4.1. Therapeutic indications

Treatment of influenza

Xofluza is indicated for the treatment of uncomplicated influenza in patients aged 3 weeks and above.

Post‑exposure prophylaxis of influenza

Xofluza is indicated for post-exposure prophylaxis of influenza in individuals aged 3 weeks and above.

Xofluza should be used in accordance with official recommendations.

4.2. Posology and method of administration

Posology

Treatment of influenza

A single dose of baloxavir marboxil should be taken as soon as possible within 48 hours of symptom(s) onset.

Post‑exposure prophylaxis of influenza

A single dose of baloxavir marboxil should be taken as soon as possible within 48 hours following close contact with an individual known or suspected to have influenza (see section 5.1).

Adults, adolescents, children and infants (≥ 3 weeks of age)

The recommended single oral dose of baloxavir marboxil is determined by body weight (see Table 1).

Adults, adolescents and children who are unable to, or experience difficulty swallowing tablets, or those who require enteral administration may instead receive treatment with Xofluza granules for oral suspension. Refer to the Xofluza granules for oral suspension prescribing information.

Table 1. Baloxavir marboxil dosing by patient body weight (≥ 3 weeks of age)

Patient body weight

Recommended oral dose

< 20 kg

Refer to the Xofluza granules for oral suspension prescribing information.

≥ 20 kg to < 80 kg

Single dose of 40 mg taken as

1 x 40 mg tablet

≥ 80 kg

Single dose of 80 mg taken as

1 x 80 mg tablet

OR

2 x 40 mg tablets

There are no clinical data on the use of a repeat dose of baloxavir marboxil for the treatment of uncomplicated influenza or for post-exposure prophylaxis in any one influenza season.

Special populations

Elderly

No dose adjustment is required (see section 5.2).

Hepatic impairment

No dose adjustment is required for patients with mild or moderate hepatic impairment (Child‑Pugh class A or B). The safety and efficacy of baloxavir marboxil have not been established in patients with severe hepatic impairment (Child‑Pugh class C).

Renal impairment

No dose adjustment is required in patients with renal impairment (see section 5.2).

Paediatric population

The safety and efficacy of baloxavir marboxil in preterm neonates and children aged < 3 weeks have not been established. No data are available.

Method of administration

Oral use. The tablets should be taken with water.

Xofluza may be taken with or without food (see section 5.2).

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 (see section 4.5).

4.3. Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4. Special warnings and precautions for use

Lactose intolerance

Xofluza contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Sodium

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 'sodium- free'.

4.5. Interaction with other medicinal products and other forms of interaction

Effects of other medicinal products on baloxavir marboxil or its active metabolite baloxavir

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.

Immune response to influenza virus

Interaction studies with influenza vaccines and baloxavir marboxil have not been conducted. In studies of naturally acquired influenza, treatment with Xofluza did not impair the humoral antibody response to influenza infection.

Paediatric population

Interaction studies have only been performed in adults.

4.6. Fertility, pregnancy and lactation

Pregnancy

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 (see section 5.3).

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

Breast-feeding

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 Xofluza therapy taking into account the benefit of breast‑feeding for the child and the benefit of therapy for the woman.

Fertility

No effects on male or female fertility were observed in animal studies performed with baloxavir marboxil (see section 5.3).

4.7. Effects on ability to drive and use machines

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

4.8. Undesirable effects

Summary of the safety profile

Hypersensitivity reactions have been observed in the post-marketing, 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 post-marketing experience with baloxavir marboxil (Table 2) 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). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.

Table 2. Adverse drug reactions from post-marketing experience in adults, adolescents and paediatric patients

System organ class (SOC)

Adverse reaction

(preferred term (PT), MedDRA)

Frequency

Immune system disorders

Anaphylaxisa

Not known

Anaphylactic reactionsa

Not known

Hypersensitivitya

Not known

Gastrointestinal disorders

Diarrhoeab

Common

Vomitingb

Common

Skin and subcutaneous disorders

Urticariab

Uncommon

Angioedemaa

Not known

aNot reported in clinical studies.

bThe frequency calculation is based on completed clinical studies.

Paediatric population

The safety profile of baloxavir marboxil in paediatric patients (3 weeks to < 12 years) was determined from data collected from treatment and post-exposure prophylaxis studies. Table 3 presents adverse drug reactions identified from clinical trial experience.

Anaphylactic reaction, anaphylaxis, urticaria and angioedema (face, eyelid and lip swelling) have been reported post-marketing in the paediatric population (see Table 2).

Table 3. Adverse drug reactions in children from clinical trial experience

System organ class (SOC)

Adverse reaction

(preferred term (PT), MedDRA)

Frequency

Gastrointestinal disorders

Diarrhoea

Common

Vomiting

Common

Skin and subcutaneous disorders

Rash

Common

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 Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Reports of overdoses with baloxavir marboxil have been received from clinical trials and during post-marketing experience. In the majority of cases reporting overdose, no adverse reactions were reported. Data are insufficient to determine what symptoms may be anticipated as a result of an overdose.

Management

No known specific antidote exists for Xofluza. In the event of overdose, standard supportive medical care should be initiated based on the patient's signs and symptoms.

Baloxavir is unlikely to be significantly removed by dialysis due to high serum protein binding.