Wainzua

Treatment should be prescribed and supervised by a physician experienced in the treatment of patients with hereditary transthyretin-mediated amyloidosis. Posology The recommended dose of eplontersen is 45 mg administered monthly. 4).

1). 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. Missed dose If a dose of Wainzua is missed, then the next dose should be administered as soon as possible.

Dosing should be resumed at monthly intervals from the date of the last dose; a double dose should not be administered. 2). 73 m2). 2) and should only be used in these patients if the anticipated clinical benefit outweighs the potential risk.

Hepatic impairment No dose adjustment is necessary in patients with mild hepatic impairment. 2). Patients undergoing liver transplant The safety and efficacy of Wainzua have not been evaluated in patients undergoing liver transplant.

No data are available. Paediatric population The safety and efficacy of Wainzua in children and adolescents below 18 years of age have not been established. 1). Method of administration Wainzua is for subcutaneous use. Wainzua is a pre-filled pen for single-use only.

The first injection administered by the patient or caregiver should be performed under the guidance of an appropriately qualified health care professional. Patients and/or caregivers should be trained in the subcutaneous administration of Wainzua.

The pre-filled pen should be removed from refrigerated storage at least 30 minutes before use and allowed to reach room temperature prior to injection. Other warming methods should not be used. Inspect solution visually before use. The solution should appear colourless to yellow.

Do not use if cloudiness, particulate matter, or discolouration is observed prior to administration. If self-administered, Wainzua should be injected in the abdomen or upper thigh region. If a caregiver administers the injection, the back of the upper arm can also be used.

Wainzua should not be injected into skin that is bruised, tender, red, or hard, into scars or damaged skin, the area around the navel should be avoided. Comprehensive instructions for administration using the pre-filled pen are provided in the ‘Instructions for Use’.

Summary of the safety profile The most frequent adverse reactions during treatment with eplontersen were vitamin A decreased (97% of patients) and vomiting (9% of patients). Tabulated list of adverse reactions The safety data reflects exposure to Wainzua in 144 patients with polyneuropathy caused by ATTRv (ATTRv-PN) randomised to eplontersen and who received at least one dose of eplontersen.

130 patients completed treatment with eplontersen through Week 85. The mean duration of treatment was 541 days (range: 57 to 582 days). Adverse reactions are organised by MedDRA System Organ Class (SOC). Within each SOC, preferred terms are arranged by decreasing frequency and then by decreasing seriousness.

Frequencies of occurrence of adverse reactions are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000) and not known (cannot be estimated from available data).

6 Table 1: Adverse reactions reported for Wainzua System organ class Adverse reaction Frequency Gastrointestinal disorders Vomiting Common General disorders and administration site conditions Injection site erythema Common Injection site pain Common Injection site pruritus Common Investigations Vitamin A decreased Very common* * Based on laboratory findings of vitamin A below the lower limit of normal during the study.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

1). Serum vitamin A levels below the lower limit of normal should be corrected and any ocular symptoms or signs related to vitamin A deficiency should be evaluated prior to initiation of treatment with Wainzua. Patients receiving Wainzua should take oral supplementation of approximately, but not exceeding, 2 500 IU (female) to 3 000 IU (male) of vitamin A per day to reduce the potential risk of ocular symptoms due to vitamin A deficiency.

Referral for ophthalmological assessment is recommended if patients develop ocular symptoms consistent with 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 and too low vitamin A levels may be associated with an increased risk of foetal malformation. 6). If a woman intends to become pregnant, Wainzua and vitamin A supplementation should be discontinued, and serum vitamin A levels should be monitored and have returned to normal before conception is attempted.

In the event of an unplanned pregnancy, Wainzua should be discontinued. 2), a vitamin A deficit may even develop after cessation of treatment. 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 Wainzua. However, increasing vitamin A supplementation to above 3 000 IU per day during pregnancy is unlikely to correct serum retinol levels due to the mechanism of action of eplontersen and may be harmful to the mother and foetus.

1.