Dificlir

1 

ANNEX I 

SUMMARY OF PRODUCT CHARACTERISTICS 



2 

1. NAME OF THE MEDICINAL PRODUCT 
 
DIFICLIR 200 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains 200 mg of fidaxomicin. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet. 
 
Capsule shaped tablets of 14 mm, white to off-white in colour, debossed with “FDX” on one side and 
“200” on the other side. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
DIFICLIR film-coated tablets is indicated for the treatment of Clostridioides difficile infections (CDI) 
also known as C. difficile-associated diarrhoea (CDAD) in adult and paediatric patients with a body 
weight of at least 12.5 kg (see section 4.2 and 5.1). 
 
Consideration should be given to official guidelines on the appropriate use of antibacterial agents. 
 
4.2 Posology and method of administration 
 
Posology 
 
Adults 
The recommended dose is 200 mg (one tablet) administered twice daily (once every 12 hours) for 
10 days. 
 
DIFICLIR 40 mg/ml granules for oral suspension may be used in adult patients with difficulties in 
swallowing tablets. 
 
Special populations 
 
Elderly population 
No dose adjustment is considered necessary (see section 5.2). 
 
Renal impairment 
No dose adjustment is considered necessary. Due to the limited clinical data in this population, 
fidaxomicin should be used with caution in patients with severe renal impairment (see sections 4.4 and 
5.2). 
 
Hepatic impairment 
No dose adjustment is considered necessary. Due to the limited clinical data in this population, 
fidaxomicin should be used with caution in patients with moderate to severe hepatic impairment (see 
sections 4.4 and 5.2). 
 
Paediatric population 



3 

The recommended dose in paediatric patients weighing at least 12.5 kg is 200 mg administered twice 
daily (once every 12 hours) for 10 days using the film-coated tablets or the granules for oral 
suspension. 
  
Reduced doses are recommended for patients with a body weight of less than 12.5 kg. See the SmPC 
of DIFICLIR 40 mg/ml granules for oral suspension. 
 
Method of administration 
 
DIFICLIR is intended for oral use. 
The film-coated tablets should be administered whole with water. 
They can be taken with or without food. 
 
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 
 
Hypersensitivity reactions  
 
Hypersensitivity reactions including severe angioedema have been reported (see section 4.8). If a 
severe allergic reaction occurs during treatment with fidaxomicin, the medicinal product should be 
discontinued and appropriate measures taken. 
Some patients with hypersensitivity reactions reported a history of allergy to macrolides. Fidaxomicin 
should be used with caution in patients with a known macrolides allergy. 
 
Renal and hepatic impairment 
 
Due to limited clinical data, fidaxomicin should be used with caution in patients with severe renal 
impairment or moderate to severe hepatic impairment (see section 5.2). 
 
Pseudomembranous colitis, fulminant or life threatening CDI 
 
Due to limited clinical data, fidaxomicin should be used with caution in patients with 
pseudomembranous colitis, fulminant or life threatening CDI. 
 
Co-administration of potent P-glycoprotein inhibitors 
 
Co-administration of potent P-glycoprotein inhibitors such as cyclosporine, ketoconazole, 
erythromycin, clarithromycin, verapamil, dronedarone and amiodarone is not recommended (see 
sections 4.5 and 5.2). In case fidaxomicin is administered concomitantly with potent P-glycoprotein 
inhibitors, caution is advised. 
 
Paediatric population 
 
Only one paediatric patient below 6 months of age has been exposed to fidaxomicin in clinical trials. 
Therefore, patients below 6 months of age should be treated with caution. 
 
Testing for C. difficile colonization or toxin is not recommended in children younger than 1 year due 
to high rate of asymptomatic colonisation unless severe diarrhoea is present in infants with risk factors 
for stasis such as Hirschsprung disease, operated anal atresia or other severe motility disorders. 
Alternative aetiologies should always be sought and C. difficile enterocolitis be proven. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Effect of P-gp inhibitors on fidaxomicin 



4 

 
Fidaxomicin is a substrate of P-gp. Co-administration of single doses of the P-gp inhibitor 
cyclosporine A and fidaxomicin in healthy volunteers, resulted in a 4- and 2-fold increase in 
fidaxomicin Cmax and AUC, respectively and in a 9.5 and 4-fold increase in Cmax and AUC, 
respectively, of the main active metabolite OP-1118. As the clinical relevance of this increase in 
exposure is unclear, co-administration of potent inhibitors of P-gp, such as cyclosporine, ketoconazole, 
erythromycin, clarithromycin, verapamil, dronedarone and amiodarone is not recommended (see 
sections 4.4 and 5.2). 
 
Effect of fidaxomicin on P-gp substrates 
 
Fidaxomicin may be a mild to moderate inhibitor of intestinal P-gp. 
Fidaxomicin (200 mg twice daily) had a small but not clinically relevant effect on digoxin exposure. 
However, a larger effect on P-gp substrates with lower bioavailability more sensitive to intestinal P-gp 
inhibition such as dabigatran etexilat cannot be excluded. 
 
Effect of fidaxomicin on other transporters 
 
Fidaxomicin does not have a clinically significant effect on the exposure of rosuvastatin, a substrate 
for the transporters OATP2B1 and BCRP. Co-administration of 200 mg fidaxomicin twice daily with 
a single dose of 10 mg rosuvastatin to healthy subjects did not have a clinically significant effect on 
the AUCinf of rosuvastatin.  
 
Paediatric population 
 
Interaction studies have only been performed in adults. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no data available from the use of fidaxomicin in pregnant women. Animal studies did not 
indicate direct or indirect harmful effects with respect to reproductive toxicity. As a precautionary 
measure, it is preferable to avoid the use of fidaxomicin during pregnancy. 
 
Breast-feeding 
 
It is unknown whether fidaxomicin and its metabolites are excreted in human milk. Although no 
effects on the breastfed newborns/infants are anticipated since the systemic exposure to fidaxomicin is 
low, a risk to the newborns/infants cannot be excluded. A decision must be made whether to 
discontinue breast-feeding or to discontinue/abstain from fidaxomicin therapy, taking into account the 
benefit of breast feeding for the child and the benefit of therapy for the woman.  
 
Fertility 
 
Fidaxomicin had no effects on fertility when evaluated in rats (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
DIFICLIR has no or negligible influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The most common adverse reactions are vomiting (1.2%), nausea (2.7%) and constipation (1.2%). 
 



5 

Tabulated list of adverse reactions 
 
Table 1 displays adverse reactions associated with twice daily administration of fidaxomicin in the 
treatment of C. difficile infection, reported in at least two patients, presented by system organ class. 
 
The frequency of adverse reactions is defined as follows: 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), not 
known (cannot be estimated from the available data). Within each frequency grouping, adverse 
reactions are presented in order of decreasing seriousness. 
 
Table 1: Adverse reactions 

MedDRA 
system organ 
class 

Common Uncommon Frequency not known 

Immune 
system 
disorders 

 rash,  
pruritus 

hypersensitivity reactions 
(angioedema, dyspnea) 

Metabolism 
and nutrition 
disorders 

 decreased appetite  

Nervous 
system 
disorders 

 dizziness,  
headache,  
dysgeusia 

 

Gastrointestinal 
disorders 

vomiting,  
nausea,  
constipation 

abdominal distention,  
flatulence,  
dry mouth  

 

 
Description of selected adverse reactions 
 
Acute hypersensitivity reactions, such as angioedema and dyspnea, have been reported during 
post-marketing (see section 4.3 and 4.4).  
 
Paediatric population 
 
The safety and efficacy of fidaxomicin has been evaluated in 136 patients from birth to less than 18 
years of age. Frequency, type and severity of adverse reactions in children are expected to be the same 
as in adults. In addition to the ADRs shown in table 1, two cases of urticaria were reported. 
 
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 
 
No adverse reactions for acute overdose have been reported during clinical studies or from 
post-marketing data.  However, the potential for adverse reactions cannot be ruled out and general 
supportive measures are recommended. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


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Pharmacotherapeutic group: Antidiarrheals, intestinal antiinflammatory/antiinfective agents, 
antibiotics, ATC code: A07AA12 
 
Mechanism of action 
 
Fidaxomicin is an antibiotic belonging to the macrocyclic class of antibacterials. 
Fidaxomicin is bactericidal and inhibits RNA synthesis by bacterial RNA polymerase. It interferes 
with RNA polymerase at a distinct site from that of rifamycins. Inhibition of the Clostridial RNA 
polymerase occurs at a concentration 20-fold lower than that for the E. coli enzyme (1 μM vs. 20 μM), 
partly explaining the significant specificity of fidaxomicin activity. Fidaxomicin has been shown to 
inhibit C. difficile sporulation in vitro.  
 
Pharmacokinetic/Pharmacodynamic (PK/PD) relationship 
 
Fidaxomicin is a locally acting drug. As a topical agent, systemic PK/PD relationships cannot be 
established, however in vitro data show fidaxomicin to have time-dependent bactericidal activity and 
suggest time over MIC may be the parameter most predicative of clinical efficacy. 
 
Breakpoints 
 
Fidaxomicin is a topically acting drug that cannot be used to treat systemic infections; therefore the 
establishment of a clinical breakpoint is not relevant. The epidemiological cut-off value for 
fidaxomicin and C. difficile, distinguishing the wild-type population from isolates with acquired 
resistance traits, is ≥1.0 mg/L. 
 
Antimicrobial spectrum 
 
Fidaxomicin is a narrow spectrum antimicrobial drug with bactericidal activity against C. difficile. 
Fidaxomicin has an MIC90  of 0.25 mg/L versus C. difficile, and its main metabolite, OP-1118, has an 
MIC90  of 8 mg/L. Gram negative organisms are intrinsically not susceptible to fidaxomicin.  
 
Effect on the intestinal flora 
 
Studies have demonstrated that fidaxomicin treatment did not affect Bacteroides concentrations or 
other major components of the microbiota in the faeces of CDI patients.  
 
Mechanism of resistance 
 
There are no known transferable elements that confer resistance to fidaxomicin. Also no cross-
resistance has been discovered with any other antibiotic class including β-lactams, macrolides, 
metronidazole, quinolones, rifampin, and vancomycin. Specific mutations of RNA polymerase are 
associated with reduced susceptibility to fidaxomicin. 
 
Clinical efficacy in adults 
 
In the pivotal clinical trials in adult patients the rate of recurrence in the 30 days following treatment 
was assessed as a secondary endpoint. The rate of recurrence (including relapses) was significantly 
lower with fidaxomicin (14.1% versus 26.0% with a 95% CI of [-16.8%, -6.8%]), however these trials 
were not prospectively designed to prove prevention of reinfection with a new strain. 
 
Description of the patient population in clinical trials in adults 
In the two pivotal clinical trials of patients with CDI, 47.9% (479/999) of patients (per protocol 
population) were ≥65 years of age and 27.5% (275/999) of patients were treated with concomitant 
antibiotics during the study period. Twenty-four percent of patients met at least one of the following 
three criteria at baseline for scoring severity: body temperature >38.5°C, leukocyte count >15,000, or 
creatinine value ≥1.5 mg/dl. Patients with fulminant colitis and patients with multiple episodes 



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(defined as more than one prior episode within the previous 3 months) of CDI were excluded from the 
studies. 
 
Paediatric population 
 
 The safety and efficacy of fidaxomicin in paediatric patients from birth to less than 18 years of age 
was investigated in a multicentre, investigator-blind, randomised, parallel group study where 148 
patients were randomised to either fidaxomicin or vancomycin in a 2:1 ratio. A total of 30, 49, 40 and 
29 patients were randomised in the age groups of birth to < 2 years, 2 to < 6 years, 6 to < 12 years and 
12 to < 18 years, respectively. Confirmed clinical response 2 days after end of treatment was similar 
between the fidaxomicin and vancomycin group (77.6% vs 70.5% with a point difference of 7.5% and 
95% CI for the difference of [-7.4%, 23.9%]). The rate of recurrence 30 days after end of treatment 
was numerically lower with fidaxomicin (11.8% vs 29.0%), but the rate difference is not statistically 
significant (point difference of -15.8% and 95% CI for the difference of [-34.5%, 0.5%]). Both 
treatments had a similar safety profile. 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
The bioavailability in humans is unknown. In healthy adults, Cmax is approximately 9.88 ng/ml and 
AUC0-t  is 69.5 ng•hr/ml following administration of 200 mg fidaxomicin, with a T max of 1.75 hours. In 
CDI patients, average peak plasma levels of fidaxomicin and its main metabolite OP-1118 tend to be 
2- to 6-fold higher than in healthy adults. There was very limited accumulation of fidaxomicin or 
OP-1118 in plasma following administration of 200 mg fidaxomicin every 12 hours for 10 days. 
 
Cmax for fidaxomicin and OP-1118 in plasma were 22% and 33% lower following a high fat meal vs 
fasting, but the extent of exposure (AUC0-t ) was equivalent. 
 
Fidaxomicin and the metabolite OP-1118 are substrates of P-gp. 
In vitro studies showed that fidaxomicin and the metabolite OP-1118 are inhibitors of the transporters 
BCRP, MRP2 and OATP2B1, but were not found to be substrates. Under conditions of clinical use, 
fidaxomicin has no clinically relevant effect on the exposure of rosuvastatin, a substrate for OATP2B1 
and BCRP (see section 4.5). The clinical relevance of MRP2 inhibition is not yet known. 
 
Distribution 
 
The volume of distribution in humans is unknown, due to very limited absorption of fidaxomicin. 
 
Biotransformation 
 
No extensive analysis of metabolites in plasma has been performed, due to low levels of systemic 
absorption of fidaxomicin. A main metabolite, OP-1118, is formed through hydrolysis of the 
isobutyryl ester. In vitro metabolism studies showed that the formation of OP-1118 is not dependent 
on CYP450 enzymes. This metabolite also shows antimicrobial activity (see section 5.1). 
 
Fidaxomicin does not induce or inhibit CYP450 enzymes in vitro. 
 
Elimination 
 
Following a single dose of 200 mg fidaxomicin, the majority of the administered dose (over 92%) was 
recovered in the stool as fidaxomicin or its metabolite OP-1118 (66%). The main elimination 
pathways of systemically available fidaxomicin have not been characterized. Elimination through 
urine is negligible (<1%). Only very low levels of OP-1118 and no fidaxomicin was detectable in 
human urine. The half life of fidaxomicin is approximately 8-10 h.  
 
Special populations 



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Elderly 
Plasma levels appear to be elevated in the elderly (age ≥ 65 years). Fidaxomicin and OP-1118 levels 
were approximately 2 times higher in patients ≥ 65 years compared to patients < 65 years. This 
difference is not considered clinically relevant. 
 
Paediatric population 
After administration of film-coated tablets, the mean (SD) plasma levels in the paediatric patients from 
6 to less than 18 years was 48.53 (69.85) ng/ml and 143.63 (286.31) ng/ml for fidaxomicin and its 
main metabolite OP-1118, respectively, at 1 to 5 hours postdose. 
 
Inflammatory bowel disease 
Data from an open label, single arm study in adult CDI patients with concomitant inflammatory bowel 
disease (IBD) indicated no major difference in plasma concentrations of fidaxomicin or its main 
metabolite OP-1118 in patients with IBD as compared with patients without IBD in other studies. The 
maximum fidaxomicin and OP-1118 plasma levels in CDI patients with concomitant IBD were within 
the range of levels found in CDI patients without IBD. 
 
Hepatic impairment 
Limited data from adult patients with an active history of chronic hepatic cirrhosis in the Phase 3 
studies showed that median plasma levels of fidaxomicin and OP-1118 may be approximately 2- and 
3-fold higher, respectively, than in non-cirrhotic patients. 
 
Renal impairment 
Limited data from adult patients suggest that there is no major difference in plasma concentration of 
fidaxomicin or OP-1118 between patients with reduced renal function (creatinine clearance 
< 50 ml/min) and patients with normal renal function (creatinine clearance ≥ 50 ml/min). 
 
Gender, weight and race 
Limited data suggest that gender, weight and race do not have any major influence on the plasma 
concentration of fidaxomicin or OP-1118. 
 
5.3 Preclinical safety data 
 
Nonclinical data revealed no special hazard for humans based on conventional studies of safety 
pharmacology, repeat dose toxicity, genotoxicity, and reproductive toxicity. 
 
Reproductive and fertility parameters showed no statistically significant differences in rats treated with 
fidaxomicin at doses up to 6.3 mg/kg/day (intravenous). 
 
No target organs for toxicity were observed in juvenile animals, and no important potential risks have 
been observed in the nonclinical studies that might be relevant for paediatric patients. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Core tablets: 
 
Microcrystalline cellulose 
Pregelatinised starch (maize) 
Hydroxypropyl cellulose 
Butylated hydroxytoluene 
Sodium starch glycolate 
Magnesium stearate 
 



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Coating: 
 
Polyvinyl alcohol 
Titanium dioxide (E171) 
Talc 
Polyethylene glycol 
Lecithin (soy) 
 
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 storage conditions. 
 
6.5 Nature and contents of container  
 
100 x 1 film-coated tablet in alu/alu perforated unit dose blisters. 
20 x 1 film-coated tablet in alu/alu perforated unit dose blisters. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal  
 
Any unused product or waste material should be disposed of in accordance with local requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Astellas Pharma Europe B.V. 
Sylviusweg 62 
2333 BE Leiden 
The Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/733/003-004 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 5 December 2011 
Date of latest renewal: 22 August 2016 
 
 
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/


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1. NAME OF THE MEDICINAL PRODUCT 
 
DIFICLIR 40 mg/ml granules for oral suspension 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml of oral suspension contains 40 mg of fidaxomicin when reconstituted with water. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Granules for oral suspension. 
 
White to yellowish white granules. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
DIFICLIR granules for oral suspension is indicated for the treatment of Clostridioides  difficile 
infections (CDI) also known as C. difficile-associated diarrhoea (CDAD) in adults and paediatric 
patients from birth to < 18 years of age (see section 4.2 and 5.1). 
 
Consideration should be given to official guidelines on the appropriate use of antibacterial agents. 
 
4.2 Posology and method of administration 
 
Posology 
 
Adults 
The recommended dose is 200 mg (5 ml) administered twice daily (once every 12 hours) for 10 days. 
 
Special populations 
 
Renal impairment 
No dose adjustment is considered necessary. Due to the limited clinical data in this population, 
fidaxomicin should be used with caution in patients with severe renal impairment (see sections 4.4 and 
5.2). 
 
Hepatic impairment 
No dose adjustment is considered necessary. Due to the limited clinical data in this population, 
fidaxomicin should be used with caution in patients with moderate to severe hepatic impairment (see 
sections 4.4 and 5.2).  
 
Paediatric population 
For appropriate dosing in the paediatric population, granules for oral suspension or film-coated tablets 
may be used. 
 
The recommended dose in paediatric patients weighing at least 12.5 kg is 200 mg (5 ml oral 
suspension) administered twice daily (once every 12 hours) for 10 days.  
 
The recommended dose of the oral suspension in paediatric patients, by body weight, to be 
administered twice daily (once every 12 hours) for 10 days, is presented in the table below.  



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Table 1: Dosing instruction for the oral suspension 

Weight band of 
patient 

 

Mg per dose 
(every 12 hours) 

Volume of fidaxomicin oral 
suspension  

(every 12 hours) 
< 4.0 kg 40 mg 1 ml 

4.0 - < 7.0 kg 80 mg 2 ml 
7.0 - < 9.0 kg 120 mg 3 ml 

9.0 - < 12.5 kg 160 mg 4 ml 
≥ 12.5 kg 200 mg 5 ml 

 
Method of administration 
 
DIFICLIR is intended for oral use (by ingestion or via an enteral feeding tube using a syringe, if 
necessary). 
The granules for oral suspension can be taken with or without food. 
 
For instructions on reconstitution of the medicinal product before administration and administration 
via an enteral feeding tube, see section 6.6. 
 
Instructions for use for the oral suspension: 
The bottle should be taken from the refrigerator 15 minutes prior to administration and approximately 
10 times gently shaken. Once reconstituted, the oral suspension should only be administered using the 
oral syringe and adaptor provided by the healthcare professional. The bottle should be stored in a 
refrigerator after each use. 
 
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 
 
Hypersensitivity reactions  
 
Hypersensitivity reactions including severe angioedema have been reported (see section 4.8). If a 
severe allergic reaction occurs during treatment with fidaxomicin, the medicinal product should be 
discontinued and appropriate measures taken. 
Some patients with hypersensitivity reactions reported a history of allergy to macrolides. Fidaxomicin 
should be used with caution in patients with a known macrolides allergy. 
 
Renal and hepatic impairment 
 
Due to limited clinical data, fidaxomicin should be used with caution in patients with severe renal 
impairment or moderate to severe hepatic impairment (see section 5.2). 
 
Pseudomembranous colitis, fulminant or life threatening CDI 
 
Due to limited clinical data, fidaxomicin should be used with caution in patients with 
pseudomembranous colitis, fulminant or life threatening CDI. 
 
Co-administration of potent P-glycoprotein inhibitors 
 
Co-administration of potent P-glycoprotein inhibitors such as cyclosporine, ketoconazole, 
erythromycin, clarithromycin, verapamil, dronedarone and amiodarone is not recommended (see 
sections 4.5 and 5.2). In case fidaxomicin is administered concomitantly with potent P-glycoprotein 
inhibitors, caution is advised. 



12 

 
DIFICLIR contains sodium 
 
DIFICLIR contains less than 1 mmol sodium (23 mg) per 5 ml suspension, that is to say essentially 
‘sodium-free’. 
 
Paediatric population 
 
Only one paediatric patient below 6 months of age and no patients with a body weight below 4 kg 
have been exposed to fidaxomicin in clinical trials. Therefore, fidaxomicin should be used with 
caution in these patients. 
 
Testing for C. difficile colonization or toxin is not recommended in children younger than 1 year due 
to high rate of asymptomatic colonisation unless severe diarrhoea is present in infants with risk factors 
for stasis such as Hirschsprung disease, operated anal atresia or other severe motility disorders. 
Alternative aetiologies should always be sought and C. difficile enterocolitis be proven. 
 
Sodium benzoate content 
This medicine contains 2.5 mg sodium benzoate (E 211) in each ml oral suspension. Sodium benzoate 
(E 211) may increase jaundice in newborn babies (up to 4 weeks old). 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Effect of P-gp inhibitors on fidaxomicin 
 
Fidaxomicin is a substrate of P-gp. Co-administration of single doses of the P-gp inhibitor 
cyclosporine A and fidaxomicin in healthy volunteers, resulted in a 4- and 2-fold increase in 
fidaxomicin Cmax and AUC, respectively and in a 9.5 and 4-fold increase in Cmax and AUC, 
respectively, of the main active metabolite OP-1118. As the clinical relevance of this increase in 
exposure is unclear, co-administration of potent inhibitors of P-gp, such as cyclosporine, ketoconazole, 
erythromycin, clarithromycin, verapamil, dronedarone and amiodarone is not recommended (see 
section 4.4 and 5.2). 
 
Effect of fidaxomicin on P-gp substrates 
 
Fidaxomicin may be a mild to moderate inhibitor of intestinal P-gp. 
Fidaxomicin (200 mg twice daily) had a small but not clinically relevant effect on digoxin exposure. 
However, a larger effect on P-gp substrates with lower bioavailability more sensitive to intestinal P-gp 
inhibition such as dabigatran etexilat cannot be excluded. 
 
Effect of fidaxomicin on other transporters 
 
Fidaxomicin does not have a clinically significant effect on the exposure of rosuvastatin, a substrate 
for the transporters OATP2B1 and BCRP. Co-administration of 200 mg fidaxomicin twice daily with 
a single dose of 10 mg rosuvastatin to healthy subjects did not have a clinically significant effect on 
the AUCinf of rosuvastatin.  
 
Paediatric population 
 
Interaction studies have only been performed in adults. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 



13 

There are no data available from the use of fidaxomicin in pregnant women. Animal studies did not 
indicate direct or indirect harmful effects with respect to reproductive toxicity. As a precautionary 
measure, it is preferable to avoid the use of fidaxomicin during pregnancy. 
 
Breast-feeding 
 
It is unknown whether fidaxomicin and its metabolites are excreted in human milk. Although no 
effects on the breastfed newborns/infants are anticipated since the systemic exposure to fidaxomicin is 
low, a risk to the newborns/infants cannot be excluded. A decision must be made whether to 
discontinue breast-feeding or to discontinue/abstain from fidaxomicin therapy, taking into account the 
benefit of breast feeding for the child and the benefit of therapy for the woman.  
 
Fertility 
 
Fidaxomicin had no effects on fertility when evaluated in rats (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
DIFICLIR has no or negligible influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The most common adverse reactions are vomiting (1.2%), nausea (2.7%) and constipation (1.2%). 
 
Tabulated list of adverse reactions 
 
Table 2 displays adverse reactions associated with twice daily administration of fidaxomicin in the 
treatment of C. difficile infection, reported in at least two patients, presented by system organ class. 
 
The frequency of adverse reactions is defined as follows: 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), not 
known (cannot be estimated from the available data). Within each frequency grouping, adverse 
reactions are presented in order of decreasing seriousness. 
 
Table 2: Adverse reactions 

MedDRA 
system organ 
class 

Common Uncommon Frequency not known 

Immune 
system 
disorders 

 rash,  
pruritus 

hypersensitivity reactions 
(angioedema, dyspnea) 

Metabolism 
and nutrition 
disorders 

 decreased appetite  

Nervous 
system 
disorders 

 dizziness,  
headache,  
dysgeusia 

 

Gastrointestinal 
disorders 

vomiting,  
nausea,  
constipation 

abdominal distention,  
flatulence,  
dry mouth  

 

 
Description of selected adverse reactions 
 



14 

Acute hypersensitivity reactions, such as angioedema and dyspnea, have been reported during 
post-marketing (see section 4.3 and 4.4).  
 
Paediatric population 
 
The safety and efficacy of fidaxomicin has been evaluated in 136 patients from birth to less than 18 
years of age. Frequency, type and severity of adverse reactions in children are expected to be the same 
as in adults. In addition to the ADRs shown in table 2, two cases of urticaria were reported. 
 
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 
 
No adverse reactions for acute overdose have been reported during clinical studies or from 
post-marketing data.  However, the potential for adverse reactions cannot be ruled out and general 
supportive measures are recommended. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antidiarrheals, intestinal antiinflammatory/antiinfective agents, 
antibiotics, ATC code: A07AA12 
 
Mechanism of action 
 
Fidaxomicin is an antibiotic belonging to the macrocyclic class of antibacterials. 
Fidaxomicin is bactericidal and inhibits RNA synthesis by bacterial RNA polymerase. It interferes 
with RNA polymerase at a distinct site from that of rifamycins. Inhibition of the Clostridial RNA 
polymerase occurs at a concentration 20-fold lower than that for the E. coli enzyme (1 μM vs. 20 μM), 
partly explaining the significant specificity of fidaxomicin activity. Fidaxomicin has been shown to 
inhibit C. difficile sporulation in vitro.  
 
Pharmacokinetic/Pharmacodynamic (PK/PD) relationship 
 
Fidaxomicin is a locally acting drug. As a topical agent, systemic PK/PD relationships cannot be 
established, however in vitro data show fidaxomicin to have time-dependent bactericidal activity and 
suggest time over MIC may be the parameter most predicative of clinical efficacy. 
 
Breakpoints 
 
Fidaxomicin is a topically acting drug that cannot be used to treat systemic infections; therefore the 
establishment of a clinical breakpoint is not relevant. The epidemiological cut-off value for 
fidaxomicin and C. difficile, distinguishing the wild-type population from isolates with acquired 
resistance traits, is ≥1.0 mg/L. 
 
Antimicrobial spectrum 
 
Fidaxomicin is a narrow spectrum antimicrobial drug with bactericidal activity against C. difficile. 
Fidaxomicin has an MIC90  of 0.25 mg/L versus C. difficile, and its main metabolite, OP-1118, has an 
MIC90  of 8 mg/L. Gram negative organisms are intrinsically not susceptible to fidaxomicin.  

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


15 

Effect on the intestinal flora 

Studies have demonstrated that fidaxomicin treatment did not affect Bacteroides concentrations or 
other major components of the microbiota in the faeces of CDI patients.  

Mechanism of resistance 

There are no known transferable elements that confer resistance to fidaxomicin. Also no cross-
resistance has been discovered with any other antibiotic class including β-lactams, macrolides, 
metronidazole, quinolones, rifampin, and vancomycin. Specific mutations of RNA polymerase are 
associated with reduced susceptibility to fidaxomicin. 

Clinical efficacy in adults 

In the pivotal clinical trials in adult patients using the tablet formulation the rate of recurrence in the 
30 days following treatment was assessed as a secondary endpoint. The rate of recurrence (including 
relapses) was significantly lower with fidaxomicin (14.1% versus 26.0% with a 95% CI of [-16.8%, -
6.8%]), however these trials were not prospectively designed to prove prevention of reinfection with a 
new strain. 

Description of the patient population in clinical trials in adults 
In the two pivotal clinical trials of patients with CDI, 47.9% (479/999) of patients (per protocol 
population) were ≥65 years of age and 27.5% (275/999) of patients were treated with concomitant 
antibiotics during the study period. Twenty-four percent of patients met at least one of the following 
three criteria at baseline for scoring severity: body temperature >38.5°C, leukocyte count >15,000, or 
creatinine value ≥1.5 mg/dl. Patients with fulminant colitis and patients with multiple episodes 
(defined as more than one prior episode within the previous 3 months) of CDI were excluded from the 
studies. 

Paediatric population 

The safety and efficacy of fidaxomicin in paediatric patients from birth to less than 18 years of age 
was investigated in a multicentre, investigator-blind, randomised, parallel group study where 148 
patients were randomised to either fidaxomicin or vancomycin in a 2:1 ratio. A total of 30, 49, 40 and 
29 patients were randomised in the age groups of birth to < 2 years, 2 to < 6 years, 6 to < 12 years and 
12 to < 18 years, respectively. Confirmed clinical response 2 days after end of treatment was similar 
between the fidaxomicin and vancomycin group (77.6% vs 70.5% with a point difference of 7.5% and 
95% CI for the difference of [-7.4%, 23.9%]). The rate of recurrence 30 days after end of treatment 
was numerically lower with fidaxomicin (11.8% vs 29.0%), but the rate difference is not statistically 
significant (point difference of -15.8% and 95% CI for the difference of [-34.5%, 0.5%]). Both 
treatments had a similar safety profile. 

5.2 Pharmacokinetic properties 

Absorption 

The bioavailability in humans is unknown. After administration of fidaxomicin film-coated tablets in 
healthy adults, Cmax is approximately 9.88 ng/ml and AUC0-t  is 69.5 ng•hr/ml following administration 
of 200 mg fidaxomicin, with a T max of 1.75 hours. In CDI patients, average peak plasma levels of 
fidaxomicin and its main metabolite OP-1118 tend to be 2- to 6-fold higher than in healthy adults. 
There was very limited accumulation of fidaxomicin or OP-1118 in plasma following administration 
of 200 mg fidaxomicin every 12 hours for 10 days. 

Cmax for fidaxomicin and OP-1118 in plasma were 22% and 33% lower following a high fat meal vs 
fasting, but the extent of exposure (AUC0-t ) was equivalent. 



16 

Fidaxomicin and the metabolite OP-1118 are substrates of P-gp. 
In vitro studies showed that fidaxomicin and the metabolite OP-1118 are inhibitors of the transporters 
BCRP, MRP2 and OATP2B1, but were not found to be substrates. Under conditions of clinical use, 
fidaxomicin has no clinically relevant effect on the exposure of rosuvastatin, a substrate for OATP2B1 
and BCRP (see section 4.5). The clinical relevance of MRP2 inhibition is not yet known. 

Distribution 

The volume of distribution in humans is unknown, due to very limited absorption of fidaxomicin. 

Biotransformation 

No extensive analysis of metabolites in plasma has been performed, due to low levels of systemic 
absorption of fidaxomicin. A main metabolite, OP-1118, is formed through hydrolysis of the 
isobutyryl ester. In vitro metabolism studies showed that the formation of OP-1118 is not dependent 
on CYP450 enzymes. This metabolite also shows antimicrobial activity (see section 5.1). 

Fidaxomicin does not induce or inhibit CYP450 enzymes in vitro. 

Elimination 

Following a single dose of 200 mg fidaxomicin, the majority of the administered dose (over 92%) was 
recovered in the stool as fidaxomicin or its metabolite OP-1118 (66%). The main elimination 
pathways of systemically available fidaxomicin have not been characterized. Elimination through 
urine is negligible (<1%). Only very low levels of OP-1118 and no fidaxomicin was detectable in 
human urine. The half life of fidaxomicin is approximately 8-10 h.  

Special populations 

Paediatric population 
After administration of the oral suspension, the mean (SD) plasma levels in the paediatric patients 
from birth to less than 18 years was 34.60 (57.79) ng/ml and 102.38 (245.19) ng/ml for fidaxomicin 
and its main metabolite OP-1118, respectively, at 1 to 5 hours postdose. 

Elderly 
Plasma levels appear to be elevated in the elderly (age ≥ 65 years). Fidaxomicin and OP-1118 levels 
were approximately 2 times higher in patients ≥ 65 years compared to patients < 65 years. This 
difference is not considered clinically relevant. 

Inflammatory bowel disease 
Data from an open label, single arm study in adult CDI patients with concomitant inflammatory bowel 
disease (IBD) using the tablet formulation indicated no major difference in plasma concentrations of 
fidaxomicin or its main metabolite OP-1118 in patients with IBD as compared with patients without 
IBD in other studies. The maximum fidaxomicin and OP-1118 plasma levels in CDI patients with 
concomitant IBD were within the range of levels found in CDI patients without IBD. 

Hepatic impairment 
Limited data from adult patients with an active history of chronic hepatic cirrhosis using the tablet 
formulation in the Phase 3 studies showed that median plasma levels of fidaxomicin and OP-1118 may 
be approximately 2- and 3-fold higher, respectively, than in non-cirrhotic patients. 

Renal impairment 
Limited data from adult patients using the tablet formulation suggest that there is no major difference 
in plasma concentration of fidaxomicin or OP-1118 between patients with reduced renal function 
(creatinine clearance < 50 ml/min) and patients with normal renal function (creatinine clearance 
≥ 50 ml/min). 



17 

Gender, weight and race 
Limited data suggest that gender, weight and race do not have any major influence on the plasma 
concentration of fidaxomicin or OP-1118. 

5.3 Preclinical safety data 

Nonclinical data revealed no special hazard for humans based on conventional studies of safety 
pharmacology, repeat dose toxicity, genotoxicity, and reproductive toxicity. 

Reproductive and fertility parameters showed no statistically significant differences in rats treated with 
fidaxomicin at doses up to 6.3 mg/kg/day (intravenous). 

No target organs for toxicity were observed in juvenile animals, and no important potential risks have 
been observed in the nonclinical studies that might be relevant for paediatric patients. 

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients 

Cellulose, microcrystalline 
Sodium starch glycolate 
Xanthan gum 
Citric acid 
Sodium citrate 
Sodium benzoate (E211)  
Sucralose 
Mixed berry flavour 

6.2 Incompatibilities 

Not applicable. 

6.3 Shelf life 

3 years. 

The reconstituted suspension is stable for 12 days in a refrigerator (2°C – 8°C). 

6.4 Special precautions for storage 

This medicinal product does not require any special temperature storage conditions. 
For storage conditions after reconstitution, see section 6.3. 

Store in the original package in order to protect from light. 

6.5 Nature and contents of container 

Amber glass bottle with a polypropylene child-resistant cap in an aluminium pouch containing 7.7 g of 
granules for oral suspension. 

6.6 Special precautions for disposal and other handling 

DIFICLIR granules for oral suspension should be reconstituted by a pharmacist or other healthcare 
professional prior to dispensing to the patient. Patients or caregivers should not prepare the oral 
suspension at home. 



18 

Instructions for reconstitution: 
1. Shake the glass bottle to ensure the granules move around freely and no caking of the granules has

occurred. 
2. Measure 105 ml of purified water and add to the glass bottle. Note that the stability of fidaxomicin

granules suspended in mineral water, tap water, or other liquids has not been established. 
3. Close the glass bottle and shake vigorously for at least 1 minute.
4. Verify that the resulting liquid has no remaining caked granules left at the bottom of the bottle or

any lumps. If caked granules or any lumps are observed, shake the glass bottle vigorously again
for at least 1 minute.

5. Let the bottle stand for 1 minute.
6. Verify if a homogenous suspension is obtained.
7. Write the date of expiration of the reconstituted suspension on the bottle label (the shelf-life of the

reconstituted suspension is 12 days).
8. Store the bottle at refrigerated temperature (2-8°C) before and during use.
9. Select an appropriate oral syringe and bottle adaptor suitable for dispensing liquid medicinal

product to measure the correct dose.

After reconstitution, the suspension (110 ml) will appear as white to yellowish white. 

An appropriate commercially available oral syringe and adaptor suitable for dispensing of liquid 
medicines should be selected by the healthcare professional in order to allow the patient or caregiver 
to measure the correct dose. The adaptor should be suitable for use in combination with the selected 
oral syringe and fits the bottle neck size, for example a press-in bottles adaptor (27 mm) or universal 
bottle adapter. 

In case the treatment with fidaxomicin started in a hospital setting and the patient is discharged before 
the end of the treatment at the hospital, the patient should be provided with the oral suspension and a 
suitable oral syringe and adaptor. Patients or caregivers should not prepare the oral suspension at 
home. 

Recommended oral syringe capacity for measuring the dose of the oral suspension is presented in the 
table below. 

Table 3: Suggested oral syringe capacity for accurate dispensing 

Prescribed dosing volume Recommended oral syringe capacity 
1 ml 1 ml oral syringe 

2 – 5 ml 5 ml oral syringe 

If possible, the graduation corresponding to the appropriate dose should be marked or highlighted 
(according to the dosing table in section 4.2) on the oral syringe. 

Administration via an enteral feeding tube: 
In case of administration using an enteral feeding tube, an appropriate commercially available tube 
should be selected by the healthcare professional. Enteral feeding tubes made of polyvinylchloride 
(PVC) and polyurethane (PUR) have been shown compatible with the oral suspension. The 
recommended enteral feeding tube size and flush volume of water are provided in the table below. 

Table 4: Recommended enteral feeding tube size and flush volume 

Recommended tube size (diameter) Recommended flush volume* 
4 Fr at least 1 mL 
5 Fr at least 2 mL 

6 – 7 Fr at least 3 mL 
8 Fr at least 4 mL 

* Based on tubes of 120 cm



19 

Any unused product or waste material should be disposed of in accordance with local requirements. 

7. MARKETING AUTHORISATION HOLDER

Astellas Pharma Europe B.V. 
Sylviusweg 62 
2333 BE Leiden 
The Netherlands 

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/11/733/005 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

Date of first authorisation: 5 December 2011 
Date of latest renewal:  

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/


20 

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 



21 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

Name and address of the manufacturer responsible for batch release 

Astellas Pharma Europe B.V. 
Sylviusweg 62 
2333 BE Leiden 
The Netherlands 

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. 

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.



22 

ANNEX III  

LABELLING AND PACKAGE LEAFLET 



23 

A. LABELLING 



24 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

CARTON 

1. NAME OF THE MEDICINAL PRODUCT 

DIFICLIR 200 mg film-coated tablets 
fidaxomicin 

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each film-coated tablet contains 200 mg of fidaxomicin. 

3. LIST OF EXCIPIENTS

4. PHARMACEUTICAL FORM AND CONTENTS

100 x 1 film-coated tablet. 
20 x 1 film-coated tablet. 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

Read the package leaflet before use. 
Oral use. 

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

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



25 

Astellas Pharma Europe B.V. 
Sylviusweg 62 
2333 BE Leiden  
The Netherlands 

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/11/733/003 100 x 1 film-coated tablet 
EU/1/11/733/004 20 x 1 film-coated tablet 

13. BATCH NUMBER

Lot 

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE 

16. INFORMATION IN BRAILLE 

dificlir 200 mg 

17. UNIQUE IDENTIFIER – 2D BARCODE 

2D barcode carrying the unique identifier included. 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC 
SN 
NN 



26 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

BLISTER 

1. NAME OF THE MEDICINAL PRODUCT 

DIFICLIR 200 mg film-coated tablets 
fidaxomicin 

2. NAME OF THE MARKETING AUTHORISATION HOLDER

Astellas 

3. EXPIRY DATE 

EXP 

4. BATCH NUMBER

Lot 

5. OTHER



27 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

CARTON 

1. NAME OF THE MEDICINAL PRODUCT 

DIFICLIR 40 mg/ml granules for oral suspension 
fidaxomicin 

2. STATEMENT OF ACTIVE SUBSTANCE(S)

1 ml of the reconstituted suspension contains 40 mg fidaxomicin. 

3. LIST OF EXCIPIENTS

Contains sodium benzoate (E211). See leaflet for further information. 

4. PHARMACEUTICAL FORM AND CONTENTS

Granules for oral suspension 
1 bottle contains 7.7 g granules or 110 ml oral suspension after reconstitution 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

Read the package leaflet before use. 
For oral use after reconstitution. 
Shake well before use. 
Use the oral syringe and adaptor provided by your pharmacist or healthcare professional. 

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  
The reconstituted suspension can be stored for 12 days. 

9. SPECIAL STORAGE CONDITIONS

Store in the original package in order to protect from light. 
Reconstituted suspension: store in a refrigerator. 



28 

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

Astellas Pharma Europe B.V. 
Sylviusweg 62 
2333 BE Leiden  
The Netherlands 

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/11/733/005 

13. BATCH NUMBER

Lot 

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE 

16. INFORMATION IN BRAILLE 

dificlir 40 mg/ml 

17. UNIQUE IDENTIFIER – 2D BARCODE 

2D barcode carrying the unique identifier included. 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC 
SN 
NN 



29 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

POUCH AND BOTTLE 

1. NAME OF THE MEDICINAL PRODUCT 

DIFICLIR 40 mg/ml granules for oral suspension 
fidaxomicin 

2. STATEMENT OF ACTIVE SUBSTANCE(S)

1 ml of the reconstituted suspension contains 40 mg fidaxomicin. 

3. LIST OF EXCIPIENTS

Contains sodium benzoate (E211). See leaflet for further information. 

4. PHARMACEUTICAL FORM AND CONTENTS

Granules for oral suspension 
1 bottle contains 7.7 g granules or 110 ml oral suspension after reconstitution 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

Read the package leaflet before use. 
For oral use after reconstitution. 
Shake well before use. 
Use the oral syringe and adaptor provided by your pharmacist or healthcare professional 

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  
The reconstituted suspension can be stored for 12 days. 
Expiry date of the reconstituted suspension: 

9. SPECIAL STORAGE CONDITIONS

Store in the original package in order to protect from light. 
Reconstituted suspension: store in a refrigerator. 



30 

 
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 
 
Astellas 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/733/005 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
 

  



31 

B. PACKAGE LEAFLET 



32 

Package leaflet: Information for the user 

DIFICLIR 200 mg film-coated tablets 
fidaxomicin 

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 DIFICLIR is and what it is used for
2. What you need to know before you take DIFICLIR
3. How to take DIFICLIR
4. Possible side effects
5. How to store DIFICLIR
6. Contents of the pack and other information

1. What DIFICLIR is and what it is used for

DIFICLIR is an antibiotic which contains the active substance fidaxomicin. 

DIFICLIR film-coated tablets are used in adults, adolescents and children with a body weight of at 
least 12.5 kg to treat infections of the lining of the colon (large intestine) with certain bacteria called 
Clostridioides difficile. This serious illness can result in painful, severe diarrhoea. DIFICLIR works by 
killing the bacteria that cause the infection and helps to reduce the associated diarrhoea.  

2. What you need to know before you take DIFICLIR

Do not take DIFICLIR 
− If you are allergic to fidaxomicin or any of the other ingredients of this medicine (listed in 

section 6). 

Warnings and precautions 
Talk to your doctor or pharmacist before taking DIFICLIR. 

If you feel that you might have a severe allergic reaction such as trouble breathing (dyspnea), swelling 
of the face or throat (angioedema), severe rash, severe itching (pruritus) or severe hives (urticaria), 
stop taking DIFICLIR and seek medical advice urgently from your doctor, pharmacist or at your local 
hospital emergency department (see section 4). 

If you are allergic to macrolides (a class of antibiotics), ask your doctor for advice before using this 
medicine. Your doctor will tell you whether this medicine is suitable for you. 

If you have kidney or liver problems, ask your doctor for advice before using this medicine. Your 
doctor will tell you whether this medicine is suitable for you. 



33 

There are limited data available on the use of fidaxomicin in severe cases of the disease (e.g. 
pseudomembranous colitis). Your doctor will know whether your disease falls in the severe categories 
and will tell you whether this medicine is suitable for you. 
 
Children and adolescents 
Do not give this medicine to children with a body weight below 12.5 kg, because these children 
require a reduced dose. For appropriate dosing in these patients, DIFICLIR granules for oral 
suspension may be used. 
 
Other medicines and DIFICLIR 
Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines. 
 
DIFICLIR blood levels can be affected by other medicines you take, and blood levels of other 
medicines can be affected by taking DIFICLIR. Examples of such medicines are: 
− cyclosporin (a medicine used to dampen down the body’s immune reactions, used e.g. after an 

organ or bone marrow transplant, for psoriasis or eczema, or for rheumatoid arthritis or 
nephrotic syndrome) 

− ketoconazole (a medicine used to treat fungal infections) 
− erythromycin (a medicine used to treat ear, nose, throat, chest and skin infections) 
− clarithromycin (a medicine used to treat chest infections, throat and sinus infections, skin and 

tissue infections and Helicobacter pylori infections associated with duodenal or stomach ulcer) 
− verapamil (a medicine used to treat high blood pressure or to prevent chest pain attacks, or used 

following a heart attack to prevent another one) 
− dronedarone and amiodarone (medicines used to control the heartbeat) 
− dabigatran etexilat (a medicine used to prevent the formation of blood clots after hip or knee 

replacement surgery)  
You should not use DIFICLIR in combination with one of these medicines, unless your doctor tells 
you otherwise. If you use one of these medicines, please ask your doctor for advice before taking this 
medicine. 
 
Pregnancy and breast-feeding 
You should not take DIFICLIR if you are pregnant, unless your doctor tells you otherwise.  
This is because it is not known whether fidaxomicin can harm your baby.  
If you are pregnant or think you may be pregnant, ask your doctor or pharmacist for advice before 
taking this medicine. 
 
It is not known whether fidaxomicin passes into breast milk, but it is not expected to do so. 
If you are breastfeeding ask your doctor or pharmacist for advice before taking this medicine. 
 
Driving and using machines 
DIFICLIR is not expected to affect your ability to drive, use tools or machines. 
 
DIFICLIR contains sodium 
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-
free’. 
 
 
3. How to take DIFICLIR 
 
Always take this medicine exactly as your doctor or pharmacist has told you. You should check with 
your doctor or pharmacist if you are not sure. 
 
The recommended dose for patients weighing at least 12.5 kg is one tablet (200 mg) twice daily (one 
tablet every 12 hours) for 10 days. 
Swallow the tablets whole with a glass of water. You can take DIFICLIR before, during or after meals.  
 



34 

DIFICLIR granules for oral suspension should be used for patients with a body weight of less than 
12.5 kg. This form of this medicine (oral suspension) may also be more suitable for patients above 
12.5 kg; ask your doctor or pharmacist. 
 
If you take more DIFICLIR than you should 
If you have taken more tablets than you should have, talk to a doctor. Take the medicine pack with 
you so the doctor knows what you have taken. 
 
If you forget to take DIFICLIR 
Take the tablet as soon as you remember, unless it is time for the next dose. In that case, skip the 
missed dose. Do not take a double dose to make up for a forgotten dose. 
 
If you stop taking DIFICLIR 
Do not stop taking DIFICLIR, unless your doctor has advised you to do so. 
Keep taking this medicine until the course is finished, even if you feel better. 
If you stop taking this medicine too soon, the infection may come back. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
A severe allergic reaction may occur, including trouble breathing (dyspnea), swelling of the face or 
throat (angioedema), severe rash or severe itching (pruritus) (see section 2). If such reaction occurs, 
stop taking DIFICLIR and seek medical advice urgently from your doctor, pharmacist or at your local 
hospital emergency department. 
 
The most common side effects (may affect up to 1 in 10 people) are: 
− vomiting 
− nausea 
− constipation. 
 
Other possible side effects are the following: 
Uncommon side effects (may affect up to 1 in 100 people) 
− decreased appetite 
− dizziness, headache 
− dry mouth, altered taste (dysgeusia) 
− bloated feeling, wind (flatulence) 
− rash, itching (pruritus) 

 
Not known side effects (frequency cannot be estimated from the available data) 

− swelling of the face and throat (angioedema), trouble breathing (dyspnea) 
 
Additional side effects in children and adolescents 
−  hives 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. 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 DIFICLIR 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


35 

 
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 carton after “EXP”. The expiry 
date refers to the last day of that month. 
 
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 to protect the environment. 
 
 
6. Contents of the pack and other information 
 
What DIFICLIR contains  
− The active substance is fidaxomicin. Each film-coated tablet contains 200 mg of fidaxomicin.  
− The other ingredients are: 

Tablet core: microcrystalline cellulose, pregelatinised starch, hydroxypropyl cellulose, butylated 
hydroxytoluene, sodium starch glycolate and magnesium stearate 
Coating: polyvinyl alcohol, titanium dioxide (E171), talc, polyethylene glycol and lecithin (soy) 

 
What DIFICLIR looks like and contents of the pack 
DIFICLIR 200 mg film-coated tablets are capsule shaped tablets, white to off-white in colour, with 
“FDX” on one side and “200” on the other side. 
 
DIFICLIR is available in: 
100 x 1 film-coated tablet in alu/alu perforated unit dose blisters. 
20 x 1 film-coated tablet in alu/alu perforated unit dose blisters. 
 
DIFICLIR is also available in the form of granules for oral suspension. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and manufacturer 
Astellas Pharma Europe B.V. 
Sylviusweg 62 
2333 BE Leiden 
The Netherlands 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Astellas Pharma B.V. Branch 
Tél/Tel: +32 (0)2 5580710 

Lietuva 
Biocodex UAB 
Tel: +370 37 408 681 
 

България 
Астелас Фарма ЕООД 
Teл.: +359 2 862 53 72 
 

Luxembourg/Luxemburg 
Astellas Pharma B.V. Branch 
Belgique/Belgien 
Tél/Tel: +32 (0)2 5580710 
 

Česká republika 
Astellas Pharma s.r.o. 
Tel: +420 221 401 500 
 

Magyarország 
Astellas Pharma Kft. 
Tel.: +36 1577 8200 
 

Danmark  
Astellas Pharma a/s 
Tlf: +45 43430355 

Malta 
Astellas Pharmaceuticals AEBE 
Greece 



36 

Τel: +30 210 8189900 
 

Deutschland 
Astellas Pharma GmbH 
Tel: +49 (0)89 454401 
 

Nederland 
Astellas Pharma B.V. 
Tel: +31 (0)71 5455745 
 

Eesti 
Biocodex OÜ  
Tel: +372 6 056 014 
 

Norge 
Astellas Pharma 
Tlf: +47 6676 4600 
 

Ελλάδα 
Astellas Pharmaceuticals AEBE 
Tηλ: +30 210 8189900 

Österreich 
Astellas Pharma Ges.m.b.H. 
Tel: +43 (0)1 8772668 
 

España 
Astellas Pharma S.A. 
Tel: +34 91 4952700 

Polska 
Astellas Pharma Sp. z o.o. 
Tel.: +48 225451 111 
 

France 
Astellas Pharma S.A.S. 
Tél: +33 (0)1 55917500 
 

Portugal 
Astellas Farma, Lda. 
Tel: +351 21 4401320 
 

Hrvatska 
Astellas d.o.o. 
Tel: + 385 1 670 01 02 
 

România 
S.C.Astellas Pharma SRL 
Tel: +40 (0)21 361 04 95/96/92 
 

Ireland 
Astellas Pharma Co. Ltd. 
Tel: +353 (0)1 4671555 
 

Slovenija 
Astellas Pharma d.o.o. 
Tel: +386 (0) 1 401 1400 
 

Ísland 
Vistor hf. 
Tel: +354 535 7000 
 

Slovenská republika 
Astellas Pharma s.r.o. 
Tel: +421 2 4444 2157 

Italia 
Astellas Pharma S.p.A. 
Tel: +39 02 921381 
 

Suomi/Finland 
Astellas Pharma 
Puh/Tel: +358 (0)9 85606000 

Κύπρος 
Astellas Pharmaceuticals AEBE 
Ελλάδα 
Tηλ: +30 210 8189900 
 

Sverige 
Astellas Pharma AB 
Tel: +46 (0)40-650 15 00 

Latvija 
Biocodex SIA 
Tel: +371 67 619365 

United Kingdom 
Astellas Pharma Ltd. 
Tel: +44 (0) 203 379 8700 
 

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

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


37 

Package leaflet: Information for the user 
 

DIFICLIR 40 mg/ml granules for oral suspension 
fidaxomicin 

 
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 DIFICLIR is and what it is used for 
2. What you need to know before you take DIFICLIR 
3. How to take DIFICLIR 
4. Possible side effects 
5. How to store DIFICLIR 
6. Contents of the pack and other information 
 
 
1. What DIFICLIR is and what it is used for 
 
DIFICLIR is an antibiotic which contains the active substance fidaxomicin. 
 
DIFICLIR oral suspension is used in adults, adolescents and children from birth to less than 18 years 
to treat infections of the lining of the colon (large intestine) with certain bacteria called Clostridioides 
difficile. This serious illness can result in painful, severe diarrhoea. DIFICLIR works by killing the 
bacteria that cause the infection and helps to reduce the associated diarrhoea.  
 
 
2. What you need to know before you take DIFICLIR 
 
Do not take DIFICLIR 
− If you are allergic to fidaxomicin or any of the other ingredients of this medicine (listed in 

section 6).  
 
Warnings and precautions 
Talk to your doctor or pharmacist before taking DIFICLIR. 
 
If you feel that you might have a severe allergic reaction such as trouble breathing (dyspnea), swelling 
of the face or throat (angioedema), severe rash, severe itching (pruritus) or severe hives (urticaria), 
stop taking DIFICLIR and seek medical advice urgently from your doctor, pharmacist or at your local 
hospital emergency department (see section 4). 
 
If you are allergic to macrolides (a class of antibiotics), ask your doctor for advice before using this 
medicine. Your doctor will tell you whether this medicine is suitable for you. 
 
If you have kidney or liver problems, ask your doctor for advice before using this medicine. Your 
doctor will tell you whether this medicine is suitable for you. 
 
 



38 

There are limited data available on the use of fidaxomicin in severe cases of the disease (e.g. 
pseudomembranous colitis). Your doctor will know whether your disease falls in the severe categories 
and will tell you whether this medicine is suitable for you. 
 
Other medicines and DIFICLIR 
Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines. 
 
DIFICLIR blood levels can be affected by other medicines you take, and blood levels of other 
medicines can be affected by taking DIFICLIR. Examples of such medicines are: 
− cyclosporin (a medicine used to dampen down the body’s immune reactions, used e.g. after an 

organ or bone marrow transplant, for psoriasis or eczema, or for rheumatoid arthritis or 
nephrotic syndrome) 

− ketoconazole (a medicine used to treat fungal infections) 
− erythromycin (a medicine used to treat ear, nose, throat, chest and skin infections) 
− clarithromycin (a medicine used to treat chest infections, throat and sinus infections, skin and 

tissue infections and Helicobacter pylori infections associated with duodenal or stomach ulcer) 
− verapamil (a medicine used to treat high blood pressure or to prevent chest pain attacks, or used 

following a heart attack to prevent another one) 
− dronedarone and amiodarone (medicines used to control the heartbeat) 
− dabigatran etexilat (a medicine used to prevent the formation of blood clots after hip or knee 

replacement surgery)  
You should not use DIFICLIR in combination with one of these medicines, unless your doctor tells 
you otherwise. If you use one of these medicines, please ask your doctor for advice before taking this 
medicine. 
 
Pregnancy and breast-feeding 
You should not take DIFICLIR if you are pregnant, unless your doctor tells you otherwise.  
This is because it is not known whether fidaxomicin can harm your baby.  
If you are pregnant or think you may be pregnant, ask your doctor or pharmacist for advice before 
taking this medicine. 
 
It is not known whether fidaxomicin passes into breast milk, but it is not expected to do so. 
If you are breastfeeding ask your doctor or pharmacist for advice before taking this medicine. 
 
Driving and using machines 
DIFICLIR is not expected to affect your ability to drive, use tools or machines. 
 
DIFICLIR contains sodium benzoate (E211) 
This medicine contains 2.5 mg sodium benzoate (E 211) in each ml oral suspension. Sodium benzoate 
(E 211) may increase jaundice (yellowing of the skin and eyes) in newborn babies (up to 4 weeks old). 
 
DIFICLIR contains sodium 
This medicine contains less than 1 mmol sodium (23 mg) per 5 ml suspension, that is to say essentially 
‘sodium-free’. 
 
 
3. How to take DIFICLIR 
 
Always take this medicine exactly as your doctor or pharmacist has told you. You should check with 
your doctor or pharmacist if you are not sure. 
 
Your doctor will determine your dose depending on your weight. 
 
The recommended dose for patients weighing at least 12.5 kg is 200 mg (5 ml oral suspension) 
administered twice daily (once every 12 hours) for 10 days. Another form of this medicine (tablets) 
may be more suitable for adults and older children (e.g. adolescents); ask your doctor or pharmacist.  



39 

 
The recommended dose for children by body weight is as follows: 
 

Weight band of 
patient 

 

Mg per dose 
(every 12 hours) 

Volume of fidaxomicin oral 
suspension  

(every 12 hours) 
< 4.0 kg 40 mg 1 ml 

4.0 - < 7.0 kg 80 mg 2 ml 
7.0 - < 9.0 kg 120 mg 3 ml 

9.0 - < 12.5 kg 160 mg 4 ml 
≥ 12.5 kg 200 mg 5 ml 

 
You can take DIFICLIR before, during or after meals.  
 
How to take the DIFICLIR dose using an oral syringe 
 
Your pharmacist or heatlthcare professional will prepare DIFICLIR oral suspension before giving it to 
you. If the product is not provided to you as a suspension, please contact your pharmacist or healthcare 
professional. 
 
Instructions for use: 
Use the oral syringe and adaptor provided by the pharmacist or healthcare professional to make sure 
you measure the right amount. If an oral syringe and adaptor has not been provided to you, please 
contact your pharmacist or healthcare professional.  
Your pharmacist will advise you how to measure the medicine using the oral syringe. Please see 
instructions below before using DIFICLIR suspension. 
 
1. Take the bottle from the refrigerator 15 minutes prior to administration. 
2. After 15 minutes, shake the bottle gently 10 times and let the bottle stand for 1 minute. 
3. Verify if the liquid is smooth and not lumpy (i.e. homogenous). 
4. Remove the cap and attach the adaptor to the bottle according to the instructions by your 

pharmacist or healthcare professional. 
5. Insert the tip of the oral syringe into the adaptor until it is firmly in place. 
6. Invert the bottle 3 times and turn the bottle upside down, so the syringe is on the bottom. 
7. Pull back the plunger of the oral syringe to withdraw the amount prescribed by your doctor from 

the inverted bottle. 
8. Leave the syringe in place and turn the bottle upright, ensuring the plunger does not move. Gently 

remove the syringe from the adaptor and confirm the appropriate dose has been measured. 
9. Slowly dispense the oral suspension directly into the patient’s mouth until all of the liquid 

medicine is given. 
10. If you have been given a press-in adaptor, leave the bottle adaptor in the neck of the bottle or 

follow the instructions by your pharmacist or healthcare professional. 
11. After administration, store the remaining suspension in a refigerator.  
12. To allow reuse of the oral syringe, flush the syringe with warm drinking water (3 times minimally) 

or until clear water comes out of the syringe. Dry external surfaces and internal surfaces as much 
as possible. Leave to dry until further use. 

 
If you started using this product in a hospital, your pharmacist or healthcare professional will provide 
you with the suspension, oral syringe and adaptor at your discharge. 
 
If you take more DIFICLIR than you should 
If you have taken more of the oral suspension than you should have, talk to a doctor. Take the 
medicine pack with you so the doctor knows what you have taken. 
 
If you forget to take DIFICLIR 



40 

Take the oral suspension as soon as you remember, unless it is time for the next dose. In that case, skip 
the missed dose. Do not take a double dose to make up for a forgotten dose. 
 
If you stop taking DIFICLIR 
Do not stop taking DIFICLIR, unless your doctor has advised you to do so. 
Keep taking this medicine until the course is finished, even if you feel better. 
If you stop taking this medicine too soon, the infection may come back. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
A severe allergic reaction may occur, including trouble breathing (dyspnea), swelling of the face or 
throat (angioedema), severe rash or severe itching (pruritus) (see section 2). If such reaction occurs, 
stop taking DIFICLIR and seek medical advice urgently from your doctor, pharmacist or at your local 
hospital emergency department. 
 
The most common side effects (may affect up to 1 in 10 people) are: 
− vomiting 
− nausea 
− constipation. 
 
Other possible side effects are the following: 
Uncommon side effects (may affect up to 1 in 100 people) 
− decreased appetite 
− dizziness, headache 
− dry mouth, altered taste (dysgeusia) 
− bloated feeling, wind (flatulence) 
− rash, itching (pruritus) 

 
Not known side effects (frequency cannot be estimated from the available data) 
− swelling of the face and throat (angioedema), trouble breathing (dyspnea) 
 
Additional side effects in children and adolescents 
− hives 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. 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 DIFICLIR 
 
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 carton after “EXP”. The expiry 
date refers to the last day of that month. 
 
DIFICLIR will be supplied to you as a suspension, which can be stored for up to 12 days. Store in a 
refrigerator (2°C - 8°C). Do not use the suspension after the expiry date which is written on the bottle 
label. 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


41 

 
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 to protect the environment. 
 
 
6. Contents of the pack and other information 
 
What DIFICLIR contains  
− The active substance is fidaxomicin.  
− The other ingredients are: microcrystalline cellulose, sodium starch glycolate, xanthan gum, 

citric acid, sodium citrate, sodium benzoate (see section 2), sucralose and mixed berry flavour 
 

What DIFICLIR looks like and contents of the pack 
DIFICLIR is presented in an amber glass bottle as white to yellowish white granules for oral 
suspension. DIFICLIR will be supplied to you as a suspension by your pharmacist or healthcare 
professional, which will appear as white to yellowish white suspension.  
The pack does not contain the oral syringe and adaptor for use with this product. These will be 
provided to you by your pharmacist or other healthcare professional. 
 
DIFICLIR is also available in the form of film-coated tablets. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and manufacturer 
Astellas Pharma Europe B.V. 
Sylviusweg 62 
2333 BE Leiden 
The Netherlands 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Astellas Pharma B.V. Branch 
Tél/Tel: +32 (0)2 5580710 

Lietuva 
Biocodex UAB 
Tel: +370 37 408 681 
 

България 
Астелас Фарма ЕООД 
Teл.: +359 2 862 53 72 
 

Luxembourg/Luxemburg 
Astellas Pharma B.V. Branch 
Belgique/Belgien 
Tél/Tel: +32 (0)2 5580710 
 

Česká republika 
Astellas Pharma s.r.o. 
Tel: +420 221 401 500 
 

Magyarország 
Astellas Pharma Kft. 
Tel.: +36 1577 8200 
 

Danmark  
Astellas Pharma a/s 
Tlf: +45 43430355 

Malta 
Astellas Pharmaceuticals AEBE 
Greece 
Τel: +30 210 8189900 
 

Deutschland 
Astellas Pharma GmbH 
Tel: +49 (0)89 454401 
 

Nederland 
Astellas Pharma B.V. 
Tel: +31 (0)71 5455745 
 

Eesti 
Biocodex OÜ  

Norge 
Astellas Pharma 



42 

Tel: +372 6 056 014 
 

Tlf: +47 6676 4600 
 

Ελλάδα 
Astellas Pharmaceuticals AEBE 
Tηλ: +30 210 8189900 

Österreich 
Astellas Pharma Ges.m.b.H. 
Tel: +43 (0)1 8772668 
 

España 
Astellas Pharma S.A. 
Tel: +34 91 4952700 

Polska 
Astellas Pharma Sp. z o.o. 
Tel.: +48 225451 111 
 

France 
Astellas Pharma S.A.S. 
Tél: +33 (0)1 55917500 
 

Portugal 
Astellas Farma, Lda. 
Tel: +351 21 4401320 
 

Hrvatska 
Astellas d.o.o. 
Tel: + 385 1 670 01 02 
 

România 
S.C.Astellas Pharma SRL 
Tel: +40 (0)21 361 04 95/96/92 
 

Ireland 
Astellas Pharma Co. Ltd. 
Tel: +353 (0)1 4671555 
 

Slovenija 
Astellas Pharma d.o.o. 
Tel: +386 (0) 1 401 1400 
 

Ísland 
Vistor hf. 
Tel: +354 535 7000 
 

Slovenská republika 
Astellas Pharma s.r.o. 
Tel: +421 2 4444 2157 

Italia 
Astellas Pharma S.p.A. 
Tel: +39 02 921381 
 

Suomi/Finland 
Astellas Pharma 
Puh/Tel: +358 (0)9 85606000 

Κύπρος 
Astellas Pharmaceuticals AEBE 
Ελλάδα 
Tηλ: +30 210 8189900 
 

Sverige 
Astellas Pharma AB 
Tel: +46 (0)40-650 15 00 

Latvija 
Biocodex SIA 
Tel: +371 67 619365 

United Kingdom 
Astellas Pharma Ltd. 
Tel: +44 (0) 203 379 8700 
 

   
 
 
This leaflet was last revised in  
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu  
 
--------------------------------------------------------------------------------------------------------------------------- 
 
The following information is intended for healthcare professionals only: 
 
Instructions for reconstitution: 
1. Shake the glass bottle to ensure the granules move around freely and no caking of the granules has 

occurred. 
2. Measure 105 ml of purified water and add to the glass bottle. Note that the stability of fidaxomicin 

granules suspended in mineral water, tap water, or other liquids has not been established. 

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


43 

3. Close the glass bottle and shake vigorously for at least 1 minute.  
4. Verify that the resulting liquid has no remaining caked granules left at the bottom of the bottle or 

any lumps. If caked granules or any lumps are observed, shake the glass bottle vigorously again 
for at least 1 minute. 

5. Let the bottle stand for 1 minute. 
6. Verify if a homogenous suspension is obtained. 
7. Write the date of expiration of the reconstituted suspension on the bottle label (the shelf-life of the 

reconstituted suspension is 12 days). 
8. Store the bottle at refrigerated temperature (2-8°C) before and during use. 
9. Select an appropriate oral syringe and bottle adaptor suitable for dispensing liquid medicinal 

product to measure the correct dose. 
 
After reconstitution, the suspension (110 ml) will appear as white to yellowish white. 
 
An appropriate commercially available oral syringe and adaptor suitable for dispensing of liquid 
medicines should be selected by the healthcare professional in order to allow the patient or caregiver 
to measure the correct dose. The adaptor should be suitable for use in combination with the selected 
oral syringe and fits the bottle neck size, for example a press-in bottles adaptor (27 mm) or universal 
bottle adapter. 
 
In case the treatment with fidaxomicin started in a hospital setting and the patient is discharged before 
the end of the treatment at the hospital, the patient should be provided with the oral suspension and a 
suitable oral syringe and adaptor. Patients or caregivers should not prepare the oral suspension at 
home. 
  
Recommended oral syringe capacity for measuring the dose of the oral suspension is presented in the 
table below. 
 
Suggested oral syringe capacity for accurate dispensing 

Prescribed dosing volume Recommended oral syringe capacity 
1 ml 1 ml oral syringe 

2 – 5 ml 5 ml oral syringe 
 
If possible, the graduation corresponding to the appropriate dose should be marked or highlighted 
(according to the dosing table in section 3) on the oral syringe. 
 
Administration via an enteral feeding tube: 
In case of administration using an enteral feeding tube, an appropriate commercially available tube 
should be selected by the healthcare professional. Enteral feeding tubes made of polyvinylchloride 
(PVC) and polyurethane (PUR) have been shown compatible with the oral suspension. The 
recommended enteral feeding tube size and flush volume of water are provided in the table below. 
 
Recommended enteral feeding tube size and flush volume 

Recommended tube size (diameter) Recommended flush volume* 
4 Fr at least 1 mL 
5 Fr at least 2 mL 

6 – 7 Fr at least 3 mL 
8 Fr at least 4 mL 

* Based on tubes of 120 cm 


	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