Xerava

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 
 
Xerava 50 mg powder for concentrate for solution for infusion 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each vial contains 50 mg eravacycline.  
 
After reconstitution each mL contains 10 mg eravacycline. 
After further dilution 1 mL contains 0.3 mg eravacycline. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder for concentrate for solution for infusion (powder for concentrate). 
 
Pale yellow to dark yellow cake. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Xerava is indicated for the treatment of complicated intra-abdominal infections (cIAI) in adults (see 
sections 4.4 and 5.1). 
 
Consideration should be given to official guidance on the appropriate use of antibacterial agents. 
 
4.2 Posology and method of administration 
 
Posology 
 
The recommended dose regimen is 1 mg/kg eravacycline every 12 hours for 4 to 14 days.  
 
Strong CYP3A4 inducers 
In patients co-administered strong CYP3A4 inducers the recommended dose regimen is 1.5 mg/kg 
eravacycline every 12 hours for 4 to 14 days (see sections 4.4 and 4.5). 
 
Elderly (≥ 65 years old) 
No dose adjustment is required in elderly patients (see section 5.2). 
 
Renal impairment 
No dose adjustment is necessary in patients with renal impairment or in patients undergoing 
haemodialysis. Eravacycline may be administered without regard to the timing of haemodialysis (see 
section 5.2).  
 
Hepatic impairment 
No dose adjustment is necessary in patients with hepatic impairment (see sections 4.4, 4.5 and 5.2). 
 



3 

Paediatric population 
The safety and efficacy of Xerava in children and adolescents less than 18 years of age have not been 
established. No data are available. Xerava should not be used in children aged under 8 years because 
of teeth discolouration (see sections 4.4 and 4.6). 
 
Method of administration  
 
Intravenous use. 
 
Xerava is administered only by intravenous infusion over approximately 1 hour (see section 4.4). 
 
For instructions on reconstitution and dilution of the medicinal product before administration, see 
section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance, or to any of the excipients listed in section 6.1. 
Hypersensitivity to tetracycline class antibiotics. 
 
4.4 Special warnings and precautions for use 
 
Anaphylactic reactions 
 
Serious and occasionally fatal hypersensitivity reactions are possible and have been reported with 
other tetracycline class antibiotics (see section 4.3). In case of hypersensitivity reactions, treatment 
with eravacycline must be discontinued immediately and appropriate emergency measures must be 
initiated. 
 
Clostridium difficile-associated diarrhoea 
 
Antibiotic-associated colitis and pseudomembranous colitis have been reported with the use of nearly 
all antibiotics and may range in severity from mild to life-threatening. It is important to consider this 
diagnosis in patients who present with diarrhoea during or subsequent to treatment with eravacycline 
(see section 4.8). In such circumstances, the discontinuation of eravacycline and the use of supportive 
measures together with the administration of specific treatment for Clostridium difficile should be 
considered. Medicinal products that inhibit peristalsis should not be given. 
 
Infusion-site reactions 
 
Eravacycline is administered via intravenous infusion, using an infusion time of approximately 1 hour 
to minimise the risk of infusion-site reactions. Infusion-site erythema, pain/tenderness, phlebitis and 
thrombophlebitis were observed with intravenous eravacycline in clinical trials (see section 4.8). In 
case of serious reactions, eravacycline should be discontinued until a new intravenous access site is 
established. Additional measures to reduce the occurrence and severity of infusion site reactions 
include decreasing the eravacycline infusion rate and/or concentration. 
 
Non-susceptible micro-organisms 
 
Prolonged use may result in the overgrowth of non-susceptible micro-organisms, including fungi. If 
superinfection occurs during therapy, it may require interruption of treatment. Other appropriate 
measures should be taken and alternative antimicrobial treatment should be considered in accordance 
with existing therapeutic guidelines. 
 



4 

Pancreatitis 
 
Pancreatitis has been reported with eravacycline and other tetracycline class antibiotics, and has been 
severe in some cases (see section 4.8). If pancreatitis is suspected, eravacycline should be 
discontinued. 
 
Paediatric population 
 
Xerava should not be used during tooth development (during the 2nd and 3rd trimester of pregnancy, 
and in children under 8 years of age) as it may cause permanent discolouration of the teeth (yellow-
grey-brown) (see sections 4.2 and 4.6). 
 
Concomitant use of strong CYP3A4 inducers  
 
Medicines that induce CYP3A4 are expected to increase the rate and extent of metabolism of 
eravacycline. CYP3A4 inducers exert their effect in a time-dependent manner, and may take at least 2 
weeks to reach maximal effect after introduction. Conversely, on discontinuation, CYP3A4 induction 
may take at least 2 weeks to decline. Co-administration of a strong CYP3A4 inducer (such as 
phenobarbital, rifampicin, carbamazepine, phenytoin, St. John’s Wort) is expected to reduce the effect 
of eravacycline (see sections 4.2 and 4.5). 
 
Patients with severe hepatic impairment 
 
Exposure may be increased in patients with severe hepatic impairment (Child-Pugh Class C). 
Therefore, such patients should be monitored for adverse reactions (see Section 4.8), particularly if 
these patients are obese and/or are also being treated with strong CYP3A inhibitors where the 
exposure may be further increased (see sections 4.5 and 5.2). In these cases, no recommendation on a 
posology can be made. 
 
Limitations of the clinical data 
 
In clinical trials in cIAI, there were no immunocompromised patients, and the majority of patients 
(80%) had APACHE II scores <10 at baseline; 5.4% of the patients had concurrent bacteraemia at 
baseline; 34% of the patients had complicated appendicitis. 
 
Urinary tract infections  
 
Clinical trials have failed to demonstrate the efficacy of Xerava for the treatment of complicated 
urinary tract infections. Xerava is therefore not indicated for the treatment of complicated urinary tract 
infections. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Potential for other medicinal products to affect the pharmacokinetics of eravacycline 
 
Concomitant administration of the strong CYP 3A4/3A5 inducer rifampicin altered the 
pharmacokinetics of eravacycline, decreasing exposure by approximately 32% and increasing clearance 
by approximately 54%. The eravacycline dose should be increased by approximately 50% (1.5 mg/kg 
IV q12h) when co-administered with rifampicin or other strong CYP3A inducers such as phenobarbital, 
carbamazepine, phenytoin and St. John’s Wort (see sections 4.2 and 4.4). 
 
Concomitant administration of the strong CYP3A inhibitor itraconazole altered the pharmacokinetics of 
eravacycline, increasing Cmax by approximately 5% and AUC0-24 by approximately 23%, and decreasing 
clearance. The increased exposure is not likely to be clinically significant; thus, no dose adjustment is 
required when eravacycline is co-administered with CYP3A inhibitors. However, patients receiving 
strong CYP3A inhibitors (for example ritonavir, itraconazole, clarithromycin) with a combination of 



5 

factors that may increase the exposure, such as severe hepatic impairment and/or obesity should be 
monitored for adverse reactions (see sections 4.4 and 4.8). 
 
In vitro, eravacycline was shown to be a substrate for the transporters P-gp, OATP1B1 and OATP1B3. 
A drug-drug interaction in vivo cannot be excluded and co-administration of eravacycline and other 
medicinal products that inhibit these transporters (examples of OATP1B1/3 inhibitors; atazanavir, 
cyclosporine, lopinavir, and saquinavir) may increase the eravacycline plasma concentration.   
 
Potential for eravacycline to affect the pharmacokinetics of other medicinal products 
 
In vitro, eravacycline and its metabolites are not inhibitors or inducers of CYP enzymes or transport 
proteins (see section 5.2). Interactions with medicinal products that are substrates for these enzymes or 
transporters are therefore unlikely.  
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are limited data on the use of eravacycline in pregnant women. Studies in animals have shown 
reproductive toxicity (see section 5.3). The potential risk for humans is unknown.  
 
As for other tetracycline class antibiotics, eravacycline may induce permanent dental defects 
(discolouration and enamel defects) and a delay in ossification processes in foetuses exposed in utero 
during the 2nd and 3rd trimester, due to accumulation in tissues with a high calcium turnover and 
formation of calcium chelate complexes (see sections 4.4 and 5.3). Xerava should not be used during 
pregnancy unless the clinical condition of the woman requires treatment with eravacycline. 
 
Women of childbearing potential 
 
Women of childbearing potential should avoid becoming pregnant while receiving eravacycline. 
 
Breast-feeding 
 
It is unknown whether eravacycline and its metabolites are excreted in human breast milk. Animal 
studies have shown excretion of eravacycline and its metabolites in breast milk (see section 5.3).  
 
Long term use of other tetracyclines during breast-feeding may result in significant absorption by the 
breast-fed infant and is not recommended because of the risk of dental discolouration and delay in 
ossification processes of the breast-fed infant. 
 
A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with 
Xerava should be made, taking into account the benefit of breast-feeding for the child, and the benefit 
of therapy for the woman.  
 
Fertility 
 
There are no human data on the effect of eravacycline on fertility. Eravacycline did affect mating and 
fertility in male rats at clinically relevant exposures (see section 5.3).  
 
4.7 Effects on ability to drive and use machines 
 
Eravacycline may have a minor influence on the ability to drive and use machines. Dizziness may 
occur following administration of eravacycline (see section 4.8).  
 



6 

4.8 Undesirable effects 
 
Summary of the safety profile 
 
In clinical trials, the most common adverse reactions in patients with cIAI treated with eravacycline 
(n=576) were nausea (3.0%), vomiting, infusion site phlebitis (each 1.9%), phlebitis (1.4%), infusion 
site thrombosis (0.9%), diarrhoea (0.7%), vessel puncture site erythema (0.5%), hyperhidrosis, 
thrombophlebitis, infusion site hypoaesthesia, and headache (each 0.3%), which were generally mild 
or moderate in severity.  
 
Tabulated list of adverse reactions 
 
The adverse reactions identified with eravacycline are presented in Table 1. Adverse reactions are 
classified according to MedDRA system organ classification and frequency. Frequency categories are 
derived according to the following conventions: 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). Within each 
frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 
Table 1  Tabulated list of adverse reactions to eravacycline in clinical trials 

System Organ Class Common Uncommon 

Hepatobiliary disorders  
Aspartate aminotransferase (AST) increased 
Alanine aminotransferase (ALT) increased 
Hyperbilirubinaemia 

Immune system disorders  Hypersensitivity 

Nervous system disorders  Dizziness Headache 

Vascular disorders Thrombophlebitis
a 

Phlebitisb 
 

Gastrointestinal disorders  Nausea Vomiting 
Pancreatitis 
Diarrhoea 

Skin and subcutaneous tissue 
disorders 

 Rash 
Hyperhidrosis 

General disorders and 
administration site conditions Infusion site reactions

c  

a. Thrombophlebitis includes the preferred terms thrombophlebitis and infusion site thrombosis  
b. Phlebitis includes the preferred terms phlebitis, infusion site phlebitis, superficial phlebitis and injection 

site phlebitis 
c. Infusion site reactions includes the preferred terms injection site erythema, infusion site hypoaesthesia, 

vessel puncture site erythema and vessel puncture site pain 
 
Description of selected adverse reactions 
 
Infusion site reactions 
Mild to moderate infusion site reactions, including pain or discomfort, erythema and swelling or 
inflammation at the injection site as well as superficial thrombophlebitis and/or phlebitis have been 
reported in patients treated with eravacycline. Infusion site reactions can be mitigated by reducing the 
eravacycline infusion concentration or the infusion rate. 
 
Tetracycline class effects 
Tetracycline class adverse reactions include photosensitivity, pseudotumor cerebri, and anti-anabolic 
action which have led to increased BUN, azotaemia, acidosis, and hyperphosphataemia. 
 
Diarrhoea 
Antibiotic class adverse reactions include pseudomembranous colitis, and overgrowth of non-
susceptible organisms, including fungi (see section 4.4). In clinical trials, treatment-related diarrhoea 
occurred in 0.7% of patients; all cases were mild in severity. 
 



7 

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 
 
In studies administering up to 3 mg/kg eravacycline to healthy volunteers it has been observed that doses 
higher than the recommended dose lead to a higher rate of nausea and vomiting.  
In the case of suspected overdose Xerava should be discontinued and the patient monitored for adverse 
reactions.  
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antibacterials for systemic use, tetracyclines, ATC code: J01AA13. 
 
Mechanism of action 
 
The mechanism of action of eravacycline involves the disruption of bacterial protein synthesis by 
binding to the 30S ribosomal subunit thus preventing the incorporation of amino acid residues into 
elongating peptide chains.  
 
The C-7 and C-9 substitutions in eravacycline are not present in any naturally occurring or semisynthetic 
tetracyclines and the substitution pattern imparts microbiological activities including retention of in vitro 
potency against Gram-positive and Gram-negative strains expressing tetracycline-specific resistance 
mechanism(s) (i.e., efflux mediated by tet(A), tet(B), and tet(K); ribosomal protection as encoded by 
tet(M) and tet(Q)). Eravacycline is not a substrate for the MepA pump in Staphylococcus aureus that has 
been described as a resistance mechanism for tigecycline. Eravacycline is also not affected by 
aminoglycoside inactivating or modifying enzymes. 
 
Mechanism of resistance 
 
Resistance to eravacycline has been observed in Enterococcus harbouring mutations in rpsJ. There is 
no target-based cross-resistance between eravacycline and other classes of antibiotics such as 
quinolones, penicillins, cephalosporins, and carbapenems. 
 
Other bacterial resistance mechanisms that could potentially affect eravacycline are associated with 
upregulated, non-specific intrinsic multidrug-resistant (MDR) efflux. 
 
Susceptibility testing breakpoints 
 
Minimum inhibitory concentration (MIC) breakpoints established by the European Committee on 
Antimicrobial Susceptibility Testing (EUCAST) for eravacycline are: 
 

Pathogen MIC Breakpoints (µg/mL) Susceptible (S ≤) Resistant (R >) 
Escherichia coli 0.5 0.5 
Staphylococcus aureus  0.25 0.25 
Enterococcus spp.  0.125 0.125 
Viridans Streptococcus spp. 0.125 0.125 
 

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


8 

Pharmacokinetic/pharmacodynamic relationship 
 
The area under the plasma concentration-time curve (AUC) divided by the minimum inhibitory 
concentration (MIC) of eravacycline has been shown to be the best predictor of efficacy in vitro, 
utilising human steady state exposures in a chemostat and confirmed in vivo in animal models of 
infection.  
 
Clinical efficacy against specific pathogens 
 
Efficacy has been demonstrated in clinical studies against the pathogens listed for cIAI that were 
susceptible to eravacycline in vitro: 
 
• Escherichia coli 
• Klebsiella pneumoniae 
• Staphylococcus aureus  
• Enterococcus faecalis  
• Enterococcus faecium  
• Viridans Streptococcus spp. 
 
Antibacterial activity against other relevant pathogens 
 
In vitro data indicate that the following pathogen is not susceptible to eravacycline: 
• Pseudomonas aeruginosa 
 
Paediatric population 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Xerava in one or more subsets of the paediatric population in cIAI (see section 4.2 for information on 
paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Absorption  
 
Eravacycline is administered intravenously and therefore has 100% bioavailability. 
 
The mean pharmacokinetic parameters of eravacycline after single and multiple intravenous infusions 
(60 minutes) of 1 mg/ kg administered to healthy adults every 12 hours are presented in Table 2. 
 
Table 2 Mean (%CV) plasma pharmacokinetic parameters of eravacycline after single and  

multiple intravenous and in healthy adults 

Eravacycline dosing 

 PK parameters 
arithmetic mean (%CV) 

Cmax 
(ng/mL) 

tmaxa 
(h) 

AUC0-12b 
(ng*h/mL) 

t1/2 
(h) 

1.0 mg/kg IV every 12 hours (n=6) Day 1 2125 (15) 1.0 (1.0-1.0) 4305 (14) 9 (21) Day 10 1825 (16) 1.0 (1.0-1.0) 6309 (15) 39 (32) 
a Mean (range) represented 
b AUC of Day 1 = AUC 0-12 after the first dose and AUC for Day 10 = steady state AUC0- 12 
 
Distribution 
 
The in vitro binding of eravacycline to human plasma proteins increases with increasing 
concentrations, with 79%, 86% and 90% (bound) at 0.1, 1 and10 µg/mL, respectively. The mean 
(%CV) volume of distribution at steady-state in healthy normal volunteers following 1 mg/kg every 
12h is approximately 321 L (6.35), which is greater than total body water. 
 



9 

Biotransformation 
 
Unchanged eravacycline is the major medicinal product-related component in human plasma and 
human urine. Eravacycline is metabolised primarily by CYP3A4- and FMO-mediated oxidation of the 
pyrrolidine ring to TP-6208, and by chemical epimerisation at C-4 to TP-498. Additional minor 
metabolites are formed by glucuronidation, oxidation and hydrolysis. TP-6208 and TP-498 are not 
considered to be pharmacologically active. 
 
Eravacycline is a substrate for the transporters P-gp, OATP1B1 and OATP1B3 but not for BCRP.  
 
Elimination 
 
Eravacycline is excreted in both urine and faeces. Renal clearance and biliary and direct intestinal 
excretion account for approximately 35% and 48% of total body clearance after administration of a 
single IV dose of 60 mg 14C-eravacycline, respectively. 
 
Linearity/non-linearity 
 
The Cmax and AUC of eravacycline in healthy adults increase approximately in proportion to an 
increase in dose. There is approximately a 45% accumulation following intravenous dosing of 1 mg/kg 
every 12 hours. 
 
Within the range of eravacycline multiple intravenous doses studied clinically, the pharmacokinetic 
parameters AUC and Cmax demonstrate linearity, but with increasing doses the increase in both AUC 
and Cmax are slightly less than dose-proportional. 
 
Potential for drug-drug interactions 
 
Eravacycline and its metabolites are not inhibitors of CYP1A2, CYP2B6, CYP2C8, CYP2C9, 
CYP2C19, CYP2D6 or CYP3A4 in vitro. Eravacycline, TP-498 and TP-6208 are not inducers of 
CYP1A2, CYP2B6 or CYP3A4. 
 
Eravacycline, TP-498 and TP-6208 are not inhibitors of BCRP, BSEP, OATP1B1, OATP1B3, OAT1, 
OAT3, OCT1, OCT2, MATE1 or MATE2-K transporters. The metabolites TP-498 and TP-6208 are 
not inhibitors of P-gp in vitro. 
 
Special populations 
 
Renal impairment 
The geometric least square mean Cmax for eravacycline was increased by 8.8% for subjects with end 
stage renal disease (ESRD) versus healthy subjects with 90% CI -19.4, 45.2. The geometric least 
square mean AUC0-inf for eravacycline was decreased by 4.0% for subjects with ESRD versus healthy 
subjects with 90% CI -14.0, 12.3.  
 
Hepatic impairment 
The geometric mean Cmax for eravacycline was increased by 13.9%, 16.3%, and 19.7% for subjects 
with mild (Child-Pugh Class A), moderate (Child-Pugh Class B), and severe (Child-Pugh Class C) 
hepatic impairment versus healthy subjects, respectively. The geometric mean AUC0-inf for 
eravacycline was increased by 22.9%, 37.9%, and 110.3% for subjects with mild, moderate, and 
severe hepatic impairment versus healthy subjects, respectively.  
 
Gender 
In a population pharmacokinetic analysis of eravacycline, no clinically relevant differences in AUC by 
gender were observed for eravacycline.  
 



10 

Elderly (≥ 65 years) 
In a population pharmacokinetic analysis of eravacycline, no clinically relevant differences in the 
pharmacokinetics of eravacycline were observed with respect to age.  
 
Body weight 
In a population pharmacokinetic analysis it was shown that eravacycline disposition (clearance and 
volume) was dependent on body weight. However, the resulting difference in exposure to eravacycline 
in terms of AUC does not warrant dose adjustments in the weight range studied. No data are available 
for patients weighing more than 137 kg. The potential influence of severe obesity on eravacycline 
exposure has not been studied. 
 
5.3 Preclinical safety data 
 
In repeated dose toxicity studies in rats, dogs and monkeys, lymphoid depletion/atrophy of lymph 
nodes, spleen and thymus, decreased erythrocytes, reticulocytes, leukocytes, and platelets (dog and 
monkey), in association with bone marrow hypocellularity, and adverse gastrointestinal effects (dog 
and monkey) were observed with eravacycline. These findings were reversible or partially reversible 
during recovery periods of 3- to 7-weeks.  
 
Bone discolouration (in the absence of histological findings), which was not fully reversible over 
recovery periods of up to 7-weeks, was observed in rats and monkeys after 13 weeks of dosing. 
 
Intravenous administration of high doses of eravacycline has been associated with cutaneous responses 
(including hives, scratching, swelling, and/or skin erythema) in rat and dog studies. 
 
In fertility studies in male rats, eravacycline administered at about 5 times the clinical exposure (based 
on AUC), gave rise to a significantly reduced number of pregnancies. These findings were reversible 
following a 70-day (10-week) recovery period, equivalent to a spermatogenic cycle in the rat. Findings 
on the male reproductive organs were also observed in rats in the repeated dose toxicity studies for 14 
days or 13 weeks at exposures more than 10- or 5-fold the clinical exposure based on AUC. The 
observations included degeneration of the seminiferous tubules, oligospermia, and cellular debris in 
the epididymides, spermatid retention in the seminiferous tubules, increase of spermatid head retention 
in Sertoli cells, and vacuolation of Sertoli cells and decreased sperm counts. No adverse effects on 
mating or fertility were observed in female rats. 
 
In embryo-foetal studies, no adverse effects were observed in rats at exposures comparable to clinical 
exposure or in rabbits at exposures 1.9-fold higher than the clinical exposure (based on AUC) in rats 
and rabbits respectively. Doses more than 2- or 4-fold higher than the clinical exposure (based on 
AUC) were associated with maternal toxicity (clinical observations and reduced body weight gain and 
food consumption), and reduced foetal body weights and delays in skeletal ossification in both species 
and abortion in the rabbit. 
 
Animal studies indicate that eravacycline crosses the placenta and is found in foetal plasma. 
Eravacycline (and metabolites) is excreted in the milk of lactating rats. 
 
Eravacycline is not genotoxic. Carcinogenicity studies with eravacycline have not been conducted. 
 
Environmental risk assessment studies have shown that Xerava may pose a risk for the aquatic 
compartment.  
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Mannitol (E421) 
Sodium hydroxide (for pH adjustment) 
Hydrochloric acid (for pH adjustment) 



11 

6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6.  
 
6.3 Shelf life 
 
3 years  
 
Chemical and physical in-use stability after reconstitution in the vial has been demonstrated for 1 hour 
at 25°C. 
 
Chemical and physical in-use stability after dilution in the infusion bag has been demonstrated for 
12 hours at 25°C.  
 
Chemical and physical in-use stability after dilution in the infusion bag has been demonstrated for 
72 hours at refrigerated conditions (2-8°C) . 
 
From a microbiological point of view, unless the method of opening/reconstitution/dilution precludes 
the risk of microbial contamination, the product should be used immediately. If not used immediately, 
in-use storage times and conditions are the responsibility of the user. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C–8°C). Keep the vial in the carton in order to protect from light. 
 
For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container  
 
10mL Type I glass vial with chlorobutyl rubber stopper and aluminium cap. 
 
Pack sizes: 1 vial and multipacks containing 12 (12 packs of 1) vials. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
General precautions 
 
Each vial is for single use only. 
 
Aseptic technique must be followed when preparing the infusion solution. 
 
Instructions for reconstitution 
The contents of the required number of vials should each be reconstituted with 5 mL water for 
injections, and swirled gently until the powder has dissolved entirely. Shaking or rapid movement 
should be avoided as it may cause foaming.  
 
Reconstituted Xerava should be a clear, pale yellow to orange solution. The solution should not be 
used if any particles are noticed or the solution is cloudy. 
 
Preparation of the infusion solution 
For administration, the reconstituted solution must be further diluted using sodium chloride 9 mg/mL 
(0.9%) solution for injection. The calculated volume of the reconstituted solution should be added to 
the infusion bag to a target concentration of 0.3 mg/mL, within a range of 0.2 to 0.6 mg/mL. See 
example calculations in Table 3. 



12 

 
Gently invert the bag to mix the solution. 
 
Table 3  Example calculations for weights ranging from 40 kg to 200 kg 
Patient weight  
(kg) 

Total Dose 
(mg) 

Number of vials 
to needed to 
reconstitute 

Total volume to be 
diluted (mL) 

Recommended infusion 
bag size 

40 40 1 4 100 mL 
60 60 2 6 250 mL 
80 80 2 8 250 mL 
100 100 2 10 250 mL 
150 150 3 15 500 mL 
200 200 4 20 500 mL 
1 The exact dose needs to be calculated based on the specific patient weight. 
  
For patients weighing ≥ 40 kg – 49 kg: 
Calculate the required volume of the reconstituted solution based on the patient’s weight and inject into a 100 
mL infusion bag. 
For patients weighing 50 kg – 100 kg: 
Calculate the required volume of the reconstituted solution based on the patient’s weight and inject into a 250 
mL infusion bag. 
For patients weighing >100 kg: 
Calculate the required volume of the reconstituted solution based on the patient’s weight and inject into a 500 
mL infusion bag. 
 
Infusion 
The ready to use solution should be inspected visually for particulate matter prior to administration. 
Reconstituted and diluted solutions containing visible particles or that are cloudy in appearance should 
be discarded.  
 
Following dilution, Xerava is administered intravenously over approximately 1 hour. 
 
The reconstituted and diluted solution must be administered as an intravenous infusion only. It must 
not be administered as an intravenous bolus.  
 
If the same intravenous line is used for sequential infusion of several different medicinal products, the 
line should be flushed before and after infusion with sodium chloride 9 mg/ml (0.9%) solution for 
injection. 
 
Disposal 
 
This medicinal product may pose a risk to the environment (See section 5.3).  
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Tetraphase Pharmaceuticals Ireland Limited 
10 Earlsfort Terrace  
Dublin 2, D02 T380, Ireland  
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/18/1312/001 
EU/1/18/1312/002 
 



13 

 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 20 September 2018 
 
 
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 

 



15 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
   

Name and address of the manufacturer(s) responsible for batch release 
Patheon Italia S.p.A. 
2° Trav. SX Via Morolense, 5 
03013 
Ferentino 
Italy 

 
 

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  
 

The requirements for submission of periodic safety update reports 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 the first periodic safety update report 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 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 
 
OUTER CARTON: 1 VIAL  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Xerava 50 mg powder for concentrate for solution for infusion 
eravacycline  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial contains 50 mg eravacycline 
After reconstitution 1 mL contains 10 mg eravacycline. 
 
 
3. LIST OF EXCIPIENTS 
 
mannitol (E421), sodium hydroxide, hydrochloric acid 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for concentrate for solution for infusion 
1 vial 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For intravenous use after reconstitution and dilution. 
 
 
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 a refrigerator. Keep the vial in the carton in order to protect from light. 
 
 



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 
 
Tetraphase Pharmaceuticals Ireland Limited 
10 Earlsfort Terrace  
Dublin 2, D02 T380 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/18/1312/001  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  
 



20 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON: MULTIPACK, CONTAINS BLUE BOX  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Xerava 50 mg powder for concentrate for solution for infusion 
eravacycline  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial contains 50 mg eravacycline 
After reconstitution 1 mL contains 10 mg eravacycline. 
 
 
3. LIST OF EXCIPIENTS 
 
mannitol (E421), sodium hydroxide, hydrochloric acid 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for concentrate for solution for infusion 
Multipack: 12 (12x1) vials 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For intravenous use after reconstitution and dilution. 
 
 
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 a refrigerator. Keep the vial in the inner carton in order to protect from light. 
 
 



21 

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 
 
Tetraphase Pharmaceuticals Ireland Limited 
10 Earlsfort Terrace  
Dublin 2, D02 T380 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/18/1312/002  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  



22 

 
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
INNER CARTON: MULTIPACK, CONTAINS NO BLUE BOX 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Xerava 50 mg powder for concentrate for solution for infusion 
eravacycline  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial contains 50 mg eravacycline 
After reconstitution 1 mL contains 10 mg eravacycline. 
 
 
3. LIST OF EXCIPIENTS 
 
mannitol (E421), sodium hydroxide, hydrochloric acid 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for concentrate for solution for infusion 
1 vial. Component of a multipack, can’t be sold seperately. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For intravenous use after reconstitution and dilution. 
 
 
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 a refrigerator. Keep the vial in the carton in order to protect from light. 
 
 



23 

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 
 
Tetraphase Pharmaceuticals Ireland Limited 
10 Earlsfort Terrace  
Dublin 2, D02 T380 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/18/1312/002  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 



24 

 
 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Xerava 50 mg powder for concentrate  
eravacycline 
IV  
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
 
6. OTHER 
 
 
 
 



25 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
B. PACKAGE LEAFLET 



26 

Package leaflet: Information for the patient 
 

Xerava 50 mg powder for concentrate for solution for infusion 
eravacycline  

 
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 receive 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 nurse. 
- If you get any side effects, talk to your doctor or nurse. This includes any possible side effects 

not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Xerava is and what it is used for  
2. What you need to know before you are given Xerava  
3. How you will be given Xerava 
4. Possible side effects  
5. How to store Xerava 
6. Contents of the pack and other information 
 
 
1. What Xerava is and what it is used for 
 
What Xerava is 
 
Xerava is an antibiotic medicine that contains the active substance eravacycline. It belongs to a group 
of antibiotics called ‘tetracyclines’ which work by stopping the growth of certain infectious bacteria.  
 
What Xerava is used for 
 
Xerava is used to treat adults with a complicated infection in the abdomen.  
 
 
2. What you need to know before you are given Xerava  
 
You must not receive Xerava:  
 
- if you are allergic to eravacycline or any of the other ingredients of this medicine (listed in 

section 6).  
- if you are allergic to any tetracycline antibiotics (e.g., minocycline and doxycycline) because 

you may also be allergic to eravacycline.  
 
Warnings and precautions  
 
Talk to your doctor or nurse before you receive Xerava if you are concerned about any of the 
following: 
 
Anaphylactic reactions 
Anaphylactic (allergic) reactions have been reported with other tetracycline antibiotics. These can 
develop suddenly and can potentially be life-threatening. Seek urgent medical attention if you 
suspect you have an anaphylactic reaction whilst receiving Xerava. Symptoms to look out for include 



27 

rash, swelling of the face, feeling lightheaded or faint, tightness of the chest, breathing difficulties, fast 
heartbeat, or losing consciousness (see also section 4).  
 
Diarrhoea 
Talk to your doctor or nurse if you are suffering from diarrhoea before being given Xerava. If you 
develop diarrhoea during or after your treatment, tell your doctor straight away. Do not take any 
medicine to treat your diarrhoea without first checking with your doctor (see also section 4). 
 
Infusion site reactions 
Xerava is given by an infusion (drip) directly into your vein. Tell your doctor or nurse if you notice 
any of the following at the site of infusion during or after your treatment: redness of the skin, rash, 
inflammation, or pain or tenderness.  
 
New infection 
Although antibiotics including Xerava fight certain bacteria, other bacteria and fungi may continue to 
grow. This is called ‘overgrowth’ or ‘superinfection’. Your doctor will monitor you closely for any 
new infections or stop treatment with Xerava and give you another treatment if necessary.  
 
Pancreatitis 
Severe pain in the abdomen and back with fever may be signs of inflammation of the pancreas. Tell 
your doctor or nurse if you notice any of these side effects during your treatment with Xerava. 
 
Liver problems  
Talk to your doctor if you have liver problems or if you are overweight, particularly if you are also 
taking itraconazole (a medicine to treat fungal infections), ritonavir (a medicine used to treat viral 
infections) or clarithromycin (an antibiotic) as your doctor will monitor you for side effects. 
 
Children and adolescents 
 
This medicine should not be used in children and adolescents under the age of 18 years as it has not 
been studied enough in these populations. Xerava must not be used in children below 8 years of age 
because it can cause permanent effects on their teeth such as discolouration. 
 
Other medicines and Xerava 
 
Tell your doctor or nurse if you are taking, have recently taken or might take any other medicines 
including rifampicin and clarithromycin (antibiotics), phenobarbital, carbamazepine and phenytoin 
(used to treat epilepsy), St. John’s Wort (a herbal remedy used for treatment of depression and 
anxiety) itraconazole (a medicine to treat fungal infections), ritonavir, atazanavir, lopinavir and 
saquinavir (medicines used to treat viral infections), and cyclosporine (a medicine used to suppress the 
immune system). 
 
Pregnancy and breast-feeding  
 
If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for 
advice before receiving this medicine. Xerava is not recommended for use during pregnancy as it can:  

• permanently stain your unborn child’s teeth 
• delay the natural formation of the bones of your unborn child. 

 
It is not known if Xerava passes into breast milk. Long-term use of other similar antibiotic medicines 
by breast-feeding mothers can stain the child’s teeth permanently. Ask your doctor for advice before 
breast-feeding your baby. 
 
Driving and using machines 
 
Xerava may affect your ability to drive or use machines safely. Do not drive or use machines if you 
feel dizzy, light-headed or unsteady after receiving this medicine.  



28 

3. How you will be given Xerava 
 
Xerava will be given to you by a doctor or nurse. 
 
The recommended dose for adults is based on body weight and is 1 mg/kg every 12 hours. 
Your doctor may increase your dose (1.5 mg/kg every 12 hours) if you are taking other medicines 
including rifampicin, phenobarbital, carbamazepine, phenytoin, or St. John’s Wort. 
 
It will be given to you through a drip directly into a vein (intravenously) over approximately 1 hour. 
 
A course of treatment usually lasts for 4 to 14 days. Your doctor will decide how long you should be 
treated for.  
 
If you are given more Xerava than you should 
 
Xerava will be given to you in hospital by a doctor or nurse. It is, therefore, unlikely that you will be 
given too much. Tell your doctor or nurse immediately if you are concerned that you may have been 
given too much Xerava. 
 
If you miss a dose of Xerava 
 
Xerava will be given to you in hospital by a doctor or nurse. It is, therefore, unlikely that you will miss 
a dose. Tell your doctor or nurse immediately if you are concerned that you may have missed a dose. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Seek urgent medical attention if you suspect you have an anaphylactic reaction, or develop any of 
the following symptoms, whilst receiving Xerava: 

• Rash 
• Swelling of the face 
• Feeling lightheaded or faint 
• Tightness of the chest 
• Breathing difficulties 
• Fast heartbeat 
• Losing consciousness  

 
Tell your doctor or nurse straightaway if you develop diarrhoea during or after your treatment. Do 
not take any medicine to treat your diarrhoea without first checking with your doctor. 
 
Other side effects may include: 
 
Common side effects (may affect up to 1 in 10 people): 

• Nausea  
• Vomiting  
• Inflammation and pain caused by blood clots at the injection site (thrombophlebitis) 
• Inflammation of a vein causing pain and swelling (phlebitis) 
• Redness or swelling at the site of the injection 
 

Uncommon side effects (may affect up to 1 in 100 people): 
• Diarrhoea 
• Allergic reaction  
• Inflammation of the pancreas which causes severe pain in the abdomen or back (pancreatitis) 
• Rash 



29 

• Dizziness 
• Headache 
• Increased sweating 
• Abnormal blood test results for liver 

 
Tell your doctor or nurse if you have any of these side effects. 
 
Other tetracycline antibiotics 
Other side effects have been reported with other tetracycline antibiotics including minocycline and 
doxycycline. These include sensitivity to light, headaches, vision problems, or abnormal blood tests. 
Tell your doctor or nurse if you notice any of these during your treatment with Xerava. 
 
Reporting of side effects 
 
If you get any side effects, talk to your doctor or nurse. 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 Xerava 
 
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 vial label and carton after ‘EXP’. 
The expiry date refers to the last day of that month. 
 
Store in a refrigerator (2°C to 8°C). Keep the vial in the carton in order to protect from light. 
 
Once the powder has been made into a solution and diluted ready for use, it should be given to you 
immediately. If not, it may be stored at room temperature and used within 12 hours.  
 
Reconstituted Xerava should be a clear, pale yellow to orange solution. The solution should not be 
used if it appears to contain any particles or the solution is cloudy. 
 
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 Xerava contains  
 
- The active substance is eravacycline. Each vial contains 50 mg of eravacycline. 
- The other ingredients are mannitol (E421), hydrochloric acid (for pH adjustment) and sodium 

hydroxide (for pH adjustment).  
 
What Xerava looks like and contents of the pack 
 
Xerava is a pale yellow to dark yellow cake in a 10mL glass vial. The powder for concentrate for 
solution for infusion (powder for concentrate) will be reconstituted in the vial with 5 mL of water for 
injections. The reconstituted solution will be withdrawn from the vial and added to an infusion bag of 
sodium chloride 9 mg/mL (0.9%) solution for injection in the hospital. 
 
Xerava is available in packs containing 1 vial or multipacks comprising 12 cartons, each containing 1 
vial. 
 

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


30 

Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder  
 
Tetraphase Pharmaceuticals Ireland Limited 
10 Earlsfort Terrace  
Dublin 2, D02 T380, Ireland  
 
Manufacturer 
 
Patheon Italia S.p.A. 
2° Trav. SX. Via Morolense, 5 
03013 Ferentino (FR) 
Italy 
 
For any information about this medicine, please contact the Marketing Authorisation Holder. 
 
This leaflet was last revised in {MM/YYYY}. 
 
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: 
 
Important: Please refer to the Summary of Product Characteristics (SmPC) before prescribing. 
 
Xerava must be reconstituted with water for injections and subsequently diluted using sodium chloride 
9 mg/mL (0.9%) solution for injection. 
 
Xerava must not be mixed with other medicinal products. If the same intravenous line is used for 
sequential infusion of different medicinal products, the line should be flushed before and after infusion 
with sodium chloride 9 mg/ml (0.9%) solution for injection. 
 
The dose should be calculated based on the patient’s weight; 1 mg/kg body weight. 
 
Instructions for reconstitution 
 
Aseptic technique must be followed when preparing the infusion solution. Each vial should be 
reconstituted with 5 mL water for injections, and swirled gently until the powder has dissolved 
entirely. Shaking or rapid movement should be avoided as it may cause foaming.  
 
Reconstituted Xerava should be a clear, pale yellow to orange solution. The solution should not be 
used if particles are present or the solution is cloudy. 
 
Preparation of the infusion solution 
 
For administration, the reconstituted solution must be further diluted using sodium chloride 9 mg/ml 
(0.9%) solution for injection. The calculated volume of the reconstituted solution should be added to 
the infusion bag to a target concentration of 0.3 mg/mL, within a range of 0.2 to 0.6 mg/mL. See 
example calculations in Table 1. 
 
Gently invert the bag to mix the solution. 
 



31 

Table 1 Example calculations for weights ranging from 40 kg to 200 kg 
 
Patient weight  
(kg) 

Total Dose 
(mg) 

Number of vials 
to reconstitute 

Total volume to be 
diluted (mL) 

Recommended infusion 
bag size 

40 40 1 4 100 mL 
60 60 2 6 250 mL 
80 80 2 8 250 mL 
100 100 2 10 250 mL 
150 150 3 15 500 mL 
200 200 4 20 500 mL 
1 The exact dose needs to be calculated based on the specific patient weight. 
  
For patients weighing ≥ 40 kg – 49 kg: 
Calculate the required volume of the reconstituted solution based on the patient’s weight and inject into a 100 
mL infusion bag. 
For patients weighing 50 kg – 100 kg: 
Calculate the required volume of the reconstituted solution based on the patient’s weight and inject into a 250 
mL infusion bag. 
For patients weighing >100 kg: 
Calculate the required volume of the reconstituted solution based on the patient’s weight and inject into a 500 
mL infusion bag. 
 
Infusion 
 
The infusion solution should be inspected visually for particulate matter prior to administration. 
Reconstituted and diluted solutions containing visible particles or that are cloudy in appearance should 
be discarded.  
 
Following dilution, Xerava is administered intravenously over approximately 1 hour. The 
recommended dose regimen of Xerava is 1 mg/kg every 12 hours for 4 to 14 days. 
 
The reconstituted and diluted solution must be administered as an intravenous infusion only. It must 
not be administered as an intravenous bolus.  
 
For single use only, any unused solution should be discarded. 


	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