WAINZUA Solution for injection Ref.[114921] Active ingredients: Eplontersen

Vitamin A deficiency

Based on the mechanism of action, Wainzua is expected to reduce serum vitamin A (retinol) below normal levels (see section 5.1). 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. Therefore, pregnancy should be excluded before treatment initiation and women of childbearing potential should practise effective contraception (see section 4.6). 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. Due to the long half-life of eplontersen (see section 5.2), 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.

Excipients with known effect

This medicinal product contains less than 1 mmol sodium (23 mg) per dose of 0.8 ml, that is to say essentially ‘sodium-free’.

No interaction studies have been performed.

In vitro studies indicate that eplontersen is not a substrate or inhibitor of transporters, does not interact with highly plasma protein bound medicinal products, and is not an inhibitor or inducer of CYP enzymes.

Women of child-bearing potential

Wainzua will reduce the plasma levels of vitamin A, which is crucial for normal foetal development. It is not known whether vitamin A supplementation will be sufficient to reduce the risk to the foetus (see section 4.4). For this reason, pregnancy should be excluded before initiation of Wainzua therapy and women of child-bearing potential should practice effective contraception.

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 (see section 4.4). Serum vitamin A levels may remain reduced for more than 15 weeks after the last dose of treatment.

Pregnancy

There are no data on the use of eplontersen in pregnant women. Animal studies are insufficient with respect to reproductive toxicity (see section 5.3). Due to the potential teratogenic risk arising from unbalanced vitamin A levels, Wainzua should not be used during pregnancy and in women of childbearing potential not using contraception. In case of pregnancy, close monitoring of the foetus and vitamin A status should be carried out, especially during the first trimester (see section 4.4).

Breast-feeding

It is unknown whether eplontersen or its metabolites are excreted in human milk. A risk to the breastfed child cannot be excluded.

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Wainzua therapy, taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

Fertility

There is no information available on the effects of eplontersen on human fertility. No impact on male or female fertility was detected in animal studies (see section 5.3).

Eplontersen has no or negligible influence on the ability to drive and use machines.

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).

Table 1. Adverse reactions reported for Wainzua:

^* 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.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.