Ketek® (telithromycin)

Table 2 (continued)
Mean concentration (µg/mL)
(telithromycin) Tablets
Tissue or
Ketek is contraindicated in patients with myasthenia gravis. There have been reports of fatal
and life-threatening respiratory failure in patients with myasthenia gravis associated with the use of Ketek. (See CONTRAINDICATIONS.)
To reduce the development of drug-resistant bacteria and maintain the effectiveness of KETEK and other antibacterial drugs, KETEK should be used only to treat infections that are proven or strongly DESCRIPTION
KETEK® tablets contain telithromycin, a semisynthetic antibacterial in the ketolide class for oral
administration. Chemically, telithromycin is designated as Erythromycin, 3-de[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranosyl)oxy]-11,12-dideoxy-6-O-methyl-3-oxo-12,11-[oxycarbonyl[[4-[4-(3- Telithromycin concentration in white blood cells exceeds the concentration in plasma and is eliminated pyridinyl)-1H-imidazol-1-yl]butyl]imino]]-.
more slowly from white blood cells than from plasma. Mean white blood cell concentrations of Telithromycin, a ketolide, differs chemically from the macrolide group of antibacterials by the lack of telithromycin peaked at 72.1 µg/mL at 6 hours, and remained at 14.1 µg/mL 24 hours after 5 days of α-L-cladinose at position 3 of the erythronolide A ring, resulting in a 3-keto function. It is further repeated dosing of 600 mg once daily. After 10 days, repeated dosing of 600 mg once daily, white blood characterized by a C11-12 carbamate substituted by an imidazolyl and pyridyl ring through a butyl cell concentrations remained at 8.9 µg/mL 48 hours after the last dose.
chain. Its empirical formula is C H N O and its molecular weight is 812.03. Telithromycin is a white to off-white crystalline powder. The following represents the chemical structure of telithromycin.
In total, metabolism accounts for approximately 70% of the dose. In plasma, the main circulating
compound after administration of an 800-mg radio-labeled dose was parent compound, representing
56.7% of the total radioactivity. The main metabolite represented 12.6% of the AUC of telithromycin.
Three other plasma metabolites were quantified, each representing 3% or less of the AUC of
telithromycin.
It is estimated that approximately 50% of its metabolism is mediated by CYP 450 3A4 and the remaining
50% is CYP 450-independent.
Elimination
The systemically available telithromycin is eliminated by multiple pathways as follows: 7% of the dose
is excreted unchanged in feces by biliary and/or intestinal secretion; 13% of the dose is excreted
unchanged in urine by renal excretion; and 37% of the dose is metabolized by the liver.
Special populations
Gender
There was no significant difference between males and females in mean AUC, C
half-life in two studies; one in 18 healthy young volunteers (18 to 40 years of age) and the other in KETEK tablets are available as light-orange, oval, film-coated tablets, each containing 400 mg or 300 14 healthy elderly volunteers (65 to 92 years of age), given single and multiple once daily doses of mg of telithromycin, and the following inactive ingredients: croscarmellose sodium, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, povidone, red ferric oxide, talc, titanium dioxide, and yellow ferric oxide.
In a single-dose study (800 mg) in 12 patients and a multiple-dose study (800 mg) in 13 patients with CLINICAL PHARMACOLOGY
mild to severe hepatic insufficiency (Child Pugh Class A, B and C), the C Pharmacokinetics
telithromycin were similar to those obtained in age- and sex-matched healthy subjects. In both studies, an increase in renal elimination was observed in hepatically impaired patients indicating that this Following oral administration, telithromycin reached maximal concentration at about 1 hour (0.5 – 4 pathway may compensate for some of the decrease in metabolic clearance. No dosage adjustment is recommended due to hepatic impairment.
It has an absolute bioavailability of 57% in both young and elderly subjects.
(See PRECAUTIONS, General and DOSAGE AND ADMINISTRATION)
The rate and extent of absorption are unaffected by food intake, thus KETEK tablets can be given without regard to food.
In healthy adult subjects, peak plasma telithromycin concentrations of approximately 2 µg/mL are In a multiple-dose study, 36 subjects with varying degrees of renal impairment received 400 mg, 600 attained at a median of 1 hour after an 800-mg oral dose.
mg, or 800 mg KETEK once daily for 5 days. There was a 1.4-fold increase in C Steady-state plasma concentrations are reached within 2 to 3 days of once daily dosing with increase in AUC (0–24) at 800 mg multiple doses in the severely renally impaired group (CL mL/min) compared to healthy volunteers. Renal excretion may serve as a compensatory elimination Following oral dosing, the mean terminal elimination half-life of telithromycin is 10 hours.
pathway for telithromycin in situations where metabolic clearance is impaired. Patients with severe renal The pharmacokinetics of telithromycin after administration of single and multiple (7 days) once daily impairment are prone to conditions that may impair their metabolic clearance. Therefore, in the 800-mg doses to healthy adult subjects are shown in Table 1.
recommended. (See DOSAGE AND ADMINISTRATION)
In a single-dose study in patients with end-stage renal failure on hemodialysis (n=10), the mean Cmax Mean (SD)
and AUC values were similar to normal healthy subjects when KETEK was administered 2 hourspost-dialysis. However, the effect of dialysis on removing telithromycin from the body has not been Parameter
Single dose (n=18)
Multiple dose (n=18)
The effects of co-administration of ketoconazole in 12 subjects (age ≥ 60 years), with impaired renal function were studied (CL = 24 to 80 mL/min). In this study, when severe renal insufficiency (CL < 30 mL/min, n=2) and concomitant impairment of CYP 3A4 metabolism pathway were present, telithromycin exposure (AUC (0–24)) was increased by approximately 4- to 5-fold compared with the exposure in healthy subjects with normal renal function receiving telithromycin alone. In the presence < 30 mL/min), with coexisting hepatic impairment, a reduced dosage of KETEK is recommended. (See PRECAUTIONS, General and DOSAGE AND ADMINISTRATION)
AUC=Area under concentration vs. time curve Pharmacokinetic data show that there is an increase of 1.4-fold in exposure (AUC) in 20 patients ≥ 65 years of age with community acquired pneumonia in a Phase III study, and a 2.0-fold increase in C =Plasma concentration at 24 hours post-dose exposure (AUC) in 14 subjects ≥ 65 years of age as compared with subjects less than 65 years of age in a Phase I study. No dosage adjustment is required based on age alone.
Drug-drug interactions
In a patient population, mean peak and trough plasma concentrations were 2.9 µg/mL (±1.55), (n=219) and 0.2 µg/mL (±0.22), (n=204), respectively, after 3 to 5 days of KETEK 800 mg once daily.
Distribution In vitro studies using a model compound have shown that telithromycin may act as an inhibitor for the Total in vitro protein binding is approximately 60% to 70% and is primarily due to human serum albumin.
hepatic uptake transporters OATP1B1 and OATP1B3. Although the clinical relevance of this finding is Protein binding is not modified in elderly subjects and in patients with hepatic impairment.
unknown, it is possible that concomitant administration of telithromycin with drugs that are substrates The volume of distribution of telithromycin after intravenous infusion is 2.9 L/kg.
of OATP family members could result in increased plasma concentrations of the co-administered drug.
Telithromycin concentrations in bronchial mucosa, epithelial lining fluid, and alveolar macrophages after 800 mg once daily dosing for 5 days in patients are displayed in Table 2.
Studies were performed to evaluate the effect of CYP 3A4 inhibitors on telithromycin and the effect oftelithromycin on drugs that are substrates of CYP 3A4 and CYP 2D6. In addition, drug interaction studies were conducted with several other concomitantly prescribed drugs.
CYP 3A4 inhibitors Mean concentration (µg/mL)
Tissue or
A multiple-dose interaction study with itraconazole showed that C A multiple-dose interaction study with ketoconazole showed that C When telithromycin was given with 240 mL of grapefruit juice after an overnight fast to healthy subjects, Telithromycin has been shown to be active against most strains of the following microorganisms, both the pharmacokinetics of telithromycin were not affected.
in vitro and in clinical settings as described in the INDICATIONS AND USAGE section.
Aerobic gram-positive microorganisms Streptococcus pneumoniae (including multi-drug resistant isolates [MDRSP2]) Steady-state peak plasma concentrations of cisapride (an agent with the potential to increase QT Aerobic gram-negative microorganisms interval) were increased by 95% when co-administered with repeated doses of telithromycin, resulting in significant increases in QTc. (See CONTRAINDICATIONS)
When simvastatin was co-administered with telithromycin, there was a 5.3-fold increase in simvastatin Chlamydophila (Chlamydia) pneumoniae , an 8.9-fold increase in simvastatin AUC, a 15-fold increase in the simvastatin active metabolite , and a 12-fold increase in the simvastatin active metabolite AUC. (See PRECAUTIONS)
The following in vitro data are available, but their clinical significance is unknown.
In another study, when simvastatin and telithromycin were administered 12 hours apart, there was a At least 90% of the following microorganisms exhibit in vitro minimum inhibitory concentrations (MICs) , a 4.0-fold increase in simvastatin AUC, a 3.2-fold increase in the less than or equal to the susceptible breakpoint for telithromycin. However, the safety and efficacy of , and a 4.3-fold increase in the active metabolite AUC. (See PRECAUTIONS)
telithromycin in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.
Concomitant administration of telithromycin with intravenous or oral midazolam resulted in 2- and 6-fold Aerobic gram-positive microorganisms increases, respectively, in the AUC of midazolam due to inhibition of CYP 3A4-dependent metabolism Staphylococcus aureus (methicillin and erythromycin susceptible isolates only) of midazolam. (See PRECAUTIONS)
Streptococcus pyogenes (erythromycin susceptible isolates only) There was no pharmacokinetic effect on paroxetine when telithromycin was co-administered.
MetoprololWhen metoprolol was co-administered with telithromycin, there was an increase of approximately 38% 2MDRSP=Multi-drug resistant Streptococcus pneumoniae includes isolates known as PRSP (penicillin- and AUC of metoprolol, however, there was no effect on the elimination half-life of resistant S. pneumoniae), and are isolates resistant to two or more of the following antimicrobials: metoprolol. Telithromycin exposure is not modified with concomitant single-dose administration of penicillin, 2nd generation cephalosporins (e.g., cefuroxime), macrolides, tetracyclines, and trimetho- metoprolol. (See PRECAUTIONS, Drug interactions)
When available, the clinical microbiology laboratory should provide cumulative results of in vitro The plasma peak and trough levels of digoxin were increased by 73% and 21%, respectively, in healthy susceptibility test results for antimicrobial drugs used in local hospitals and practice areas to the volunteers when co-administered with telithromycin. However, trough plasma concentrations of digoxin physician as periodic reports that describe the susceptibility profile of nosocomial and community- (when equilibrium between plasma and tissue concentrations has been achieved) ranged from 0.74 to acquired pathogens. These reports should aid the physician in selecting the most effective antimi- 2.17 ng/mL. There were no significant changes in ECG parameters and no signs of digoxin toxicity.
(See PRECAUTIONS)
Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs).
When theophylline was co-administered with repeated doses of telithromycin, there was an increase These MICs provide estimates of the susceptibility of bacteria to antibacterial compounds. The MICs of approximately 16% and 17% on the steady-state C and AUC of theophylline. Co-administration should be determined using a standardized procedure. Standardized procedures are based on dilution of theophylline may worsen gastrointestinal side effects such as nausea and vomiting, especially in methods (broth or agar dilution)1,3 or equivalent with standardized inoculum and concentrations of female patients. It is recommended that telithromycin should be taken with theophylline 1 hour apart telithromycin powder. The MIC values should be interpreted according to criteria provided in Table 3.
to decrease the likelihood of gastrointestinal side effects.
Quantitative methods that require measurement of zone diameters also provide reproducible estimates Telithromycin has been shown to decrease the C and AUC of sotalol by 34% and 20%, respectively, of the susceptibility of bacteria to antibiotics. One such standardized procedure2,3 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 15 µg telithromycin to test the susceptibility of microorganisms to telithromycin. Disc diffusion zone sizes When co-administered with telithromycin in healthy subjects, there were no pharmacodynamic or should be interpreted according to criteria in Table 3.
pharmacokinetic effects on racemic warfarin.
Oral contraceptives Table 3. Susceptibility Test Result Interpretive Criteria for Telithromycin
When oral contraceptives containing ethinyl estradiol and levonorgestrel were co-administered with Minimal Inhibitory Concentrations
Disk Diffusion
telithromycin, the steady-state AUC of ethinyl estradiol did not change and the steady-state AUC of (µg/mL)
(zone diameters in mm)
levonorgestrel was increased by 50%. The pharmacokinetic/pharmacodynamic study showed that Pathogen
telithromycin did not interfere with the antiovulatory effect of oral contraceptives containing ethinylestradiol and levonorgestrel.
There was no clinically relevant pharmacokinetic interaction of ranitidine or antacids containing aluminum and magnesium hydroxide on telithromycin.
RifampinDuring concomitant administration of rifampin and KETEK in repeated doses, C A report of ″Susceptible″ indicates that the antimicrobial is likely to inhibit growth of the pathogen if telithromycin were decreased by 79%, and 86%, respectively. (See PRECAUTIONS, Drug Interac-
the antibacterial compound in the blood reaches the concentrations usually achievable. A report of ″Intermediate″ indicates that the result should be considered equivocal, and, if the microorganism is Microbiology
not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category Telithromycin belongs to the ketolide class of antibacterials and is structurally related to the macrolide implies possible clinical applicability in body sites where the drug is physiologically concentrated or in family of antibiotics. Telithromycin concentrates in phagocytes where it exhibits activity against situations where high dosage of drug can be used. This category also provides a buffer zone that intracellular respiratory pathogens. In vitro, telithromycin has been shown to demonstrate concentra- prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A tion-dependent bactericidal activity against isolates of Streptococcus pneumoniae (including multi-drug report of ″Resistant″ indicates that the antimicrobial is not likely to inhibit growth of the pathogen if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapyshould be selected.
Quality control 1MDRSP=Multi-drug resistant Streptococcus pneumoniae includes isolates known as PRSP (penicillin- Standardized susceptibility test procedures require the use of quality control microorganisms to resistant Streptococcus pneumoniae), and are isolates resistant to two or more of the following determine the performance of the test procedures1,2,3. Standard telithromycin powder should provide antimicrobials: penicillin, 2nd generation cephalosporins (e.g., cefuroxime), macrolides, tetracyclines, the MIC ranges for the quality control organisms in Table 4. For the disk diffusion technique, the 15-µg telithromycin disk should provide the zone diameter ranges for the quality control organisms in Table Telithromycin blocks protein synthesis by binding to domains II and V of 23S rRNA of the 50S ribosomalsubunit. By binding at domain II, telithromycin retains activity against gram-positive cocci (e.g., Table 4. Acceptable Quality Control Ranges for Telithromycin
Streptococcus pneumoniae) in the presence of resistance mediated by methylases (erm genes) that QC Strain
Minimum Inhibitory
Disk Diffusion
alter the domain V binding site of telithromycin. Telithromycin may also inhibit the assembly of nascent Concentrations
(Zone diameter in mm)
(µg/mL)
Staphylococcus aureus and Streptococcus pyogenes with the constitutive macrolide-lincosamide- streptogramin B (cMLS ) phenotype are resistant to telithromycin.
Mutants of Streptococcus pneumoniae derived in the laboratory by serial passage in subinhibitory concentrations of telithromycin have demonstrated resistance based on L22 riboprotein mutations (telithromycin MICs are elevated but still within the susceptible range), one of two reported mutations affecting the L4 riboprotein, and production of K-peptide. The clinical significance of these laboratorymutants is not known.
INDICATIONS AND USAGE
KETEK tablets are indicated for the treatment of community-acquired pneumonia (of mild to moderate Telithromycin does not induce resistance through methylase gene expression in erythromycin-inducibly severity) due to Streptococcus pneumoniae, (including multi-drug resistant isolates [MDRSP3]), resistant bacteria, a function of its 3-keto moiety. Telithromycin has not been shown to induce resistance Haemophilus influenzae, Moraxella catarrhalis, Chlamydophila pneumoniae, or Mycoplasma pneumo- niae, for patients 18 years old and above.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of KETEK and PRECAUTIONS
other antibacterial drugs, KETEK should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are Prescribing KETEK in the absence of a proven or strongly suspected bacterial infection or a available, they should be considered in selecting or modifying antibacterial therapy. In the absence of prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of development of drug-resistant bacteria.
Telithromycin is principally excreted via the liver and kidney. Telithromycin may be administered withoutdosage adjustment in the presence of hepatic impairment. In the presence of severe renal impairment 3MDRSP, Multi-drug resistant Streptococcus pneumoniae includes isolates known as PRSP (penicillin- < 30 mL/min), a reduced dosage of KETEK is recommended. (See DOSAGE AND ADMIN-
resistant Streptococcus pneumoniae), and are isolates resistant to two or more of the following ISTRATION)
antibiotics: penicillin, 2nd generation cephalosporins, e.g., cefuroxime, macrolides, tetracyclines and Information for patients
A Medication Guide is provided to patients when Ketek is dispensed. Patients should be instructed to CONTRAINDICATIONS
read the MedGuide when Ketek is received. In addition, the complete text of the MedGuide is reprinted KETEK is contraindicated in patients with myasthenia gravis. Exacerbations of myasthenia gravis
have been reported in patients and sometimes occurred within a few hours of the first dose of The following information and instructions should be communicated to the patient.
telithromycin. Reports have included fatal and life-threatening acute respiratory failure with a rapid • KETEK may cause problems with vision particularly when looking quickly between objects close by and objects far away. These events include blurred vision, difficulty focusing, and objects KETEK is contraindicated in patients with previous history of hepatitis and/or jaundice associated with looking doubled. Most events were mild to moderate; however, severe cases have been reported.
the use of KETEK tablets, or any macrolide antibiotic.
Problems with vision were reported as having occurred after any dose during treatment, but most KETEK is contraindicated in patients with a history of hypersensitivity to telithromycin and/or any occurred following the first or second dose. These problems lasted several hours and in some components of KETEK tablets, or any macrolide antibiotic.
patients came back with the next dose. (See WARNINGS and ADVERSE REACTIONS.)
Concomitant administration of KETEK with cisapride or pimozide is contraindicated. (See CLINICAL
Patients should be advised that avoiding quick changes in viewing between objects in the distance and PHARMACOLOGY, Drug-drug Interactions and PRECAUTIONS.)
objects nearby may help to decrease the effects of these visual difficulties.
Concomitant administration of KETEK and colchicine is contraindicated in patients with renal or hepatic • Because of potential visual difficulties, loss of consciousness, confusion or hallucinations,
impairment. (See WARNINGS, Drug Interactions and PRECAUTIONS, Drug interactions.)
patients should attempt to minimize activities such as driving a motor vehicle, operating
WARNINGS
heavy machinery or engaging in other hazardous activities during treatment with KETEK.
Hepatotoxicity
Acute hepatic failure and severe liver injury, in some cases fatal, have been reported in patients
If patients experience visual difficulties, loss of consciousness / fainting, confusion or hallucination treated with KETEK. These hepatic reactions included fulminant hepatitis and hepatic necrosis
• patients should seek advice from their physician before taking another dose leading to liver transplant, and were observed during or immediately after treatment. In some
• patients should not drive a motor vehicle, operate heavy machinery, or engage in otherwise of these cases, liver injury progressed rapidly and occurred after administration of a few doses of KETEK. (See ADVERSE REACTIONS)
Physicians and patients should monitor for the appearance of signs or symptoms of hepatitis, such as • Ketek is contraindicated in patients with myasthenia gravis.
fatigue, malaise, anorexia, nausea, jaundice, bilirubinuria, acholic stools, liver tenderness or hepatome- (See CONTRAINDICATIONS)
galy. Patients with signs or symptoms of hepatitis must be advised to discontinue KETEK and
• of the possibility of liver injury, associated with KETEK, which in rare cases may be severe.
immediately seek medical evaluation, which should include liver function tests. (See ADVERSE
Patients developing signs or symptoms of liver injury should be instructed to discontinue
REACTIONS, PRECAUTIONS, Information to Patients.) If clinical hepatitis or transaminase eleva-
KETEK and seek medical attention immediately. Symptoms of liver injury may include nausea,
tions combined with other systemic symptoms occur, KETEK should be permanently discontinued.
fatigue, anorexia, jaundice, dark urine, light-colored stools, pruritus, or tender abdomen. Ketek Ketek must not be re-administered to patients with a previous history of hepatitis and/or jaundice must not be taken by patients with a previous history of hepatitis/jaundice associated with the use associated with the use of KETEK tablets, or any macrolide antibiotic. (See CONTRAINDICATIONS)
In addition, less severe hepatic dysfunction associated with increased liver enzymes, hepatitis and in (See CONTRAINDICATIONS and WARNINGS)
some cases jaundice was reported with the use of KETEK. These events associated with less severe • antibacterial drugs including KETEK should only be used to treat bacterial infections. They do not forms of liver toxicity were reversible.
treat viral infections (e.g., the common cold). When KETEK is prescribed to treat a bacterial QTc prolongation
infection, patients should be told that although it is common to feel better early in the course of Telithromycin has the potential to prolong the QTc interval of the electrocardiogram in some patients.
therapy, the medication should be taken exactly as directed. Skipping doses or not completing QTc prolongation may lead to an increased risk for ventricular arrhythmias, including torsades de the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) pointes. Thus, telithromycin should be avoided in patients with congenital prolongation of the QTc increase the likelihood that bacteria will develop resistance and will not be treatable by KETEK interval, and in patients with ongoing proarrhythmic conditions such as uncorrected hypokalemia or or other antibacterial drugs in the future.
hypomagnesemia, clinically significant bradycardia, and in patients receiving Class IA (e.g., quinidine • KETEK has the potential to produce changes in the electrocardiogram (QTc interval prolongation) and procainamide) or Class III (e.g., dofetilide) antiarrhythmic agents.
and that they should report any fainting occurring during drug treatment.
Cases of torsades de pointes have been reported post-marketing with KETEK. In clinical trials, no cardiovascular morbidity or mortality attributable to QTc prolongation occurred with telithromycin KETEK should be avoided in patients receiving Class 1A (e.g., quinidine, procainamide) or Class treatment in 4780 patients in clinical trials, including 204 patients having a prolonged QTc at baseline.
III (e.g., dofetilide) antiarrhythmic agents.
Visual disturbances*
• to inform their physician of any personal or family history of QTc prolongation or proarrhythmic KETEK may cause visual disturbances particularly in slowing the ability to accommodate and
conditions such as uncorrected hypokalemia, or clinically significant bradycardia.
the ability to release accommodation. Visual disturbances included blurred vision, difficulty focusing,
• diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is and diplopia. Most events were mild to moderate; however, severe cases have been reported.
discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and Loss of Consciousness*
bloody stools (with or without stomach cramps and fever) even as late as two or more months There have been post-marketing adverse event reports of transient loss of consciousness
after having taken the last dose of the antibiotic. If this occurs, patients should contact their including some cases associated with vagal syndrome.
physician as soon as possible.
*Because of potential visual difficulties or loss of consciousness, patients should attempt to
• simvastatin, lovastatin, or atorvastatin should be avoided in patients receiving KETEK. If KETEK minimize activities such as driving a motor vehicle, operating heavy machinery or engaging in
is prescribed, therapy with simvastatin, lovastatin, or atorvastatin should be stopped during the other hazardous activities during treatment with KETEK. If patients experience visual disorders
course of treatment. (See CLINICAL PHARMACOLOGY, Drug-drug interactions)
or loss of consciousness while taking KETEK, patients should not drive a motor vehicle, operate
• colchicine should be avoided in patients receiving KETEK. If KETEK is prescribed in patients with heavy machinery or engage in other hazardous activities.
normal kidney and liver function, the dose is colchicine should be reduced. Concomitant treatment (See PRECAUTIONS, Information for Patients)
with KETEK and colchicine is contraindicated in patients with kidney or liver impairment. (See Drug Interactions
CONTRAINDICATIONS and WARNINGS, Drug interactions.)
Serious adverse reactions have been reported in patients taking KETEK concomitantly with CYP 3A4 • KETEK tablets can be taken with or without food.
substrates. These include colchicine toxicity with colchicine; rhabdomyolysis with simvastatin, lovas- • to inform their physician of any other medications taken concurrently with KETEK, including tatin, and atorvastatin; and hypotension with calcium channel blockers metabolized by CYP 3A4 (e.g., over-the-counter medications and dietary supplements.
verapamil, amlodipine, diltiazem). (See PRECAUTIONS, Drug interactions.)
Drug interactions
Life-threatening and fatal drug interactions have been reported in patients treated with colchicine and Telithromycin is a strong inhibitor of the cytochrome P450 3A4 system. Co-administration of KETEK strong CYP 3A4 inhibitors. Telithromycin is a strong CYP 3A4 inhibitor and this interaction may occur tablets and a drug primarily metabolized by the cytochrome P450 3A4 enzyme system may result in while using both drugs at their recommended doses. If co-administration of telithromycin and colchicine increased plasma concentration of the drug co-administered with telithromycin that could increase or is necessary in patients with normal renal and hepatic function, the dose of colchicine should be prolong both the therapeutic and adverse effects. Therefore, appropriate dosage adjustments may be reduced. Patients should be monitored for clinical symptoms of colchicine toxicity. Concomitant necessary for the drug co-administered with telithromycin.
administration of KETEK and colchicine is contraindicated in patients with renal or hepatic impairment.
(See CONTRAINDICATIONS and PRECAUTIONS, Drug interactions.)
The use of KETEK is contraindicated with cisapride. (See CONTRAINDICATIONS and CLINICAL
Pseudomembranous colitis
PHARMACOLOGY, Drug-drug interactions)
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial The use of KETEK is contraindicated with pimozide. Although there are no studies looking at the agents, including KETEK, and may range in severity from mild diarrhea to fatal colitis. Treatment with interaction between KETEK and pimozide, there is a potential risk of increased pimozide plasma levels antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
by inhibition of CYP 3A4 pathways by KETEK as with macrolides. (See CONTRAINDICATIONS)
C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing In a pharmacokinetic study, simvastatin levels were increased due to CYP 3A4 inhibition by strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to telithromycin. (See CLINICAL PHARMACOLOGY, Drug-drug interactions) Similarly, an interaction
antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present may occur with lovastatin or atorvastatin but not with statins which are not metabolized by CYP3A4.
with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been High levels of HMG-CoA reductase inhibitors increase the risk of myopathy and rhabdomyolysis. Use reported to occur over two months after the administration of antibacterial agents.
of simvastatin, lovastatin, or atorvastatin concomitantly with KETEK should be avoided. If KETEK is If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need prescribed, therapy with simvastatin, lovastatin, or atorvastatin should be suspended during the course to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic of treatment. Patients concomitantly treated with statins should be carefully monitored for signs and treatment of C difficile, and surgical evaluation should be instituted as clinically indicated.
symptoms of myopathy and rhabdomyolysis.
Colchicine is a substrate for both CYP 3A4 and the efflux transporter, P-glycoprotein (P-gp), and a significant increase in colchicine plasma concentration is anticipated when co-administered with strong
CYP 3A4 inhibitors such as telithromycin. (See CONTRAINDICATIONS and WARNINGS, Drug
All and Possibly Related Treatment-Emergent Adverse Events Reported in Controlled
Phase III Clinical Studies (Percent Incidence)
interactions).
Monitoring of digoxin side effects or serum levels should be considered during concomitant adminis-
Adverse Event*
All TEAEs
Possibly-Related TEAEs
tration of digoxin and KETEK. (See CLINICAL PHARMACOLOGY, Drug-drug interactions.)
Comparator†
Comparator†
Hypotension, bradyarrhythmia and loss of consciousness have been observed in patients receiving concomitant treatment with calcium channel blockers that are substrates of CYP 3A4 (e.g., verapamil,amlodipine, diltiazem).
Patients should be monitored with concomitant administration of midazolam and dosage adjustment of midazolam should be considered if necessary. Precaution should be used with other benzodiazepines,which are metabolized by CYP 3A4 and undergo a high first-pass effect (e.g., triazolam). (See CLINICAL PHARMACOLOGY, Drug-drug interactions.)
Concomitant treatment of KETEK with rifampin, a CYP 3A4 inducer, should be avoided. Concomitantadministration of other CYP 3A4 inducers such as phenytoin, carbamazepine, or phenobarbital is likely to result in subtherapeutic levels of telithromycin and loss of effect. (See CLINICAL PHARMACOLOGY,
Other drug interactions.)
In patients treated with metoprolol for heart failure, the increased exposure to metoprolol, a CYP 2D6
substrate, may be of clinical importance. Therefore, co-administration of KETEK and metoprolol in *Based on a frequency of all and possibly related treatment-emergent adverse events of ≥ 2% in patients with heart failure should be considered with caution. (See CLINICAL PHARMACOLOGY,
Drug-drug interactions.)
†Includes comparators from all controlled Phase III studies.
Spontaneous post-marketing reports suggest that administration of KETEK and oral anticoagulantsconcomitantly may potentiate the effects of the oral anticoagulants. Consideration should be given to The following events judged by investigators to be at least possibly drug related were observed monitoring prothrombin times/INR while patients are receiving KETEK and oral anticoagulants infrequently (≥ 0.2% and < 2%), in KETEK-treated patients in the controlled Phase III studies.
Gastrointestinal system: abdominal distension, dyspepsia, gastrointestinal upset, flatulence, consti-
No specific drug interaction studies have been performed to evaluate the following potential drug-drug pation, gastroenteritis, gastritis, anorexia, oral candidiasis, glossitis, stomatitis, watery stools.
interactions with KETEK. However, these drug interactions have been observed with macrolide Liver and biliary system: abnormal liver function tests: increased transaminases, increased liver
enzymes (e.g., ALT, AST) were usually asymptomatic and reversible. ALT elevations above 3 times theupper limit of normal were observed in 1.6%, and 1.7% of patients treated with KETEK and Drugs metabolized by the cytochrome P450 system such as carbamazepine, cyclosporine, tacrolimus, comparators, respectively. Hepatitis, with or without jaundice, occurred in 0.07% of patients treated with sirolimus, hexobarbital, and phenytoin: elevation of serum levels of these drugs may be observed when KETEK, and was reversible. (See PRECAUTIONS, General.)
co-administered with telithromycin. As a result, increases or prolongation of the therapeutic and/or Nervous system: dry mouth, somnolence, insomnia, vertigo, increased sweating
adverse effects of the concomitant drug may be observed.
Body as a whole: abdominal pain, upper abdominal pain, fatigue
Ergot alkaloid derivatives (such as ergotamine or dihydroergotamine): acute ergot toxicity characterized Special senses: Visual adverse events most often included blurred vision, diplopia, or difficulty
by severe peripheral vasospasm and dysesthesia has been reported when macrolide antibiotics were focusing. Most events were mild to moderate; however, severe cases have been reported. Some co-administered. Without further data, the co-administration of KETEK and these drugs is not patients discontinued therapy due to these adverse events. Visual adverse events were reported as having occurred after any dose during treatment, but most visual adverse events (65%) occurred Laboratory test interactions
following the first or second dose. Visual events lasted several hours and recurred upon subsequent There are no reported laboratory test interactions.
dosing in some patients. For patients who continued treatment, some resolved on therapy while others Carcinogenesis, mutagenesis, impairment of fertility
continued to have symptoms until they completed the full course of treatment. (See WARNINGS and
PRECAUTIONS, Information for patients.)
Long-term studies in animals to determine the carcinogenic potential of KETEK have not been Females and patients under 40 years old experienced a higher incidence of telithromycin-associated visual adverse events. (See CLINICAL STUDIES.)
Telithromycin showed no evidence of genotoxicity in four tests: gene mutation in bacterial cells, gene Urogenital system: vaginal candidiasis, vaginitis, vaginosis fungal
mutation in mammalian cells, chromosome aberration in human lymphocytes, and the micronucleus Skin: rash
Hematologic: increased platelet count
No evidence of impaired fertility in the rat was observed at doses estimated to be 0.61 times the human Other possibly related clinically-relevant events occurring in Ͻ0.2% of patients treated with
daily dose on a mg/m2 basis. At doses of 1.8–3.6 times the human daily dose, at which signs of parental KETEK from the controlled Phase III studies included: anxiety, bradycardia, eczema, elevated blood
toxicity were observed, moderate reductions in fertility indices were noted in male and female animals bilirubin, erythema multiforme, flushing, hypotension, increased blood alkaline phosphatase, increased eosinophil count, paresthesia, pruritus, urticaria.
Pregnancy
Post-Marketing Adverse Event Reports
In addition to adverse events reported from clinical trials, the following events have been reported from
worldwide post-marketing experience with KETEK.
Allergic: face edema, rare reports of severe allergic (hypersensitivity) reactions, including angioedema Telithromycin was not teratogenic in the rat or rabbit. Reproduction studies have been performed in rats and rabbits, with effect on pre-post natal development studied in the rat. At doses estimated to be 1.8 Cardiovascular: atrial arrhythmias, palpitations times (900 mg/m2) and 0.49 times (240 mg/m2) the daily human dose of 800 mg (492 mg/m2) in the rat and rabbit, respectively, no evidence of fetal terata was found. At doses higher than the 900 mg/m2 Liver and biliary system: Hepatic dysfunction has been reported.
and 240 mg/m2 in rats and rabbits, respectively, maternal toxicity may have resulted in delayed fetal Severe and in some cases fatal hepatotoxicity, including fulminant hepatitis, hepatic necrosis and maturation. No adverse effects on prenatal and postnatal development of rat pups were observed at hepatic failure have been reported in patients treated with KETEK. These hepatic reactions were 1.5 times (750 mg/m2/d) the daily human dose.
observed during or immediately after treatment. In some of these cases, liver injury progressed rapidly There are no adequate and well-controlled studies in pregnant women. Telithromycin should be used and occurred after administration of only a few doses of KETEK. (See CONTRAINDICATIONS and
WARNINGS.) Severe reactions, in some but not all cases, have been associated with serious
during pregnancy only if the potential benefit justifies the potential risk to the fetus.
underlying diseases or concomitant medications.
Nursing mothers
Data from post-marketing reports and clinical trials show that most cases of hepatic dysfunction were Telithromycin is excreted in breast milk of rats. Telithromycin may also be excreted in human milk.
mild to moderate. (See PRECAUTIONS, General.)
Because many drugs are excreted in human milk, caution should be exercised when KETEK is Musculoskeletal: muscle cramps, rare reports of exacerbation of myasthenia gravis. (See CONTRAIN-
DICATIONS.) arthralgia, myalgia
Pediatric use
Nervous system: loss of consciousness, in some cases associated with vagal syndrome.
The safety and effectiveness of KETEK in pediatric patients has not been established.
Psychiatric disorders: confusion, hallucinations (mostly visual) Geriatric use
Special senses: taste/smell perversion and/or loss In all Phase III clinical trials (n=4,780), KETEK was administered to 694 patients who were 65 years OVERDOSAGE
and older, including 231 patients who were 75 years and older. Efficacy and safety in elderly patients In the event of acute overdosage, the stomach should be emptied by gastric lavage. The patient should ≥ 65 years were generally similar to that observed in younger patients; however, greater sensitivity of be carefully monitored (e.g., ECG, electrolytes) and given symptomatic and supportive treatment.
some older individuals cannot be ruled out. No dosage adjustment is required based on age alone.
Adequate hydration should be maintained. The effectiveness of hemodialysis in an overdose situation (See CLINICAL PHARMACOLOGY, Special populations, Geriatric and DOSAGE AND ADMINIS-
TRATION.)
DOSAGE AND ADMINISTRATION
ADVERSE REACTIONS
The dose of KETEK tablets is 800 mg (2 tablets of 400 mg) taken orally once every 24 hours, for 7–10 In Phase III clinical trials, 4,780 patients (n=2702 in controlled trials) received daily oral doses of KETEK days. KETEK tablets can be administered with or without food.
800 mg once daily for 5 days or 7 to 10 days. Most adverse events were mild to moderate in severity.
KETEK may be administered without dosage adjustment in the presence of hepatic impairment.
In the combined Phase III studies, discontinuation due to treatment-emergent adverse events occurred In the presence of severe renal impairment (CL < 30 mL/min), including patients who need dialysis, in 4.4% of KETEK-treated patients and 4.3% of combined comparator-treated patients. Most the dose should be reduced to KETEK 600 mg once daily. In patients undergoing hemodialysis, KETEK discontinuations in the KETEK group were due to treatment-emergent adverse events in the should be given after the dialysis session on dialysis days. (See CLINICAL PHARMACOLOGY, Renal
gastrointestinal body system, primarily diarrhea (0.9% for KETEK vs. 0.7% for comparators), nausea insufficiency.)
(0.7% for KETEK vs. 0.5% for comparators).
In the presence of severe renal impairment (CL < 30 mL/min), with coexisting hepatic impairment, All and possibly related treatment-emergent adverse events (TEAEs) occurring in controlled clinical the dose should be reduced to KETEK 400 mg once daily. (See CLINICAL PHARMACOLOGY,
studies in ≥ 2.0% of all patients are included below: Multiple insufficiency.)
HOW SUPPLIED
KETEK® 400 mg tablets are supplied as light-orange, oval, film-coated tablets, imprinted ″H3647″ on
Visual Adverse Events
one side and ″400″ on the other side. These are packaged in bottles and blister cards (Ketek Pak™ Table 9 provides the incidence of all treatment-emergent visual adverse events in controlled Phase III studies by age and gender. The group with the highest incidence was females under the age of 40, while males over the age of 40 had rates of visual adverse events similar to comparator-treated Ketek Pak™, 10-tablet cards (2 tablets per blister cavity) Table 9. Incidence of All Treatment-Emergent Visual Adverse Events in Controlled Phase
KETEK® 300 mg tablets are supplied as light-orange, oval, film-coated tablets, imprinted ″38AV″ on III Studies
one side and blank on the other side. These are packaged in bottles as follows:Bottles of 20 Gender/Age
Telithromycin
Comparators*
Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) [see USP Controlled RoomTemperature].
CLINICAL STUDIES
Community-acquired pneumonia (CAP)
KETEK was studied in four randomized, double-blind, controlled studies and four open-label studies for the treatment of community-acquired pneumonia. Patients with mild to moderate CAP who wereconsidered appropriate for oral outpatient treatment were enrolled in these trials. Patients with severe pneumonia were excluded based on any one of the following: ICU admission, need for parenteral antibiotics, respiratory rate > 30/minute, hypotension, altered mental status, < 90% oxygen saturationby pulse oximetry, or white blood cell count < 4000/mm3. Total number of clinically evaluable patients in the telithromycin group included 2016 patients.
Table 6. CAP: Clinical cure rate at post-therapy follow-up (17–24 days)
Patients (n)
Clinical cure rate
Controlled Studies
Comparator
Comparator
ANIMAL PHARMACOLOGY
Repeated dose toxicity studies of 1, 3, and 6 months’ 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. There was evidence of reversibility after cessation of treatment.
Plasma exposures based on free fraction of drug at the no observed adverse effect levels ranged from1 to 10 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 beenobserved with the administration of telithromycin in rats at repeated doses of 900 mg/m2/day (1.8× the human dose) or more for 1 month, and 300 mg/m2/day (0.61× the human dose) or more for 3–6 months. Similarly, phospholipidosis has been observed in dogs with telithromycin at repeated doses of 3000 mg/m2/day (6.1× the human dose) or more for 1 month and 1000 mg/m2/day (2.0× the human *This study was stopped prematurely after trovafloxacin was restricted for use in hospitalized patients dose) or more for 3 months. The significance of these findings for humans is unknown.
Pharmacology/toxicology studies showed an effect both in prolonging QTc interval in dogs in vivo andin vitro action potential duration (APD) in rabbit Purkinje fibers. These effects were observed at Clinical cure rates by pathogen from the four CAP controlled clinical trials in microbiologically evaluable concentrations of free drug at least 8.8 (in dogs) times those circulating in clinical use. In vitro patients given KETEK for 7–10 days or a comparator are displayed in Table 7.
electrophysiological studies (hERG assays) suggested an inhibition of the rapid activating component Table 7. CAP: Clinical cure rate by pathogen at post-therapy follow-up (17–24 days)
of the delayed rectifier potassium current (I ) as an underlying mechanism.
Pathogen
Comparator
Bridgewater, NJ 08807 2010 sanofi-aventis U.S. LLC REFERENCES
1. National Committee for Clinical Laboratory Standards. Methods for Dilution Antimicrobial Sus- ceptibility Tests for Bacteria That Grow Aerobically – Sixth Edition; Approved Standard, NCCLS Document M7-A6, Vol. 23, No. 2, NCCLS, Wayne, PA, January, 2003.
2. National Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial Clinical cure rates for patients with CAP due to Streptococcus pneumoniae were determined from Disk Susceptibility Tests - Eighth Edition; Approved Standard, NCCLS Document M2-A8, Vol. 23, patients in controlled and uncontrolled trials. Of 333 evaluable patients with CAP due to Streptococcus No. 1, NCCLS, Wayne, PA, January, 2003.
pneumoniae, 312 (93.7%) achieved clinical success. Only patients considered appropriate for oral 3. National Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial outpatient therapy were included in these trials. More severely ill patients were not enrolled. Blood Susceptibility Testing: Twelfth Informational Supplement; Approved Standard, NCCLS Document cultures were obtained in all patients participating in the clinical trials of mild to moderate community- M2-A8 and M7-A6, Vol. 23, No. 1, NCCLS, Wayne, PA, January, 2004.
acquired pneumonia. In a limited number of outpatients with incidental pneumococcal bacteremiatreated with KETEK, a clinical cure rate of 88% (67/76) has been observed. KETEK is not indicated Medication Guide
for the treatment of severe community-acquired pneumonia or suspected pneumococcal bacteremia.
Clinical cure rates for patients with CAP due to multi-drug resistant Streptococcus pneumoniae KETEK® (KEE tek)
(MDRSP*) were determined from patients in controlled and uncontrolled trials. Of 36 evaluable patients (telithromycin)
with CAP due to MDRSP, 33 (91.7%) achieved clinical success.
*MDRSP: Multi-drug resistant Streptococcus pneumoniae includes isolates known as PRSP (penicillin- Read the Medication Guide that comes with KETEK before you start resistant Streptococcus pneumoniae), and are isolates resistant to two or more of the followingantibiotics: penicillin, 2nd generation cephalosporins, e.g., cefuroxime, macrolides, tetracyclines and taking it and each time you get a new prescription. There may be new information. Talk to your doctor if you have any questions about KETEK.
Table 8. Clinical cure rate for 36 evaluable patients with MDRSP treated with KETEK in
This Medication Guide does not take the place of talking with your doctor studies of community-acquired pneumonia
about your medical condition or treatment.
Screening Susceptibility
Clinical Success in Evaluable MDRSP
What is the most important information I should know about
Patients
KETEK?
Do not take KETEK if you have myasthenia gravis (a rare disease
which causes muscle weakness). Worsening of myasthenia gravis
symptoms including life-threatening breathing problems have hap-
pened in people with myasthenia gravis after taking KETEK, in
some cases leading to death.
KETEK can cause other serious side effects, including:
1. Severe liver damage (hepatotoxicity). Severe liver damage, in
some cases leading to a liver transplant or death has happened in *n = the number of patients successfully treated; N = the number with resistance to the listed drug of people treated with KETEK. Severe liver damage has happened the 36 evaluable patients with CAP due to MDRSP.
during treatment, even after a few doses, or right after treatment †Includes isolates tested for resistance to either tetracycline or doxycycline.
with KETEK has ended.
Stop taking KETEK and call your doctor right away if you have
KETEK and other medicines may affect or interact with each other, signs of liver problems. Do not take another dose of KETEK unless
sometimes causing serious side effects.
your doctor tells you to.
Signs of liver problems include:
• colchicine (Colcrys®) while you take KETEK• certain medicines called calcium channel blockers, such as: vera- pamil (Calan®), amlodipine (Norvasc®), diltiazem (Cardizem®), or other medications containing these products while you take KETEK • cholesterol lowering medicines; you should not take these choles- terol lowering medicines while taking KETEK: Do not take KETEK if you have ever had liver problems while taking KETEK or macrolide antibiotics. Macrolide antibiotics include: Ask your doctor if you are not sure if the medicine you take is included Know the medicines you take. Keep a list of your medicines with you to 2. Vision problems. KETEK may cause you to have blurred vision,
Do not take other medicines with KETEK without first checking with your trouble focusing your eyes, and double vision. You may especially doctor. Your doctor will tell you if you can take other medicines while notice vision problems if you look quickly between objects close to How should I take KETEK?
3. Fainting. KETEK may cause you to faint, especially if you also
• Take KETEK exactly as your doctor tells you.
have nausea, vomiting, and lightheadedness.
• Skipping doses or not taking all of an antibiotic may: Do not drive, operate heavy machinery, or do other dangerous
activities while taking KETEK if you have:
„ increase the chance that the bacteria will develop resistance to • If you have kidney disease, your doctor may prescribe a lower dose • seeing things that are not there (visual hallucinations) • Take KETEK with or without food.
Stop taking KETEK and call your doctor right away if you have any
of these symptoms. Do not take another dose of KETEK unless
• If you take too much KETEK, call your doctor, or go to the nearest your doctor tells you to.
4. Low blood pressure, slow heart rate, and fainting. Ketek may
What are the possible side effects of KETEK?
cause you to have low blood pressure, a slow heart rate, and fainting See ″What is the most important information I should know about when you also take certain medicines called calcium channel blockers.
KETEK may cause serious side effects, including: • Pseudomembranous colitis (an intestine infection). Pseudomem-
branous colitis can happen with most antibiotics, including KETEK.
Call your doctor if you get watery diarrhea, diarrhea that does not • or other medications containing these products.
go away, or bloody stools. You may also have stomach cramps and See ЉWhat are the possible side effects of KETEK?Љ
a fever. Pseudomembranous colitis can happen up to 2 months after What is KETEK?
KETEK is an antibiotic. KETEK is used to treat adults 18 years of age The most common side effects of KETEK are: and older with a lung infection called ″community acquired pneumonia″ that is caused by certain germs called bacteria.
• KETEK is not for other types of infections.
• KETEK does not kill viruses like the common cold.
Who should not take KETEK?
Tell your doctor if you have any side effect that bothers you or that does • have had liver problems while taking KETEK or macrolide antibi- These are not all of the possible side effects of KETEK. For more • have ever had an allergic reaction to telithromycin in KETEK or information ask your doctor or pharmacist.
Call your doctor for medical advice about side effects. You may report • take cisapride (Propulsid®) or pimozide (Orap®).
side effects to FDA at 1-800-FDA-1088.
• take colchicine (Colcrys®) and have kidney or liver problems.
You may also report side effects to sanofi-aventis U.S. at 1-800-633- Talk to your doctor before taking KETEK if you have any of the How should I store KETEK?
What should I tell my doctor before taking KETEK?
• Store KETEK tablets at room temperature, between 59°F to 86°F Before taking KETEK, tell your doctor if you:
• Keep KETEK and all medicines out of the reach of children.
• have a heart problem called ″QTc prolongation″ or have a family General Information about KETEK
• Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use KETEK for a condition for • are pregnant or plan to become pregnant. It is not known if KETEK which it was not prescribed. Do not share KETEK with other people, will harm your unborn baby. Talk to your doctor if you are pregnant even if they have the same symptoms that you have. It may harm • are breast-feeding or plan to breast-feed. It is not known if KETEK This Medication Guide summarizes the most important information passes into your breast milk. Talk to your doctor about the best way about KETEK. If you would like more information, talk with your doctor.
to feed your baby if you take KETEK.
You can ask your doctor or pharmacist for information about KETEK that Tell your doctor about all of the medicines you take, including prescrip- was written for healthcare professionals. This information is also avail- tion and nonprescription medicines, vitamins, and herbal supplements.
able on the KETEK website at www.KETEK.com or call 1-800-446-6267.
What are the ingredients in KETEK?
Active Ingredient: telithromycin
Inactive Ingredients: croscarmellose sodium, hypromellose, magne-
sium stearate, microcrystalline cellulose, polyethylene glycol, povidone,
red ferric oxide, talc, titanium dioxide, and yellow ferric oxide
This Medication Guide has been approved by the U.S. Food and DrugAdministration.
sanofi-aventis U.S. LLCBridgewater, NJ 08807 BIAXIN® (clarithromycin) is a registered trademark of Abbott Laborato-ries.
ZITHROMAX® (azithromycin) is a registered trademark of Pfizer Inc.
DYNABAC® (dirithromycin) is a registered trademark of Eli Lilly andCompany.
PROPULSID® (cisapride) is a registered trademark of Johnson &Johnson.
ORAP® (pimozide) is a registered trademark of Teva PharmaceuticalsUSA, Inc.
LIPITOR® (atorvastatin) is a registered trademark of Pfizer Inc.
ZOCOR® (simvastatin) is a registered trademark of Merck & Co Inc.
VYTORIN® (simvastatin and ezetimibe) is a registered trademark ofMerck/Schering Plough Pharmaceuticals.
MEVACOR® (lovastatin) is a registered trademark of Merck & Co Inc.

Source: http://products.sanofi.us/ketek/ketek.pdf