Vaborem

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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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 
 
Vaborem 1 g/1 g powder for concentrate for solution for infusion 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each vial contains meropenem trihydrate equivalent to 1 g meropenem, and 1 g vaborbactam. 
 
After reconstitution, 1 ml of the solution contains 50 mg meropenem and 50 mg vaborbactam (see section 
6.6). 
 
Excipient with known effect: 
 
Each vial contains 10.9 mmol of sodium (approximately 250 mg). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM  
 
Powder for concentrate for solution for infusion (powder for concentrate). 
 
White to light yellow powder. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Vaborem is indicated for the treatment of the following infections in adults (see sections 4.4 and 5.1): 

• Complicated urinary tract infection (cUTI), including pyelonephritis  
• Complicated intra-abdominal infection (cIAI) 
• Hospital-acquired pneumonia (HAP), including ventilator associated pneumonia (VAP). 

 
Treatment of patients with bacteraemia that occurs in association with, or is suspected to be associated 
with, any of the infections listed above. 
 
Vaborem is also indicated for the treatment of infections due to aerobic Gram-negative organisms in 
adults with limited treatment options (see sections 4.2, 4.4 and 5.1). 
 
Consideration should be given to official guidance on the appropriate use of antibacterial agents. 
 
 
 
 
 



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4.2 Posology and method of administration 
 
Vaborem should be used to treat infections due to aerobic Gram-negative organisms in adult patients with 
limited treatment options only after consultation with a physician with appropriate experience in the 
management of infectious diseases (see sections 4.4 and 5.1). 
 
Posology 
 
Table 1 shows the recommended intravenous dose for patients with a creatinine clearance 
(CrCl) ≥40 ml/min (see sections 4.4 and 5.1). 
 
Table 1:  Recommended intravenous dose for patients with a creatinine clearance 
(CrCl) ≥40 ml/min1 
Type of infection Dose of Vaborem 

(meropenem/ 
vaborbactam)2 

 

Frequency Infusion time Duration of 
treatment 

Complicated UTI (cUTI), 
including pyelonephritis 
 

2 g/2 g 
 

Every  
8 hours 

3 hours 5 to 10 days2 

cIAI 
 

2 g/2 g Every  
8 hours 

 

3 hours 5 to 10 days2 

Hospital-acquired 
pneumonia (HAP), 
including VAP 
 

2 g/2 g Every  
8 hours 

3 hours 7 to 14 days 

Bacteraemia, in 
association with, or 
suspected to be 
associated with, any of 
the infections listed 
above 
 

2 g/2 g Every  
8 hours 

3 hours  Duration in 
accordance with 

the site of 
infection 

Infections due to aerobic 
Gram-negative organisms 
in patients with limited 
treatment options 
 
 

2 g/2 g Every  
8 hours 

3 hours  Duration in 
accordance with 

the site of 
infection 

1 As calculated using the Cockcroft-Gault formula 
2 Treatment may continue up to 14 days  
 
Special populations 
 
Elderly population 
No dose adjustment based on age is required (see section 5.2). 
 
Renal impairment 
Table 2 shows the recommended dose adjustments for patients with a CrCl ≤39 ml/min.  
 
Meropenem and vaborbactam are removed by haemodialysis (see section 5.2). Doses adjusted for renal 
impairment should be administered after a dialysis session. 



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Table 2:  Recommended intravenous doses for patients with a CrCl ≤39 ml/min1 
CrCl (ml/min)1 Recommended Dosage 

Regimen2 
Dosing Interval Infusion Time 

20 to 39 1 g/1 g Every 8 hours 3 hours 

10 to 19 1 g/1 g Every 12 hours 3 hours 

Less than 10 0.5 g/0.5 g Every 12 hours 3 hours 
1 As calculated using the Cockcroft-Gault formula 
2 Refer to Table 1 for the recommended duration of treatment 
 
Hepatic impairment 
No dose adjustment is required in patients with hepatic impairment (see sections 4.4 and 5.2). 
 
Paediatric population 
The safety and efficacy of meropenem/vaborbactam in children and adolescents younger than 18 years of 
age have not yet been established. No data are available. 
 
Method of administration  
 
Intravenous use. 
 
Vaborem is administered by intravenous infusion over 3 hours.  
 
For instructions on reconstitution and dilution of the medicinal product before administration, see section 
6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1. 
 
Hypersensitivity to any carbapenem antibacterial agent. 
 
Severe hypersensitivity (e.g. anaphylactic reaction, severe skin reaction) to any other type of beta-lactam 
antibacterial agent (e.g. penicillins, cephalosporins or monobactams). 
 
4.4 Special warnings and precautions for use 
 
Hypersensitivity reactions 
 
Serious and occasionally fatal hypersensitivity reactions have been reported with meropenem and/or 
meropenem/vaborbactam (see sections 4.3 and 4.8). 
 
Patients who have a history of hypersensitivity to carbapenems, penicillins or other beta-lactam 
antibacterial agents may also be hypersensitive to meropenem/vaborbactam. Before initiating therapy with 
Vaborem, careful inquiry should be made concerning previous hypersensitivity reactions to beta-lactam 
antibiotics. 
 
If a severe allergic reaction occurs, treatment with Vaborem must be discontinued immediately and 
adequate emergency measures must be initiated. 
 
 



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Seizures 
 
Seizures have been reported during treatment with meropenem (see section 4.8). 
 
Patients with known seizure disorders should continue anticonvulsant therapy. Patients who develop focal 
tremors, myoclonus, or seizures should be evaluated neurologically and placed on anticonvulsant therapy 
if not already instituted. If necessary, the dose of meropenem/vaborbactam should be adjusted based on 
renal function (see section 4.2). Alternatively, meropenem/vaborbactam should be discontinued (see 
section 4.5). 
 
Hepatic function monitoring 
 
Hepatic function should be closely monitored during treatment with meropenem/vaborbactam due to the 
risk of hepatic toxicity (hepatic dysfunction with cholestasis and cytolysis) (see section 4.8).  
 
Patients with pre-existing liver disorders should have liver function monitored during treatment with 
meropenem/vaborbactam. There is no dose adjustment necessary (see section 4.2).  
 
Antiglobulin test (Coombs test) seroconversion 
 
A positive direct or indirect Coombs test may develop during treatment with meropenem/vaborbactam as 
seen with meropenem (see section 4.8). 
 
Clostridium difficile-associated diarrhoea 
 
Clostridium difficile-associated diarrhoea has been reported with meropenem/vaborbactam. The condition 
can range in severity from mild diarrhoea to fatal colitis and should be considered in patients who present 
with diarrhoea during or subsequent to the administration of Vaborem (see section 4.8). Discontinuation 
of therapy with Vaborem and the administration of specific treatment for Clostridium difficile should be 
considered. Medicinal products that inhibit peristalsis should not be given. 
 
Concomitant use with valproic acid/sodium valproate/valpromide  
 
Case reports in the literature have shown that co-administration of carbapenems, including meropenem, to 
patients receiving valproic acid or divalproex sodium may reduce plasma levels of valproic acid to 
concentrations below the therapeutic range as a result of this interaction, thus increasing the risk of 
breakthrough seizures. If administration of Vaborem is necessary, supplemental anticonvulsant therapy 
should be considered (see section 4.5). 
 
Limitations of the clinical data 
 
Complicated intra-abdominal infections  
The use of Vaborem to treat patients with complicated intra-abdominal infections is based on experience 
with meropenem alone and pharmacokinetic-pharmacodynamic analyses of meropenem/vaborbactam.  
 
Hospital-acquired pneumonia, including ventilator-associated pneumonia 
The use of  Vaborem to treat patients with hospital-acquired pneumonia, including ventilator-associated 
pneumonia, is based on experience with meropenem alone and pharmacokinetic-pharmacodynamic 
analyses for meropenem/vaborbactam. 
 
Patients with limited treatment options 



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The use of Vaborem to treat patients with infections due to bacterial organisms who have limited 
treatment options is based on pharmacokinetic/pharmacodynamic analyses for meropenem/vaborbactam 
and on limited data from a randomised clinical trial in which 32 patients were treated with Vaborem and 
15 patients were treated with best available therapy for infections caused by carbapenem-resistant 
organisms (see section 5.1).  
 
Spectrum of activity of meropenem/vaborbactam 
 
Meropenem does not have activity against methicillin-resistant Staphylococcus aureus (MRSA) and 
Staphylococcus epidermidis (MRSE) or vancomycin-resistant Enterococci (VRE). Alternative or 
additional antibacterial agents should be used when these pathogens are known or suspected to be 
contributing to the infectious process.  
 
The inhibitory spectrum of vaborbactam includes class A carbapenemases (such as KPC) and Class C 
carbapenemases. Vaborbactam does not inhibit class D carbapenemases such as OXA-48 or class B 
metallo-β-lactamases such as NDM and VIM (see section 5.1). 
 
Non-susceptible organisms 
 
The use of meropenem/vaborbactam may result in the overgrowth of non-susceptible organisms, which 
may require interruption of treatment or other appropriate measures. 
  
Controlled sodium diet 
 
Vaborem contains 10.9 mmol (approximately 250 mg) of sodium per vial. This should be taken into 
consideration while treating patients on a controlled sodium diet.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Caution should be used when administering meropenem/vaborbactam concomitantly with medicinal 
products with a narrow therapeutic window that are predominantly metabolised by CYP450 enzymes (e.g. 
immunosuppressants such as tacrolimus, everolimus and cyclosporine, lovastatin, midazolam, sildenafil 
and warfarin) as conclusive data on whether meropenem or vaborbactam may be inhibitors or inducers of 
CYP450 enzymes is not yet available. It is unknown whether a potential interaction would result in 
increased or decreased plasma concentrations, and thus patients should be monitored both for signs of 
toxicity and lack of efficacy of the narrow therapeutic index drug. 
 
In vitro data suggest that vaborbactam may inhibit CYP2D6, and a risk for increased plasma 
concentrations of sensitive CYP2D6 substrates in vivo cannot be excluded. Patients taking CYP2D6 
substrates with narrow therapeutic index (e.g. dextromethorphan, desipramine, venlafaxine, and 
metoprolol) should be monitored for signs of toxicity. 
 
Meropenem alone is not known to interact with active transport systems. 
 
Meropenem is a substrate of OAT1 and OAT3 and as such, probenecid competes with meropenem for 
active tubular secretion and thus inhibits the renal excretion of meropenem. Co-administration of 
probenecid with Vaborem is not recommended, as it may result in increased plasma concentrations of 
meropenem. 
 
Concomitant administration of meropenem and valproic acid has been associated with reductions in 
valproic acid concentrations with subsequent loss in seizure control. Data from in vitro and animal studies 
suggest that carbapenems may inhibit the hydrolysis of valproic acid’s glucuronide metabolite (VPA g) 
back to valproic acid, thus decreasing the serum concentrations of valproic acid. Therefore, supplemental 



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anticonvulsant therapy should be administered when concomitant administration of valproic acid and 
meropenem/vaborbactam cannot be avoided (see section 4.4). 
 
Oral anticoagulants 
 
Simultaneous administration of antibacterial agents with warfarin may augment its anticoagulant effects. 
There have been many reports of increases in the anticoagulant effects of orally administered 
anticoagulants, including warfarin in patients, who are concomitantly receiving antibacterial agents. The 
risk may vary with the underlying infection, age and general status of the patient so that the contribution 
of the antibacterial agent to the increase in international normalised ratio (INR) is difficult to assess. It is 
recommended that the INR should be monitored frequently during and shortly after co-administration of 
Vaborem with an oral anticoagulant. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of 
meropenem/vaborbactam in pregnant women. Animal studies do not indicate direct or indirect harmful 
effects with respect to reproductive toxicity (see section 5.3).  
 
As a precautionary measure, it is preferable to avoid the use of Vaborem during pregnancy. 
 
Breast-feeding 
 
Meropenem has been reported to be excreted in human milk. It is unknown whether vaborbactam is 
excreted in human milk or animal milk. Because a risk to the newborns/infants cannot be excluded, 
breastfeeding must be discontinued prior to initiating therapy. 
 
Fertility 
 
The effects of meropenem/vaborbactam on fertility in humans have not been studied. Animal studies 
conducted with meropenem and vaborbactam do not indicate harmful effects with respect to fertility (see 
section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Vaborem has moderate influence on the ability to drive and use machines. Seizures have been reported 
during treatment with meropenem alone, especially in patients treated with anticonvulsants (see section 
4.4). Meropenem/vaborbactam may cause headache, paraesthesia, lethargy and dizziness (see section 4.8). 
Therefore, caution should be exercised when driving or using machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The most common adverse reactions that occurred among 322 patients from the pooled Phase 3 trials were 
headache (8.1%), diarrhoea (4.7%), infusion site phlebitis (2.2%) and nausea (2.2%). 
 
Severe adverse reactions were observed in two patients (0.6 %), one infusion related reaction and one 
blood alkaline phosphatase increased respectively.  In one additional patient, a serious adverse reaction of 
infusion related reaction was reported (0.3%). 
 



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Tabulated list of adverse reactions 
 
The following adverse reactions have been reported with meropenem alone and/or identified during the 
Phase 3 trials with Vaborem. Adverse reactions are classified according to frequency and System Organ 
Class. Adverse reactions listed in the table with a frequency of “unknown” were not observed in patients 
participating in trials with Vaborem or meropenem, but have been reported in the post-marketing setting 
for meropenem alone. 
 
Frequencies are defined as: 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); unknown (cannot be estimated from the 
available data). Within each System Organ Class, undesirable effects are presented in order of decreasing 
seriousness.  
 
Table 3:  Frequency of adverse reactions by system organ class  
System Organ 
Class 

Common 
(≥1/100 to <1/10) 

Uncommon 
(≥1/1,000 to 
<1/100) 

Rare 
(≥1/10,000 to 
<1/1,000) 

Unknown 
(cannot be 
estimated from the 
available data) 

Infections and 
infestations 

 Clostridium 
difficile colitis  
 
Vulvovaginal 
candidiasis 
 
Oral candidiasis 

  

Blood and 
lymphatic system 
disorders 

Thrombocythaemia Leucopenia  
 
Neutropenia 
 
Eosinophilia 
 
Thrombocytopenia  

 Agranulocytosis 
 
Haemolytic 
anaemia 

Immune system 
disorders 

 Anaphylactic 
reaction 
 
Hypersensitivity 

 Angioedema 
 

Metabolism and 
nutrition disorders 

Hypokalaemia 
 
Hypoglycaemia 

Decreased appetite 
 
Hyperkalaemia 
 
Hyperglycaemia 

  

Psychiatric disorders  Insomnia  
 
Hallucination 
 
 

  

Nervous system 
disorders 

Headache Tremor 
 
Lethargy 
 
Dizziness 
 
Paraesthesia 

Convulsions   

Vascular disorders Hypotension 
 

Phlebitis 
 
Vascular pain 

  

Respiratory,  Bronchospasm   



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System Organ 
Class 

Common 
(≥1/100 to <1/10) 

Uncommon 
(≥1/1,000 to 
<1/100) 

Rare 
(≥1/10,000 to 
<1/1,000) 

Unknown 
(cannot be 
estimated from the 
available data) 

thoracic and 
mediastinal 
disorders 
Gastrointestinal 
disorders 

Diarrhoea 
 
Nausea 
 
Vomiting 

Abdominal 
distension 
 
Abdominal pain 

  

Hepatobiliary 
disorders 

Alanine 
aminotransferase 
increased  
 
Aspartate 
aminotransferase 
increased  
 
Blood alkaline 
phosphatase 
increased 
 
Blood lactate 
dehydrogenase 
increased 

Blood bilirubin 
increased 
 

  

Skin and 
subcutaneous 
disorders 

 Pruritus 
 

Rash 
 
Urticaria 

 Toxic epidermal 
necrolysis 
 
Stevens Johnson 
syndrome 
 
Erythema 
multiforme 
 
Drug reaction with 
eosinophilia and 
systemic 
symptoms 
(DRESS 
syndrome) 

Renal and urinary 
disorders 

 Renal impairment 
 
Incontinence 
 
Blood creatinine 
increased 
 
Blood urea 
increased 

  

General disorders 
and administration 
site conditions 

Infusion site 
phlebitis 
 

Pyrexia 
 
 

Chest discomfort 
 
Infusion site 
reaction 
 
Infusion site 
erythema 

  



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System Organ 
Class 

Common 
(≥1/100 to <1/10) 

Uncommon 
(≥1/1,000 to 
<1/100) 

Rare 
(≥1/10,000 to 
<1/1,000) 

Unknown 
(cannot be 
estimated from the 
available data) 

 
Injection site 
phlebitis 
 
Infusion site 
thrombosis 
 
Pain 

Investigations  Blood creatine 
phosphokinase 
increased 

 Direct and indirect 
Coombs test 
positive 

Injury, poisoning 
and procedural 
complications 

 Infusion related 
reaction 

  

 
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 
 
There is no experience with overdose of Vaborem.  
 
Limited post-marketing experience with meropenem alone indicates that if adverse reactions occur 
following overdose, they are consistent with the adverse reaction profile described in section 4.8, are 
generally mild in severity and resolve on withdrawal or dose reduction.   
 
In the event of overdose, discontinue Vaborem and institute general supportive treatment. In individuals 
with normal renal function, rapid renal elimination will occur. 
 
Meropenem and vaborbactam can be removed by haemodialysis. In subjects with end stage renal disease 
(ESRD) administered 1 g meropenem and 1 g vaborbactam, the mean total recovery in dialysate following 
a haemodialysis session was 38% and 53% for meropenem and vaborbactam, respectively. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: antibacterials for systemic use, carbapenems, ATC code: J01DH52 
 
Mechanism of action 
 
Meropenem exerts bactericidal activity by inhibiting peptidoglycan cell wall synthesis as a result of 
binding to and inhibition of activity of essential penicillin-binding proteins (PBPs).  
 
Vaborbactam is a non-beta-lactam inhibitor of class A and class C serine beta-lactamases, including 
Klebsiella pneumoniae carbapenemase, KPC. It acts by forming a covalent adduct with beta-lactamases 

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


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and is stable to beta-lactamase-mediated hydrolysis. Vaborbactam does not inhibit class B enzymes 
(metallo-β-lactamases) or class D carbapenemases.  Vaborbactam has no antibacterial activity. 
 
Resistance  
 
Mechanisms of resistance in Gram-negative bacteria that are known to affect meropenem/vaborbactam 
include organisms that produce metallo-β-lactamases or oxacillinases with carbapenemase activity.  
 
Mechanisms of bacterial resistance that could decrease the antibacterial activity of 
meropenem/vaborbactam include porin mutations affecting outer membrane permeability and 
overexpression of efflux pumps. 
 
Antibacterial activity in combination with other antibacterial agents 
 
In vitro studies demonstrated no antagonism between meropenem/vaborbactam and levofloxacin, 
tigecycline, polymyxin, amikacin, vancomycin, azithromycin, daptomycin or linezolid. 
 
Susceptibility testing break points 
 
Minimum inhibitory concentration (MIC) breakpoints established by the European Committee on 
Antimicrobial Susceptibility Testing (EUCAST) are as follows: 
 
 
Organisms 

Minimum Inhibitory Concentrations (mg/l) 
Susceptible Resistant 

Enterobacteriaceae ≤81 >81  
Pseudomonas aeruginosa ≤81  >81  
1For susceptibility testing purposes, the concentration of vaborbactam is fixed at 8 mg/l. 
 
Pharmacokinetic/pharmacodynamic relationship  
 
The antimicrobial activity of meropenem has been shown to best correlate with the percent of the dosing 
interval during which the free meropenem concentrations in plasma exceed the meropenem minimum 
inhibitory concentration. For vaborbactam, the PK-PD index associated with antimicrobial activity is the 
ratio of free vaborbactam plasma AUC: meropenem/vaborbactam MIC. 
 
Clinical efficacy against specific pathogens 
 
Efficacy has been demonstrated in clinical studies against the following pathogens that were susceptible to 
meropenem/vaborbactam in vitro. 

Complicated urinary-tract infections, including pyelonephritis 
Gram-negative micro-organisms: 

• Escherichia coli 
• Klebsiella pneumoniae 
• Enterobacter cloacae species complex 

 
Clinical efficacy has not been established against the following pathogens that are relevant to the approved 
indications although in vitro studies suggest that they would be susceptible to meropenem and/or 
meropenem/vaborbactam in the absence of acquired mechanisms of resistance.  

Gram-negative micro-organisms: 
• Citrobacter freundii 



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• Citrobacter koseri 
• Enterobacter aerogenes 
• Klebsiella oxytoca 
• Morganella morganii 
• Proteus mirabilis 
• Providencia spp. 
• Pseudomonas aeruginosa 
• Serratia marcescens 

Gram-positive micro-organisms: 
• Staphylococcus saprophyticus 
• Staphylococcus aureus (methicillin susceptible isolates only) 
• Staphylococcus epidermidis (methicillin susceptible isolates only) 
• Streptococcus agalactiae 

Anaerobic micro-organisms: 
• Bacteroides fragilis 
• Bacteroides thetaiotaomicron 
• Clostridium perfringens 
• Peptoniphilus asaccharolyticus 
• Peptostreptococcus species (including P. micros, P anaerobius, P. magnus) 
• Bacteroides caccae 
• Prevotella bivia 
• Prevotella disiens 

 
Paediatric population 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Vaborem in one or more subsets of the paediatric population in the treatment of infections due to Gram-
negative bacteria (see section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Distribution 
 
The plasma protein binding of meropenem is approximately 2%. The plasma protein binding of 
vaborbactam is approximately 33%.  
 
The steady-state volumes of distribution of meropenem and vaborbactam in patients were 20.2 L and 
18.6 L, respectively, following doses of 2 g meropenem/2 g vaborbactam infused over 3 hours every 
8 hours, indicating that both compounds distribute into a volume of distribution consistent with the 
extracellular fluid compartment. 
 
Both meropenem and vaborbactam penetrate into human bronchial epithelial lining fluid (ELF) with 
concentrations around 65% and 79% of unbound plasma concentrations of meropenem and vaborbactam, 
respectively. The concentration time profiles are similar for ELF and plasma. 
 
Biotransformation 
 
Meropenem is mostly eliminated unchanged. About 25% of the administered dose is eliminated as the 
inactive open ring form.  



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Vaborbactam does not undergo metabolism. 
 
Elimination 
 
The terminal half-life (t½) is 2.30 hours and 2.25 hours for meropenem and vaborbactam, respectively. 
 
Both meropenem and vaborbactam are primarily excreted via the kidneys. Approximately 40-60% of a 
meropenem dose is excreted unchanged within 24 - 48 hours with a further 25% recovered as the 
microbiologically inactive hydrolysis product. The elimination of meropenem by the kidneys resulted in 
high therapeutic concentrations in urine. The mean renal clearance for meropenem was 7.7 L/h. The mean 
non-renal clearance for meropenem was 4.8 L/h, which comprises both fecal elimination (~2% of the 
dose) and degradation due to hydrolysis. 
 
Approximately 75 to 95% of vaborbactam is excreted unchanged in the urine over a 24 - 48 hour period. 
The elimination of vaborbactam by the kidneys resulted in high concentrations in the urine. The mean 
renal clearance for vaborbactam was 10.5 L/h.  
 
Linearity/non-linearity 
 
The Cmax and AUC of meropenem and vaborbactam are linear across the dose range studied (1 g to 2 g for 
meropenem and 0.25 g to 2 g for vaborbactam) when administered as a single 3-hour intravenous infusion. 
There is no accumulation of meropenem or vaborbactam following multiple intravenous infusions 
administered every 8 hours for 7 days in subjects with normal renal function.  
 
Special populations 
 
Renal impairment 
Pharmacokinetic studies with meropenem and vaborbactam in patients with renal impairment have shown 
that the plasma clearance of both meropenem and vaborbactam correlates with creatinine clearance. 
 
Hepatic impairment 
As meropenem/vaborbactam does not undergo hepatic metabolism, the systemic clearance of 
meropenem/vaborbactam is not expected to be affected by hepatic impairment. 
 
Elderly 
Pharmacokinetic data from a population pharmacokinetic analysis showed a reduction in plasma clearance 
of meropenem/vaborbactam that correlates with age-associated reduction in creatinine clearance. 
 
Gender and race 
In a population pharmacokinetic analysis there was no effect of gender or race on the pharmacokinetics of 
meropenem and vaborbactam. 
 
5.3 Preclinical safety data 
 
Meropenem 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, reproduction toxicity or genotoxicity. Carcinogenicity studies have not been conducted 
with meropenem. 
 
 
 



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Vaborbactam 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, reproduction toxicity or genotoxicity. Carcinogenicity studies have not been conducted 
with vaborbactam. 
 
In repeat dose toxicity studies in dogs, minimal hepatic inflammation was observed after 14 days and 28 
days of exposure to vaborbactam alone or combined meropenem/vaborbactam. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Sodium carbonate 
 
6.2 Incompatibilities 
 
Vaborem is not chemically compatible with glucose-containing solutions. This medicinal product must not 
be mixed with other medicinal products except those mentioned in section 6.6.  
 
6.3 Shelf life 
 
3 years 
 
After reconstitution 
 
The reconstituted vial should be further diluted immediately. 
 
After dilution 
 
The chemical and physical in-use stability has been demonstrated for up to 4 hours at 25 °C or within 
22 hours at 2 – 8 °C.  
 
From a microbiological point of view, the medicinal product should be used immediately upon 
reconstitution and dilution. 
 
6.4 Special precautions for storage 
 
Do not store above 25 °C. 
 
For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container  
 
50 ml clear glass vial (Type 1) closed with a rubber (bromobutyl) stopper and aluminium overseal with 
flip-off cap. 
 
The medicinal product is supplied in packs of 6 vials.  
 
6.6 Special precautions for disposal and other handling 
 
Standard aseptic techniques must be used for solution preparation and administration. 



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The powder for concentrate for solution for infusion must be reconstituted and further diluted prior to use.  
 
Reconstitution  
 
20 ml of sodium chloride 9 mg/ml (0.9%) solution for injection (normal saline) should be withdrawn from 
a 250 ml infusion bag of sodium chloride 9 mg/ml (0.9%) solution for injection for each vial and 
reconstituted with the appropriate number of vials of meropenem/vaborbactam for the corresponding 
Vaborem dosage:  
 

• Reconstitute 2 vials for the Vaborem 2 g/2 g dose 
• Reconstitute 1 vial for the Vaborem 1 g/1 g and Vaborem 0.5 g/0.5 g doses 

 
After mixing gently to dissolve, the reconstituted meropenem/vaborbactam solution will have an 
approximate meropenem concentration of 0.05 g/ml and an approximate vaborbactam concentration of 
0.05 g/ml. The final volume is approximately 21.3 ml. The reconstituted solution is not for direct 
injection. The reconstituted solution must be diluted before intravenous infusion. 
 
Dilution 
 
To prepare the Vaborem 2 g/2 g dose for intravenous infusion: Immediately after reconstitution of two 
vials, the entire reconstituted vial contents should be withdrawn from each of the two vials and added back 
into the 250 ml infusion bag of sodium chloride 9 mg/ml (0.9%) solution for injection (normal saline). The 
final infusion concentration of meropenem and vaborbactam will be about 8 mg/ml each. 
 
To prepare the Vaborem 1 g/1 g dose for intravenous infusion: Immediately after reconstitution of one 
vial, the entire reconstituted vial contents should be withdrawn from the vial and added back into the 
250 ml infusion bag of sodium chloride 9 mg/ml (0.9%) solution for injection (normal saline). The final 
infusion concentration of meropenem and vaborbactam will be about 4 mg/ml each. 
 
To prepare the Vaborem 0.5 g/0.5 g dose for intravenous infusion: Immediately after reconstitution of one 
vial,10.5 ml of the reconstituted vial contents should be withdrawn from the vial and added back into the 
250 ml infusion bag of sodium chloride 9 mg/ml (0.9%) solution for injection (normal saline). The final 
infusion concentration of meropenem and vaborbactam will be 2 mg/ml each. 
 
The diluted solution should be inspected visually for particulate matter. The colour of the diluted solution 
is clear to light yellow.  
 
Following dilution, the infusion should be completed within 4 hours when stored at 25° C, or within 
22 hours when refrigerated at 2 – 8 °C. 
 
Any unused product or waste material should be disposed of in accordance with local requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Menarini International Operations Luxembourg S.A.  
1, Avenue de la Gare  
L-1611, Luxembourg  
Luxembourg 
 
 
 



16 

8. MARKETING AUTHORISATION NUMBER(S)  
EU/1/18/1334/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 20 November 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/


17 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 

 
 



18 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

Name and address of the manufacturer(s) responsible for batch release 

 

ACS Dobfar, S.p.A.  
Nucleo Industriale S. Atto  
(loc. S. Nicolo’ a Tordino)  
64100 Teramo (TE) 
Italy 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
  

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.  



19 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



20 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



21 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON   
 

1. NAME OF THE MEDICINAL PRODUCT 
 
Vaborem 1 g/1 g powder for concentrate for solution for infusion  
meropenem/vaborbactam 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial contains meropenem trihydrate equivalent to 1 g meropenem and 1 g vaborbactam. 
 
3. LIST OF EXCIPIENTS 
 
Sodium carbonate. See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for concentrate for solution for infusion 
6 vials 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
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 
 
Do not store above 25 °C. 
 
 



22 

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

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Menarini International O. L. S.A.  
1, Avenue de la Gare, L-1611 Luxembourg  
Luxembourg 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/18/1334/001 
 
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:  
 
  



23 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
VIAL LABEL  
 

1. NAME OF THE MEDICINAL PRODUCT 
 
Vaborem 1 g/1 g powder for concentrate 
meropenem/vaborbactam 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 g meropenem/1 g vaborbactam 
 
3. LIST OF EXCIPIENTS 
 
Sodium carbonate 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for concentrate 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet. 
Intravenous use. 
For single use only. 
 
 
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 
 
Do not store above 25° C.  
 



24 

 
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 
 
Menarini International O. L. S.A.  
1, Avenue de la Gare, L-1611 Luxembourg  
Luxembourg 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/18/1334/001 
 
 
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 
 
 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
 
  



25 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



26 

Package leaflet: Information for the patient 
 

Vaborem 1 g/1 g powder for concentrate for solution for infusion 
 

meropenem/vaborbactam 
 

This medicine is subject to additional monitoring. This will allow quick identification of new safety 
information. You can help by reporting any side effects you may get. See the end of section 4 for how to 
report side effects. 
 
Read all of this leaflet carefully before you start using 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 Vaborem is and what it is used for  
2. What you need to know before you are given Vaborem  
3. How you will be given Vaborem  
4. Possible side effects  
5. How to store Vaborem  
6. Contents of the pack and other information 
 
 
1. What Vaborem is and what it is used for  
 
What Vaborem is 
Vaborem is an antibiotic medicine that contains two active substances: meropenem and vaborbactam. 
• Meropenem belongs to group of antibiotics called “carbapenems”. It can kill many types of bacteria 

by preventing them from building the protective walls that surround their cells. 
• Vaborbactam is a “beta lactamase inhibitor”. It blocks the action of an enzyme that allows some 

bacteria to resist the action of meropenem. This helps meropenem kill some bacteria that it cannot 
kill on its own.   

 
What Vaborem is used for 
Vaborem is used in adults to treat certain serious bacterial infections: 
• of the bladder or kidneys (urinary tract infections) 
• of the stomach and gut (intra-abdominal infections) 
• of the lungs (pneumonia) 
 
It is also used to treat infections 
• of the blood associated with any of the infections mentioned above 
• caused by bacteria that other antibiotics may not be able to kill 
 
 
 
 
 
 
 



27 

2. What you need to know before you are given Vaborem  
 
You must not be given Vaborem if 
• you are allergic to meropenem, vaborbactam or the other ingredients of this medicine (listed in 

section 6). 
• you are allergic to other carbapenem antibiotics (the group to which meropenem belongs). 
• you have ever had a severe allergic reaction to related antibiotics belonging to the beta-lactam group 

(including penicillins, cephalosporins or monobactams).  
 
Warnings and precautions  
Talk to your doctor or nurse before receiving Vaborem if: 
• you have ever had any allergic reaction to other antibiotics belonging to the beta-lactam group 

(including carbapenems, penicillins, cephalosporins, or monobactams) 
• you have ever developed severe diarrhoea during or after antibiotic treatment 
• you have ever suffered from seizures 
 
If any of the above apply to you or you are not sure, talk to your doctor or nurse before using Vaborem. 
 
Talk to your doctor or nurse if you suffer from diarrhoea during your treatment. 
 
This medicine can affect your liver. Your doctor may take some blood to check how well your liver is 
working while taking the medicine. 
 
New infection 
Although Vaborem can fight certain bacteria, there is a possibility that you may get a different infection 
caused by another organism during or after your treatment. Your doctor will monitor you closely for any 
new infections and give you another treatment if necessary. 
 
Blood tests 
Tell your doctor that you are taking Vaborem if you are going to have any blood tests. This is because you 
may get an abnormal result with something called a “Coombs test”. This test looks for the presence of 
antibodies that can destroy red blood cells or may be affected by the response of your immune system to 
Vaborem. 
 
Children or adolescents 
Vaborem should not be used in children or adolescents under 18 years of age. This is because it is not 
known if the medicine is safe to use in these age groups. 
 
Other medicines and Vaborem 
Tell your doctor if you are using, have recently used or might use any other medicines. 
 
It is particularly important to tell your doctor if you are taking any of the following medicines: 
• medicines used to treat epilepsy called valproic acid, sodium valproate or valpromide because 

Vaborem may decrease their effect  
• a medicine for gout called probenecid 
• oral anticoagulant medicines, such as warfarin (used to treat or prevent blood clots) 
• medicines that weaken your body’s immune system, such as tacrolimus, everolimus and 

cyclosporine 
• a cholesterol-lowering medicine called lovastatin 
• a medicine used to treat seizures or given prior to a surgery or certain examinations inside your body 

such as a colonoscopy, called midazolam 
• a medicine to treat issues with getting an erection in men or to treat high blood pressure in the lungs 

called sildenafil 



28 

• a medicine commonly used in medicines to treat a cough called dextromethorphan 
• a medicine used to treat depression called desipramine 
• a medicine used to treat depression or anxiety called venlafaxine 
• a medicine used to treat high blood pressure or chest pain called metoprolol 
 
Tell your doctor before using Vaborem if any of the above apply to you. 
 
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. 
 
It is important that you tell your doctor if you are breast-feeding or if you intend to breast-feed before 
receiving Vaborem. Small amounts of this medicine may pass into the breast milk and it may affect the 
baby. Therefore, you must discontinue breastfeeding before you are given Vaborem. 
 
Driving and using machines 
Vaborem may make you feel dizzy, sleepy and sluggish, give you a headache or tingling sensation (like 
“pins and needles”) or, in rare cases, cause a fit or seizure. This may affect your ability to drive, use tools 
or machines.  
 
Vaborem contains sodium 
This product contains approximately 250 mg of sodium per vial. This should be taken into consideration if 
you are on a controlled sodium diet. 
 
 
3. How you will be given Vaborem 
 
Vaborem will be given to you by a doctor or nurse by infusion (a drip) into a vein, lasting 3 hours.  
 
The recommended dose is 2 vials (a total of 2 g meropenem and 2 g vaborbactam), given every 8 hours. 
Your doctor will decide how many days of treatment are needed, depending on the type of infection. 
 
Patients with kidney problems 
If you have kidney problems, your doctor may lower your dose. Your doctor may also want to do some 
blood tests to see how well your kidneys are working. 
 
If you are given more Vaborem than you should 
Vaborem will be given to you by a doctor or a nurse, so it is unlikely you will be given the wrong dose. If 
you think you have been given too much Vaborem, tell your doctor or nurse straight away.  
 
If you miss a dose of Vaborem 
If you think you have missed a dose, tell your doctor or nurse straight away. 
 
If you have any further questions on the use of this medicine, ask your doctor or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Serious side effects 
Tell your doctor straight away if you notice any of the following serious side effects – you may need 
urgent medical treatment: 



29 

• Severe allergic reactions that could include sudden swelling of your lips, face, throat or tongue, 
difficulty swallowing or breathing or a severe rash or other severe skin reactions, or a decrease in 
blood pressure (which could make you feel faint or dizzy). Such reactions may be life-threatening. 

• Diarrhoea that keeps getting worse or does not go away, or stools that contains blood or mucus – 
this may happen during or after treatment with Vaborem is stopped. It may be due to bacteria called 
Clostridium difficile. If this happens, do not take medicines that stop or slow bowel movement. 

 
Other side effects 
Tell your doctor or nurse if you notice any of the following side effects:  
 
Common: (may affect up to 1 in 10 people) 
• Increase in the number of platelets (a type of blood cell) – shown in blood tests 
• Decrease in the amount of potassium or sugar- seen in blood tests 
• Headache 
• Low blood pressure 
• Diarrhoea 
• Feeling sick (nausea) or being sick (vomiting) 
• Swelling, redness and/or pain around the needle where the medicine is given into a vein 
• Fever 
• Increase in the amount of enzymes produced by your liver called alanine aminotransferase or 

aspartate aminotransferase – shown in blood tests 
• Increase in the level of an enzyme called alkaline phosphatase that may be a sign of your liver, 

gallbladder or bones working less well – shown in blood tests 
• Increase in the level of an enzyme called lactate dehydrogenase that may be a sign of damage to 

some of your body organs – shown in blood tests 
 
Uncommon: (may affect up to 1 in 100 people) 
• Swelling and irritation in the large intestine or colon – this can cause diarrhoea, fever and stomach 

cramps and is due to another colon infection 
• Fungal infections, including those of the vagina or mouth  
• Decrease in the number of white blood cells or some types of white blood cells called neutrophils 

and a decrease of platelets – shown in blood tests 
• Increase in a type of white blood cell called eosinophils – shown in blood tests 
• Sudden and serious allergic reaction that needs urgent medical treatment and may include itching, 

skin color change, abdominal cramps, swelling, difficulty breathing, fainting and drop in blood 
pressure 

• Less severe allergic reaction that may include redness, red bumps, flaking of the skin, itching, 
generally feeling unwell 

• A feeling of being less hungry  
• Increase in the amount of potassium or sugar – shown in blood tests 
• Inability to sleep 
• Seeing, hearing or sensing things that are not there 
• Feeling dizzy 
• Tremor or shaking 
• A tingling feeling (pins and needles) 
• A feeling of being sleepy and sluggish 
• Swollen and red and irritated veins 
• Painful veins 
• Difficulty breathing 
• Bloating or a feeling of fullness in your abdomen 
• Stomach pain 
• Itchy skin 
• Rash 



30 

• Raised itchy skin rash (“hives”) 
• Difficulty to control the bladder 
• Reduction in the way your kidneys work 
• Abnormal feeling in the chest  
• The following reactions may develop, alone or in combination, where Vaborem is given into a 

vein: reddened skin (erythema); hot, tender and swollen vein around the needle (phlebitis); a blood 
clot in the vein where the needle was put through your skin (infusion site thrombosis) 

• Pain 
• Increase in the level of a substance in the blood called creatine phosphokinase that is a sign of 

possible damage to certain tissues such as your muscles and/or other organs – shown in blood tests 
• Increase in the level of a substance in the blood called bilirubin that is a sign of possible damage to 

your red blood cells or that your liver is working less well – shown in blood tests 
• Increase in the level of some types of substances in the blood called urea and creatinine that are 

signs that your kidneys are working less well – shown in blood tests 
• Reaction that occurs during or shortly after Vaborem is given that presents as a malaise (generally 

feeling unwell) possibly with any of the following: reduced blood pressure, nausea, vomiting, 
abdominal cramps, fever, flushing, rapid heart beats or difficulty to breathe, headache 

 
Rare (may affect up to 1 in 1000 people) 
• Seizures (fits) 
 
Unknown: (frequency cannot be estimated from the available data) 
• A severe and very low white blood cell count – shown in blood tests 
• Haemolytic anaemia (a condition where red blood cells are damaged and reduced in number), 

which may make you feel tired and turn your skin and eyes yellow 
• Swelling of the tongue, face, lips or throat 
• Sudden onset of a severe rash with bullseye-like spots or blistering or peeling skin, possibly with a 

high fever, joint pain, abnormal function of your liver, kidney or lung (these may be signs of more 
serious medical conditions called toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema 
multiforme or a condition known as drug reaction with eosinophilia and systemic symptoms 
(DRESS)) 

• A positive result from a test called“Coombs”used to identify haemolytic anemia (see above) or 
reaction of your immune system to Vaborem 

 
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 Vaborem 
 
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 container. The expiry date refers to 
the last day of that month. 
 
Do not store above 25 °C. 
 
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. 
 
 

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


31 

6. Contents of the pack and other information 
 
What Vaborem  contains  
• The active substances are meropenem and vaborbactam. Each vial contains 1 g meropenem (as 

meropenem trihydrate) and 1 g vaborbactam. 
• The other ingredient is sodium carbonate. 
 
What Vaborem  looks like and contents of the pack 
Vaborem is a white to light yellow powder for concentrate for solution for infusion supplied in a vial.  
 
Vaborem is available in packs containing 6 vials.  
 
Marketing Authorisation Holder 
Menarini International Operations Luxembourg S.A.  
1, Avenue de la Gare  
L-1611, Luxembourg  
Luxembourg 
 
Manufacturer 
ACS Dobfar, S.p.A.  
Nucleo Industriale S. Atto  
(loc. S. Nicolo’ a Tordino)  
64100 Teramo (TE) 
Italy 
 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Menarini Benelux NV/SA 
Tél/Tel: + 32 (0)2 721 4545 
 

Lietuva 
UAB “BERLIN-CHEMIE MENARINI 
BALTIC” 
Tel: +370 52 691 947 
 

България 
Берлин-Хеми/А. Менарини България EООД 
тел.: +359 24540950 

Luxembourg/Luxemburg 
Menarini Benelux NV/SA 
Tél/Tel: + 32 (0)2 721 4545 
 

Česká republika 
Berlin-Chemie/A.Menarini Ceska republika s.r.o. 
Tel: +420 267 199 333 
 

Magyarország 
Berlin-Chemie/A. Menarini Kft. 
Tel.: +36 23501301 

Danmark 
Menarini International Operations Luxembourg 
S.A. 
Tlf: +352 264976 

Malta 
Menarini International Operations Luxembourg 
S.A. 
Tel: +352 264976 
 

Deutschland 
Berlin-Chemie AG 
Tel: +49 (0) 30 67070 

Nederland 
Menarini Benelux NV/SA 
Tel: +32 (0)2 721 4545 
 
 



32 

 
Eesti 
OÜ Berlin-Chemie Menarini Eesti 
Tel: +372 667 5001 

Norge 
Menarini International Operations Luxembourg 
S.A. 
Tlf: +352 264976 
 

Ελλάδα 
MENARINI HELLAS AE 
Τηλ: +30 210 8316111-13 

Österreich 
A. Menarini Pharma GmbH 
Tel: +43 1 879 95 85-0 
 

España 
Laboratorios Menarini S.A. 
Tel: +34-93 462 88 00 

Polska 
Berlin-Chemie/Menarini Polska Sp. z o.o. 
Tel.: +48 22 566 21 00 
 

France 
MENARINI France 
Tél: +33 (0)1 45 60 77 20 

Portugal 
A. Menarini Portugal – Farmacêutica, S.A. 
Tel: +351 210 935 500 
 

Hrvatska 
Berlin-Chemie Menarini Hrvatska d.o.o. 
Tel: + 385 1 4821 361 
 

România 
Berlin-Chemie A.Menarini S.R.L. 
Tel: +40 21 232 34 32 
 

Ireland 
A. Menarini Pharmaceuticals Ireland Ltd 
Tel: +353 1 284 6744 

Slovenija 
Berlin-Chemie / A. Menarini Distribution 
Ljubljana d.o.o.  
Tel: +386 01 300 2160 
 

Ísland 
Menarini International Operations Luxembourg 
S.A. 
Sími: +352 264976  
 

Slovenská republika 
Berlin-Chemie / A. Menarini Distribution 
Slovakia s.r.o  
Tel: +421 2 544 30 730 

Italia 
A. Menarini - Industrie Farmaceutiche Riunite -  
s.r.l. 
Tel: +39-055 56801 
 

Suomi/Finland 
Berlin-Chemie/A.Menarini Suomi OY 
Puh/Tel: +358 403 000 760 
 

Κύπρος 
MENARINI HELLAS AE 
Τηλ: +30 210 8316111-13 

Sverige 
Menarini International Operations Luxembourg 
S.A. 
Tel: +352 264976 
 

Latvija 
SIA Berlin-Chemie/Menarini Baltic 
Tel: +371 67103210 

United Kingdom 
A. Menarini Farmaceutica Internazionale S.R.L. 
Tel: +44 (0)1628 856400 

 
 
 
 
 
This leaflet was last revised in: 
 



33 

 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency website: 
http://www.ema.europa.eu. 
 
------------------------------------------------------------------------------------------------------------------------ 
 
The following information is intended for healthcare professionals only: 
 
Vaborem  is intended for intravenous (IV) administration, only after reconstitution and dilution. 
Standard aseptic techniques must be used for solution preparation and administration. 
 
The number of vials used for a single dose will depend on the creatinine clearance (CrCl) of the patient.  
 
Reconstitution:  
20 ml of sodium chloride 9 mg/ml (0.9%) solution for injection (normal saline) should be withdrawn from 
a 250 ml infusion bag of sodium chloride 9 mg/ml (0.9%) solution for injection for each vial and 
reconstituted with the appropriate number of vials of meropenem/vaborbactam for the corresponding 
Vaborem dosage:  
 

• Reconstitute 2 vials for the Vaborem  2 g/2 g dose 
• Reconstitute 1 vial for the Vaborem  1 g/1 g and Vaborem 0.5 g/0.5 g doses 

 
After mixing gently to dissolve, the reconstituted meropenem/vaborbactam solution will have an 
approximate meropenem concentration of 0.05 g/ml and an approximate vaborbactam concentration of 
0.05 g/ml. The final volume is approximately 21.3 ml. The reconstituted solution is not for direct 
injection. The reconstituted solution must be diluted before intravenous infusion. 
 
Dilution:  
To prepare the Vaborem  2 g/2 g for intravenous infusion: Immediately after reconstitution of two vials, 
the entire reconstituted vial contents should be withdrawn from each of the two vials and added back into 
the 250 ml infusion bag of sodium chloride 9 mg/ml (0.9%) solution for injection (normal saline). The 
final infusion concentration of meropenem and vaborbactam will be about 8 mg/ml each. 
 
To prepare the Vaborem  1 g/1 g for intravenous infusion: Immediately after reconstitution of one vial, the 
entire reconstituted vial contents should be withdrawn from the vial and added back into the 250 ml 
infusion bag of sodium chloride 9 mg/ml (0.9%) solution for injection (normal saline). The final infusion 
concentration of meropenem and vaborbactam will be about 4 mg/ml each. 
 
To prepare the Vaborem  0.5 g/0.5 g for intravenous infusion: Immediately after reconstitution of one vial, 
10.5 ml of the reconstituted vial contents should be withdrawn from the vial and added back into the 
250 ml infusion bag of sodium chloride 9 mg/ml (0.9%) solution for injection (normal saline). The final 
infusion concentration of meropenem and vaborbactam will be 2 mg/ml each. 
 
The diluted solution should be inspected visually for particulate matter. The colour of the diluted solution 
is clear to light yellow.  
 
Following dilution, the infusion should be completed within 4 hours when stored at 25 °C, or within 
22 hours when refrigerated at 2 – 8 °C. 
 
From a microbiological point of view, the medicinal product should be used immediately upon 
reconstitution and dilution. 

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


34 

 
Vaborem  is not chemically compatible with glucose-containing solutions. This medicinal product must 
not be mixed with other medicinal products except those mentioned in section 6.6 of the SmPC. 


	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