Vibativ

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 
 
VIBATIV 250 mg powder for concentrate for solution for infusion  
VIBATIV 750 mg powder for concentrate for solution for infusion  
 
 
2.  QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
VIBATIV 250 mg powder for concentrate for solution for infusion 
Each vial contains 250 mg telavancin (as hydrochloride).  
 
VIBATIV 750 mg powder for concentrate for solution for infusion  
Each vial contains 750 mg telavancin (as hydrochloride).  
 
After reconstitution, each ml contains 15 mg of telavancin.  
 
For the full list of excipients, see section 6.1.  
 
 
3.  PHARMACEUTICAL FORM 
 
Powder for concentrate for solution for infusion  
A white to pale pink, whole or fragmented cake  
 
 
4.  CLINICAL PARTICULARS 
 
4.1  Therapeutic indications 
 
VIBATIV is indicated for the treatment of adults with nosocomial pneumonia (NP) including 
ventilator associated pneumonia, known or suspected to be caused by methicillin-resistant 
Staphylococcus aureus (MRSA). 
 
VIBATIV should be used only in situations where it is known or suspected that other alternatives are 
not suitable (see sections 4.3, 4.4, 4.8 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  
 
Adults  
The recommended dosage regimen is 10 mg/kg, once every 24 hours, for 7 to 21 days. 
 
Special populations 
 
Elderly patients 
Elderly patients should receive a telavancin dose in accordance with their bodyweight and renal 
function (see sections 4.3 and 5.2).  
 

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Renal impairment  
Patients with renal impairment should receive an initial dose according to calculated or measured 
creatinine clearance as presented in the table below. During treatment dose adjustments according to 
the table should be made based on calculated or measured creatinine clearance in patients with 
clinically relevant changes in renal function.  
 
Creatinine clearance* (ml/min) Dosage regimen  
> 50 10 mg/kg every 24 hours  
30-50 7.5 mg/kg every 24 hours  
*As calculated using the Cockcroft-Gault formula  
 
The use in patients with acute renal failure or creatinine clearance (CrCl) <30 ml/min including 
patients undergoing haemodialysis is contraindicated (see section 4.3).  
 
Hepatic impairment  
Mild to moderate degrees of hepatic impairment (Child-Pugh class B) (see section 5.2) did not result 
in a relevant change in pharmacokinetics of telavancin. Therefore, no dose adjustment is necessary 
when administering telavancin to subjects with mild or moderate degrees of hepatic impairment. No 
data are available in subjects with severe hepatic impairment (Child-Pugh class C). Therefore, caution 
should be exercised if telavancin is given to subjects with severe hepatic impairment.  
 
Obese patients  
Obese patients (defined as those with BMI > 30 kg/m2) should receive telavancin at the reduced dose 
of 7.5 mg/kg once every 24 hours (see section 5.2). 
 
Paediatric patients  
The safety and efficacy of VIBATIV in children and adolescents aged below 18 years have not yet 
been established. No data are available.  
 
Method of administration  
 
For intravenous use. 
 
VIBATIV must be reconstituted and then further diluted prior to administration by intravenous 
infusion through a dedicated line or through a Y-site over a 60 minute period. Bolus injections must 
not be administered. For instructions on reconstitution and dilution, see section 6.6.  
 
4.3  Contraindications  
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.  
 
Patients with severe renal impairment, i.e. creatinine clearance (CrCl) <30 ml/min, including patients 
undergoing haemodialysis (see section 4.4).  
 
Acute renal failure (see section 4.4).  
 
Pregnancy (see section 4.6).  
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4.4  Special warnings and precautions for use 
 
Renal impairment  
 
In the clinical studies, patients with pre existing acute renal failure receiving telavancin had an 
increased risk of mortality. All-cause mortality was 32/73 (44%) in the telavancin group and 16/64 
(25%) in the vancomycin group, whereas in patients without acute renal failure at baseline it was 
118/678 (17%) and 124/688 (18%), respectively. Therefore, the use of telavancin in patients with 
pre-existing acute renal failure and in patients with severe renal impairment is contraindicated (see 
section 4.3).  
 
Renal adverse reactions 
 
In the pooled clinical studies (NP and complicated skin and soft tissue infection (cSSTI)), renal 
adverse reactions were reported more frequently in patients receiving telavancin compared with 
vancomycin (3.8% vs. 2.2%, respectively). Renal function (serum creatinine and urinary output for 
oliguria/anuria) should be monitored daily for at least the first 3 to 5 days of therapy and every 48 to 
72 hours thereafter in all patients receiving telavancin. Initial dose and dosage adjustments during 
treatment should be made based on calculated or measured creatinine clearance according to the 
dosing regimen in section 4.2. If renal function markedly decreases during treatment, the benefit of 
continuing telavancin should be assessed.  
 
Other factors that may increase the risk of nephrotoxicity 
 
Caution should be used when prescribing VIBATIV to patients receiving concomitant nephrotoxic 
medicines, those with pre existing renal disease or with co-morbidity known to predispose to kidney 
dysfunction (e.g. diabetes mellitus, congestive heart failure, hypertension). 
 
Infusion related reactions  
 
Rapid intravenous infusions of antimicrobial agents of the class of glycopeptides have been associated 
with red man syndrome-like reactions, including flushing of the upper body, urticaria, pruritus or rash 
(see section 4.8). Stopping or slowing the infusion may result in cessation of these reactions. Infusion 
related reactions can be limited if the daily dose is infused over a 1 hour period.  
 
Hypersensitivity 
 
Hypersensitivity reactions, including anaphylaxis, have been reported with telavancin, and may be 
life-threatening. If an allergic reaction to telavancin occurs, discontinue treatment and institute 
appropriate therapy. 
 
Cross hypersensitivity reactions, including anaphylaxis, have been reported in patients with a history 
of vancomycin allergy. Caution should be exercised when prescribing telavancin to patients with a 
prior history of hypersensitivity reaction to vancomycin. If an allergic reaction to telavancin occurs, 
discontinue treatment and institute appropriate therapy. 
 
QTc prolongation  
 
A clinical QTc study with telavancin doses of 7.5 and 15 mg/kg versus vehicle and an active 
comparator (400 mg moxifloxacin) showed that once daily dosing for 3 days resulted in a mean 
vehicle corrected increase in QTcF by 4.1 and 4.5 millisecond, respectively, compared to a 
9.2 millisecond increase observed with the comparator.  
 
Caution is warranted when using telavancin to treat patients taking medicinal products known to 
prolong the QT interval. In addition, caution is warranted when using telavancin to treat patients with 
congenital long QT syndrome, known prolongation of the QTc interval, uncompensated heart failure, 

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or severe left ventricular hypertrophy. Patients with these conditions were not included in clinical trials 
of telavancin.  
 
Ototoxicity  
 
As with other glycopeptides, ototoxicity (deafness and tinnitus) has been reported in patients treated 
with telavancin (see section 4.8). Patients who develop signs and symptoms of impaired hearing or 
disorders of the inner ear during treatment with telavancin should be carefully evaluated and 
monitored (see section 4.8). Patients receiving telavancin in conjunction with or sequentially with 
other medicinal products with known ototoxic potential should be carefully monitored and the benefit 
of telavancin evaluated if hearing deteriorates.  
 
Superinfection  
 
The use of antibiotics may promote the overgrowth of non-susceptible micro-organisms. If 
superinfection occurs during therapy, appropriate measures should be taken.  
 
Antibiotic-associated colitis and pseudomembranous colitis  
 
Antibiotic-associated colitis and pseudomembranous colitis have been reported with nearly all 
antibacterial agents, including telavancin (see section 4.8), and may range in severity from mild to 
life-threatening. Therefore, it is important to consider this diagnosis in patients who present with 
diarrhoea during or shortly following treatment.  
 
Concomitant antibiotic coverage 
 
Telavancin is active against Gram-positive bacteria only (see section 5.1 for information on the 
antimicrobial spectrum). In mixed infections where Gram-negative and/or certain types of anaerobic 
bacteria are suspected, VIBATIV should be co-administered with appropriate antibacterial agent(s).  
 
Specific patient groups  
 
The nosocomial pneumonia (NP) studies excluded known or suspected pulmonary disease like 
granulomatous diseases, lung cancer, or other malignancy metastatic to the lungs; cystic fibrosis or 
active tuberculosis; Legionella pneumophila pneumonia; meningitis, endocarditis, or osteomyelitis; 
refractory shock defined as supine systolic blood pressure <90 mm Hg for >2 hours with evidence of 
hypoperfusion or requirement for high-dose sympathomimetic agents. Also patients with baseline 
QTc >500 msec, congenital long QT syndrome, uncompensated heart failure, or abnormal K+ or Mg2+ 
blood levels that could not be corrected, severely neutropenic (absolute neutrophil count <500/mm3) or 
anticipated to develop severe neutropenia due to prior or planned chemotherapy, or who had HIV with 
CD4 count <100/mm3 during the last 6 months were excluded. 
 
4.5  Interaction with other medicinal products and other forms of interaction 
 
In studies in healthy subjects, the pharmacokinetics of telavancin were not significantly altered by 
simultaneous administration of aztreonam or piperacillin-tazobactam. Also, the pharmacokinetics of 
aztreonam or piperacillin tazobactam were not altered by telavancin. Based on their pharmacokinetic 
properties, no interaction is expected with other beta-lactams, clindamycin, metronidazole, or 
fluoroquinolones. 
 
It was demonstrated in a clinical study with intravenous midazolam that multiple doses of telavancin 
had no effect on the pharmacokinetics of midazolam, which is a sensitive substrate for CYP3A4. 
In vitro experiments indicate that telavancin will not affect the clearance of medicinal products 
metabolised by CYP isoforms 1A2, 2C9, 2C19 and 2D6. Since telavancin is primarily excreted 
unchanged by renal clearance and multiple CYP enzymes are able to metabolise telavancin, no 
relevant interactions are expected with inhibitors or inducers of the CYP450 system. 
 

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Although telavancin does not interfere with coagulation, it interfered with certain tests used to monitor 
coagulation (see below), when tests are conducted using samples drawn between 0 to 18 hours after 
telavancin administration to patients being treated once every 24 hours. Blood samples for coagulation 
tests should be collected as closely as possible prior to a patient’s next dose of telavancin or 
consideration given to using a test unaffected by telavancin.  
 
Coagulation tests affected by telavancin Coagulation tests unaffected by telavancin  
International normalised ratio Whole blood (Lee-White) clotting time 
Activated partial thromboplastin time Ex vivo platelet aggregation 
Activated clotting time Chromogenic factor Xa assay 
Coagulation based factor Xa tests Functional (chromogenic) factor X assay  
 Bleeding time  
 D-dimer  
 Fibrin degradation products 
 
No evidence of increased bleeding risk has been observed in clinical trials with telavancin. Telavancin 
has no effect on platelet aggregation. Furthermore, no evidence of hypercoagulability has been seen, as 
healthy subjects receiving telavancin have normal levels of D-dimer and fibrin degradation products. 
 
Telavancin interferes with urine qualitative dipstick protein assays, as well as quantitative dye 
methods (e.g. pyrogallol red molybdate). Microalbumin assays based on immunoassay utilizing 
nephelometric (turbidity) detection are not affected and can be used to monitor urinary protein 
excretion during telavancin treatment. For routine monitoring of renal function it is recommended to 
use serum creatinine concentration or estimated creatinine clearance.  
 
4.6  Fertility, pregnancy and lactation 
 
Pregnancy  
 
The use of VIBATIV is contraindicated during pregnancy (see section 4.3).  
There is no human experience with telavancin. Studies in animals have shown reproductive toxicity 
(see section 5.3).  
 
The pregnancy status of women of childbearing potential has to be established prior to dosing with 
telavancin. Women of childbearing potential have to use effective contraception during treatment.  
 
Breastfeeding  
 
It is unknown whether telavancin is excreted in human breast milk. The excretion of telavancin in milk 
has not been studied in animals. A decision on whether to continue/discontinue breast-feeding or to 
continue/discontinue therapy with telavancin should be made taking into account the benefit of 
breastfeeding to the child and the benefit of telavancin therapy to the woman.  
 
Fertility  
 
Telavancin has been shown to affect sperm quantity and quality of male rats (see section 5.3) although 
no effect on fertility, mating, or early embryogenesis has been reported. The potential risk for humans 
is unknown.  
 
4.7  Effects on ability to drive and use machines 
 
Dizziness, somnolence, confusion and blurred vision may occur and VIBATIV may have an influence 
on the ability to drive and use machines (see section 4.8). 
 

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4.8  Undesirable effects 
 
Summary of the safety profile 
 
In phase 3 clinical trials involving 1680 patients (751 and 929, NP and cSSTI, respectively) who 
received telavancin at a daily dose of 10 mg/kg, adverse reactions were reported in 47.3% of patients. 
Treatment was discontinued due to adverse reactions in 5.0% of patients who received telavancin.  
 
The most commonly reported related adverse reactions (occurring in >1% of patients) were: fungal 
infection, insomnia, dysgeusia, headache, dizziness, nausea, constipation, diarrhoea, vomiting, alanine 
aminotransferase increased, aspartate aminotransferase increased, pruritus, rash, renal failure acute, 
blood creatinine increased, urine abnormality (foamy urine), fatigue and chills.  
 
Tabulated list of adverse reactions 
 
The frequency of adverse reactions is defined as follows: very common (≥1/10); common (≥1/100 to 
<1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not 
known (cannot be estimated from the available data). Within each frequency grouping, undesirable 
effects are presented in order of decreasing seriousness.  
 
Infections and infestations  
Common: fungal infection  
Uncommon:  clostridium colitis, urinary tract infection 
  
Blood and lymphatic system disorders  
Uncommon: anaemia, leukopenia, thrombocythaemia, thrombocytopenia, 

eosinophil count increased, neutrophil count increased  
  
Immune system disorders  
Uncommon: hypersensitivity  
Not known*  anaphylaxis 
  
Metabolism and nutrition disorders  
Uncommon: decreased appetite, hyperglycaemia, hyperkalaemia, hypoglycaemia, 

hypokalaemia, hypomagnesaemia  
  
Psychiatric disorders  
Common: insomnia  
Uncommon: agitation, anxiety, confusional state, depression  
  
Nervous system disorders  
Very common: dysgeusia  
Common: headache, dizziness  
Uncommon: ageusia, migraine, paraesthesia, parosmia, somnolence, tremor  
  
Eye disorders   
Uncommon: eye irritation, blurred vision  
  
Ear and labyrinth disorders  
Uncommon: tinnitus  
Rare: deafness  
  
Cardiac disorders   
Uncommon: angina pectoris, atrial fibrillation, bradycardia, cardiac failure 

congestive, electrocardiogram QT corrected interval prolonged, 
palpitations, sinus tachycardia, supraventricular extrasystoles, 
ventricular extrasystoles  

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Vascular disorders   
Uncommon: flushing, hypertension, hypotension, phlebitis  
  
Respiratory, thoracic and mediastinal disorders  
Uncommon: dyspnoea, hiccups, nasal congestion, pharyngolaryngeal pain  
  
Gastrointestinal disorders  
Very common: nausea  
Common: constipation, diarrhoea, vomiting  
Uncommon: abdominal pain, dry mouth, dyspepsia, flatulence, hypoaesthesia 

oral  
  
Hepatobiliary disorders  
Common: alanine aminotransferase increased, aspartate aminotransferase 

increased  
Uncommon: hepatitis 
  
Skin and subcutaneous tissue disorders 
Common: pruritus, rash  
Uncommon: erythema, face oedema, hyperhidrosis, urticaria  
  
Musculoskeletal and connective tissue disorders  
Uncommon: arthralgia, back pain, muscle cramp, myalgia  
  
Renal and urinary disorders  
Common: renal failure acute, blood creatinine increased, foamy urine (lower 

level term)  
Uncommon: blood urea increased, dysuria, haematuria, microalbuminuria, 

oliguria, pollakiuria, renal impairment, urine odour abnormal  
  
General disorders and administration site conditions  
Common: fatigue, chills  
Uncommon: asthenia, infusion site reactions, malaise, non-cardiac chest pain, 

peripheral oedema, pain, pyrexia, Red Man syndrome  
  
Investigations  
Uncommon: international normalised ratio increased  
 
* Based on post-marketing reports. Since these reactions are reported voluntarily from a population of 
uncertain size, it is not possible to reliably estimate their frequency which is therefore categorised as 
not known. 
 
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 healthy volunteers who received a dose of 15 mg/kg, a higher incidence of adverse reactions to 
telavancin was seen: dysgeusia, nausea, vomiting, injection site erythema, headache, macular rash, and 
red man syndrome.  
 

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In the event of overdose, telavancin should be discontinued and supportive care is advised with 
maintenance of glomerular filtration and careful monitoring of renal function. Following 
administration of a single dose of telavancin 7.5 mg/kg to subjects with end-stage renal disease, 
approximately 5.9% of the administered dose of telavancin was recovered in the dialysate following 
4 hours of haemodialysis. However, no information is available on the use of haemodialysis to treat an 
overdose. 
 
The clearance of telavancin by continuous venovenous haemofiltration (CVVH) was evaluated in an in 
vitro study. Telavancin was cleared by CVVH and the clearance of telavancin increased with 
increasing ultrafiltration rate. However, the clearance of telavancin by CVVH has not been evaluated 
in a clinical study; thus, the clinical significance of this finding and use of CVVH to treat an overdose 
are unknown. 
 
 
5.  PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antibacterials for systemic use, glycopeptide antibacterials, ATC code: 
J01XA03 
 
Mechanism of action 
 
Telavancin exerts concentration-dependent bactericidal activity against susceptible Gram-positive 
bacteria. Telavancin inhibits cell wall biosynthesis by binding to late-stage peptidoglycan precursors, 
including lipid II, which prevents polymerisation of the precursor into peptidoglycan and subsequent 
cross-linking events. Telavancin also binds to bacterial membranes and causes depolarisation of 
membrane potential and an increase in membrane permeability that results in inhibition of protein, 
RNA, and lipid synthesis. 
 
Mechanism of resistance 
 
S. aureus that exhibit high level resistance to glycopeptide antibacterial agents (GRSA) are not 
susceptible to telavancin. There is no known cross-resistance between telavancin and other 
non-glycopeptide classes of antibiotics. 
 
Breakpoints 
 
The minimum inhibitory concentration (MIC) breakpoints are as follows: 
 

Pathogen MIC (µg/ml) 

S. aureus (including methicillin-resistant strains) ≤0.12 
 
Microbiological susceptibility 
The prevalence of acquired resistance may vary geographically and with time for selected species and 
local information on resistance is desirable, particularly when treating severe infections. As necessary, 
expert advice should be sought when the local prevalence of resistance is such that the utility of the 
agent in at least some types of infections is questionable.  
 
Clinical efficacy and safety 
Telavancin demonstrated efficacy against MSSA and MRSA in two randomised controlled studies in 
patients with nosocomial pneumonia, including ventilator-associated pneumonia, involving 
751 patients who received telavancin. Despite in vitro susceptibility, there are insufficient clinical data 
to assess the potential for efficacy of telavancin in infections due to hGISA/GISA. 
 

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Paediatric population 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
telavancin in one or more subsets of the paediatric population in nosocomial pneumonia. See 4.2 for 
information on paediatric use. 
 
5.2  Pharmacokinetic properties 
 
Telavancin exhibited linear pharmacokinetics at doses up to 15 mg/kg administered as a daily 
60 minute intravenous infusion for 7 days in healthy volunteers. The mean (SD) maximum telavancin 
concentration (Cmax) amounts to 108 (26) µg/ml at steady state at a once daily dose of 10 mg/kg 
infused over a period of 1 h (tmax) and then falls to a trough value of 8.55 (2.84) µg/ml (C24h ). Mean 
(SD) AUC0-24 amounts to 780 (125) µg.h/ml. Telavancin has a small volume of distribution. At a dose 
of 10 mg/kg, mean Vss averaged between 133 (SD 24) ml/kg after multiple dosing, corresponding to a 
value of approximately 10 l for a 75 kg person. This data indicate that telavancin is not extensively 
distributed. Telavancin is a low clearance active substance with a mean (SD) CL of 13.1 (2.0) ml/hr/kg 
in subjects with normal renal function, corresponding to a total CL of approximately 1 l/hr in a 75 kg 
subject. In combination with the small Vss, this results in a t1/2 of about 8 h. 
 
Distribution 
 
The apparent distribution volume of telavancin at steady-state in healthy adult subjects was 
approximately 133 ml/kg.  
 
Human plasma protein binding is approximately 90%, primarily to serum albumin.  
 
At a dose of 10 mg/kg for 3 consecutive days to healthy volunteers subjected to bronchoalveolar 
lavage, the concentration ratio in pulmonary epithelial lining fluid/plasma ranged from 0.050 and 
0.121 over a period of 4 to 24 hours after start of infusion. Higher concentrations were observed in 
alveolar macrophages with ratios varying between 0.360 (at 4 h) and 6.67 (at 24 h). In vitro studies 
showed that telavancin retained full activity in the presence of pulmonary surfactant. 
 
Biotransformation 
 
In vitro studies have shown that CYP1A1, 1A2, 2B6, 2C18, 2C19, 2D6, 2E1, 2J2, 3A4, 3A5 and 4F12 
are able to metabolise telavancin, resulting in hydroxylation at the 7, 8 and 9 position of the 
2-(decylamino) ethyl side chain of telavancin. 
 
In a mass balance study in male subjects using radiolabeled telavancin, 3 hydroxylated metabolites 
were identified with the predominant metabolite (THRX-651540) accounting for <10% of the 
radioactivity in urine and <2% of the radioactivity in plasma. 
 
In healthy young adults, three hydroxylated metabolites were identified after infusion of telavancin. 
The AUC of the predominant metabolite accounted for approximately 2-3% of AUC of telavancin. 
 
Elimination 
 
Renal excretion is the major route of elimination for telavancin in humans. In healthy young adults, 
after infusion of radiolabeled telavancin, approximately 76% of the administered dose was recovered 
from urine and less than 1% of the dose was recovered from faeces (collected for up to 9 days), based 
on total radioactivity. Telavancin is mainly excreted unchanged accounting for approximately 82% of 
the total amount recovered over 48 hours in urine. The elimination half-life in subjects with normal 
renal function is approximately 8 hours. 
 
Because renal excretion is the primary route of elimination, dosage adjustment is necessary in patients 
with a creatinine clearance of 30-50 ml/min (see section 4.2). 
 

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Special populations 
 
Elderly 
No clinically significant differences in pharmacokinetics of telavancin were observed between healthy 
elderly and healthy young subjects. Analysis of patient population pharmacokinetic data did not show 
a relevant effect of age on pharmacokinetics. Therefore, no dose adjustment is needed in elderly 
patients except in those with creatinine clearance of 30-50 ml/min (see sections 4.2 and 4.3).  
 
Paediatric patients 
The pharmacokinetics of telavancin in patients below 18 years of age have not been established (see 
section 4.2). 
 
Gender 
No clinically significant gender-related differences in telavancin pharmacokinetics have been 
observed. Therefore, no dosage adjustment is necessary based on gender.  
 
Renal insufficiency 
Pharmacokinetic parameters (mean (SD)) following a single dose administration of 7.5 mg/kg 
telavancin in volunteers with varying degrees of renal function are provided below.  
 
 Degree of Renal Impairment 
 Normal Mild Moderate Severe ESRDa 
CrCL (ml/min)b 93.8 

(10.8) 
64.1 
(9.7) 

40.3 
(7.0) 

21.0 
(6.3) NA 

Cmax (μg/ml) 70.6 
(11.2) 

65.9 
(2.7) 

65.8 
(12.1) 

71.8 
(7.1) 

52.1 
(10.1) 

AUCinf (µg⋅h/ml)  560 
(93) 

633 
(101) 

721 
(200) 

1220 
(120) 

1010 
(341) 

t1/2 (h) 6.90 
(0.60) 

9.6 
(2.9) 

10.6 
(2.4) 

14.5 
(1.3) 

11.8 
(2.8) 

CL (ml/h/kg) 13.7 
(2.1) 

12.1 
(1.9) 

11.1 
(3.3) 

6.18 
(0.63) 

8.18 
(2.65) 

a ESRD= End-stage renal disease maintained on haemodialysis 
b Baseline mean creatinine clearance as calculated by Cockcroft-Gault equation 
 
The effect of renal impairment on the pharmacokinetics of telavancin has been evaluated in 2 clinical 
pharmacology studies in healthy subjects with normal renal function and subjects with mild to severe 
renal impairment. Both studies consistently showed that the area under the curve (AUC) of telavancin, 
but not the maximum plasma concentration (Cmax) increases with decreasing renal function. Changes 
in AUC only become clinically relevant in patients with moderate and severe renal impairment. 
Therefore, the same dose of 10 mg/kg/24 hr can be used in patients with normal renal function or mild 
renal impairment. To ensure a comparable exposure in patients with moderate renal impairment, the 
dose should be lowered to 7.5 mg/kg/24 hr. 
 
Recommendations for dose adjustment can be found in section 4.2. 
 
Hepatic impairment 
Following administration of a single 10 mg/kg dose of telavancin, the pharmacokinetics of telavancin 
in subjects with moderate hepatic impairment (Child-Pugh class B) were similar to that observed in 
subjects with normal hepatic function. No adjustment of dosage is required for patients with mild to 
moderate degrees of hepatic impairment (see section 4.2). The pharmacokinetics of telavancin have 
not been evaluated in severe hepatic impairment (Child-Pugh class C). 
 
Obese patients 
Body mass index (BMI) at baseline was found to influence telavancin pharmacokinetics in the 
population pharmacokinetic analysis in healthy (without infection) adult subjects. Exposure to 
telavancin increases with increase in BMI; for each 10-unit increase in BMI, it is estimated that plasma 

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exposure will increase by up to 25%. A dose adjustment should be made in obese patients with BMI > 
30 kg/m2 (see section 4.2). 
 
5.3  Preclinical safety data  
 
The telavancin medicinal product, which contains the excipient hydroxypropylbetadex (HP-β-CD), 
induced adverse effects in animal studies at plasma concentrations that were in the same range as 
clinical exposure levels and with possible relevance to clinical use.  
 
The liver, kidney, macrophages and testis were identified as target organs of toxicity in animals. 
In the liver, treatment for 13 weeks or longer resulted in reversible degeneration/necrosis of 
hepatocytes accompanied by elevations in serum AST and ALT in rats and dogs. 
 
Effects on the kidney occurred after a minimum of 4 weeks of dosing and were a combination of renal 
tubular injury and tubular epithelial vacuolisation. The tubular injury was characterised by 
degeneration and necrosis of proximal tubular cells, and was associated with increases in BUN and 
creatinine that reach a maximum of 2 times the control values at the highest doses. The tubular injury 
was reversible, but not all animals had yet reached full recovery 4 weeks after the end of treatment.  
 
Vacuolisation of tubular epithelium was a common observation in animals treated with the telavancin 
medicinal product and with the vehicle (HP-β-CD). At higher doses or longer treatment durations, 
vacuolisation of the urothelium in the bladder also occurred. Vacuolisation was not associated with 
renal function impairment, but was not reversible after 4 weeks of recovery. Vacuolisation is 
considered to represent a cytoprotective event and is expected to reverse with the same half-life as the 
turnover time of the proximal tubular cells. The presence of hydroxypropylbetadex in the formulation 
at a ratio of 1:10 reduces the incidence and severity of the changes due to telavancin and attenuates the 
glycopeptides-like toxicity of telavancin. 
 
Systemic macrophage hypertrophy and hyperplasia occurred in rats and dogs, in many organ systems 
that normally contain macrophages. The macrophages were shown to contain telavancin and 
HP-β-CD. 
 
Genotoxicity was addressed with a standard in vitro and in vivo test battery. The studies did not 
provide any evidence for a genotoxic potential of telavancin. 
 
After 13 weeks of treatment, reversible seminiferous tubular degeneration was observed in the testis of 
rats. In studies on fertility in male rats, decreases in sperm motility and epididymal sperm counts as 
well as an increase in the frequency of abnormal sperm were demonstrated after 10 weeks of 
intravenous administration of telavancin. Male fertility was unaffected. In a second study, 6 weeks of 
dosing was associated with sloughed testicular germ cells in the epididymis, indicative of testicular 
injury, and effects upon sperm quality and quantity were observed. Both effects were reversible 
following an 8 week recovery period. The potential risk for humans is unknown (see section 4.6). 
 
In rats and dogs vacuolisation of the epididymal tubular epithelium cells was also noted, and this 
finding did not show reversibility after a recovery period of 4 weeks. Vacuolisation is considered to be 
a cytoprotective event, which is not associated with functional impairment. 
 
In embryo-fetal development studies malformations of digits and limbs were observed in rats, rabbits 
and minipigs. In the rat embryo-fetal development study dilatation of lateral ventricles of the brain was 
observed in the high dose group. An increase in the number of stillborn pups was observed in these 
pre- and post-natal studies (see section 4.3). 
 
 

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6.  PHARMACEUTICAL PARTICULARS 
 
6.1  List of excipients 
 
Hydroxypropylbetadex; the ratio of telavancin to hydroxypropylbetadex is 1:10 (w/w). 
Mannitol (E421) 
Sodium hydroxide (for pH adjustment) (E524) 
Hydrochloric acid (for pH adjustment) (E507) 
 
6.2  Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products except those mentioned in section 6.6.  
 
6.3  Shelf life 
 
Shelf life of powder as packaged for sale: 4 years 
 
Shelf life of reconstituted concentrate: The reconstituted concentrate should be diluted immediately 
after preparation.  
 
Shelf life of diluted product: Chemical and physical in use stability of the reconstituted solution and 
the diluted solution in the infusion bag has been demonstrated for 24 hours under refrigeration 
(2-8°C).  
From a microbiological point of view the product should be used immediately. If not used 
immediately, in use storage times are the responsibility of the user and should not be longer than 
24 hours at 2-8°C.  
 
6.4  Special precautions for storage 
 
Powder as packed for sale 
 
Store in a refrigerator (2–8°C). Keep the vial in the outer carton in order to protect from light.  
 
For storage conditions of the reconstituted or diluted medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
Type I clear glass vials with rubber stoppers and aluminium/plastic flip off cap.  
 
Pack sizes:  
 
VIBATIV 250 mg powder for concentrate for solution for infusion 
1 vial of 30 ml with 250 mg telavancin 
 
VIBATIV 750 mg powder for concentrate for solution for infusion 
1 vial of 50 ml with 750 mg telavancin  
 
6.6 Special precautions for disposal and other handling 
 
The powder must be reconstituted and the resulting concentrate must then be immediately diluted 
further prior to use.  
 
For single use only. 
 

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Preparation of the reconstituted concentrate 
 
VIBATIV 250 mg powder for concentrate for solution for infusion 
The contents of the vial containing 250 mg telavancin must be reconstituted with 15 ml of either 
dextrose 50 mg/ml (5%) solution for injection, or water for injections or sodium chloride 9 mg/ml 
(0.9%) solution for injection to obtain a concentration of approximately 15 mg/ml (total volume of 
approximately 17 ml).  
 
VIBATIV 750 mg powder for concentrate for solution for infusion 
The contents of the vial containing 750 mg telavancin must be reconstituted with 45 ml of either 
dextrose 50 mg/ml (5%) solution for injection, or water for injections or sodium chloride 9 mg/ml 
(0.9%) solution for injection to obtain a concentration of approximately 15 mg/ml (total volume of 
approximately 50 ml).  
 
Discard the vial if the vacuum does not pull the diluent into the vial. 
 
Aseptic technique must be used to reconstitute VIBATIV. After addition of either dextrose 50 mg/ml 
(5%) solution for injection, or water for injections or sodium chloride 9 mg/ml (0.9%) solution for 
injection, the contents of the vial are mixed by swirling gently to facilitate reconstitution. 
 
Reconstitution time is not more than 5 minutes for the vial containing 250 mg and not more than 
10 minutes for the vial containing 750 mg. 
Mixing is continued until the content of the vial is completely dissolved and is free of particulate 
matter by visual inspection. 
 
Appearance of reconstituted concentrate 
 
A reconstituted concentrate of VIBATIV is a clear, colourless to pale pink solution. Foaming may 
occur during reconstitution but will dissipate upon standing. 
 
Preparation of final diluted solution for infusion 
 
Reconstituted concentrate must be further diluted prior to administration. 
 
The following formula can be used to calculate the volume of reconstituted VIBATIV concentrate 
required to prepare a dose:  
Telavancin dose (mg) = 10 mg/kg (or 7.5 mg/kg) x patient body weight (in kg) 
Volume of reconstituted concentrate (ml) = Telavancin dose (mg)/15 (mg/ml)  
 
For doses of 150 to 800 mg, the appropriate volume of reconstituted concentrate must be further 
diluted in 100 to 250 ml prior to infusion. Doses less than 150 mg or greater than 800 mg should be 
further diluted in a volume resulting in a final solution of 0.6 to 8 mg/ml. Appropriate infusion 
solutions include: dextrose 50 mg/ml (5%) solution for injection, sodium chloride 9 mg/ml (0.9%) 
solution for injection or lactated Ringer’s solution for injection. The dilution is to be made under 
aseptic conditions. 
 
The solution is to be inspected visually for particulate matter and discoloration prior to administration. 
The solution should only be used if the solution is clear and free from particles. 
 
Disposal 
Discard any unused solution. 
 
Any unused product or waste material should be disposed of in accordance with local requirements. 
 
 

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7.  MARKETING AUTHORISATION HOLDER 
 
Theravance Biopharma Ireland Limited 
Connaught House 1, Burlington Road, Fourth Floor 
D04 C5Y6 
Dublin 4, Ireland  
 
8.  MARKETING AUTHORISATION NUMBER(S) 
 
VIBATIV 250 mg powder for concentrate for solution for infusion 
EU/1/11/705/001 
 
VIBATIV 750 mg powder for concentrate for solution for infusion 
EU/1/11/705/002 
 
 
9.  DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 02 September 2011 
Date of latest renewal: 26 May 2016 
 
 
10.  DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency: http://www.ema.europa.eu/ 
 
 

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16 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND 
USE 

 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 
 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE 
SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 
 

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A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Biotec Services International Limited 
Biotec House 
Central Park, Western Avenue 
Bridgend Industrial Estate 
Bridgend, CF31 3RT 
United Kingdom 
 
 
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. 
 
 
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. 

 
• Additional risk minimisation measures 
 
The Marketing Authorisation Holder shall agree the format and content of the Healthcare Professional 
Guide with the National Competent Authority in the Member State.  
The Marketing Authorisation Holder shall ensure that all physicians who are expected to prescribe or 
use Vibativ are provided with a healthcare professional educational pack containing the following:  
• The Summary of Product Characteristics  
• The Patient Information Leaflet  
• The Healthcare Professional Guide  
 

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The Healthcare Professional Guide should contain the following key messages:  
• That Vibativ has a risk of nephrotoxicity including increased risk of mortality in patients with 

pre existing acute renal failure and is therefore contraindicated in patients with pre-existing 
acute renal failure and in patients with creatinine clearance < 30ml/min, including patients 
undergoing haemodialysis. Vibativ should be used with caution with other nephrotoxic 
medicinal products.  

• That the benefit risk balance for the Complicated Skin and Soft Tissue Infections indication was 
assessed as negative by the Committee for Medicinal Products for Human Use (CHMP), 
therefore Vibativ should not be used in this or other indications not approved.  

• That patients’ renal function should be assessed and monitored and initial dose and dosage 
adjustments should be calculated based on the creatinine clearance.  

• That there is a potential risk of teratogenicity and Vibativ is contraindicated during pregnancy. 
The pregnancy status of women of childbearing potential must be established prior to dosing 
with telavancin and women of childbearing potential must use effective contraception during 
treatment.  

• The role and use of the Prescriber Checklist sticker included in the product package to 
document the established pregnancy status prior to dosing.  

• The existence and scope of the pregnancy register and details of how to enter patients into it.  
• There is a risk of QTc prolongation and Vibativ should be used with caution in patients taking 

medicinal products known to prolong the QT interval.  
• That there is a risk of infusion related reactions including red man syndrome-like reactions.  
• That there is an identified risk of ototoxicity and patients developing ototoxicity signs or 

symptoms or patients receiving other medicinal products with ototoxic potential should be 
carefully evaluated and monitored.  

• Healthcare professionals should be aware that the administration of Vibativ may interfere with 
some coagulation laboratory tests and qualitative and quantitative urine protein tests.  

• The need to counsel patients on important risks associated with Vibativ therapy and appropriate 
precautions when using the medicine.  

 
The MAH shall ensure that at the launch of Vibativ, all physicians who are expected to prescribe or 
use Vibativ are provided with a Direct Healthcare Professional Communication letter, the text of 
which is appended to the CHMP assessment report. The MAH shall agree the communication plan for 
the DHPC letter with the National Competent Authority in the Member States where the letter will be 
distributed. 
 
• Obligation to conduct post-authorisation measures 
 
The MAH shall complete, within the stated timeframe, the below measures: 
 
Description Due date 
A retrospective, chart review, post authorisation safety study (PASS) shall be 
conducted with the objective to further characterise the adverse drug reaction 
profile of telavancin when used in the clinical setting. Information to be collected 
shall include data on renal impairment, fatal outcomes (assessed for causality), 
cardiac disorders, liver and hepatobiliary disorders, tinnitus and hearing loss, 
adherence to the SmPC and off label use. The final protocol for the PASS should be 
provided to the CHMP by 30 April 2014. Progress on enrolment will be submitted 
with the PSURs. Intermediate analysis results should be provided starting May 
2015. Final results of the study and the re-evaluation of the benefit/risk ratio for 
Vibativ should be provided to CHMP no later than 31 December 2017. 

Final study 
results by 31 
December 
2017 

The MAH shall continue to monitor the activity of telavancin and the 
microbiological resistance as compared to other agents, through the longitudinal 
resistance surveillance program. At least 10,000 Gram-positive isolates per year 
shall be included in the study from the surveillance networks in Europe, USA, 
Latin America and Asia-Pacific. The results shall be reported to the CHMP on an 
annual basis and the final report shall be submitted no later than 31 May 2017. 

Final study 
results by 31 
May 2017 

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19 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 

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20 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 
 
CARTON AND VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
VIBATIV 250 mg powder for concentrate for solution for infusion 
telavancin 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
250 mg telavancin (as hydrochloride) per vial 
After reconstitution each ml contains 15 mg of telavancin. 
 
 
3. LIST OF EXCIPIENTS 
 
Hydroxypropylbetadex 
Mannitol (E421) 
Sodium hydroxide (E524) 
Hydrochloric acid (E507)  
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for concentrate for solution for infusion 
250 mg 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Intravenous use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

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

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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 
 
Theravance Biopharma Ireland Limited 
Connaught House 1, Burlington Road, Fourth Floor 
D04 C5Y6 
Dublin 4, Ireland  
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/705/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 
 
 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 
 
CARTON AND VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
VIBATIV 750 mg powder for concentrate for solution for infusion 
telavancin 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
750 mg telavancin (as hydrochloride) per vial 
After reconstitution each ml contains 15 mg of telavancin. 
 
 
3. LIST OF EXCIPIENTS 
 
Hydroxypropylbetadex 
Mannitol (E421) 
Sodium hydroxide (E524) 
Hydrochloric acid (E507)  
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for concentrate for solution for infusion 
750 mg 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Intravenous use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

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

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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 
 
Theravance Biopharma Ireland Limited 
Connaught House 1, Burlington Road, Fourth Floor 
D04 C5Y6 
Dublin 4, Ireland  
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/705/002  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 
 
 

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B. PACKAGE LEAFLET 
 

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PACKAGE LEAFLET: INFORMATION FOR THE USER 
 
 

VIBATIV 250 mg powder for concentrate for solution for infusion 
VIBATIV 750 mg powder for concentrate for solution for infusion 

telavancin 
 

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 are given this medicine because it contains important 
information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- If you get any side effects, talk your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet:  
1. What VIBATIV is and what it is used for 
2. What you need to know before you use VIBATIV 
3. How to use VIBATIV 
4. Possible side effects 
5. How to store VIBATIV 
6. Contents of the pack and other information 
 
1. What VIBATIV is and what it is used for 
 
VIBATIV contains telavancin as active substance, which is an antibiotic of the glycopeptide group. 
VIBATIV is used to treat adult patients with infections of the lungs that have developed in the 
hospital, including patients on artificial ventilation, when these infections are known or suspected to 
be caused by bacteria called methicillin-resistant Staphylococcus aureus (MRSA).  
It is only used when the bacteria that cause these infections can be killed with telavancin. VIBATIV 
can only be used when other antibiotics are not suitable. 
 
If you also have other bacteria that cause your infection, your doctor may prescribe other antibiotics in 
addition to VIBATIV. 
 
 
2. What you need to know before you use VIBATIV 
 
Do not use VIBATIV 
- if you are allergic (hypersensitive) to telavancin or any of the other ingredients of VIBATIV 

(listed in section 6) 
- If you suffer from severe kidney problems, or receive haemodialysis  
- if you are pregnant 
 
Warnings and precautions 
Talk to your doctor or nurse before you are given VIBATIV 

 

- if you have kidney problems. Your doctor may decide to reduce the dose of VIBATIV and 
monitor you more closely during treatment. Alternatively, your doctor may decide that this 
medicine is not suitable for you.  

- if you are at greater risk of developing kidney disorders or if you are receiving other 
medicines that can affect your kidney. Your doctor will tell you if this is the case and may 
decide to monitor you more closely during treatment. 

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- if you experience skin reactions to the product. Your doctor may decide to adjust the rate of the 
infusion. 

- if you are allergic to antibiotics such as vancomycin. Tell your doctor immediately if this is the 
case. 

- if you are suffering from heart disorders. Tell your doctor immediately if this is the case. 
- if you notice a change in your hearing. Tell your doctor immediately if this is the case. Your 

doctor may monitor your hearing during treatment. Ringing in the ears and deafness are possible 
side effects. 

- While antibiotics including VIBATIV fight certain bacteria, other bacteria and fungi may 
continue to grow. This is called overgrowth. Your doctor will monitor you for any potential 
infections and treat you if necessary.  

- if you develop diarrhoea during or shortly after your treatment, tell your doctor immediately. Do 
not take any diarrhoea medicine without first checking with your doctor.  

- if you are suffering from more than one infection. Your doctor will treat you as necessary.  
 
Children and adolescents  
Telavancin is not to be used in children or adolescents under 18 years of age. 
 
Other medicines and VIBATIV 
Please tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 
 
Telavancin may interfere with some laboratory tests that measure how well your blood is clotting. The 
test results can suggest poor blood clotting when, in fact, there is no problem. Tell your doctor that 
you are receiving VIBATIV. 
 
Telavancin may interfere with some laboratory tests that measure proteins in the urine. Tell your 
doctor that you are receiving VIBATIV. 
 
Pregnancy and breast-feeding 
Telavancin must not be given to pregnant women. Tell your doctor if you are pregnant, think you may 
be pregnant, or are trying to become pregnant. You have to use effective contraception during 
treatment with VIBATIV.  
 
It is not known if telavancin passes into breast milk in humans. Ask your doctor for advice before 
breastfeeding your baby.  
 
Driving and using machines 
VIBATIV may cause side effects, such as dizziness, sleepiness, confusion or blurred vision that can 
have an influence on the ability to drive or operate machinery. 
 
Important information about some of the ingredients of VIBATIV 
This medicine contains less than 1 mmol sodium (23 mg) per vial, i.e. essentially ‘sodium-free’. 
 
 
3. How to use VIBATIV 
 
VIBATIV will be given to you by a doctor or a nurse.  
The dose given will depend on how much you weigh. The dose for adults (18 years and older) is 
10 milligrams (mg) for every kilogram (kg) of body weight, given once a day. This dose is given as an 
infusion (drip into a vein) over a period of about 60 minutes. 
If your kidneys do not work well or if you are overweight, the dose may be reduced. 
 
A course of treatment usually lasts for 7 to 21 days. Your doctor will decide how long you should be 
treated.  
 

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If you use more VIBATIV than you should  
If you are given more VIBATIV than you should receive, the chance of experiencing the following 
side effects increases: disturbed taste, nausea (feeling sick), vomiting, reactions at the site of the 
infusion, headache, rash, skin flushing of the upper body. If this happens, the infusion of telavancin 
will be stopped and the doctor will check the functioning of your kidneys.  
 
If you have any further questions on the use of this product, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, VIBATIV can cause side effects, although not everybody gets them. 
 
VIBATIV may cause the following side effects: 
 
Very common: may affect more than 1 in 10 people 
- taste disturbance  
- nausea (feeling sick)  
 
Common: may affect up to 1 in 10 people 
- fungal infections 
- sleeplessness  
- headache, dizziness  
- constipation, diarrhoea; vomiting  
- raised blood levels of liver enzymes  
- itching, rash 
- kidney disorder, abnormal kidney function tests, foamy urine 
- tiredness, chills 
 
Uncommon: may affect up to 1 in 100 people 
- intestinal bacterial infection; urinary tract infection 
- anaemia, changes in white blood cell counts; changes in blood platelet counts 
- allergic reactions 
- decreased appetite; changes in blood levels of glucose; changes in blood levels of potassium and 

magnesium 
- restlessness; anxiety; confusion; depression 
- loss of taste, migraine, abnormal touch sensation, smell disturbance, sleepiness, trembling 
- eye irritation; blurred vision 
- ringing in your ears 
- chest pain; heart failure; abnormal heart rhythm or heart beat  
- flushing; high or low blood pressure; inflammation of a vein 
- breathlessness, hiccups, nasal congestion, sore throat 
- abdominal pain; dry mouth; indigestion, bloating; numbness of the mouth  
- liver inflammation 
- skin redness; swelling of face; sweating, hives 
- joint pain; back pain; muscle cramp; muscle pain 
- painful urination; blood in urine; low urine output, frequent urination; abnormal urine odour 
- lack of energy; irritation at infusion site; feeling unwell; chest discomfort; accumulation of fluid 

in the lower legs; pain; fever; skin flushing of upper body  
- abnormal blood clotting tests 
 
Rare: may affect up to 1 in 1,000 people 
- deafness 
 

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Not known: frequency cannot be estimated from the available data 
- severe allergic reactions (anaphylaxis).  The first signs of a severe allergic reaction may include 

swelling of the skin, face and/or throat and/or difficulty breathing. If these symptoms occur you 
must inform your doctor or nurse immediately. 

 
Reporting of side effects 
If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this 
leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. 
By reporting side effects you can help provide more information on the safety of this medicine. 
 
 
5. How to store VIBATIV 
 
Keep out of the sight and reach of children. 
 
Do not use VIBATIV after the expiry date that is stated on the label and carton after EXP: The expiry 
date refers to the last day of that month. 
 
Store in a refrigerator (2°C – 8°C). 
Keep the vial in the outer carton to protect the product from light.  
 
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to 
dispose of medicines no longer required. These measures will help to protect the environment. 
 
 
6. Contents of the pack and other information 
 
What VIBATIV contains 
 
Each vial contains 250 mg or 750 mg telavancin (as hydrochloride). After reconstitution, each ml of 
concentrated solution contains 15 mg of telavancin.  
The other ingredients are hydroxypropylbetadex, mannitol (E421), sodium hydroxide (E524) (for pH 
adjustment) and hydrochloric acid (E507) (for pH adjustment). 
 
What VIBATIV looks like and contents of the pack 
 
VIBATIV powder for concentrate for solution for infusion is provided as a 30 ml or 50 ml clear glass 
vial with rubber stopper, with an aluminium closure with plastic flip-off caps. The vial contains a 
white to pale pink powder.  
 
Pack sizes: 
1 vial of 30 ml with 250 mg telavancin 
1 vial of 50 ml with 750 mg telavancin 
 
Marketing Authorisation Holder 
 
Theravance Biopharma Ireland Limited 
Connaught House 1, Burlington Road, Fourth Floor 
D04 C5Y6 
Dublin 4, Ireland  
 

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Manufacturer 
 
Biotec Services International Limited 
Biotec House 
Central Park, Western Avenue 
Bridgend Industrial Estate 
Bridgend, CF31 3RT 
United Kingdom 
 
 
This leaflet was last approved in {MM/YYYY}. 
 
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 medical or healthcare professionals only: 
 
Method of administration  
VIBATIV must be reconstituted and then further diluted prior to administration by intravenous 
infusion through a dedicated line or through a Y-site over a 60 minute period. Bolus injections must 
not be administered.  
 
The following formula can be used to calculate to volume of reconstituted VIBATIV concentrate 
required to prepare a dose:  
 
Telavancin dose (mg) = 10 mg/kg (or 7.5 mg/kg) x patient body weight (in kg)  
 
Volume of reconstituted concentrate (ml) = Telavancin dose (mg)/15 (mg/ml)  
 
Incompatibilities  
 
In the absence of compatibility studies, this medicine must not be mixed with other medicines. 
 
Shelf life  
 
Shelf life of reconstituted concentrate: The reconstituted concentrate should be diluted immediately 
after preparation.  
 
Shelf life of diluted product: Chemical and physical in use stability of the reconstituted solution and 
the diluted solution in the infusion bag has been demonstrated for 24 hours under refrigeration 
(2-8°C). From a microbiological point of view the product should be used immediately. If not used 
immediately, in use storage times are the responsibility of the user and should not be longer than 
24 hours at 2-8°C.  
 
Special precautions for disposal and other handling 
 
The powder must be reconstituted and the resulting concentrate must then be immediately diluted 
further prior to use.  
 
Preparation of the reconstituted concentrate (VIBATIV 250 mg vial)  
The contents of the vial containing 250 mg telavancin must be reconstituted with 15 ml of either 
dextrose 50 mg/ml (5%) solution for injection, or water for injections or sodium chloride 9 mg/ml 

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(0.9%) solution for injection to obtain a concentration of approximately 15 mg/ml (total volume of 
approximately 17 ml).  
 
Preparation of the reconstituted concentrate (VIBATIV 750 mg vial)  
The contents of the vial containing 750 mg telavancin must be reconstituted with 45 ml of either 
dextrose 50 mg/ml (5%) solution for injection, or water for injections or sodium chloride 9 mg/ml 
(0.9%) solution for injection to obtain a concentration of approximately 15 mg/ml (total volume of 
approximately 50 ml).  
 
Discard the vial if the vacuum does not pull the diluent into the vial.  
 
Aseptic technique must be used to reconstitute VIBATIV. After addition of either dextrose 50 mg/ml 
(5%) solution for injection, or water for injections or sodium chloride 9 mg/ml (0.9%) solution for 
injection, the contents of the vial are mixed by swirling gently to facilitate reconstitution.  
 
Reconstitution time is not more than 5 minutes for the vial containing 250 mg.  
Reconstitution time is not more than 10 minutes for the vial containing 750 mg.  
Mixing is continued until the content of the vial is completely dissolved and is free of particulate 
matter by visual inspection.  
 
Appearance of reconstituted concentrate  
A reconstituted concentrate of VIBATIV is a clear, colourless to pale pink solution. Foaming may 
occur during reconstitution but will dissipate upon standing.  
 
Preparation of final diluted solution for infusion  
Reconstituted concentrate must be further diluted prior to administration.  
For doses of 150 to 800 mg, the appropriate volume of reconstituted concentrate must be further 
diluted in 100 to 250 ml prior to infusion. Doses less than 150 mg or greater than 800 mg should be 
further diluted in a volume resulting in a final solution of 0.6 to 8 mg/ml. Appropriate infusion 
solutions include: dextrose 50 mg/ml (5%) solution for injection, sodium chloride 9 mg/ml (0.9%) 
solution for injection or lactated Ringer’s solution for injection. The dilution is to be made under 
aseptic conditions.  
 
The solution is to be inspected visually for particulate matter and discoloration prior to administration. 
The solution should only be used if the solution is clear and free from particles.  
 
Disposal  
For single use only. Discard any unused solution.  
 
Any unused product or waste material should be disposed of in accordance with local requirements.  
 

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	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER 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