Tigecycline Accord

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 
 Tigecycline Accord  50 mg powder for solution for infusion 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each 5 ml Tigecycline Accord vial contains 50 mg of tigecycline. After reconstitution, 1 ml contains 
10 mg of tigecycline. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder for solution for infusion (powder for infusion). 
 
Orange cake or powder. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Tigecycline Accord  is indicated in adults and in children from the age of eight years for the treatment 
of the following infections (see sections 4.4 and 5.1): 
 
• Complicated skin and soft tissue infections (cSSTI), excluding diabetic foot infections (see 

section 4.4); 
• Complicated intra-abdominal infections (cIAI). 

 
Tigecycline Accord  should be used only in situations where other alternative antibiotics are not 
suitable (see sections 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 dose for adults is an initial dose of 100 mg followed by 50 mg every 12 hours for 
5 to 14 days. 
 
The duration of therapy should be guided by the severity, site of the infection, and the patient’s 
clinical response. 
 
Children and adolescents (8 to 17 years of age) 
 
Tigecycline Accord  is only to be used to treat patients aged 8 years and older after consultation with 
a physician with appropriate experience in the management of infectious diseases. 



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Children aged 8 to <12 years: 1.2 mg/kg of tigecycline every 12 hours intravenously to a 
maximum dose of 50 mg every 12 hours for 5 to 14 days. 
 
Adolescents aged 12 to <18 years: 50 mg of tigecycline every 12 hours for 5 to 14 days. 
 

Elderly 
No dosage adjustment is necessary in elderly patients (see section 5.2). 
 
Hepatic impairment 
No dosage adjustment is warranted in patients with mild to moderate hepatic impairment (Child Pugh 
A and Child Pugh B). 
 
In patients (including paediatrics) with severe hepatic impairment (Child Pugh C), the dose of 
tigecycline should be reduced by 50%. Adult dose should be reduced to 25 mg every 12 hours 
following the 100 mg loading dose. Patients with severe hepatic impairment (Child Pugh C) should be 
treated with caution and monitored for treatment response (see sections 4.4 and 5.2). 
 
Renal impairment 
No dosage adjustment is necessary in patients with renal impairment or in patients undergoing 
haemodialysis (see section 5.2). 
 
Paediatric population 
The safety and efficacy of Tigecycline Accord  in children under 8 years of age have not been 
established. No data are available. Tigecycline Accord  should not be used in children aged under 8 
years because of teeth discolouration (see sections 4.4 and 5.1). 
 
Method of administration 
 
Tigecycline is administered only by intravenous infusion over 30 to 60 minutes (see sections 4.4 
and 6.6). Tigecycline should be preferably administered over a 60-minute length of infusion in 
paediatric patients (see section 4.4). 
 
For instructions on reconstitution & dilution of the medicinal product before administration, see 
section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
Patients hypersensitive to tetracycline class antibiotics may be hypersensitive to tigecycline. 
 
4.4 Special warnings and precautions for use 
 
In clinical studies in complicated skin and soft tissue infections (cSSTI), complicated intra-abdominal 
infections (cIAI), diabetic foot infections, nosocomial pneumonia and studies in resistant pathogens, a 
numerically higher mortality rate among tigecycline treated patients has been observed as compared 
to the comparator treatment. The causes of these findings remain unknown, but poorer efficacy and 
safety than the study comparators cannot be ruled out. 
 
Superinfection 
 
In clinical trials in cIAI patients, impaired healing of the surgical wound has been associated with 
superinfection. A patient developing impaired healing should be monitored for the detection of 
superinfection (see section 4.8). 
 



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Patients who develop superinfections, in particular nosocomial pneumonia, appear to be associated 
with poorer outcomes. Patients should be closely monitored for the development of superinfection. If 
a focus of infection other than cSSTI or cIAI is identified after initiation of tigecycline therapy 
consideration should be given to instituting alternative antibacterial therapy that has been 
demonstrated to be efficacious in the treatment of the specific type of infection(s) present. 
 
Anaphylaxis 
 
Anaphylaxis/anaphylactoid reactions, potentially life-threatening, have been reported with tigecycline 
(see sections 4.3 and 4.8). 
 
Hepatic failure 
 
Cases of liver injury with a predominantly cholestatic pattern have been reported in patients receiving 
tigecycline treatment, including some cases of hepatic failure with a fatal outcome. Although hepatic 
failure may occur in patients treated with tigecycline due to the underlying conditions or concomitant 
medicinal products, a possible contribution of tigecycline should be considered (see section 4.8). 
 
Tetracycline class antibiotics 
 
Glycylcycline class antibiotics are structurally similar to tetracycline class antibiotics. Tigecycline 
may have adverse reactions similar to tetracycline class antibiotics. Such reactions may include 
photosensitivity, pseudotumour cerebri, pancreatitis, and anti-anabolic action which has led to 
increased BUN, azotaemia, acidosis, and hyperphosphataemia (see section 4.8).  
 
Pancreatitis 
 
Acute pancreatitis, which can be serious, has occurred (frequency: uncommon) in association with 
tigecycline treatment (see section 4.8). The diagnosis of acute pancreatitis should be considered in 
patients taking tigecycline who develop clinical symptoms, signs, or laboratory abnormalities 
suggestive of acute pancreatitis. Most of the reported cases developed after at least one week of 
treatment. Cases have been reported in patients without known risk factors for pancreatitis. Patients 
usually improve after tigecycline discontinuation. Consideration should be given to the cessation of 
the treatment with tigecycline in cases suspected of having developed pancreatitis. 
 
Underlying diseases 
 
Experience in the use of tigecycline for treatment of infections in patients with severe underlying 
diseases is limited. 
 
In clinical trials in cSSTI, the most common type of infection in tigecycline treated-patients was 
cellulitis (58.6 %), followed by major abscesses (24.9 %). Patients with severe underlying disease, 
such as those that were immunocompromised, patients with decubitus ulcer infections, or patients that 
had infections requiring longer than 14 days of treatment (for example, necrotizing fasciitis), were not 
enrolled. A limited number of patients were enrolled with co-morbid factors such as diabetes 
(25.8 %), peripheral vascular disease (10.4 %), intravenous substance abuse (4.0 %), and HIV-
positive infection (1.2 %). Limited experience is also available in treating patients with concurrent 
bacteraemia (3.4 %). Therefore, caution is advised when treating such patients. The results in a large 
study in patients with diabetic foot infection, showed that tigecycline was less effective than 
comparator, therefore, tigecycline is not recommended for use in these patients (see section 4.1). 
 
In clinical trials in cIAI, the most common type of infection in tigecycline-treated patients was 
complicated appendicitis (50.3 %), followed by other diagnoses less commonly reported such as 
complicated cholecystitis (9.6 %), perforation of intestine (9.6 %), intra-abdominal abscess (8.7 %), 
gastric or duodenal ulcer perforation (8.3 %), peritonitis (6.2 %) and complicated diverticulitis (6.0 
%). Of these patients, 77.8 % had surgically-apparent peritonitis. There were a limited number of 



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patients with severe underlying disease such as immunocompromised patients, patients with 
APACHE II scores > 15 (3.3 %), or with surgically apparent multiple intra-abdominal abscesses 
(11.4 %). Limited experience is also available in treating patients with concurrent bacteraemia 
(5.6 %). Therefore, caution is advised when treating such patients. 
 
Consideration should be given to the use of combination antibacterial therapy whenever tigecycline is 
to be administered to severely ill patients with cIAI secondary to clinically apparent intestinal 
perforation or patients with incipient sepsis or septic shock (see section 4.8). 
 
The effect of cholestasis in the pharmacokinetics of tigecycline has not been properly established. 
Biliary excretion accounts for approximately 50 % of the total tigecycline excretion. Therefore, 
patients presenting with cholestasis should be closely monitored. 
 
Prothrombin time or other suitable anticoagulation test should be used to monitor patients if 
tigecycline is administered with anticoagulants (see section 4.5). 
 
Pseudomembranous colitis has been reported with nearly all antibacterial agents 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 subsequent to the administration of any antibacterial agent (see 
section 4.8). 
 
The use of tigecycline may result in overgrowth of non-susceptible organisms, including fungi. 
Patients should be carefully monitored during therapy (see section 4.8).  
 
Results of studies in rats with tigecycline have shown bone discolouration. Tigecycline may be 
associated with permanent tooth discolouration in humans if used during tooth development (see 
section 4.8). 
 
Paediatric population 
 
Clinical experience in the use of tigecycline for the treatment of infections in paediatric patients aged 
8 years and older is very limited (see sections 4.8 and 5.1). Consequently, use in children should be 
restricted to those clinical situations where no alternative antibacterial therapy is available. 
 
Nausea and vomiting are very common adverse reactions in children and adolescents (see section 4.8). 
Attention should be paid to possible dehydration. Tigecycline should be preferably administered over 
a 60-minute length of infusion in paediatric patients.  
 
Abdominal pain is commonly reported in children as it is in adults. Abdominal pain may be indicative 
of pancreatitis. If pancreatitis develops, treatment with tigecycline should be discontinued.     
 
Liver function tests, coagulation parameters, haematology parameters, amylase and lipase should be 
monitored prior to treatment initiation with tigecycline and regularly while on treatment. 
 
Tigecycline Accord  should not be used in children under 8 years of age due to the lack of safety and 
efficacy data in this age group and because tigecycline may be associated with permanent teeth 
discolouration (see sections 4.2 and 4.8). 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Interaction studies have only been performed in adults. 
 
Concomitant administration of tigecycline and warfarin (25 mg single-dose) to healthy subjects 
resulted in a decrease in clearance of R-warfarin and S-warfarin by 40 % and 23 %, and an increase in 
AUC by 68 % and 29 %, respectively. The mechanism of this interaction is still not elucidated. 
Available data does not suggest that this interaction may result in significant INR changes. However, 



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since tigecycline may prolong both prothrombin time (PT) and activated partial thromboplastin time 
(aPTT), the relevant coagulation tests should be closely monitored when tigecycline is 
co-administered with anticoagulants (see section 4.4). Warfarin did not affect the pharmacokinetic 
profile of tigecycline. 
 
Tigecycline is not extensively metabolised. Therefore, clearance of tigecycline is not expected to be 
affected by active substances that inhibit or induce the activity of the CYP450 isoforms. In vitro, 
tigecycline is neither a competitive inhibitor nor an irreversible inhibitor of CYP450 enzymes (see 
section 5.2). 
 
Tigecycline in recommended dosage did not affect the rate or extent of absorption, or clearance of 
digoxin (0.5 mg followed by 0.25 mg daily) when administered in healthy adults. Digoxin did not 
affect the pharmacokinetic profile of tigecycline. Therefore, no dosage adjustment is necessary when 
tigecycline is administered with digoxin. 
 
In in vitro studies, no antagonism has been observed between tigecycline and other commonly used 
antibiotic classes. 
 
Concurrent use of antibiotics with oral contraceptives may render oral contraceptives less effective. 
 
Based on an in vitro study tigecycline is a P-gp substrate. Co-administration of P-gp inhibitors (e.g., 
ketoconazole or cyclosporine) or P-gp inducers (e.g., rifampicin) could affect the pharmacokinetics of 
tigecycline (see section 5.2). 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no or limited amount of data from the use of tigecycline in pregnant women. Studies in 
animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. 
As it is known for tetracycline class antibiotics, tigecycline may also induce permanent dental defects 
(discolouration and enamel defects) and a delay in ossification processes in foetuses, exposed in utero 
during the last half of gestation, and in children under eight years of age due to the enrichment in 
tissues with a high calcium turnover and formation of calcium chelate complexes (see section 4.4). 
Tigecycline should not be used during pregnancy unless the clinical condition of the woman requires 
treatment with tigecycline. 
 
Breast-feeding 
 
It is unknown whether tigecycline/metabolites are excreted in human milk. Available 
pharmacodynamic/toxicological data in animals have shown excretion of tigecycline/metabolites in 
milk (see section 5.3). A risk to the newborns/infants cannot be excluded. A decision must be made 
whether to discontinue breast-feeding or to discontinue/abstain from tigecycline therapy taking into 
account the benefit of breast-feeding for the child and the benefit of therapy for the woman. 
 
Fertility 
 
Tigecycline did not affect mating or fertility in rats at exposures up to 4.7 times the human daily dose 
based on AUC. In female rats, there were no compound-related effects on ovaries or oestrus cycles at 
exposures up to 4.7 times the human daily dose based on AUC. 
 
4.7 Effects on ability to drive and use machines 
 
Dizziness may occur and this may have an effect on driving and use of machines (see section 4.8). 



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4.8 Undesirable effects 
 
Summary of safety profile 
 
The total number of cSSTI and cIAI patients treated with tigecycline in Phase 3 and 4 clinical studies 
was 2,393. 
 
In clinical trials, the most common medicinal product-related treatment emergent adverse reactions 
were reversible nausea (21 %) and vomiting (13 %), which usually occurred early (on treatment days 
1-2) and were generally mild or moderate in severity. 
 
Adverse reactions reported with tigecycline, including clinical trials and post-marketing experience, 
are tabulated below. 
 
Tabulated list of adverse reactions 
 
System Organ 
Class 

Very Common 
 ≥ 1/10 
 

Common 
≥ 1/100 to < 1/10 
 

Uncommon 
≥ 1/1,000 to 
< 1/100 
 

Frequency 
not known 
(cannot be 
estimated 
from the available 
data) 

Infections and 
infestations 

 sepsis/septic shock, 
pneumonia, abscess, 
infections 

  

Blood and 
lymphatic 
system 
disorders 

 prolonged activated 
partial 
thromboplastin time 
(aPTT), prolonged 
prothrombin time 
(PT) 

thrombocytopenia, 
increased 
international 
normalised ratio 
(INR) 

hypofibrinogenaemia 

Immune system 
disorders 

   anaphylaxis/ 
anaphylactoid 
reactions* (see 
sections 4.3 and 
4.4) 

Metabolism and 
nutrition 
disorders 

 hypoglycaemia, 
hypoproteinaemia 

  

Nervous system 
disorders  

 dizziness   

Vascular 
disorders  

 phlebitis thrombophlebitis  

Gastrointestinal 
disorders  

nausea, vomiting, 
diarrhoea 

abdominal pain, 
dyspepsia, anorexia 

acute pancreatitis 
(see section 4.4) 

 

Hepatobiliary 
disorders  

 elevated aspartate 
aminotransferase 
(AST) in serum, and 
elevated alanine 
aminotransferase 
(ALT) in serum, 
hyperbilirubinaemia 

jaundice, liver 
injury, mostly 
cholestatic 

hepatic failure* (see 
section 4.4) 

Skin and 
subcutaneous 

 pruritus, rash  severe skin 
reactions, including 



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System Organ 
Class 

Very Common 
 ≥ 1/10 
 

Common 
≥ 1/100 to < 1/10 
 

Uncommon 
≥ 1/1,000 to 
< 1/100 
 

Frequency 
not known 
(cannot be 
estimated 
from the available 
data) 

tissue disorders  Stevens-Johnson 
Syndrome* 

General 
disorders and 
administration 
site conditions 

 impaired healing, 
injection site 
reaction, headache 

injection site 
inflammation, 
injection site pain, 
injection site 
oedema, injection 
site phlebitis 

 

Investigations  elevated amylase in 
serum, increased 
blood urea nitrogen 
(BUN) 

  

*ADR identified post-marketing 
 
Description of selected adverse reactions 
 
Antibiotic class effects 
 
Pseudomembranous colitis which may range in severity from mild to life threatening (see section 4.4). 
 
Overgrowth of non-susceptible organisms, including fungi (see section 4.4). 
 
Tetracycline class effects 
 
Glycylcycline class antibiotics are structurally similar to tetracycline class antibiotics. Tetracycline 
class adverse reactions may include photosensitivity, pseudotumour cerebri, pancreatitis, and anti-
anabolic action which has led to increased BUN, azotaemia, acidosis, and hyperphosphataemia (see 
section 4.4).  
 
Tigecycline may be associated with permanent tooth discolouration if used during tooth development 
(see section 4.4). 
 
In Phase 3 and 4 cSSTI and cIAI clinical studies, infection-related serious adverse reactions were 
more frequently reported for subjects treated with tigecycline (7.1 %) vs comparators (5.3 %). 
Significant differences in sepsis/septic shock with tigecycline (2.2 %) vs comparators (1.1 %) were 
observed. 
 
AST and ALT abnormalities in tigecycline-treated patients were reported more frequently in the post 
therapy period than in those in comparator-treated patients, which occurred more often on therapy. 
 
In all Phase 3 and 4 (cSSTI and cIAI) studies, death occurred in 2.4 % (54/2216) of patients receiving 
tigecycline and 1.7% (37/2206) of patients receiving active comparators. 
 
Paediatric population 
 
Very limited safety data were available from two PK studies (see section 5.2). No new or unexpected 
safety concerns were observed with tigecycline in these studies. 
 



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In an open-label, single ascending dose PK study, the safety of tigecycline was investigated in 
25 children aged 8 to 16 years who recently recovered from infections. The adverse reaction profile of 
tigecycline in these 25 subjects was generally consistent with that in adults. 
 
The safety of tigecycline was also investigated in an open-label, ascending multi-dose PK study in 
58 children aged 8 to 11 years with cSSTI (n=15), cIAI (n=24) or community-acquired pneumonia 
(n=19). The adverse reaction profile of tigecycline in these 58 subjects was generally consistent with 
that in adults, with the exception of nausea (48.3 %), vomiting (46.6 %) and elevated lipase in serum 
(6.9 %) which were seen at greater frequencies in children than in adults. 
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
No specific information is available on the treatment of overdosage. Intravenous administration of 
tigecycline at a single dose of 300 mg over 60 minutes in healthy volunteers resulted in an increased 
incidence of nausea and vomiting. Tigecycline is not removed in significant quantities by 
haemodialysis. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antibacterials for systemic use, tetracyclines, ATC code: J01AA12. 
 
Mechanism of action 
 
Tigecycline, a glycylcycline antibiotic, inhibits protein translation in bacteria by binding to the 30S 
ribosomal subunit and blocking entry of amino-acyl tRNA molecules into the A site of the ribosome. 
This prevents incorporation of amino acid residues into elongating peptide chains. 
 
In general, tigecycline is considered bacteriostatic. At 4 times the minimum inhibitory concentration 
(MIC), a 2-log reduction in colony counts was observed with tigecycline against Enterococcus spp., 
Staphylococcus aureus, and Escherichia coli.  
 
Mechanism of resistance 
 
Tigecycline is able to overcome the two major tetracycline resistance mechanisms, ribosomal 
protection and efflux. Cross-resistance between tigecycline and minocycline-resistant isolates among 
the Enterobacteriaceae due to multi-drug resistance (MDR) efflux pumps has been shown. There is 
no target-based cross-resistance between tigecycline and most classes of antibiotics. 
 
Tigecycline is vulnerable to chromosomally-encoded multi-drug efflux pumps of Proteeae and 
Pseudomonas aeruginosa. Pathogens of the family Proteeae (Proteus spp., Providencia spp., and 
Morganella spp.) are generally less susceptible to tigecycline than other members of the 
Enterobacteriaceae. Decreased susceptibility in both groups has been attributed to the overexpression 
of the non-specific AcrAB multi-drug efflux pump. Decreased susceptibility in Acinetobacter 
baumannii has been attributed to the overexpression of the AdeABC efflux pump. 
 
Breakpoints 

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


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Minimum inhibitory concentration (MIC) breakpoints established by the European Committee on 
Antimicrobial Susceptibility Testing (EUCAST) are as follows: 
 
Staphylococcus spp. S ≤ 0.5 mg/L and R > 0.5 mg/L 
Streptococcus spp. other than S. pneumoniae S ≤ 0.25 mg/L and R > 0.5 mg/L 
Enterococcus spp. S ≤ 0.25 mg/L and R > 0.5 mg/L 
Enterobacteriaceae S ≤ 1(^) mg/L and R > 2 mg/L 
 
(^)Tigecycline has decreased in vitro activity against Proteus, Providencia, and Morganella spp. 
 
For anaerobic bacteria there is clinical evidence of efficacy in polymicrobial intra-abdominal 
infections, but no correlation between MIC values, PK/PD data and clinical outcome. Therefore, no 
breakpoint for susceptibility is given. It should be noted that the MIC distributions for organisms of 
the genera Bacteroides and Clostridium are wide and may include values in excess of 2 mg/L 
tigecycline. 
 
There is limited evidence of the clinical efficacy of tigecycline against enterococci. However, 
polymicrobial intra-abdominal infections have shown to respond to treatment with tigecycline in 
clinical trials. 
 
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. 
 
Pathogen 
 
Commonly Susceptible Species 
Gram-positive Aerobes 
Enterococcus spp.† 
Staphylococcus aureus* 
Staphylococcus epidermidis 
Staphylococcus haemolyticus 
Streptococcus agalactiae* 
Streptococcus anginosus group* (includes S. anginosus, S. intermedius and S. constellatus) 
Streptococcus pyogenes* 
Viridans group streptococci 
 
Gram-negative Aerobes 
Citrobacter freundii* 
Citrobacter koseri 
Escherichia coli* 
Klebsiella oxytoca* 
 
Anaerobes 
Clostridium perfringens† 
Peptostreptococcus spp.† 
Prevotella spp. 
Species for which acquired resistance may be a problem 
Gram-negative Aerobes 
Acinetobacter baumannii 
Burkholderia cepacia 



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Pathogen 
 
Enterobacter aerogenes 
Enterobacter cloacae* 
Klebsiella pneumoniae* 
Morganella morganii 
Proteus spp. 
Providencia spp. 
Serratia marcescens 
Stenotrophomonas maltophilia 
Anaerobes 
Bacteroides fragilis group† 
Inherently resistant organisms 
Gram-negative Aerobes 
Pseudomonas aeruginosa 
*denotes species against which it is considered that activity has been satisfactorily demonstrated in 
clinical studies. 
† see section 5.1, Breakpoints above. 
 
Cardiac Electrophysiology  
 
No significant effect of a single intravenous dose of tigecycline 50 mg or 200 mg on QTc interval was 
detected in a randomized, placebo- and active-controlled four-arm crossover thorough QTc study of 
46 healthy subjects. 
 
Paediatric population 
 
In an open-label, ascending multiple-dose study, 39 children aged 8 to 11 years with cIAI or cSSTI 
were administered tigecycline (0.75, 1, or 1.25 mg/kg). All patients received IV tigecycline for a 
minimum of 3 consecutive days to a maximum of 14 consecutive days, with the option to be switched 
to an oral antibiotic on or after day 4.  
 
Clinical cure was assessed between 10 and 21 days after the administration of the last dose of 
treatment. The summary of clinical response in the modified intent-to-treat (mITT) population results 
is shown in the following table.  
 

Clinical Cure, mITT Population 
 0.75 mg/kg 1 mg/kg 1.25 mg/kg 
Indication n/N (%) n/N (%) n/N (%) 
cIAI 6/6 (100.0) 3/6 (50.0) 10/12 (83.3) 
cSSTI 3/4 (75.0) 5/7 (71.4) 2/4 (50.0) 
Overall 9/10 (90.0) 8/13 (62.0 %) 12/16 (75.0) 

 
Efficacy data above shown should be viewed with caution as concomitant antibiotics were allowed in 
this study. In addition, the small number of patients should also be taken into consideration.  
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
Tigecycline is administered intravenously and therefore has 100 % bioavailability. 



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Distribution 
 
The in vitro plasma protein binding of tigecycline ranges from approximately 71 % to 89 % at 
concentrations observed in clinical studies (0.1 to 1.0 mcg/ml). Animal and human pharmacokinetic 
studies have demonstrated that tigecycline readily distributes to tissues. 
In rats receiving single or multiple doses of 14C-tigecycline, radioactivity was well distributed to most 
tissues, with the highest overall exposure observed in bone marrow, salivary glands, thyroid gland, 
spleen, and kidney. In humans, the steady-state volume of distribution of tigecycline averaged 500 to 
700 L (7 to 9 L/kg), indicating that tigecycline is extensively distributed beyond the plasma volume 
and concentrates into tissues. 
 
No data are available on whether tigecycline can cross the blood-brain barrier in humans. 
In clinical pharmacology studies using the therapeutic dosage regimen of 100 mg followed by 50 mg 
q12h, serum tigecycline steady-state Cmax was 866±233 ng/ml for 30-minute infusions and 634±97 
ng/ml for 60-minute infusions. The steady-state AUC0-12h was 2349±850 ng•h/ml. 
 
Biotransformation 
 
On average, it is estimated that less than 20 % of tigecycline is metabolised before excretion. In 
healthy male volunteers, following the administration of 14C-tigecycline, unchanged tigecycline was 
the primary 14C-labelled material recovered in urine and faeces, but a glucuronide, an N-acetyl 
metabolite and a tigecycline epimer were also present. 
 
In vitro studies in human liver microsomes indicate that tigecycline does not inhibit metabolism 
mediated by any of the following 6 cytochrome P450 (CYP) isoforms: 1A2, 2C8, 2C9, 2C19, 2D6, 
and 3A4 by competitive inhibition. In addition, tigecycline did not show NADPH-dependency in the 
inhibition of CYP2C9, CYP2C19, CYP2D6 and CYP3A, suggesting the absence of mechanism-based 
inhibition of these CYP enzymes.  
 
Elimination 
 
The recovery of the total radioactivity in faeces and urine following administration of 14C-tigecycline 
indicates that 59 % of the dose is eliminated by biliary/faecal excretion, and 33 % is excreted in urine. 
Overall, the primary route of elimination for tigecycline is biliary excretion of unchanged tigecycline. 
Glucuronidation and renal excretion of unchanged tigecycline are secondary routes. 
 
The total clearance of tigecycline is 24 L/h after intravenous infusion. Renal clearance is 
approximately 13 % of total clearance. Tigecycline shows a polyexponential elimination from serum 
with a mean terminal elimination half-life after multiple doses of 42 hours although high 
interindividual variability exists. 
 
In vitro studies using Caco-2 cells indicate that tigecycline does not inhibit digoxin flux, suggesting 
that tigecycline is not a P-glycoprotein (P-gp) inhibitor. This in vitro information is consistent with 
the lack of effect of tigecycline on digoxin clearance noted in the in vivo drug interaction study 
described above (see section 4.5). 

Tigecycline is a substrate of P-gp based on an in vitro study using a cell line overexpressing P-gp. The 
potential contribution of P-gp-mediated transport to the in vivo disposition of tigecycline is not 
known. Co-administration of P-gp inhibitors (e.g., ketoconazole or cyclosporine) or P-gp inducers 
(e.g., rifampicin) could affect the pharmacokinetics of tigecycline. 
 



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Special populations 
 
Hepatic impairment 
The single-dose pharmacokinetic disposition of tigecycline was not altered in patients with mild 
hepatic impairment. However, systemic clearance of tigecycline was reduced by 25 % and 55 % and 
the half-life of tigecycline was prolonged by 23 % and 43 % in patients with moderate or severe 
hepatic impairment (Child Pugh B and C), respectively (see section 4.2). 
 
Renal impairment 
The single dose pharmacokinetic disposition of tigecycline was not altered in patients with renal 
insufficiency (creatinine clearance <30 ml/min, n=6). In severe renal impairment, AUC was 30 % 
higher than in subjects with normal renal function (see section 4.2). 
 
Elderly 
No overall differences in pharmacokinetics were observed between healthy elderly subjects and 
younger subjects (see section 4.2). 
 
Paediatric population 
Tigecycline pharmacokinetics was investigated in two studies. The first study enrolled children aged 
8-16 years (n=24) who received single doses of tigecycline (0.5, 1, or 2 mg/kg, up to a maximum dose 
of 50 mg, 100 mg, and 150 mg, respectively) administered intravenously over 30 minutes. The second 
study was performed in children aged 8 to 11 years who received multiple doses of tigecycline (0.75, 
1, or 1.25 mg/kg up to a maximum dose of 50 mg) every 12 hours administered intravenously over 30 
minutes. No loading dose was administered in these studies. Pharmacokinetic parameters are 
summarised in the table below. 
 

Dose Normalized to 1 mg/kg Mean ± SD Tigecycline Cmax and AUC in Children 
Age (yr) N Cmax (ng/mL) AUC (ng•h/mL)* 

Single dose    
8 – 11 8 3881 ± 6637 4034 ± 2874 
12 - 16 16 8508 ± 11433 7026 ± 4088 

Multiple dose 
8 - 11 42 1911 ± 3032 2404 ± 1000 

* single dose AUC0-∞, multiple dose AUC0-12h 
 
The target AUC0-12h in adults after the recommended dose of 100 mg loading and 50 mg every 12 
hours, was approximately 2500 ng•h/mL. 
 
Population PK analysis of both studies identified body weight as a covariate of tigecycline clearance 
in children aged 8 years and older. A dosing regimen of 1.2 mg/kg of tigecycline every 12 hours (to a 
maximum dose of 50 mg every 12 hours) for children aged 8 to <12 years and of 50 mg every 
12 hours for adolescents aged 12 to <18 years would likely result in exposures comparable to those 
observed in adults treated with the approved dosing regimen. 
 
Higher Cmax values than in adult patients were observed in several children in these studies. As a 
consequence, care should be paid to the rate of infusion of tigecycline in children and adolescents.  
 
Gender 
There were no clinically relevant differences in the clearance of tigecycline between men and women. 
AUC was estimated to be 20 % higher in females than in males. 
 
Race 
There were no differences in the clearance of tigecycline based on race. 
 
 



14 

Weight 
Clearance, weight-normalised clearance, and AUC were not appreciably different among patients with 
different body weights, including those weighing ≥125 kg. AUC was 24 % lower in patients weighing 
≥125 kg. No data is available for patients weighing 140 kg and more. 
 
5.3 Preclinical safety data 
 
In repeated dose toxicity studies in rats and dogs, lymphoid depletion/atrophy of lymph nodes, spleen 
and thymus, decreased erythrocytes, reticulocytes, leukocytes, and platelets, in association with bone 
marrow hypocellularity, and adverse renal and gastrointestinal effects have been seen with tigecycline 
at exposures of 8 and 10 times the human daily dose based on AUC in rats and dogs, respectively. 
These alterations were shown to be reversible after two weeks of dosing. 
 
Bone discolouring was observed in rats which was not reversible after two weeks of dosing. 
 
Results of animal studies indicate that tigecycline crosses the placenta and is found in foetal tissues. 
In reproduction toxicity studies, decreased foetal weights in rats and rabbits (with associated delays in 
ossification) and foetal loss in rabbits have been observed with tigecycline. Tigecycline was not 
teratogenic in the rat or rabbit. Tigecycline did not affect mating or fertility in rats at exposures up to 
4.7 times the human daily dose based on AUC. In female rats, there were no compound-related effects 
on ovaries or oestrus cycles at exposures up to 4.7 times the human daily dose based on AUC. 
 
Results from animal studies using 14C-labelled tigecycline indicate that tigecycline is excreted readily 
via the milk of lactating rats. Consistent with the limited oral bioavailability of tigecycline, there is 
little or no systemic exposure to tigecycline in the nursing pups as a result of exposure via maternal 
milk. 
 
Lifetime studies in animals to evaluate the carcinogenic potential of tigecycline have not been 
performed, but short-term genotoxicity studies of tigecycline were negative.  
 
Bolus intravenous administration of tigecycline has been associated with a histamine response in 
animal studies. These effects were observed at exposures of 14 and 3 times the human daily dose 
based on the AUC in rats and dogs respectively. 
 
No evidence of photosensitivity was observed in rats following administration of tigecycline. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
 Maltose  monohydrate 
Hydrochloric acid (for pH adjustment)  
Sodium hydroxide (for pH adjustment) 
 
6.2 Incompatibilities 
 
The following active substances should not be administered simultaneously through the same Y-site 
as tigecycline: Amphotericin B, amphotericin B lipid complex, diazepam, esomeprazole, omeprazole 
and intravenous solutions that could result in an increase of pH above 7. 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6.  
 
6.3 Shelf life 
  



15 

 2 years. 
 
Reconstituted solution: Chemical and physical in-use stability has been demonstrated for 6 hours at 
20-25 °C. From a microbiological point of view, the product should be used immediately. If not used 
immediately, in-use storage times and conditions prior to use are the responsibility of the user and would 
not be longer than the times stated above for the chemical and physical in-use stability. 
 
Diluted solution: Chemical and physical in-use stability has been demonstrated for 24 hours at 
20-25 °C and 48 hours at 2-8 °C. From a microbiological point of view, the product should be used 
immediately. If not used immediately, in-use storage times and conditions prior to use are the 
responsibility of the user and would not be longer than the times stated above for the chemical and 
physical in-use stability. 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage condition. 
 
For storage conditions after reconstitution of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container  
 
 
10 ml Type 1 clear glass vials fitted with grey bromobutyl rubber stopper and flip-off aluminium seal.  
Pack size of one or ten vials.  
Not all pack sizes may be marketed.  
 
6.6 Special precautions for disposal and other handling 
 
The powder should be reconstituted with 5.3 ml of sodium chloride 9 mg/ml (0.9 %) solution for 
injection, dextrose 50 mg/ml (5 %) solution for injection, or Lactated Ringer’s solution for injection 
to achieve a concentration of 10 mg/ml of tigecycline. The vial should be gently swirled until the 
medicinal product is dissolved. Thereafter, 5 ml of the reconstituted solution should be immediately 
withdrawn from the vial and added to a 100 ml intravenous bag for infusion or other suitable infusion 
container (e.g., glass bottle). 
 
For a 100 mg dose, reconstitute using two vials into a 100 ml intravenous bag or other suitable 
infusion container (e.g., glass bottle). Note: The vial contains a 6 % overage. Thus, 5 ml of 
reconstituted solution is equivalent to 50 mg of the active substance. 
The reconstituted solution should be yellow to orange in colour; if not, the solution should be 
discarded. Parenteral products should be inspected visually for particulate matter and discolouration 
(e.g., green or black) prior to administration. 
 
Tigecycline should be administered intravenously through a dedicated line or through a Y-site. If the 
same intravenous line is used for sequential infusion of several active substances, the line should be 
flushed before and after infusion of tigecycline with either sodium chloride 9 mg/ml (0.9 %) solution 
for injection or dextrose 50 mg/ml (5 %) solution for injection. Injection should be made with an 
infusion solution compatible with tigecycline and any other medicinal product(s) via this common line 
(see section 6.2) 
 
This medicinal product is for single use only; any unused medicinal product or waste material should 
be disposed of in accordance with local requirements. 
 
Compatible intravenous solutions include: sodium chloride 9 mg/ml (0.9 %) solution for injection, 
dextrose 50 mg/ml (5 %) solution for injection, and Lactated Ringer’s solution for injection. 
 



16 

When administered through a Y-site, compatibility of tigecycline diluted in sodium chloride 0.9 % for 
injection is demonstrated with the following medicinal products or diluents: amikacin, dobutamine, 
dopamine HCl, gentamicin, haloperidol, Lactated Ringer’s, lidocaine HCl, metoclopramide, 
morphine, norepinephrine, piperacillin/tazobactam (EDTA formulation), potassium chloride, 
propofol, ranitidine HCl, theophylline, and tobramycin. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Accord Healthcare S.L.U.  
World Trade Center,  
Moll de Barcelona, s/n,  
Edifici Est 6ª planta,  
08039 Barcelona, Spain 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/19/1394/001  (10 vials) 
EU/1/19/1394/002  (1 vial) 
 
 
9. DATE OF FIRST AUTHORISATION 
 
Date of first authorisation:  
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this 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. MANUFACTURERS 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. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturers responsible for batch release 
 
Accord Healthcare Limited 
Sage House  
319, Pinner Road 
North Harrow 
Middlesex HA1 4HF 
United Kingdom 
 
Accord Healthcare Polska Sp.z.o.o. 
Ul. Lutomierska 50,  
95-200, Pabianice, Poland 
 
Laboratori Fundació Dau 
C/ C, 12-14 Pol. Ind. 
Zona Franca, Barcelona, 08040, Spain  
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch.  
 
 
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 (PSURs) 
 
The requirements for submission of PSURs for this medicinal product are set out in the list of 
Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC 
and any subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk management plan (RMP) 
 
The marketing authorisation holder (MAH)shall perform the required pharmacovigilance activities 
and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing 
authorisation and any agreed subsequent updates of the RMP. 
 
An updated RMP should be submitted: 
• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information 

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



19 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



20 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



21 

 
 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Tigecycline Accord 50 mg powder for solution for infusion   
 tigecycline 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE  
 
Each vial contains 50 mg tigecycline. 
 
 
3. LIST OF EXCIPIENTS 
 
Each vial contains maltose monohydrate. The pH is adjusted with hydrochloric acid, and if necessary 
sodium hydroxide. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for solution for infusion  
1 vial 
10 vials 
 
 
5. METHOD AND ROUTEOF ADMINISTRATION 
 
Read the package leaflet before use for directions on reconstitution and dilution. 
For intravenous use after reconstitution and dilution. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING, IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 



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 
 
Accord Healthcare S.L.U.  
World Trade Center,  
Moll de Barcelona, s/n,  
Edifici Est 6ª planta,  
08039 Barcelona, Spain  
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/19/1394/001 (10 vials) 
EU/1/19/1394/002 (1 vial) 
 
 
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 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTEOF ADMINISTRATION 
 
Tigecycline Accord 50 mg powder for infusion  
 tigecycline 
 Intravenous use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
50 mg 
 
 
6. OTHER 



24 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



25 

 
 

Package leaflet: Information for the user 
 

Tigecycline Accord 50 mg powder for solution for infusion  
 tigecycline 

 
Read all of this leaflet carefully before you are given this medicine because it contains 
important information for you or your child. 
- 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 Tigecycline Accord is and what it is used for  
2. What you need to know before you receive  Tigecycline Accord 
3. How Tigecycline Accord is given 
4. Possible side effects 
5. How to store Tigecycline Accord 
6. Contents of the pack and other information 
 
 
1. What Tigecycline Accord is and what it is used for 
 
Tigecycline Accord  is an antibiotic of the glycylcycline group that works by stopping the growth of 
bacteria that cause infections. 
 
Your doctor has prescribed Tigecycline Accord because you or your child at least 8 years old has one 
of the following types of serious infections:  
 
• Complicated infection of the skin and soft tissues (the tissue below the skin), excluding diabetic 

foot infections. 
 
• Complicated infection in the abdomen 
 
Tigecycline Accord  is only used when your doctor thinks other antibiotics are not suitable. 
 
 
2. What you need to know before you receive  Tigecycline Accord 
 
Do not use  Tigecycline Accord  
• If you are allergic to tigecycline, or any of the other ingredients of this medicine (listed in 
section 6). If you are allergic to tetracycline class antibiotics (e.g., minocycline, doxycycline, etc.), 
you may be allergic to tigecycline. 
 
Warnings and precautions 
  
Talk to your doctor or nurse before receiving Tigecycline Accord:  
• If you have poor or slow wound healing. 
• If you are suffering from diarrhoea before you are given Tigecycline Accord. If you develop 

diarrhoea during or after your treatment, tell your doctor at once. Do not take any diarrhoea 
medicine without first checking with your doctor.   

• If you have or previously had any side effects due to antibiotics belonging to the tetracycline 
class (e.g., skin sensitization to sun light, staining on developing teeth, pancreas inflammation, 



26 

and alteration of certain laboratory values aimed at measuring how well your blood clots). 
• If you have, or previously had liver problems. Depending on the condition of your liver, your 

doctor may reduce the dose to avoid potential side effects. 
• If you have blockage of the bile ducts (cholestasis). 
 
During treatment with Tigecycline Accord: 
• Tell your doctor immediately if you develop symptoms of an allergic reaction. 
• Tell your doctor immediately if you develop severe abdominal pain, nausea, and vomiting. 

These may be symptoms of acute pancreatitis (inflamed pancreas which may result in severe 
abdominal pain, nausea, and vomiting). 

• In certain serious infections, your doctor may consider to use Tigecycline Accord in 
combination with other antibiotics. 

• Your doctor will monitor you closely for the development of any other bacterial infections. If 
you develop another bacterial infection, your doctor may prescribe a different antibiotic 
specific for the type of infection present. 

• Although antibiotics including Tigecycline Accord  fight certain bacteria, other bacteria and 
fungi may continue to grow. This is called overgrowth. Your doctor will monitor you closely 
for any potential infections and treat you if necessary. 

 
Children 
Tigecycline Accord  is not to be used in children less than 8 years of age due to the lack of data on 
safety and efficacy in this age group and because it may induce permanent dental defects such as 
staining on the developing teeth. 
 
Other medicines and  Tigecycline Accord  
Tell your doctor if you are taking, have recently taken or might take any other medicines. 
 
Tigecycline Accord may prolong certain tests that measure how well your blood is clotting. It is 
important that you tell your doctor if you are taking medicines to avoid an excess of blood clotting 
(named anticoagulants). If this were the case, your doctor will monitor you closely.  
 
Tigecycline Accord  may interfere with the contraceptive pill (birth control pill). Talk to your doctor 
about the need for an additional method of contraception while receiving Tigecycline Accord.  
 
Pregnancy and breast-feeding 
Tigecycline Accord  may cause foetal harm. If you are pregnant or breast-feeding, think you may be 
pregnant or are planning to have a baby, ask your doctor for advice before  taking this medicine. 
 
It is not known if tigecycline passes into breast milk in humans. Ask your doctor for advice before 
breast-feeding your baby.  
 
Driving and using machines 
Tigecycline Accord may cause side effects such as dizziness. This may impair your ability to drive or 
operate machinery.  
 
This medicine contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially 'sodium-
free. 
 
 
3. How Tigecycline Accord  is given 
 
Tigecycline Accord will be given to you by a doctor or a nurse.  
 
The recommended dose in adults is 100 mg given initially, followed by 50 mg every 12 hours. This 
dose is given intravenously (directly into your blood stream) over a period of 30 to 60 minutes. 



27 

 
The recommended dose in children aged 8 to <12 years is 1.2 mg/kg given every 12 hours 
intravenously to a maximum dose of 50 mg every 12 hours. 
 
The recommended dose in adolescents aged 12 to <18 years is 50 mg given every 12 hours.  
 
A course of treatment usually lasts for 5 to 14 days. Your doctor will decide how long you should be 
treated. 
 
If you receive more Tigecycline Accord than you should  
If you are concerned that you may have been given too much Tigecycline Accord, talk to your doctor 
or nurse immediately. 
 
If you miss a dose of  Tigecycline Accord  
If you are concerned that you may have missed a dose, talk to your doctor or nurse immediately. 
  
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Pseudomembranous colitis may occur with most antibiotics including Tigecycline Accord. This 
consists of severe, persistent or bloody diarrhoea associated with abdominal pain or fever, which can 
be a sign of serious bowel inflammation, which may occur during or after your treatment. 
 
Very common side effects are (may affect more than 1 in 10 people): 
• Nausea, vomiting, diarrhoea. 
 
Common side effects are (may affect up to 1 in 10 people): 
• Abscess (collection of pus), infections 
• Laboratory measurements of decreased ability to form blood clots 
• Dizziness 
• Vein irritations from the injection, including pain, inflammation, swelling and clotting 
• Abdominal pain, dyspepsia (stomach ache and indigestion), anorexia (loss of appetite) 
• Increases in liver enzymes, hyperbilirubinaemia (excess of bile pigment in the blood) 
• Pruritus (itching), rash 
• Poor or slow wound healing 
• Headache 
• Increase in amylase, which is an enzyme found in the salivary glands and pancreas, increased 

blood urea nitrogen (BUN). 
• Pneumonia 
• Low blood sugar 
• Sepsis (severe infection in the body and blood stream)/septic shock (serious medical condition 

which can lead to multiple organ failure and death as a result of sepsis) 
• Injection site reaction (pain, redness, inflammation) 
• Low protein levels in the blood 
 
Uncommon side effects are (may affect up to 1 in 100 people): 
• Acute pancreatitis (inflamed pancreas which may result in severe abdominal pain, nausea, and 

vomiting)  
• Jaundice (yellow coloration of the skin), inflammation of the liver 
• Low platelet levels in the blood(which may lead to an increased bleeding tendency and 

bruising/haematoma) 
 
Not known side effects are (frequency cannot be estimated from the available data): 



28 

• Anaphylaxis/anaphylactoid reactions (that may range from mild to severe, including a sudden, 
generalised allergic reaction that may lead to a life-threatening shock [e.g. difficulty in 
breathing, drop of blood pressure, fast pulse]). 

• Liver failure 
• Skin rash, which may lead to severe blistering and peeling of the skin (Stevens-Johnson 

Syndrome) 
• Low fibrinogen levels in the blood (a protein involved in blood clotting) 
 
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 Tigecycline Accord  
 
Keep this medicine out of the sight and reach of children. 
 
 This medicinal product does not require any special storage condition. Do not use this medicine after 
the expiry date which is stated on the vial. The expiry date refers to the last day of that month. 
 
Storage after preparation 
Reconstituted solution: Chemical and physical in-use stability has been demonstrated for 6 hours at 
20-25 °C. From a microbiological point of view, the product should be used immediately. If not used 
immediately, in-use storage times and conditions prior to use are the responsibility of the user and would 
not be longer than the times stated above for the chemical and physical in-use stability. 
 
Diluted solution: Chemical and physical in-use stability has been demonstrated for 24 hours at 
20-25 °C and 48 hours at 2-8 °C. From a microbiological point of view, the product should be used 
immediately. If not used immediately, in-use storage times and conditions prior to use are the 
responsibility of the user and would not be longer than the times stated above for the chemical and 
physical in-use stability. 
 
The Tigecycline Accord  solution should be yellow to orange in colour after dissolving; if it is not, the 
solution should be discarded. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Tigecycline Accord contains  
The active substance is tigecycline. Each vial contains 50 mg of tigecycline. 
 
The other ingredients are maltose  monohydrate, hydrochloric acid, and sodium hydroxide. 
 
What Tigecycline Accord looks like and contents of the pack  
Tigecycline Accord is supplied as a powder for solution for infusion in a vial and looks like an orange 
powder or cake before it is diluted. These vials are distributed to the hospital in a one vial pack or ten 
vial pack. Not all pack sizes may be marketed.  
 
The powder should be mixed in the vial with a small amount of solution. The vial should be gently 
swirled until the medicine is dissolved. Thereafter, the solution should be immediately withdrawn 

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


29 

from the vial and added to a 100 ml intravenous bag or other suitable infusion container in the 
hospital.   
 
Marketing Authorisation Holder and Manufacturer 
 
Marketing Authorisation Holder: 
Accord Healthcare S.L.U.  
World Trade Center,  
Moll de Barcelona, s/n,  
Edifici Est 6ª planta,  
08039 Barcelona, Spain 
 
Manufacturers: 
Accord Healthcare Limited,  
Sage House, 319 Pinner Road, North Harrow,  
Middlesex, HA1 4HF,  
United Kingdom 
 
Or 
Accord Healthcare Polska Sp.z o.o. 
ul. Lutomierska 50,  
95-200 Pabianice 
Poland 
 
Or 
Laboratori Fundació Dau 
C/ C, 12-14 Pol. Ind. 
Zona Franca, Barcelona, 08040,  
Spain 
 
 This leaflet was last revised 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. 
 
 



30 

 
 
The following information is intended for healthcare professionals only: 
 
Instructions for use and handling (see also 3. How Tigecycline Accord is given in this leaflet) 
 
The powder should be reconstituted with 5.3 ml of sodium chloride 9 mg/ml (0.9 %) solution for 
injection, dextrose 50 mg/ml (5 %) solution for injection, or Lactated Ringer’s solution for injection 
to achieve a concentration of 10 mg/ml of tigecycline. The vial should be gently swirled until the 
active substance is dissolved. Thereafter, 5 ml of the reconstituted solution should be immediately 
withdrawn from the vial and added to a 100 ml intravenous bag for infusion or other suitable infusion 
container (e.g. glass bottle). 
 
For a 100 mg dose, reconstitute using two vials into a 100 ml intravenous bag for infusion or other 
suitable infusion container (e.g. glass bottle). 
 
Note: The vial contains a 6 % overage. Thus, 5 ml of reconstituted solution is equivalent to 50 mg of 
the active substance. The reconstituted solution should be yellow to orange in colour; if not, the 
solution should be discarded. Parenteral products should be inspected visually for particulate matter 
and discolouration (e.g. green or black) prior to administration. 
 
Tigecycline should be administered intravenously through a dedicated line or through a Y-site. If the 
same intravenous line is used for sequential infusion of several active substances, the line should be 
flushed before and after infusion of tigecycline with either sodium chloride 9 mg/ml (0.9 %) solution 
for injection or dextrose 50 mg/ml (5 %) solution for injection. Injection should be made with an 
infusion solution compatible with tigecycline and any other medicinal product(s) via this common 
line. 
 
Compatible intravenous solutions include: sodium chloride 9 mg/ml (0.9 %) solution for injection, 
dextrose 50 mg/ml (5 %) solution for injection, and Lactated Ringer’s solution for injection. 
 
When administered through a Y-site, compatibility of tigecycline diluted in sodium chloride 0.9 % for 
injection is demonstrated with the following medicinal products or diluents: amikacin, dobutamine, 
dopamine HCl, gentamicin, haloperidol, Lactated Ringer’s, lidocaine HCl, metoclopramide, 
morphine, norepinephrine, piperacillin/tazobactam (EDTA formulation), potassium chloride, 
propofol, ranitidine HCl, theophylline, and tobramycin. 
 
Tigecycline Accord must not be mixed with other medicinal products for which compatibility data are 
not available. 
 
Reconstituted solution: Chemical and physical in-use stability has been demonstrated for 6 hours at 
20-25 °C. From a microbiological point of view, the product should be used immediately. If not used 
immediately, in-use storage times and conditions prior to use are the responsibility of the user and would 
not be longer than the times stated above for the chemical and physical in-use stability. 
 
Diluted solution: Chemical and physical in-use stability has been demonstrated for 24 hours at 
20-25 °C and 48 hours at 2-8 °C. From a microbiological point of view, the product should be used 
immediately. If not used immediately, in-use storage times and conditions prior to use are the 
responsibility of the user and would not be longer than the times stated above for the chemical and 
physical in-use stability.  
 
For single use only, any unused solution should be discarded. 
 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS 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