Baloxavir marboxil

Products that contain polyvalent cations may decrease plasma concentrations of baloxavir. Xofluza should not be taken with products that contain polyvalent cations such as laxatives, antacids or oral supplements containing iron, zinc, selenium, calcium or magnesium.

The safety and efficacy of baloxavir marboxil has not been established in patients with severe hepatic impairment (Child-Pugh class C).

There are no or limited data from the use of baloxavir marboxil in pregnant women.

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.

As a precautionary measure, it is preferable to avoid the use of baloxavir marboxil during pregnancy.

It is unknown whether baloxavir marboxil or baloxavir are excreted in human milk. Baloxavir marboxil and its metabolites are secreted in the milk of lactating rats. A risk to the newborns/infants cannot be excluded.

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

Carcinogenesis

Carcinogenicity studies have not been performed with baloxavir marboxil.

Mutagenesis

Baloxavir marboxil and the active metabolite, baloxavir, were not mutagenic in in vitro and in in vivo genotoxicity assays which included bacterial mutation assays in S. typhimurium and E. coli, micronucleus tests with cultured mammalian cells, and in the rodent micronucleus assay.

Impairment of Fertility

In a fertility and early embryonic development study in rats, doses of baloxavir marboxil at 20, 200, or 1,000 mg/kg/day were administered to females for 2 weeks before mating, during mating and until day 7 of pregnancy. Males were dosed for 4 weeks before mating and throughout mating. There were no effects on fertility, mating performance, or early embryonic development at any dose level, resulting in systemic drug exposure (AUC) approximately 5 times the MRHD.

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

Summary of the safety profile

Hypersensitivity reactions have been observed in the postmarketing setting which include reports of anaphylaxis/anaphylactic reactions and less severe forms of hypersensitivity reactions including urticaria and angioedema. Of these adverse reactions only urticaria has been observed in clinical studies with an estimated frequency category of “uncommon”.

Tabulated list of adverse reactions

The following adverse drug reactions have been identified from postmarketing experience with baloxavir marboxil based on spontaneous case reports and cases from non-interventional study programmes. Adverse drug reactions are listed according to system organ classes in MedDRA and the corresponding frequency category estimation for each adverse drug reaction is based on the following convention: 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 the available data).

Table 2. Adverse drug reactions from postmarketing experience:

Paediatric population

The safety profile in 109 adolescent patients (≥12 years to <18 years) was similar to that in adult patients.