Xofluza

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
ANNEX I 

 
SUMMARY OF PRODUCT CHARACTERISTICS 

 
 
  



2 

This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Xofluza 20 mg film-coated tablets 
Xofluza 40 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Xofluza 20 mg 

Each tablet contains 20 mg baloxavir marboxil. 

Excipient(s) with known effect 

Each tablet contains 77.9 mg lactose monohydrate. 
For the full list of excipients, see section 6.1. 
 
Xofluza 40 mg 

Each tablet contains 40 mg baloxavir marboxil.  
Excipient(s) with known effect 

Each tablet contains 155.8 mg lactose monohydrate. 

For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Xofluza 20 mg 
 
White to light yellow, oblong shaped film-coated tablets approximately 8.6 mm in length, debossed 
with “  772” on one side and “20” on the other side. 
 
Xofluza 40 mg 
 
White to light yellow, oblong shaped film-coated tablets approximately 11.1 mm in length, debossed 
on one side with “BXM40”. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Treatment of influenza 
 
Xofluza is indicated for the treatment of uncomplicated influenza in patients aged 12 years and above. 
 
Post-exposure prophylaxis of influenza 
 
Xofluza is indicated for post-exposure prophylaxis of influenza in individuals aged 12 years and 
above. 
 



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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 
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 and adolescents (≥ 12 years of age)  
The recommended oral dose of baloxavir marboxil depending on body weight is shown in Table 1. 
 
Table 1. Baloxavir marboxil dosing by patient weight 
 

Patient body weight Recommended oral dose 

 < 80 kg Single dose of 40 mg taken as 
2 x 20 mg tablets 

≥ 80 kg Single dose of 80 mg taken as 
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 (≥ 65 years) 
No dosage adjustment is required (see section 5.2). 
 
Renal impairment 
No dose adjustment is required in patients with renal impairment (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 has not been established in patients with 
severe hepatic impairment (Child-Pugh class C). 
 
Paediatric population 
The safety and efficacy of baloxavir marboxil in children aged < 12 years has not been established. 
 
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). 



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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 and experimental 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 baloxavir marboxil 
therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the 
woman. 
 



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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 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 (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). 
 
Table 2. Adverse drug reactions from postmarketing experience  
 

System Organ Class (SOC) Adverse Reaction 
(preferred term, MedDRA) 

Frequency 

Immune system disorders Anaphylaxis Not known  
Anaphylactic reactions Not known  
Hypersensitivity Not known  

Skin and subcutaneous disorders Urticaria Uncommon 

Angioedema Not known  
 
Paediatric population 
 
The safety profile in 109 adolescent patients (≥ 12 years to < 18 years) was similar to that in adult 
patients. 
 
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. 
 
4.9 Overdose 
 
Reports of overdoses with baloxavir marboxil have been received from clinical trials and during 
postmarketing 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. 
 

https://www.ema.europa.eu/documents/template-form/appendix-v-adverse-drug-reaction-reporting-details_en.doc


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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. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antivirals for systemic use, other anti-virals. ATC code: J05AX25. 
 
Mechanism of action 
 
Baloxavir marboxil is a prodrug that is converted by hydrolysis to baloxavir, the active form that 
exerts anti-influenza activity. Baloxavir acts on the cap-dependent endonuclease (CEN), an influenza 
virus-specific enzyme in the polymerase acidic (PA) subunit of the viral RNA polymerase complex 
and thereby inhibits the transcription of influenza virus genomes resulting in inhibition of influenza 
virus replication. 
 
In vitro activity 
The 50% inhibition concentration (IC50) of baloxavir was 1.4 to 3.1 nmol/L for influenza A viruses 
and 4.5 to 8.9 nmol/L for influenza B viruses in an enzyme inhibition assay. 
 
In a MDCK cell culture assay, the median 50% effective concentration (EC50) values of baloxavir 
were 0.73 nmol/L (n=31; range: 0.20-1.85 nmol/L) for subtype A/H1N1 strains, 0.83 nmol/L (n=33; 
range: 0.35-2.63 nmol/L) for subtype A/H3N2 strains, and 5.97 nmol/L (n=30; range: 
2.67-14.23 nmol/L) for type B strains. 
 
In an MDCK cell-based virus titre reduction assay, the 90% effective concentration (EC90) values of 
baloxavir were in the range of 0.46 to 0.98 nmol/L for subtype A/H1N1 and A/H3N2 viruses, 0.80 to 
3.16 nmol/L for avian subtype A/H5N1 and A/H7N9 viruses, and 2.21 to 6.48 nmol/L for type B 
viruses. 
 
Resistance 
Viruses bearing the PA/I38T/F/M/N mutation selected in vitro or in clinical studies show reduced 
susceptibility to baloxavir with changes in EC50 values ranging from 11 to 57-fold for influenza A 
viruses and 2 to 8-fold for influenza B viruses.  
 
In the two Phase 3 studies of treatment of uncomplicated influenza (see below) no resistance to 
baloxavir was detected in baseline isolates. Treatment-emergent mutations PA/I38T/M/N were 
detected in 36/370 (9.7%) and in 15/290 (5.2%) patients treated with baloxavir marboxil but were not 
detected in any patients treated with placebo.  
 
In the Phase 3 study of post-exposure prophylaxis (see below), treatment-emergent mutations 
PA/I38T/M were found in 10 of 374 (2.7%) baloxavir marboxil-treated subjects. PA/I38 substitutions 
were not detected in placebo-treated subjects, with the exception of 2 subjects who received baloxavir 
marboxil as rescue medication. 
 
Baloxavir is active in vitro against influenza viruses that are considered resistant to neuraminidase 
inhibitors, including strains with the following mutations: H274Y in A/H1N1, E119V and R292K in 
A/H3N2, R152K and D198E in type B virus, H274Y in A/H5N1, R292K in A/H7N9. 
 



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Clinical trials 
 
Treatment of uncomplicated influenza 
 
Capstone 1 (1601T0831), was a Phase 3 randomised, double-blind, multicentre study conducted in 
Japan and the US to evaluate the efficacy and safety of a single oral dose of baloxavir marboxil 
compared with placebo and with oseltamivir in healthy adult and adolescent patients (aged ≥ 12 years 
to ≤ 64 years) with uncomplicated influenza. Patients were randomised to receive baloxavir marboxil 
(patients who weighed 40 to < 80 kg received 40 mg and patients who weighed ≥ 80 kg received 
80 mg), oseltamivir 75 mg twice daily for 5 days (only if aged ≥ 20 years) or placebo. Dosing 
occurred within 48 hours of first onset of symptoms. 
 
A total of 1436 patients (of which 118 were aged ≥ 12 years to ≤ 17 years) were enrolled in the 2016-
2017 Northern Hemisphere influenza season. The predominant influenza virus strain in this study was 
the A/H3 subtype (84.8% to 88.1%) followed by the B type (8.3% to 9.0%) and the A/H1N1pdm 
subtype (0.5% to 3.0%).  The primary efficacy endpoint was time to alleviation of symptoms (cough, 
sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) 
(TTAS). Baloxavir marboxil elicited a statistically significant reduction in TTAS when compared with 
placebo (Table 3). 
 
Table 3. Capstone 1: Time to alleviation of symptoms (baloxavir marboxil vs placebo) 
 

Time to Alleviation of Symptoms (Median [hours])  

Baloxavir marboxil 
40/80 mg 
(95% CI) 
N=455 

Placebo 
(95% CI) 
N=230 

Difference between 
Baloxavir marboxil and 
placebo 
(95% CI for difference) 

P-value 

53.7  
(49.5, 58.5) 

80.2  
(72.6, 87.1) 

-26.5 
(−35.8, −17.8) 

< 0.0001 

CI: Confidence interval 

 
When the baloxavir marboxil group was compared to the oseltamivir group, there was no statistically 
significant difference in TTAS  (53.5 h vs 53.8 h respectively). 
 
The median (95% CI) TTAS was 49.3 (44.0, 53.1) and 82.1 (69.5, 92.9) hours for patients who were 
symptomatic for > 0 to ≤ 24 hours, and 66.2 (54.4, 74.7) and 79.4 (69.0, 91.1) hours for patients who 
were symptomatic for > 24 to ≤ 48 hours for baloxavir marboxil and placebo, respectively. 
 
The median time to resolution of fever in patients treated with baloxavir marboxil was 24.5 hours 
(95% CI: 22.6, 26.6) compared with 42.0 hours (95% CI: 37.4, 44.6) in those receiving placebo.  No 
difference was noted in duration of fever in the baloxavir marboxil group compared with the 
oseltamivir group. 
 
Capstone 2 (1602T0832) was a Phase 3 randomised, double-blind, multicentre study to evaluate the 
efficacy and safety of a single oral dose of baloxavir marboxil compared with placebo and with 
oseltamivir in adult and adolescent patients (aged ≥ 12 years) with uncomplicated influenza who had 
at least one host factor predisposing to the development of complications. Patients were randomised to 
receive a single oral dose of baloxavir marboxil (according to weight as in Capstone 1),  oseltamivir 
75 mg twice daily for 5 days, or placebo. Dosing occurred within 48 hours of first onset of symptoms. 
 
Of the total 2184 patients 59 were aged ≥ 12 to ≤ 17 years, 446 were aged ≥ 65 to ≤ 74 years, 142 
were aged ≥ 75 to ≤ 84 years and 14 were aged ≥ 85 years. The predominant influenza viruses in this 
study were the A/H3 subtype (46.9% to 48.8%) and influenza B (38.3% to 43.5%). The primary 
efficacy endpoint was time to improvement of influenza symptoms (cough, sore throat, headache, 
nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) (TTIS). Baloxavir marboxil 
elicited a statistically significant reduction in TTIS when compared with placebo (Table 4).  



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Table 4 . Capstone 2: Time to improvement of influenza symptoms (baloxavir marboxil vs 
placebo) 
 
Time to Improvement of Influenza Symptoms (Median [hours])  

Baloxavir marboxil  
40/80 mg 
(95% CI) 
N=385 
 

Placebo 
(95% CI) 
N=385 

Difference between 
Baloxavir marboxil and 
placebo 
(95% CI for difference) 

P-value 

73.2 
(67.5, 85.1) 

102.3 
(92.7, 113.1) 

-29.1 
(−42.8, −14.6) 

< 0.0001 

 
When the baloxavir marboxil group was compared to the oseltamivir group, there was no statistically 
significant difference in TTIS (73.2 h vs 81.0 h respectively). 
 
The median (95% CI) TTIS was 68.6 (62.4, 78.8) and 99.1 (79.1, 112.6) hours for patients who were 
symptomatic for > 0 to ≤ 24 hours and 79.4 (67.9, 96.3) and 106.7 (92.7, 125.4) hours for patients who 
were symptomatic for > 24 to ≤ 48 hours for baloxavir marboxil and placebo, respectively. 
 
For patients infected with type A/H3 virus, the median TTIS was shorter in the baloxavir marboxil 
group compared with the placebo group but not compared with the oseltamivir group (see Table 5). In 
the subgroup of patients infected with type B virus, the median TTIS was shorter in the baloxavir 
marboxil group compared with both the placebo and oseltamivir group (see Table 5). 
 
Table 5. Time to improvement of symptoms by influenza virus subtype  
 

Time to Improvement of Symptoms (Hours) 
Median [95% CI] 
 
Virus Baloxavir marboxil 

 
Placebo 
 
 

Oseltamivir 
 
 

A/H3  75.4 
[62.4, 91.6] 
N=180 

100.4 
[88.4, 113.4] 
N=185 

68.2 
[53.9, 81.0] 
N=190 

B 74.6 
[67.4, 90.2) 
N=166 

100.6 
[82.8, 115.8] 
N=167 

101.6  
[90.5, 114.9] 
N=148 

 
The median time to resolution of fever was 30.8 hours (95% CI: 28.2, 35.4) in the baloxavir marboxil 
group compared with 50.7 hours (95% CI: 44.6, 58.8) in the placebo group.  No clear differences 
between the baloxavir marboxil group and the oseltamivir group were observed.  
 
The overall incidence of influenza-related complications (death, hospitalisation, sinusitis, otitis media, 
bronchitis, and/or pneumonia) was 2.8% (11/388 patients) in the baloxavir marboxil group compared 
with 10.4% (40/386 patients) in the placebo group.  The lower overall incidence of influenza-related 
complications in the baloxavir marboxil group compared with the placebo group was mainly driven by 
lower incidences of bronchitis (1.8% vs. 6.0%, respectively) and sinusitis (0.3% vs. 2.1%, 
respectively).   
 
Post-exposure prophylaxis of influenza 
 
Study 1719T0834 was a Phase 3, randomised, double-blind, multicentre study conducted in 
749 subjects in Japan to evaluate the efficacy and safety of a single oral dose of baloxavir marboxil 



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compared with placebo for post-exposure prophylaxis of influenza. Subjects were household contacts 
of influenza-infected index patients. 
 
A total of 607 subjects 12 years of age and over received either baloxavir marboxil dosed according to 
weight, as in the treatment studies, or placebo. The majority (74%) was enrolled within 24 hours of 
symptom onset in the index patient group. The predominant influenza virus strains in the index 
patients were the A/H3 subtype (49.1%) and the A/H1N1pdm subtype (46.2%) followed by influenza 
B (0.9%). 
 
The primary efficacy endpoint was the proportion of household subjects who were infected with 
influenza virus and presented with fever and at least one respiratory symptom in the period from Day 
1 to Day 10. 
 
There was a statistically significant reduction in the proportion of subjects with laboratory-confirmed 
clinical influenza from 13.6% in the placebo group to 1.9% in the baloxavir marboxil group (see 
Table 6). 
 
Table 6. Proportion of subjects with influenza virus, fever, and at least one respiratory symptom 
(baloxavir vs placebo) 
 

Proportion of Subjects with Influenza Virus, Fever, and at least one Respiratory Symptom (%) mITT 
population 

Baloxavir marboxil 
(95% CI) 
 

Placebo 
(95% CI) 
 

Risk Ratio 
(95% CI for risk ratio) 

P-value 

N=374 
1.9 
(0.8, 3.8) 

N=375 
13.6 
(10.3, 17.5) 

 
0.14 
(0.06, 0.30) 

< 0.0001 

Proportion of Subjects ≥ 12 years with Influenza Virus, Fever, and at least one Respiratory Symptom 
(%) 

N=303 
1.3 
(0.4, 3.3) 

N=304 
13.2 
(9.6, 17.5) 

 
0.10 
(0.04, 0.28) 

< 0.0001 

 
Paediatric population 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Xofluza in one or more subsets of the paediatric population for the treatment of influenza and 
prevention of influenza (see section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
After oral administration, baloxavir marboxil is extensively converted to its active metabolite, baloxavir. 
The plasma concentration of baloxavir marboxil is very low or below the limit of quantitation 
(< 0.100 ng/mL). 
 
Following a single oral administration of 80 mg of baloxavir marboxil, the time to achieve peak 
plasma concentration (Tmax) is approximately 4 hours in the fasted state. The absolute bioavailability 
of baloxavir after oral dosing with baloxavir marboxil has not been established. 
 
Food effect 
 



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A food-effect study involving administration of baloxavir marboxil to healthy volunteers under fasting 
conditions and with a meal (approximately 400 to 500 kcal including 150 kcal from fat) indicated that 
the Cmax and AUC of baloxavir were decreased by 48% and 36%, respectively, under fed conditions. 
Tmax was unchanged in the presence of food. In clinical studies there were no clinically relevant 
differences in efficacy when baloxavir was taken with vs.without food. 
 
Distribution 
 
In an in-vitro study, the binding of baloxavir to human serum proteins, primarily albumin, is 92.9% to 
93.9%. The apparent volume of distribution of baloxavir during the terminal elimination phase (Vz/F) 
following a single oral administration of baloxavir marboxil is approximately 1180 litres in Caucasian 
subjects and 647 litres in Japanese subjects.  
 
Biotransformation 
 
Baloxavir is primarily metabolised by UGT1A3 to form a glucuronide with a minor contribution from 
CYP3A4 to form a sulfoxide. 
 
Drug-drug interaction studies 
 
Based on in vitro and in vivo drug-drug interaction (DDI) studies, baloxavir marboxil and baloxavir 
are not expected to inhibit isozymes of the CYP or UGT families or cause relevant induction of CYP 
enzymes. 
 
Based on in vitro transporter studies and in vivo DDI studies, no relevant pharmacokinetic interaction 
is anticipated between baloxavir marboxil or baloxavir and medicines which are substrates of the 
followingtransporters: OATP1B1, OATP1B3, OCT1, OCT2, OAT1, OAT3, MATE1, or MATE2K. 
 
Excretion 
 
Following a single oral administration of 40 mg of [14C]-labeled baloxavir marboxil, the proportion of 
total radioactivity excreted in faeces was 80.1% of the administered dose, with the urine accounting 
for 14.7% (3.3% and 48.7% of the administered dose was excreted as baloxavir in urine and faeces 
respectively). 
 
Elimination 
 
The apparent terminal elimination half-life (t1/2,z) of baloxavir after a single oral administration of 
baloxavir marboxil is 79.1 hours in Caucasian subjects. 
 
Linearity/non-linearity 
 
Following single oral administration of baloxavir marboxil, baloxavir exhibits linear pharmacokinetics 
within the dose range of 6 mg to 80 mg. 
 
Special populations 
 
Body weight 
Body weight is a significant covariate for baloxavir pharmacokinetics based on the population 
pharmacokinetic analysis. Dosing recommendations for baloxavir marboxil are based on body weight 
(see section 4.2). 
 
Gender 
A population pharmacokinetic analysis did not identify a clinically meaningful effect of gender on the 
pharmacokinetics of baloxavir. No dose adjustment based on gender is required. 
 
Race 



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Based on a population pharmacokinetic analysis, race is a covariate on oral clearance (CL/F) of 
baloxavir in addition to body weight; however, no dose adjustment of baloxavir marboxil based on 
race is required. 
 
Age 
A population pharmacokinetic analysis using plasma baloxavir concentrations from clinical studies in 
subjects aged 12 to 64 years did not identify age as a relevant covariate on the pharmacokinetics of 
baloxavir. 
 
Paediatric population 
There are limited data on the pharmacokinetics of baloxavir in paediatric patients (< 12 years of age). 
 
Elderly 
Pharmacokinetic data collected in 181 patients aged ≥ 65 years show that exposure to baloxavir in the 
plasma was similar to that in patients aged ≥ 12 to 64 years. 
 
Renal impairment 
The effects of renal impairment on the pharmacokinetics of baloxavir marboxil or baloxavir have not 
been evaluated. Renal impairment is not expected to alter the elimination of baloxavir marboxil or 
baloxavir. 
 
Hepatic impairment 
No clinically meaningful differences in the pharmacokinetics of baloxavir were observed in patients 
with mild or moderate hepatic impairment (Child-Pugh class A and B) compared with healthy controls 
with normal hepatic function. 
 
The pharmacokinetics in patients with severe hepatic impairment have not been evaluated (see section 
4.2). 
 
5.3 Preclinical safety data 
 
Nonclinical data reveal no special hazards for humans based on conventional studies of safety 
pharmacology, acute and repeated dose toxicity.  
 
Prolongation of PT and APTT were observed in rats at exposures at least equal to the human exposure 
based on AUC0-24hr under specific experimental conditions, i.e. when fasted and when the food was 
either autoclaved or radiation-treated, resulting in vitamin K limiting/deficient conditions. These 
effects were not observed in monkey studies up to 4 weeks duration at the highest tested dose 
equivalent to 8-times the human exposure based on AUC0-24hr. They are considered to be of limited 
clinical relevance. 
 
Carcinogenicity studies have not been performed with baloxavir marboxil. 
 
The pro-drug baloxavir marboxil, and its active form, baloxavir, were not considered genotoxic as 
they tested negative in bacterial reverse mutation tests, micronucleus tests with cultured mammalian 
cells, and as baloxavir marboxil was negative in an in vivo rodent micronucleus test. 
 
Baloxavir marboxil had no effects on fertility when given orally to male and female rats at doses 
providing exposure equivalent to 5-times the human exposure based on AUC0-24hr. 

 

Baloxavir marboxil did not cause malformations in rats or rabbits. 
 
The oral embryo-foetal development study of baloxavir marboxil in rats with daily doses from 
gestation day 6 to 17 revealed no signs of maternal or foetal toxicity up to the highest tested dose 
providing exposure equivalent to 5-times the human exposure based on AUC0-24hr. 

 



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In rabbits, a dose providing exposure equivalent to 14-times the human exposure based on AUC0-24hr 
following the MHRD caused maternal toxicity resulting in miscarriages and significant increase in 
incidence of foetuses with a skeletal variation (cervical rib). The skeletal variations were reabsorbed 
during the growing process of adjacent cervical vertebra. A dose providing exposure equivalent to 6-
times the human exposure based on AUC0-24hr in rabbits was without adverse effects. 
 
The pre- and postnatal study in rats did not show drug-related adverse findings in dams and pups up to 
the highest tested dose providing exposure equivalent to 5-times the human exposure based on 
AUC0-24hr. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core 
 
Lactose monohydrate 
Croscarmellose sodium (E468) 
Povidone (K25) 
Microcrystalline cellulose (E460) 
Sodium stearyl fumarate 
 
Film-coating 
 
Hypromellose  
Talc (E553b) 
Titanium dioxide (E171) 
 
6.2 Incompatibilities 
 
Not applicable.  
 
6.3 Shelf life 
 
3 years. 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special temperature storage conditions. 
Store in the original package in order to protect from moisture.  
 
6.5 Nature and contents of container 
 
Blister pack (OPA/Aluminum foil/PVC, sealed with aluminium foil). 
 
Pack of 2 tablets. 
 
6.6 Special precautions for disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.  
 
 



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7. MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH  
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/20/1500/001 
EU/1/20/1500/002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation:  
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
  

http://www.ema.europa.eu/


14 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH 
RELEASE 

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION 

 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 

 
 



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A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Roche Pharma AG 
Emil-Barell-Strasse 1  
D-79639 Grenzach-Wyhlen  
Germany 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE  
 
Medicinal product subject to medical prescription. 
 
 
C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic Safety Update Reports (PSURs) 
 
The requirements for submission of PSURs for this medicinal product are set out in the list of 
Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC 
and any subsequent updates published on the European medicines web-portal. 
 
The marketing authorisation holder shall submit a PSUR for this product within 6 months following 
authorisation. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT   
 
• Risk management plan (RMP) 

 
The marketing authorisation holder (MAH) shall perform the required pharmacovigilance 
activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of the 
Marketing Authorisation and any agreed subsequent updates of the RMP. 
 
An updated RMP should be submitted: 
• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 
  



16 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



17 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



18 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Xofluza 20 mg film-coated tablets 
baloxavir marboxil 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 20 mg baloxavir marboxil. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
2 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Oral use 
Take both tablets as a single dose 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from moisture 
 
 



19 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH  
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/20/1500/001 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Xofluza 20 mg  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 
 
  



20 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 

Xofluza 20 mg film-coated tablets 
baloxavir marboxil 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 
  



21 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Xofluza 40 mg film-coated tablets 
baloxavir marboxil 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 40 mg baloxavir marboxil. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
2  film-coated tablets  
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use  
Oral use 
Take both tablets as a single dose 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from moisture 
 
 



22 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH  
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/20/1500/002 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Xofluza 40 mg  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 
 
  



23 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 

Xofluza 40 mg film-coated tablets 
baloxavir marboxil 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Roche Registration GmbH 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
  



24 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



25 

Package leaflet: Information for the patient 
 

Xofluza 20 mg film-coated tablets 
Xofluza 40 mg film-coated tablets  

baloxavir marboxil 
 

This medicine is subject to additional monitoring. This will allow quick identification of new 
safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
• Keep this leaflet. You may need to read it again.  
• If you have any further questions, ask your doctor or pharmacist. 
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Xofluza is and what it is used for  
2. What you need to know before you take Xofluza 
3. How to take Xofluza 
4. Possible side effects  
5. How to store Xofluza 
6. Contents of the pack and other information 
 
 
1. What Xofluza is and what it is used for 
 
What Xofluza is 
 
Xofluza contains baloxavir marboxil. This is a type of antiviral medicine called a ‘cap-dependent 
endonuclease inhibitor’.  
 
Xofluza is used for treating and preventing influenza. This medicine stops the influenza virus from 
spreading in the body and helps shorten the time to recovery from symptoms.  
 
What Xofluza is used for 
 
• Xofluza is used to treat influenza in patients aged 12 years and above who have had influenza 

symptoms for less than 48 hours. 
• Xofluza is used to prevent influenza in individuals aged 12 years and above who have been in 

close contact with someone who is known or suspected to have influenza. 
 
 
2. What you need to know before you take Xofluza 
 
Do not take Xofluza if: 
 
• you are allergic to baloxavir marboxil or any of the other ingredients of this medicine (listed in 

section 6). 
 
Warnings and precautions  
 
Talk to your doctor or pharmacist before taking Xofluza. 



26 

 
Children and adolescents 
 
Do not give this medicine to children below 12 years of age. This is because the effects of Xofluza in 
this age group are not known.  
 
Other medicines and Xofluza 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines.  
 
Do not take Xofluza with:  
• laxatives, antacids or oral supplements containing iron, zinc, selenium, calcium, or magnesium 
 
The medicines listed above may decrease the effect of Xofluza.  
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, as a 
precautionary measure it is preferable to avoid the use of Xofluza. Ask your doctor or pharmacist for 
advice before taking this medicine. 
 
Driving and using machines 
 
Xofluza is not likely to change your ability to drive and to use machines. 
 
Xofluza contains lactose 
 
Xofluza contains lactose (a type of sugar). If you have been told by your doctor that you have an 
intolerance to some sugars, talk to your doctor before taking this medicine. 
 
Xofluza contains sodium 
 
This medicine contains less than 23 mg of sodium per tablet, that is to say essentially ꞌsodium-free’. 
 
 
3. How to take Xofluza 
 
Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
How to take Xofluza 
 
For treatment of influenza, take Xofluza as a single dose as soon as possible within 48 hours of your 
flu symptoms starting. 
 
For prevention of influenza, take Xofluza as a single dose as soon as possible within 48 hours 
following exposure to an infected person. 
 
How much Xofluza to take 
 
Your dose of Xofluza depends on how much you weigh. Your doctor or pharmacist will tell you how 
much to take. 
 



27 

Your weight 
 

Xofluza dose 

Up to 80 kg 
 

Single dose of 40 mg taken as 
- 2 x 20 mg tablets 

 
80 kg or more 
 

Single dose of 80 mg taken as  
- 2 x 40 mg tablets 

 
 
Xofluza can be taken with or without food. Take all the tablets with some water.   
 
If you take more Xofluza than you should 
 
If you accidentally take more of this medicine than you should, talk to your doctor or pharmacist for 
advice. 
 
If you forget to take Xofluza 
 
If you forget to take some or all of your dose, take it as soon as possible.  
 
For the treatment of influenza, Xofluza should be taken within 48 hours of your flu symptoms starting. 
 
For the prevention of influenza, Xofluza should be taken within 48 hours of close contact with 
someone who is known or suspected to have flu. 
 
 
4. Possible side effects 
Like all medicines, it is possible for this medicine to cause side effects, although not everybody gets 
them. 
 

Get medical help immediately if you get any of the following serious side effects: 
• Severe allergic reaction (anaphylaxis), with signs such as swelling of the face or skin, itchy 

rashes, low blood pressure and difficulty breathing 
 

The frequency of these side effects cannot be estimated from the available data. 
 
Other possible side effects: 
The following side effect is uncommon (this can affect up to 1 in every 100 patients): 

• Itchy rash 
 

Reporting of side effects 
 
If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this 
leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. 
By reporting side effects you can help provide more information on the safety of this medicine. 
 
 
5. How to store Xofluza 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the blister and carton after ‘EXP’. 
The expiry date refers to the last day of that month. 
 
This medicine does not need any special temperature storage conditions. 
 
Store in the original package in order to protect from moisture. 

https://www.ema.europa.eu/documents/template-form/appendix-v-adverse-drug-reaction-reporting-details_en.doc


28 

 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Xofluza contains  
 
• The active substance is baloxavir marboxil.  
• Each 20 mg film-coated tablet contains 20 mg baloxavir marboxil. Each 40 mg film-coated 

tablet contains 40 mg baloxavir marboxil. 
• The other ingredients are lactose monohydrate, croscarmellose sodium (E468), povidone, 

microcrystalline cellulose (E460), sodium stearyl fumarate in the tablet core, and hypromellose, 
talc (E553b) and titanium dioxide (E171) in the film-coating. 
 

What Xofluza looks like and contents of the pack 
 
Xofluza 20 mg tablets are white to light yellow, oblong shaped film-coated tablets with “  772” 
marked on one side and “20” on the other side. 
 
Xofluza 20 mg film-coated tablets are available in blister packs of 2.  
 
Xofluza 40 mg tablets are white to light yellow, oblong shaped film-coated tablets with “BXM40” 
marked on one side.  
 
Xofluza 40 mg film-coated tablets are available in blister packs of 2. 
 
Marketing Authorisation Holder 
 
Roche Registration GmbH 
Emil-Barell-Strasse 1 
79639 Grenzach-Wyhlen 
Germany 
 
Manufacturer 
 
Roche Pharma AG 
Emil-Barell-Strasse 1 
D-79639 Grenzach-Wyhlen 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
N.V. Roche S.A. 
Tél/Tel: +32 (0) 2 525 82 11 
 

Lietuva 
UAB “Roche Lietuva” 
Tel: +370 5 2546799 
 

България 
Рош България ЕООД 
Тел: +359 2 818 44 44 
 

Luxembourg/Luxemburg 
(Voir/siehe Belgique/Belgien) 
 

Česká republika 
Roche s. r. o. 
Tel: +420 - 2 20382111 

Magyarország 
Roche (Magyarország) Kft. 
Tel: +36 - 23 446 800 



29 

Danmark  
Roche a/s 
Tlf: +45 - 36 39 99 99 
 

Malta 
(See Ireland) 
 

Deutschland 
Roche Pharma AG 
Tel: +49 (0) 7624 140 
 

Nederland 
Roche Nederland B.V. 
Tel: +31 (0) 348 438050 
 

Eesti 
Roche Eesti OÜ 
Tel: + 372 - 6 177 380 
 

Norge 
Roche Norge AS 
Tlf: +47 - 22 78 90 00 
 

Ελλάδα 
Roche (Hellas) A.E.  
Τηλ: +30 210 61 66 100 
 

Österreich 
Roche Austria GmbH 
Tel: +43 (0) 1 27739 
 

España 
Roche Farma S.A. 
Tel: +34 - 91 324 81 00  
 

Polska 
Roche Polska Sp.z o.o. 
Tel: +48 - 22 345 18 88 
 

France 
Roche 
Tél: +33  (0)1 47 61 40 00 
 

Portugal 
Roche Farmacêutica Química, Lda 
Tel: +351 - 21 425 70 00 
 

Hrvatska 
Roche d.o.o. 
Tel: + 385 1 47 22 333 
 

România 
Roche România S.R.L. 
Tel: +40 21 206 47 01 
 

Ireland 
Roche Products (Ireland) Ltd. 
Tel: +353 (0) 1 469 0700 
 

Slovenija 
Roche farmacevtska družba d.o.o. 
Tel: +386 - 1 360 26 00 
 

Ísland  
Roche a/s 
c/o Icepharma hf 
Sími: +354 540 8000 
 

Slovenská republika  
Roche Slovensko, s.r.o. 
Tel: +421 - 2 52638201 
 

Italia 
Roche S.p.A. 
Tel: +39 - 039 2471 
 
 

Suomi/Finland 
Roche Oy  
Puh/Tel: +358 (0) 10 554 500 
 

Kύπρος  
Γ.Α.Σταμάτης & Σια Λτδ. 
Τηλ: +357 - 22 76 62 76 
 

Sverige 
Roche AB 
Tel: +46 (0) 8 726 1200 
 

Latvija 
Roche Latvija SIA 
Tel: +371 - 6 7039831 
 

United Kingdom 
Roche Products Ltd. 
Tel: +44 (0) 1707 366000 
 

This leaflet was last revised in  
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 

http://www.ema.europa.eu/

	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT  
	A. LABELLING
	B. PACKAGE LEAFLET