are reddened, inflamed, or swollen. • If injecting into the abdomen, the area around the navel should be avoided.

Tabulated list of adverse reactions The safety profile of Amvuttra was characterised based on the data from randomised-controlled phase 3 clinical studies. Adverse reactions reported in the pooled dataset of HELIOS-A and HELIOS-B studies are presented in Table 1.

The adverse reactions are presented as MedDRA preferred terms and under the MedDRA System Organ Class (SOC). The frequency of the adverse reactions is expressed according to the following category: Common (≥1/100 to <1/10).

Table 1:

Adverse reactions reported for Amvuttra System Organ Class Adverse Reaction Frequency General disorders and administration site conditions Injection site reactiona Common Investigations Alanine transaminase increased Common Blood alkaline phosphatase increased Common a Reported symptoms included bruising, erythema, pain, pruritus, and warmth.

Injection site reactions were mild, transient, and did not lead to treatment discontinuation 6 Description of selected adverse reactions Liver function tests In the HELIOS-B study, 97 (30%) of patients treated with Amvuttra and 78 (24%) patients treated with placebo had a mild increased alanine aminotransferase (ALT) greater than the ULN and less than or equal to 3×ULN.

All patients treated with Amvuttra with mild ALT elevations were asymptomatic and the majority had normalization of ALT levels with continued dosing. 3%) Amvuttra-treated patients, respectively, developed anti-drug antibodies (ADA).

In both studies, ADA titres were low and transient with no evidence of an effect on clinical efficacy, safety, or pharmacokinetic or pharmacodynamic profiles of vutrisiran. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

1). 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 with Amvuttra. Patients receiving Amvuttra should take oral supplementation of approximately, but not exceeding, 2 500 IU to 3 000 IU vitamin A per day to reduce the potential risk of ocular symptoms due to vitamin A deficiency.

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. 6). 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 Amvuttra. 6). 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.

It is not known whether vitamin A supplementation in pregnancy will be sufficient to prevent vitamin A deficiency if the pregnant female continues to receive Amvuttra. However, increasing vitamin A supplementation to above 3 000 IU per day during pregnancy is unlikely to correct plasma retinol levels due to the mechanism of action of Amvuttra and may be harmful to the mother and foetus.

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