Ketek

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Ketek 400 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains 400 mg of telithromycin. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet. 
Light orange, oblong, biconvex tablet, imprinted with ‘H3647’ on one side and ‘400’ on the other. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
When prescribing Ketek, consideration should be given to official guidance on the appropriate use of 
antibacterial agents and the local prevalence of resistance (see also sections 4.4 and 5.1). 
 
Ketek is indicated for the treatment of the following infections: 
 
In patients of 18 years and older: 

• Community-acquired pneumonia, mild or moderate (see section 4.4). 
 
• When treating infections caused by known or suspected beta-lactam and/or macrolide resistant 
strains (according to history of patients or national and/or regional resistance data) covered by 
the antibacterial spectrum of telithromycin (see sections 4.4 and 5.1): 

- Acute exacerbation of chronic bronchitis, 
- Acute sinusitis 

 
In patients of 12 years and older: 

• Tonsillitis/pharyngitis caused by Streptococcus pyogenes, as an alternative when beta lactam 
antibiotics are not appropriate in countries/regions with a significant prevalence of macrolide 
resistant S. pyogenes, when mediated by ermTR or mefA (see sections 4.4 and 5.1). 

 
4.2 Posology and method of administration 
 
Posology 
The recommended dose is 800 mg once a day i.e. two 400 mg tablets once a day.  
 
In patients of 18 years and older, according to the indication, the treatment regimen will be: 
- Community-acquired pneumonia: 800 mg once a day for 7 to 10 days, 
- Acute exacerbation of chronic bronchitis: 800 mg once a day for 5 days, 
- Acute sinusitis: 800 mg once a day for 5 days, 
- Tonsillitis/pharyngitis caused by Streptococcus pyogenes: 800 mg once a day for 5 days. 
 
In patients of 12 to 18 years old, the treatment regimen will be: 
- Tonsillitis/pharyngitis caused by Streptococcus pyogenes: 800 mg once a day for 5 days. 
 

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Elderly population 
No dosage adjustment is required in elderly patients based on age alone. 
 
Paediatric population: 
The safety and efficacy of Ketek in children below 12 years of age have not been established (see 
section 5.2). Ketek is not recommended in this population. 
 
Renal impairment 
No dosage adjustment is necessary in patients with mild or moderate renal impairment. Ketek is not 
recommended as first choice in patients with severe renal impairment (creatinine clearance 
<30 ml/min) or patients with both severe renal impairment and co-existing hepatic impairment, as an 
optimal dosage format (600 mg) is not available. If telithromycin treatment is deemed necessary, these 
patients may be treated with alternating daily doses of 800 mg and 400 mg, starting with the 800 mg 
dose. 
In haemodialysed patients, the posology should be adjusted so that Ketek 800 mg is given after the 
dialysis session (see also section 5.2). 
 
Hepatic impairment 
No dosage adjustment is necessary in patients with mild, moderate, or severe hepatic impairment, 
however the experience in patients with impaired hepatic function is limited. Hence, telithromycin 
should be used with caution (see also sections 4.4 and 5.2). 
 
Method of administration 
The tablets should be swallowed whole with a sufficient amount of water. The tablets may be taken 
with or without food. 
Consideration may be given to taking Ketek at bedtime, to reduce the potential impact of visual 
disturbances and loss of consciousness (see section 4.4). 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance, to any of the macrolide antibacterial agents, or to any of the 
excipients listed in section 6.1. 
 
Myasthenia gravis (see section 4.4). 
 
Previous history of hepatitis and/or jaundice associated with the use of telithromycin. 
 
Concomitant administration with medicinal products that prolong the QT interval and are CYP3A4 
substrates, such as cisapride, pimozide, astemizole, terfenadine, dronedarone, saquinavir (see section 
4.5). 
 
Concomitant administration with ergot alkaloid derivatives (such as ergotamine and 
dihydroergotamine) (see section 4.5). 
 
Concomitant administration with simvastatin, atorvastatin, and lovastatin. Treatment with these 
agents should be interrupted during Ketek treatment (see section 4.5). 
 
History of congenital or a family history of long QT syndrome (if not excluded by ECG) and in 
patients with known acquired QT interval prolongation.  
 
In patients with severely impaired renal and/or hepatic function, concomitant administration of Ketek 
and strong CYP3A4 inhibitors, such as protease inhibitors or azole antifungals (e.g. ketoconazole, 
fluconazole), is contraindicated. 
 
Concomitant administration of Ketek and colchicine in patients with renal and/or hepatic impairment 
(see section 4.5). 

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4.4 Special warnings and precautions for use 
 
QT interval prolongation 
Due to a potential to increase the QT interval, Ketek should be used with care in patients with 
coronary heart disease, a history of ventricular arrhythmias, uncorrected hypokalaemia and/or 
hypomagnesaemia, or bradycardia (<50 bpm), during concomitant administration of Ketek with QT 
interval prolonging agents, or in patients concomitantly treated with potent CYP 3A4 inhibitors such 
as protease inhibitors or azole antifungals (e.g. ketoconazole, fluconazole) (see sections 4.3 and 4.5). 
Ventricular arrhythmias (including ventricular tachycardia, torsade de pointes) have been reported in 
patients treated with telithromycin and sometimes occurred within a few hours of the first dose (see 
section 4.8). 
 
Clostridium difficile-associated disease 
Diarrhoea, particularly if severe, persistent and /or bloody, during or after treatment with Ketek may 
be caused by pseudomembranous colitis (see section 4.8). If pseudomembranous colitis is suspected, 
the treatment must be stopped immediately and patients should be treated with supportive measures 
and/or specific therapy. 
 
Myasthenia gravis 
Exacerbations of myasthenia gravis have been reported in patients treated with telithromycin and 
sometimes occurred within a few hours of the first dose. Reports have included death and life 
threatening acute respiratory failure with rapid onset (see section 4.8). 
 
Hepatobiliary disorders 
Alterations in hepatic enzymes have been commonly observed in clinical studies with telithromycin. 
Post-marketing cases of severe hepatitis and liver failure, including fatal cases (which have generally 
been associated with serious underlying diseases or concomitant medicinal products), have been 
reported (see section 4.8). These hepatic reactions were observed during or immediately after 
treatment, and in most cases were reversible after discontinuation of telithromycin. 
Patients should be advised to stop treatment and contact their doctor if signs and symptoms of hepatic 
disease develop such as anorexia, jaundice, dark urine, pruritus or tender abdomen. 
 
Due to limited experience, Ketek should be used with caution in patients with liver impairment (see 
section 5.2). 
 
Visual disturbances 
Ketek may cause visual disturbances particularly in slowing the ability to accommodate and the 
ability to release accommodation. Visual disturbances included blurred vision, difficulty focusing, 
and diplopia. Most events were mild to moderate; however, severe cases have been reported. The 
onset of the visual reaction may be sudden. It is important that patients prescribed telithromycin 
should be informed that visual adverse reactions may occur during the treatment (see sections 4.7 and 
4.8). 
 
Loss of consciousness 
There have been post-marketing adverse reaction reports of transient loss of consciousness including 
some cases associated with vagal syndrome (see sections 4.7 and 4.8). 
 
Consideration may be given to taking Ketek at bedtime, to reduce the potential impact of visual 
disturbances and loss of consciousness. 
 
CYP3A4 inducers 
Ketek should not be used during and 2 weeks after treatment with CYP3A4 inducers (such as 
rifampicin, phenytoin, carbamazepine, phenobarbital, St John’s wort). Concomitant treatment with 
these medicinal products is likely to result in subtherapeutic levels of telithromycin and therefore 
encompass a risk of treatment failure (see section 4.5). 

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CYP3A4 substrates 
Ketek is an inhibitor of CYP3A4 and should only be used under specific circumstances during 
treatment with other medicinal products that are metabolised by CYP3A4. Patients with concomitant 
treatment of pravastatin, rosuvastatin or fluvastatin should be carefully monitored for signs and 
symptoms of myopathy and rhabdomyolysis. (See sections 4.3 and 4.5). 
 
Resistance 
In areas with a high incidence of erythromycin A resistance, it is especially important to take into 
consideration the evolution of the pattern of susceptibility to telithromycin and other antibiotics. 
 
In community acquired pneumonia, efficacy has been demonstrated in a limited number of patients 
with risk factors such as pneumococcal bacteraemia or age higher than 65 years. 
 
Experience of treatment of infections caused by penicillin/or erythromycin resistant S. pneumoniae is 
limited, but so far, clinical efficacy and eradication rates have been similar compared with the 
treatment of susceptible S. pneumoniae.  Caution should be taken when S. aureus is the suspected 
pathogen and there is a likelihood of erythromycin resistance based on local epidemiology.  
 
L. pneumophila is highly susceptible to telithromycin in vitro, however, the clinical experience of the 
treatment of pneumonia caused by legionella is limited.  
 
As for macrolides, H. influenzae is classified as intermediately susceptible. This should be taken into 
account when treating infections caused by H. influenzae. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Interaction studies have only been performed in adults. 
 
• Effect of Ketek on other medicinal products 
 
Telithromycin is an inhibitor of CYP3A4 and a weak inhibitor of CYP2D6. In vivo studies with 
simvastatin, midazolam and cisapride have demonstrated a potent inhibition of intestinal CYP3A4 and 
a moderate inhibition of hepatic CYP3A4. The degree of inhibition with different CYP3A4 substrates 
is difficult to predict. Hence, Ketek should not be used during treatment with medicinal products that 
are CYP3A4 substrates, unless plasma concentrations of the CYP3A4 substrate, efficacy or adverse 
reactions can be closely monitored. Alternatively, interruption in the treatment with the CYP3A4 
substrate should be made during treatment with Ketek. 
 
Telithromycin is also a P-glycoprotein inhibitor. Concomitant administration of Ketek with drugs that 
are substrates of P-glycoprotein might result in increased exposure to the P-glycoprotein substrates 
such as digoxin and dabigatran etexilate. If telithromycin is co-administered with dabigatran etexilate 
close clinical monitoring (looking for signs of bleeding or anaemia) should be exercised. 
 
Cyclosporin, tacrolimus, sirolimus 
Due to its CYP3A4 inhibitory potential, telithromycin can increase blood concentrations of these 
CYP34A4 substrates. Thus, when initiating telithromycin in patients already receiving any of theses 
immunosuppressive agents, cyclosporin, tacrolimus or sirolimus levels must be carefully monitored 
and their doses decreased as necessary. When telithromycin is discontinued, cyclosporin, tacrolimus 
or sirolimus levels must be again carefully monitored and their dose increased as necessary. 
 
Metoprolol 
When metoprolol (a CYP2D6 substrate) was coadministered with Ketek, metropolol Cmax and AUC 
were increased by approximately 38%, however, there was no effect on the elimination half-life of 
metoprolol. The increase exposure to metoprolol may be of clinical importance in patients with heart 

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failure treated with metoprolol. In these patients, co-administration of Ketek and metoprolol, a 
CYP2D6 substrate, should be considered with caution. 
 
Medicinal products with a potential to prolong QT interval 
Ketek is expected to increase the plasma levels of cisapride, pimozide, astemizole, terfenadine, 
dronedarone, saquinavir. This could result in QT interval prolongation and cardiac arrhythmias 
including ventricular tachycardia, ventricular fibrillation and torsades de pointes. Concomitant 
administration of Ketek and any of these medicinal products is contraindicated (see section 4.3). 
 
Caution is warranted when Ketek is administered to patients taking other medicinal products with the 
potential to prolong the QT interval (see section 4.4). These include Class IA (e.g.quinidine, 
procainamide, disopyramide) and Class III (e.g. dofetilide, amiodarone) antiarrhythmic agents, 
citalopram, tricyclic antidepressants, methadone, some antipsychotics (e.g. phenothiazines),  
fluoroquinolones (e.g. moxifloxacin), some antifungals (e.g. fluconazole, pentamidine), and some 
antiviral drugs (e.g. telaprevir). 
 
Ergot alkaloid derivatives (such as ergotamine and dihydroergotamine) 
By extrapolation from erythromycin A and josamycin, concomitant medication of Ketek and alkaloid 
derivatives could lead to severe vasoconstriction (“ergotism”) with possibly necrosis of the 
extremities. The combination is contraindicated (see section 4.3). 
 
Statins 
When simvastatin was coadministered with Ketek, there was a 5.3-fold increase in simvastatin Cmax, 
an 8.9-fold increase in simvastatin AUC, a 15-fold increase in simvastatin acid Cmax and an 11-fold 
increase in simvastatin acid AUC. Ketek may produce a similar interaction with lovastatin and 
atorvastatin which are also mainly metabolised by CYP3A4. Ketek should therefore not be used 
concomitantly with simvastatin, atorvastatin, or lovastatin (see section 4.3). Treatment with these 
agents should be interrupted during Ketek treatment. The exposure of pravastatin, rosuvastatin and to 
a lesser extent fluvastatin, may be increased due to possible involvement of transporters proteins, but 
this increase is expected to be lesser than interactions involving CYP3A4 inhibition. However, 
patients should be carefully monitored for signs and symptoms of myopathy and rhabdomyolysis 
when co-treated with pravastatin, rosuvastatin and fluvastatin. 
 
Benzodiazepines 
When midazolam was coadministered with Ketek, midazolam AUC was increased 2.2-fold after 
intravenous administration of midazolam and 6.1-fold after oral administration. The midazolam half-
life was increased about 2.5-fold. Oral administration of midazolam concomitantly with Ketek should 
be avoided. Intravenous dosage of midazolam should be adjusted as necessary and monitoring of the 
patient should be undertaken. The same precautions should also apply to the other benzodiazepines 
which are metabolised by CYP3A4, (especially triazolam but also to a lesser extent alprazolam). For 
those benzodiazepines which are not metabolised by CYP3A4 (temazepam, nitrazepam, lorazepam) 
an interaction with Ketek is unlikely. 
 
Digoxin 
Ketek has been shown to increase the plasma concentrations of digoxin, a P-glycoprotein substrate. 
The plasma trough levels, Cmax, AUC and renal clearance were increased by 20%, 73%, 37% and 27% 
respectively, in healthy volunteers. There were no significant changes in ECG parameters and no 
signs of digoxin toxicity were observed. Nevertheless, monitoring of serum digoxin level should be 
considered during concomitant administration of digoxin and Ketek. 
 
Theophylline 
There is no clinically relevant pharmacokinetic interaction of Ketek and theophylline administered as 
extended release formulation. However, the co-administration of both medicinal products should be 
separated by one hour in order to avoid possible digestive side effects such as nausea and vomiting. 
 
Oral anticoagulants 

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Increased anticoagulant activity has been reported in patients simultaneously treated with 
anticoagulants and antibiotics, including telithromycin. The mechanisms are incompletely known. 
Although Ketek has no clinically relevant pharmacokinetic or pharmacodynamic interaction with 
warfarin after single dose administration, more frequent monitoring of prothrombin time/INR 
(International Normalised Ratio) values should be considered during concomitant treatment. 
 
Oral contraceptives 
There is no pharmacodynamic or clinically relevant pharmacokinetic interaction with low-dose 
triphasic oral contraceptives in healthy subjects. 
 
Colchicine 
Colchicine intoxication, including fatal cases, has been reported in patients treated with colchicine 
and strong CYP 3A4 inhibitors. Telithromycin is known to be a strong CYP3A4 inhibitor and is also a 
P-glycoprotein inhibitor. Exposure to colchicine, a CYP3A4 and P-glycoprotein substrate, may 
therefore be expected to increase if Ketek and colchicine are co-administered. Concomitant 
administration of Ketek and colchicine is contraindicated in patients with renal and/or hepatic 
impairment (see section 4.3).  
 
Calcium channel blockers that are metabolized by CYP3A4  
Concomitant administration of strong CYP3A4 inhibitors (such as telithromycin) and calcium channel 
blockers that are metabolized by CYP3A4 (e.g. verapamil, nifedipine, felodipine) may result in 
hypotension, bradycardia or loss of consciousness, and should therefore be avoided. In case the 
combination is considered necessary, the dose of the calcium channel blocker should be reduced and 
close clinical monitoring of efficacy and safety in the patient should be exercised. 
 
Sotalol 
Telithromycin has been shown to decrease the Cmax by 34 % and AUC of sotalol by 20 % due to 
decreased absorption. 
 
• Effect of other medicinal products on Ketek 
 
During concomitant administration of rifampicin and telithromycin in repeated doses, Cmax and AUC 
of telithromycin were on average decreased by 79% and 86% respectively. Therefore, concomitant 
administration of CYP3A4 inducers (such as rifampicin, phenytoin, carbamazepine, phenobarbital, St 
John’s wort) is likely to result in subtherapeutic levels of telithromycin and loss of effect. The 
induction gradually decreases during 2 weeks after cessation of treatment with CYP3A4 inducers. 
Ketek should not be used during and 2 weeks after treatment with CYP3A4 inducers. 
 
Interaction studies with itraconazole and ketoconazole, two CYP3A4 inhibitors, showed that 
maximum plasma concentrations of telithromycin were increased respectively by 1.22 and 1.51 fold 
and AUC by respectively 1.54 fold and 2.0 fold. These changes in the pharmacokinetics of 
telithromycin do not necessitate dosage adjustment as telithromycin exposure remains within a well 
tolerated range. The effect of ritonavir on telithromycin has not been studied and could lead to larger 
increase in telithromycin exposure. The combination should be used with caution. 
 
Strong CYP3A4 inhibitors must not be co-administered with Ketek in patients with severe renal/or 
hepatic dysfunction (see section 4.3). 
 
Ranitidine (taken 1 hour before Ketek) and antacid containing aluminium and magnesium hydroxide 
has no clinically relevant influence on telithromycin pharmacokinetics. 
 

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4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
There are no adequate data from the use of Ketek in pregnant women. Studies in animals have shown 
reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Ketek should not be 
used during pregnancy unless clearly necessary. 
 
Breastfeeding 
Telithromycin is excreted in the milk of lactating animals, at concentrations about 5 times those of 
maternal plasma. Corresponding data for humans is not available. Ketek should not be used by breast-
feeding women. 
 
Fertility 
In studies with rats a reduction in fertility indices was observed at parentally toxic doses (see section 
5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Ketek may cause adverse reactions such as visual disturbances, confusion or hallucination which may 
reduce the capacity for the completion of certain tasks. In addition, rare cases of transient loss of 
consciousness, which may be preceded by vagal symptoms, have been reported (see section 4.8). 
Because of potential visual difficulties, loss of consciousness, confusion or hallucination, patients 
should attempt to minimize activities such as driving a motor vehicle, operating heavy machinery or 
engaging in other hazardous activities during treatment with Ketek. If patients experience visual 
disorders, loss of consciousness, confusion or hallucination while taking Ketek, patients should not 
drive a motor vehicle, operate heavy machinery or engage in other hazardous activities (see sections 
4.4 and 4.8). 
Patients should be informed that these adverse reactions may occur as early as after the first dose of 
medicinal product. Patients should be cautioned about the potential effects of these events on the 
ability to drive or operate machinery. 
 
4.8 Undesirable effects 
 
Tabulated list of adverse reactions  
 
In 2,461 patients treated by Ketek in phase III clinical trials, and during post-marketing experience, 
the following undesirable effects possibly or probably related to telithromycin have been reported. 
This is shown in the table below. Diarrhoea, nausea and dizziness were the most commonly reported 
adverse reactions in phase III clinical trials. 
 
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
 

System organ 
class 

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)* 

Blood and the 
lymphatic system 
disorders 

  Eosinophilia    
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System organ 
class 

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)* 

Immune system 
disorders 

     Angio-
neurotic 
oedema, 
anaphylactic 
reactions 
including 
anaphylactic 
shock, hyper-
sensitivity 

Psychiatric 
disorders 

     Confusion, 
hallucination 

Nervous system 
disorders 

 Dizziness, 
headache, 
disturbance of 
taste 

Vertigo 
somnolence, 
nervousness, 
insomnia,  

Transient loss 
of 
consciousness, 
paraesthesia 
 

Parosmia Cases of rapid 
onset of 
exacerbation 
of myasthenia 
gravis have 
been reported 
(see sections 
4.3 and 4.4). 
Ageusia, 
anosmia, 
tremors, 
convulsions 

Eye disorders   Blurred 
vision 

Diplopia   

Cardiac disorders   Flush 
Palpitations 

Atrial 
arrhythmia, 
hypotension, 
bradycardia 

 QT/QTc 
interval 
prolongation, 
ventricular 
arrhythmia 
(including 
ventricular 
tachycardia, 
torsade de 
pointes) with 
potential fatal 
outcome (see 
section 4.4)  

Gastrointestinal 
disorders 

Diarrhoe
a 

Nausea, 
vomiting, 
gastro-
intestinal 
pain, 
flatulence 

Oral Candida 
infection, 
stomatitis 
anorexia, 
constipation 

 Pseudo- 
membranou
s colitis (see 
section 4.4) 

Pancreatitis 

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System organ 
class 

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)* 

Hepatobiliary 
disorders 

 Increase in 
liver enzymes 
(AST, ALT, 
alkaline 
phosphatase, 
gamma-
glutamyl 
transferase) 

Hepatitis Cholestatic 
jaundice 

 Severe 
hepatitis and 
liver failure 
(see section 
4.4) 

Skin and 
subcutaneous 
tissue disorders 

  Rash, 
urticaria, 
pruritus 

Eczema Erythema 
multiforme 

 

Musculoskeletal 
and connective 
tissue disorders  

    Muscle 
cramps 

Arthralgia, 
myalgia 

Reproductive 
system and 
breast disorders 

 Vaginal 
Candida 
infection  

    

*post-marketing experience 
 
Description of selected adverse reactions 
 
Visual disturbances (<1%) associated with the use of Ketek, including blurred vision, difficulty 
focusing and diplopia, were mostly mild to moderate, but severe reactions have also been reported. 
They typically occurred within a few hours after the first or second dose, recurred upon subsequent 
dosing, lasted several hours and were fully reversible either during therapy or following the end of 
treatment. The onset of the visual reaction may be sudden. These events have not been associated with 
signs of ocular abnormality (see sections 4.4 and 4.7). 
 
In clinical trials the effect on QTc was small (mean of approximately 1 msec). In comparative trials, 
similar effects to those observed with clarithromycin were seen with an on-therapy ΔQTc >30 msec in 
7.6% and 7.0% of cases, respectively. No patient in either group developed a ΔQTc >60 msec. There 
were no reports of TdP or other serious ventricular arrhythmias or related syncope in the clinical 
program and no subgroups at risk were identified. 
 
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 the event of acute overdose the stomach should be emptied. The patients should be carefully 
observed and given symptomatic and supportive treatment. Adequate hydration should be maintained. 
Blood electrolytes (especially potassium) must be controlled. Due to the potential for the prolongation 
of the QT interval and increased risk of arrhythmia, ECG monitoring must take place. 
 
 

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5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: antibacterials for systemic use, macrolides, lincosamides and 
streptogramins, ATC Code: J01FA15. 
 
Telithromycin is a semisynthetic derivative of erythromycin A belonging to the ketolides, a class of 
antibacterial agents related to macrolides. 
 
Mode of action 
 
Telithromycin inhibits protein synthesis by interacting with domains II and V of the 23S ribosomal 
RNA of the 50S ribosome subunit. Furthermore, telithromycin is able to block the formation of the 
50S and 30S ribosomal subunits. 
 
The affinity of telithromycin for the 50S ribosomal subunits of organisms susceptible to erythromycin 
A is 10-fold higher than that of erythromycin A. 
 
Pharmacokinetic/Pharmacodynamic (PK/PD) relationship: 
The AUC/MIC ratio has been shown to be the PK/PD parameter that correlates best with the efficacy 
of telithromycin. 
 
Mechanisms of resistance 
 
Telithromycin does not induce expression of macrolide-lincosamide-streptogramin B (MLSB)-
mediated resistance in vitro in Staphylococcus aureus, Streptococcus pneumoniae, or Streptococcus 
pyogenes.  
 
In some organisms that are resistant to erythromycin A due to inducible expression of the MLSB 
resistance determinant, the affinity of telithromycin for the 50S ribosomal subunit is more than 20-
fold that of erythromycin A.  
 
Telithromycin is not active against organisms that constitutively express the MLSB resistance 
determinant (cMLSB). The majority of methicillin-resistant S. aureus (MRSA) express cMLSB. 
 
In in vitro studies the activity of telithromycin was reduced against organisms that express the 
erythromycin erm(B) or mef(A) related resistance mechanisms.  
 
Exposure to telithromycin in vitro did select for pneumococcal mutants with increased MICs of 
telithromycin, generally resulting in MIC values of ≤1 mg/l.  
 
Streptococcus pneumoniae does not demonstrate cross-resistance between erythromycin A and 
telithromycin.  
 
Streptococcus pyogenes that show high-level resistance to erythromycin A are cross-resistant to 
telithromycin. 
 
Breakpoints 
 
The recommended European Committee for Antimicrobial Susceptibility Testing (EUCAST) MIC 
clinical breakpoints are presented below: 
 
Pathogen Susceptible Resistant 
Streptococcus A, B, C, G ≤0.25 mg/l >0.5 mg/l 
Streptococcus pneumoniae ≤0.25 mg/l >0.5 mg/l 

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Haemophilus influenzae1 ≤0.12 mg/l >8 mg/l 
Moraxella catarrhalis ≤0.25 mg/l >0.5 mg/l 
 
1The correlation between macrolide MICs and clinical outcome is weak for H. influenzae. Therefore 
the MIC breakpoint for telithromycin was set to categorise wild-type H. influenzae as having 
intermediate susceptibility. 
 
Antibacterial spectrum 
 
The prevalence of 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. 
 
Commonly susceptible species 
Aerobic Gram-positive bacteria 
Staphylococcus aureus methicillin susceptible (MSSA)*  
Streptococcus pneumoniae * 
Streptococcus species 
Viridans group streptococci 
 
Aerobic Gram- negative bacteria 
Haemophilus influenzae$* 
Haemophilus parainfluenzae$ 
Legionella pneumophila 
Moraxella catarrhalis* 
 
Other 
Chlamydophila pneumoniae* 
Chlamydia psittaci 
Mycoplasma pneumoniae* 
 

Species for which acquired resistance may be a problem 
Aerobic Gram-positive bacteria 
Staphylococcus aureus methicillin resistant (MRSA)+ 
Streptococcus pyogenes* 
 
Inherently resistant organisms 
Aerobic Gram- negative bacteria 
Acinetobacter  
Enterobacteriaceae 
Pseudomonas 

 
∗ Clinical efficacy has been demonstrated for susceptible isolates in the approved clinical indications. 
$ natural intermediate susceptibility 
+ Telithromycin is not active against organisms that constitutively express the MLSB resistance 
determinant (cMLSB). More than 80% of MRSA express cMLSB. 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
Following oral administration, telithromycin is fairly rapidly absorbed. A mean maximum plasma 
concentration of about 2 mg/l is reached within 1-3 hour after dose with once-daily dosing of 
telithromycin 800 mg. The absolute bioavailability is about 57% after a single dose of 800 mg. The 

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rate and extent of absorption is unaffected by food intake, and thus Ketek tablets can be given without 
regard to food. 
 
Mean steady-state trough plasma concentrations of between 0.04 and 0.07 mg/l are reached within 3 
to 4 days with once-daily dosing of telithromycin 800 mg. At steady-state AUC is approximately 1.5 
fold increased compared to the single dose. 
 
Mean peak and trough plasma concentrations at steady state in patients were 2.9±1.6 mg/l (range 
0.02-7.6 mg/l) and 0.2±0.2 mg/l (range 0.010 to 1.29 mg/l), during a therapeutic 800 mg once-daily 
dose regimen. 
 
Distribution 
 
The in vitro protein binding is approximately 60% to 70%. Telithromycin is widely distributed 
throughout the body. The volume of distribution is 2.9±1.0 l/kg. Rapid distribution of telithromycin 
into tissues results in significantly higher telithromycin concentrations in most target tissues than in 
plasma. The maximum total tissue concentration in epithelial lining fluid, alveolar macrophages, 
bronchial mucosa, tonsils and sinus tissue were 14.9±11.4 mg/l, 318.1±231 mg/l, 3.88±1.87 mg/kg, 
3.95±0.53 mg/kg and 6.96±1.58 mg/kg, respectively. The total tissue concentration 24 h after dose in 
epithelial lining fluid, alveolar macrophages, bronchial mucosa, tonsils and sinus tissue were 
0.84±0.65 mg/l, 162±96 mg/l, 0.78±0.39 mg/kg, 0.72±0.29 mg/kg and 1.58±1.68 mg/kg, respectively. 
The mean maximum white blood cell concentration of telithromycin was 83±25 mg/l. 
 
Biotransformation 
 
Telithromycin is metabolised primarily by the liver. After oral administration, two-thirds of the dose 
is eliminated as metabolites and one-third unchanged. The main circulating compound in plasma is 
telithromycin. Its principal circulating metabolite represents approximately 13% of telithromycin 
AUC, and has little antimicrobial activity compared with the parent medicinal product. Other 
metabolites were detected in plasma, urine and faeces and represent less or equal than 3% of plasma 
AUC. 
 
Telithromycin is metabolised both by CYP450 isoenzymes and non-CYP enzymes. The major 
CYP450 enzyme involved in the metabolism of telithromycin is CYP3A4. Telithromycin is an 
inhibitor of CYP3A4 and CYP2D6, but has no or limited effect on CYP1A, 2A6, 2B6, 2C8, 2C9, 
2C19 and 2E1. 
 
Elimination 
 
After oral administration of radiolabelled telithromycin, 76% of the radioactivity was recovered from 
faeces, and 17% from the urine. Approximately one-third of telithromycin was eliminated unchanged; 
20% in faeces and 12% in urine. Telithromycin displays moderate non-linear pharmacokinetics. The 
non-renal clearance is decreased as the dose is increased. The total clearance (mean ±SD) is 
approximately 58±5 l/h after an intravenous administration with renal clearance accounting for about 
22% of this. Telithromycin displays a tri-exponential decay from plasma, with a rapid distribution 
half-life of 0.17 h. The main elimination half-life of telithromycin is 2-3 h and the terminal, less 
important, half-life is about 10 h at the dose 800 mg once daily. 
 
Special populations 
 
-Renal impairment 
In a multiple-dose study, 36 subjects with varying degrees of renal impairment, a 1.4-fold increase in 
Cmax,ss, and a 2-fold increase in AUC (0-24)ss at 800 mg multiple doses in the severe renally impaired 
group (CLCR < 30 ml/min) compared to healthy volunteers were observed and a reduced dosage of 
Ketek is recommended (see section 4.2). Based on observed data, a 600 mg daily dose is 
approximately equivalent with the target exposure observed in healthy subjects. Based on simulation 

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data, an alternating daily dosing regimen of 800 mg and 400 mg in patients with severe renal 
impairment can approximate the AUC (0-48h) in healthy subjects receiving 800 mg once daily.  
 
The effect of dialysis on the elimination of telithromycin has not been assessed.  
 
-Hepatic impairment 
In a single-dose study (800 mg) in 12 patients and a multiple-dose study (800 mg) in 13 patients with 
mild to severe hepatic insufficiency (Child Pugh Class A, B and C), the Cmax, AUC and t1/2 of 
telithromycin were similar compared to those obtained in age- and sex-matched healthy subjects. In 
both studies, higher renal elimination was observed in the hepatically impaired patients. Due to 
limited experience in patients with decreased metabolic capacity of the liver, Ketek should be used 
with caution in patients with hepatic impairment (see also section 4.4). 
 
-Elderly subjects  
In subjects over 65 (median 75 years), the maximum plasma concentration and AUC of telithromycin 
were increased approximately 2-fold compared with those achieved in young healthy adults. These 
changes in pharmacokinetics do not necessitate dosage adjustment. 
 
-Paediatric population  
Limited data, obtained in paediatric patients 13 to 17 years of age, showed that telithromycin 
concentrations in this age group were similar to the concentrations in patients 18 to 40 years of age. 
 
-Gender 
The pharmacokinetics of telithromycin is similar between males and females. 
 
5.3 Preclinical safety data 
 
Repeated dose toxicity studies of 1, 3 and 6 month duration with telithromycin conducted in rat, dog 
and monkey showed that the liver was the principal target for toxicity with elevations of liver 
enzymes, and histological evidence of damage. These effects showed a tendency to regress after 
cessation of treatment. Plasma exposures based on free fraction of active substance, at the no 
observed adverse effect levels ranged from 1.6 to 13 times the expected clinical exposure.  
 
Phospholipidosis (intracellular phospholipid accumulation) affecting a number of organs and tissues 
(e.g., liver, kidney, lung, thymus, spleen, gall bladder, mesenteric lymph nodes, GI-tract) has been 
observed in rats and dogs administered telithromycin at repeated doses of 150 mg/kg/day or more for 
1 month and 20 mg/kg/day or more for 3-6 months. This administration corresponds to free active 
substance systemic exposure levels of at least 9 times the expected levels in human after 1 month and 
less than the expected level in humans after 6 months, respectively. There was evidence of 
reversibility upon cessation of treatment. The significance of these findings for humans is unknown. 
 
In similarity to some macrolides, telithromycin caused a prolongation of QTc interval in dogs and on 
action potential duration in rabbit Purkinje fibers in vitro. Effects were evident at plasma levels of 
free drug 8 to 13 times the expected clinical level. Hypokalaemia and quinidine had additive/supra-
additive effects in vitro while potentiation was evident with sotalol. Telithromycin, but not its major 
human metabolites, had inhibitory activity on HERG and Kv1.5 channels.  
 
Reproduction toxicity studies showed reduced gamete maturation in rat and adverse effects on 
fertilization. Slight reductions in fertility indices were seen in rats at parentally toxic doses higher 
than 150 mg/kg. At high doses embryotoxicity was apparent and an increase in incomplete 
ossification and in skeletal anomalies was seen. Studies in rats and rabbits were inconclusive with 
respect to potential for teratogenicity; there was equivocal evidence of adverse effects on foetal 
development at high doses. 
 
Telithromycin, and its principal human metabolites, were negative in tests on genotoxic potential in 
vitro and in vivo. No carcinogenicity studies have been conducted with telithromycin. 

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6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core: 
 
Microcrystalline cellulose  
Povidone K25 
Croscarmellose sodium 
Magnesium stearate 
 
Tablet coating: 
 
Talc 
Macrogol 8000 
Hypromellose 6 cp 
Titanium dioxide E171 
Yellow iron oxide E172 
Red iron oxide E172 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years. 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage condition. 
 
6.5 Nature and contents of container 
 
Two tablets are contained in each blister cavity. 
 
Available as packs of 10, 14, 20 and 100 tablets. 
Opaque PVC/Aluminium blisters. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
No special requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Aventis Pharma S.A. 
20, Avenue Raymond Aron 
F-92160 ANTONY 
France 
 
 

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8. MARKETING AUTHORISATION NUMBERS  
 
EU/1/01/191/001-004 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 9 July 2001 
Date of latest renewal: 9 July 2011 
 
 
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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ANNEX II 
 
A. MANUFACTURER(S) RESPONSIBLE FOR BATCH 

RELEASE 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION 

 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 

 

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A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release: 
 
 
S.C. Zentiva S.A. 
B-dul Theodor Pallady nr. 50, sector 3, Bucureşti, cod 032266, Romania 
 
 
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 marketing authorisation holder shall submit periodic safety update reports for this product 
in accordance with the requirements set out in the list of Union reference dates (EURD list) 
provided for under Article 107c(7) of Directive 2001/83/EC and 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. 

 
If the dates for submission of a PSUR and the update of a RMP coincide, they can be submitted at the 
same time. 
 

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ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 

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A. LABELLING 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
Carton 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Ketek 400 mg film-coated tablets 
telithromycin 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 400 mg of telithromycin. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
10 film-coated tablets 
14 film-coated tablets 
20 film-coated tablets 
100 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

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

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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 
 
Aventis Pharma S.A. 
20, Avenue Raymond Aron 
F-92160 ANTONY 
France 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/01/191/001 10 tablets 
EU/1/01/191/002 14 tablets 
EU/1/01/191/003 20 tablets 
EU/1/01/191/004 100 tablets 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Ketek 

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Ketek 400 mg film-coated tablets 
telithromycin  
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Aventis Pharma S.A. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Batch 
 
 
5. OTHER 
 

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B. PACKAGE LEAFLET 

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Package leaflet: Information for the user 
 

Ketek 400 mg film-coated tablets 
Telithromycin 

 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet:  
1. What Ketek is and what it is used for 
2. What you need to know before you take Ketek 
3. How to take Ketek 
4. Possible side effects 
5. How to store Ketek 
6. Contents of the pack and other information 
 
 
1.  What Ketek is and what it is used for 
 
Ketek contains the active substance telithromycin. 
 
Ketek is an antibiotic of the type macrolides. Antibiotics stop the growth of bacteria which cause 
infections. 
 
Ketek is used to treat infections due to bacteria against which the medicine is active. 
- In adults, Ketek is used to treat infections of the throat, infections of the sinuses (hollow cavities 

in the bones around the nose) and chest infections in patients with long standing breathing 
difficulties and lung infection (pneumonia). 

- In adolescents of 12 years and older, Ketek is used to treat infections of the throat.  
 
 
2. What you need to know before you take Ketek 
 
Do not take Ketek: 
- if you are allergic to telithromycin, to any of the macrolide antibiotics or to any of the other 

ingredients of this medicine (listed in section 6). If in doubt, talk to your doctor or pharmacist. 
- if you suffer from myasthenia gravis, a rare disease which causes muscle weakness. 
- if you have had a liver disease (hepatitis and/or jaundice) while taking Ketek in the past. 
- if you are taking other medicines that can prolong the QT interval of the electrocardiogram 

(ECG), such as: 
• terfenadine or astemizole (allergic problems) 
• cisapride (digestive problems) 
• pimozide (psychiatric problems) 
• dronedarone (for atrial fibrillation) 
• saquinavir (anti-HIV treatment) 

- if you are taking other medicines containing any of the following active substances: 
• ergotamine or dihydroergotamine (tablets or inhaler for migraine) 

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- if you are taking certain medicinal products to control the blood level of cholesterol or other 
lipids like simvastatin, lovastatin, or atorvastatin, as the side effects of these medicinal products 
could be increased. 

- if you or someone in your family are known to have an abnormality of electrocardiogram 
(ECG) called “long QT syndrome”. 

- if you have kidney problems (severely impaired renal function) and/or liver problems (severely 
impaired hepatic function), do not take Ketek while taking other medicines containing any of the 
following active substances: 
• ketoconazole or fluconazole (anti-fungal treatment) 
• a medicine called protease inhibitor (anti-HIV treatment) 
• colchicine (for gout) 

 
Warnings and precautions 
Talk to your doctor, pharmacist or nurse before taking Ketek: 
- if you have had certain heart problems such as coronary heart disease, ventricular arrhythmias, 

bradycardia (changes in heart rate or electrocardiogram) or if you have had certain abnormal 
blood tests due to medical conditions such as low levels of potassium (hypokalaemia), low levels 
of magnesium (hypomagnesaemia). 

- if you have liver disease. 
- if you experience fainting (transient loss of consciousness) 
Talk to your doctor, pharmacist or nurse if you experience irregular heartbeat. 
Talk to your doctor, pharmacist or nurse if you experience visual disturbances (blurred vision, 
difficulty focusing, double vision). These visual disturbances may happen suddenly and last several 
hours. You may experience this within a few hours of taking your daily dose of Ketek the first or 
second time. It may happen again when you take the next dose of Ketek. These effects usually 
disappear during treatment or after completion of treatment with Ketek. 
 
If any of these apply to you, or if you are not sure, tell your doctor before taking Ketek. 
If you develop severe or prolonged or bloody diarrhoea during or after taking Ketek tablets, consult 
your doctor immediately since it may be necessary to interrupt the treatment. This may be a sign of 
bowel inflammation which can occur following treatment with antibiotics. 
 
To reduce the potential impact of visual disturbances take the tablets before going to bed (see also 
section 3). 
 
Children and adolescents 
Ketek is not recommended for use in children less than 12 years old. 
 
Refer also to sections “Do not take Ketek”, “Other medicines and Ketek” and “Driving and using 
machines”. 
 
Other medicines and Ketek 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines, including medicines obtained without a prescription, as some of them could affect or be 
affected by Ketek. 
 
These medicines must not be taken with Ketek: 
- medicinal products to control the blood level of cholesterol or other lipids like simvastatin, 

atorvastatin, or lovastatin, as the side effects of the medicinal products could be increased. 
- other medicines that can prolong the QT interval of the electrocardiogram (ECG), such as: 

• terfenadine or astemizole (allergic problems) 
• cisapride (digestive problems) 
• pimozide (psychiatric problems) 
• dronedarone (for atrial fibrillation) 
• saquinavir (anti-HIV treatment) 

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- other medicines containing any of the following active substances: 
• ergotamine or dihydroergotamine (tablets or inhaler for migraine) 

- if you have kidney problems (severely impaired renal function) and/or liver problems (severely 
impaired hepatic function), other medicines containing any of the following active substances: 
• ketoconazole or fluconazole (anti-fungal treatment) 
• a medicine called protease inhibitor (anti-HIV treatment) 
• colchicine (for gout). 

 
It is important to tell your doctor if you are taking: 
- medicines containing phenytoin, and carbamazepine (for epilepsy) 
- rifampicin (antibiotic) 
- phenobarbital or St John’s wort (herbal medicine used to treat mild depression) 
- medicines like tacrolimus, cyclosporin and sirolimus (for organ transplantation) 
- metoprolol (for heart disorders) 
- sotalol (for heart disorders) 
- ritonavir (anti-HIV medicine). 
- medicines known to affect the way your heart beats (drugs that prolong the QT interval).  

These include medicines used for abnormal heart rhythm (antiarrhythmics such as quinidine, 
amiodarone), for depression (citalopram, tricyclic antidepressants), methadone, some 
antipsychotics (phenothiazines), some antibiotics (fluoroquinolones such as moxifloxacin), some 
antifungals (fluconazole, pentamidine), and some antiviral drugs (telaprevir). 

- medicines containing digoxin (for heart disorders) or dabigatran (for prevention of blood clots) 
- colchicine (for gout) 
- some calcium channel blockers (e.g. verapamil, nifedipine, felodipine) (for heart disorders). 
 
Ketek with food, drink and alcohol 
Ketek may be taken with or without food. 
 
Pregnancy, breast-feeding and fertility 
If you are pregnant do not take Ketek as the safety of this medicine in pregnancy is insufficiently 
established. If you are breast-feeding do not take Ketek. 
 
Driving and using machines 
Limit driving or other hazardous activities while taking Ketek. If you have vision problems, faint or 
experience confusion or hallucination while taking Ketek, do not drive, operate heavy machinery or 
engage in dangerous activities. 
 
Taking Ketek may cause side effects such as visual disturbances, confusion or hallucination which 
may reduce the capacity to carry out certain tasks. Rare cases of fainting (transient loss of 
consciousness), which may be preceded by a general feeling of being sick (e.g. nausea, stomach 
upsets) have been reported. These symptoms may appear as early as after the first dose of Ketek. 
 
 
3. How to take Ketek 
 
Your doctor will tell you how many Ketek tablets to take, at what time and for how long. Always take 
this medicine exactly as your doctor or pharmacist has told you. Check with you doctor or pharmacist 
if you are not sure. 
 
The usual duration of treatment is 5 days for infections of the throat, infections of the sinuses, chest 
infections in patients with long standing breathing difficulties and 7 to 10 days for pneumonia. 
 
The recommended dose of Ketek for adults and children of 12 years and older is two tablets of 400 mg 
once daily (800 mg once daily).  
 

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If you have kidney problems (severe renal insufficiency) you should take alternating daily doses of 
800 mg (two tablets of 400 mg) and 400 mg (one tablet of 400 mg), starting with the 800 mg dose. 
 
Swallow the tablets whole with a glass of water. 
 
It is best to take tablets at the same time each day. If possible take the tablets before going to bed, to 
reduce the potential impact of visual disturbances and loss of consciousness. 
 
If you take more Ketek than you should 
If you accidentally take one tablet too many, nothing is likely to happen. If you accidentally take 
several tablets too many, contact your doctor or pharmacist. If possible, take your tablets or the box 
with you to show the doctor or pharmacist. 
 
If you forget to take Ketek 
If you forget to take a dose, take it as soon as possible. However, if it is nearly time for your next dose 
skip the missed dose and take the next tablet at the usual time. Do not take a double dose to make up 
for a forgotten dose. 
 
If you stop taking Ketek 
Take the complete course of tablets prescribed by your doctor, even if you begin to feel better before 
you have finished them all. If you stop taking the tablets too soon, the infection may return, or your 
condition may get worse.  
 
If you stop taking the tablets too soon you may also create a bacterial resistance to the medicine. 
 
If you feel you are suffering from a side effect, tell a doctor immediately to get advice before taking 
the next dose. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects  

 
Like all medicines this medicine can cause side effects, although not everybody gets them. Most of 
them are mild and transient, but very rare cases of serious adverse liver reactions and liver failure, 
including fatal cases, have been reported. 
 
If you notice any of the following, stop taking Ketek and tell your doctor immediately: 
- Allergic or skin reactions such as face swelling, general allergic reactions including allergic 

shock, or serious skin conditions associated with red spots, blisters (frequency not known). 
- Severe, persistent or bloody diarrhoea associated with abdominal pain or fever, which can be a 

sign of serious bowel inflammation which may occur following treatment with antibiotics (very 
rare). 

- Signs and symptoms of liver disease (hepatitis) such as yellowing of skin and eyes, dark urine, 
itching, loss of appetite or abdominal pain (uncommon). 

- Worsening of a condition called myasthenia gravis, a rare disease which causes muscle 
weakness (frequency unknown). 

- Irregular heartbeat 
 
The above serious side effects may require urgent medical attention. 
 
The other side effects listed below are given with an estimation of the frequency with which they may 
occur with Ketek: 
 
Very common side effects (may affect more than 1 in 10 people) 
- diarrhoea, usually mild and temporary. 

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Common side effects (may affect up to 1 in 10 people) 
- nausea, vomiting, abdominal pain, flatulence (excess wind) 
- dizziness, headaches, disturbance of taste 
- vaginal Candida infection (fungal infection associated with local itching, burning and white 

discharge) 
- increase in liver enzymes (detected by blood test). 
 
Uncommon (may affect up to 1 in 100 people) or rare side effects (may affect up to 1 in 1,000 
people) 
- constipation, loss of appetite (anorexia) 
- inflammation in the mouth, fungal infection in the mouth (Candida infection) 
- liver problem (hepatitis) 
- rash, hives (urticaria), itching, eczema 
- drowsiness, difficulties in falling asleep (insomnia), nervousness, vertigo 
- tingling of the hands or feet (paraesthesia) 
- visual disturbances (blurred vision, difficulty in focusing, double vision)(please read section 2) 
- flushes, fainting (transient loss of consciousness) 
- changes in heart rate (e.g. slow beating) or abnormality of electrocardiogram (ECG)  
- low blood pressure (hypotension) 
- increase of certain white blood cells, detected by blood test (eosinophilia). 
 
Very rare side effects (may affect up to 1 in 10,000 people) 
- disturbance of smell, muscle cramps. 
 
Additional side effects (frequency not known – frequency cannot be estimated from available data) 
which may occur with Ketek are: 
- tremors, convulsions 
- abnormality of electrocardiogram (ECG), called prolongation of QT interval  
- inflamed pancreas 
- joint and muscle pain 
- confusion 
- hallucination (seeing or hearing things that are not there) 
- loss of taste and smell 
- liver failure. 
 
If any of these undesirable effects are troublesome, severe, or do not wear off as treatment goes on, 
tell your doctor.  
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Ketek 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the pack. The expiry date refers to 
the last day of that month. 
 
This medicinal product does not require any special storage conditions. 
 

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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 Ketek contains 

 
- The active substance is telithromycin. Each tablet contains 400 mg of telithromycin. 
- The other ingredients are microcrystalline cellulose, povidone (K25), croscarmellose sodium, 

magnesium stearate in the tablet core as well as talc, macrogol (8000 ), hypromellose (6 cp), 
titanium dioxide (E171), yellow iron oxide (E172), red iron oxide (E172) in the film-coating. 

 
What Ketek looks like and contents of the pack 
 
Ketek 400 mg tablets are light orange, oblong, biconvex, film-coated tablets imprinted with “H3647” 
on one side and “400” on the other. 
 
Ketek tablets are presented in blister packs. Two tablets are contained in each blister cavity. 
They are available in packs of 10, 14, 20 and 100 tablets. Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
 
The marketing authorisation holder of Ketek is: 
Aventis Pharma S.A. 
20 Avenue Raymond Aron 
F-92160 ANTONY 
France 
 
The manufacturer of Ketek is: 
S.C. Zentiva S.A. 
B-dul Theodor Pallady nr. 50, sector 3, Bucureşti, cod 032266, Romania 
 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder. 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 
 

Lietuva 
UAB sanofi-aventis Lietuva 
Tel: +370 5 2755224 
 

България 
sanofi-aventis Bulgaria EOOD 
Тел.: +359 (0)2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium  
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 
 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
sanofi-aventis zrt., Magyarország 
Tel.: +36 1 505 0050 
 

Danmark 
sanofi-aventis Denmark A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi Malta Ltd. 
Tel: +356 21493022 
 

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Deutschland 
Sanofi-Aventis Deutschland GmbH 
Tel: +49 (0)180 2 222010 
 

Nederland 
sanofi-aventis Netherlands B.V. 
Tel: +31 (0)182 557 755 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

Norge 
sanofi-aventis Norge AS 
Tlf: +47 67 10 71 00 
 

Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 
 

España 
sanofi-aventis, S.A. 
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp. z o.o. 
Tel.: +48 22 280 00 00 
 

France 
sanofi-aventis France 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda. 
Tel: +351 21 35 89 400 
 

Hrvatska 
sanofi-aventis Croatia d.o.o. 
Tel: +385 1 600 34 00 

România 
sanofi-aventis România S.R.L. 
Tel: +40 (0) 21 317 31 36 
 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Pharma Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

Italia 
sanofi-aventis S.p.A. 
Tel: +39 02 393 91 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 
 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 
 

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

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	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET