Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/1044
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|---|---|---|---|
| dailymed-drugs:1044 | rdf:type | http://www4.wiwiss.fu-berli... | lld:dailymed |
| dailymed-drugs:1044 | rdf:type | dailymed-instance:drugs | lld:dailymed |
| dailymed-drugs:1044 | rdfs:label | Ketek (Tablet, Film Coated) | lld:dailymed |
| dailymed-drugs:1044 | dailymed-instance:dosage | The dose of KETEK tablets is 800 mg (2 tablets of 400 mg) taken orally once every 24 hours, for 7���10 days. KETEK tablets can be administered with or without food. KETEK may be administered without dosage adjustment in the presence of hepatic impairment. In the presence of severe renal impairment (CL<30 mL/min), including patients who need dialysis, the dose should be reduced to KETEK 600 mg once daily. In patients undergoing hemodialysis, KETEK should be given after the dialysis session on dialysis days. (See CLINICAL PHARMACOLOGY, Renal insufficiency.) In the presence of severe renal impairment (CL<30 mL/min), with coexisting hepatic impairment, the dose should be reduced to KETEK 400 mg once daily. | lld:dailymed |
| dailymed-drugs:1044 | dailymed-instance:descripti... | 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-��-L-ribo-hexopyranosyl)oxy]-11,12-dideoxy-6-O-methyl-3-oxo-12,11-[oxycarbonyl[[4-[4-(3-pyridinyl)-1H-imidazol-1-yl]butyl]imino]]-. Telithromycin, a ketolide, differs chemically from the macrolide group of antibacterials by the lack of��-L-cladinose at position 3 of the erythronolide A ring, resulting in a 3-keto function. It is further characterized by a C11-12 carbamate substituted by an imidazolyl and pyridyl ring through a butyl chain. Its empirical formula is CHNOand its molecular weight is 812.03. Telithromycin is a white to off-white crystalline powder. The following represents the chemical structure of telithromycin. KETEK tablets are available as light-orange, oval, film-coated tablets, each containing 400 mg or 300 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. | lld:dailymed |
| dailymed-drugs:1044 | dailymed-instance:clinicalP... | Pharmacokinetics:<br/>Absorption: Following oral administration, telithromycin reached maximal concentration at about 1 hour (0.5���4 hours). It has an absolute bioavailability of 57% in both young and elderly subjects. 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��g/mL are attained at a median of 1 hour after an 800-mg oral dose. Steady-state plasma concentrations are reached within 2 to 3 days of once daily dosing with telithromycin 800 mg. Following oral dosing, the mean terminal elimination half-life of telithromycin is 10 hours. The pharmacokinetics of telithromycin after administration of single and multiple (7 days) once daily 800-mg doses to healthy adult subjects are shown in Table 1. In a patient population, mean peak and trough plasma concentrations were 2.9��g/mL (��1.55), (n=219) and 0.2��g/mL (��0.22), (n=204), respectively, after 3 to 5 days of KETEK 800 mg once daily.<br/>Distribution: Total in vitro protein binding is approximately 60% to 70% and is primarily due to human serum albumin. Protein binding is not modified in elderly subjects and in patients with hepatic impairment. The volume of distribution of telithromycin after intravenous infusion is 2.9 L/kg. 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. Telithromycin concentration in white blood cells exceeds the concentration in plasma and is eliminated more slowly from white blood cells than from plasma. Mean white blood cell concentrations of telithromycin peaked at 72.1��g/mL at 6 hours, and remained at 14.1��g/mL 24 hours after 5 days of repeated dosing of 600 mg once daily. After 10 days, repeated dosing of 600 mg once daily, white blood cell concentrations remained at 8.9��g/mL 48 hours after the last dose.<br/>Metabolism: In total, metabolism accounts for approximately 70% of the dose. In plasma, the main circulating compound after administration of an 800-mg radiolabeled 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.<br/>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.<br/>Special populations:<br/>Gender: There was no significant difference between males and females in mean AUC, C, and elimination half-life in two studies; one in 18 healthy young volunteers (18 to 40 years of age) and the other in 14 healthy elderly volunteers (65 to 92 years of age), given single and multiple once daily doses of 800 mg of KETEK.<br/>Hepatic insufficiency: 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 C, AUC and tof 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 pathway may compensate for some of the decrease in metabolic clearance. No dosage adjustment is recommended due to hepatic impairment.<br/>Renal insufficiency: In a multiple-dose study, 36 subjects with varying degrees of renal impairment received 400 mg, 600 mg, or 800 mg KETEK once daily for 5 days. There was a 1.4-fold increase in Cand a 1.9-fold increase in AUC (0���24)at 800 mg multiple doses in the severely renally impaired group (CL<30 mL/min) compared to healthy volunteers. Renal excretion may serve as a compensatory elimination pathway for telithromycin in situations where metabolic clearance is impaired. Patients with severe renal impairment are prone to conditions that may impair their metabolic clearance. Therefore, in the presence of severe renal impairment (CL<30 mL/min), a reduced dosage of KETEK is recommended. In a single-dose study in patients with end-stage renal failure on hemodialysis (n=10), the mean Cand AUC values were similar to normal healthy subjects when KETEK was administered 2 hours post-dialysis. However, the effect of dialysis on removing telithromycin from the body has not been studied.<br/>Multiple insufficiency: 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 of severe renal impairment (CL<30 mL/min), with coexisting hepatic impairment, a reduced dosage of KETEK is recommended.<br/>Geriatric: 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 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.<br/>Drug-drug interactions: Studies were performed to evaluate the effect of CYP 3A4 inhibitors on telithromycin and the effect of telithromycin on drugs that are substrates of CYP 3A4 and CYP 2D6. In addition, drug interaction studies were conducted with several other concomitantly prescribed drugs.<br/>CYP 3A4 inhibitors:<br/>CYP 3A4 substrates:<br/>CYP 2D6 substrates:<br/>Other drug interactions:<br/>Microbiology: Telithromycin belongs to the ketolide class of antibacterials and is structurally related to the macrolide family of antibiotics. Telithromycin concentrates in phagocytes where it exhibits activity against intracellular respiratory pathogens. In vitro, telithromycin has been shown to demonstrate concentration-dependent bactericidal activity against isolates of Streptococcus pneumoniae (including multi-drug resistant isolates [MDRSP*]). *MDRSP=Multi-drug resistant Streptococcus pneumoniae includes isolates known as PRSP (penicillin-resistant Streptococcus pneumoniae), and are isolates resistant to two or more of the following antimicrobials: penicillin, 2generation cephalosporins (e.g., cefuroxime), macrolides, tetracyclines, and trimethoprim/sulfamethoxazole.<br/>Mechanism of action: Telithromycin blocks protein synthesis by binding to domains II and V of 23S rRNA of the 50S ribosomal subunit. By binding at domain II, telithromycin retains activity against gram-positive cocci (e.g., Streptococcus pneumoniae) in the presence of resistance mediated by methylases (erm genes) that alter the domain V binding site of telithromycin. Telithromycin may also inhibit the assembly of nascent ribosomal units.<br/>Mechanism of resistance: 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 laboratory mutants is not known.<br/>Cross resistance: Telithromycin does not induce resistance through methylase gene expression in erythromycin-inducibly resistant bacteria, a function of its 3-keto moiety. Telithromycin has not been shown to induce resistance to itself.<br/>List of Microorganisms: Telithromycin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical settings as described in the INDICATIONS AND USAGE section. Aerobic gram-positive microorganisms *MDRSP=Multi-drug resistant Streptococcus pneumoniae includes isolates known as PRSP (penicillin-resistant S. pneumoniae), and are isolates resistant to two or more of the following antimicrobials: penicillin, 2generation cephalosporins (e.g., cefuroxime), macrolides, tetracyclines, and trimethoprim/sulfamethoxazole. Aerobic gram-negative microorganisms Other microorganisms The following in vitro data are available, but their clinical significance is unknown. At least 90% of the following microorganisms exhibit in vitro minimum inhibitory concentrations (MICs) less than or equal to the susceptible breakpoint for telithromycin. However, the safety and efficacy of telithromycin in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials. Aerobic gram-positive microorganisms Other microorganisms<br/>Susceptibility Test Methods: When available, the clinical microbiology laboratory should provide cumulative results of in vitro susceptibility test results for antimicrobial drugs used in local hospitals and practice areas to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting the most effective antimicrobial.<br/>INDICATIONS AND USAGE: KETEK tablets are indicated for the treatment of community-acquired pneumonia (of mild to moderate severity) due to Streptococcus pneumoniae, (including multi-drug resistant isolates [MDRSP*]), Haemophilus influenzae, Moraxella catarrhalis, Chlamydophila pneumoniae, or Mycoplasma pneumoniae, for patients 18 years old and above. *MDRSP, Multi-drug resistant Streptococcus pneumoniae includes isolates known as PRSP (penicillin-resistant Streptococcus pneumoniae), and are isolates resistant to two or more of the following antibiotics: penicillin, 2generation cephalosporins, e.g., cefuroxime, macrolides, tetracyclines and trimethoprim/sulfamethoxazole. 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 suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. | lld:dailymed |
| dailymed-drugs:1044 | dailymed-instance:activeIng... | dailymed-ingredient:telithr... | lld:dailymed |
| dailymed-drugs:1044 | dailymed-instance:supply | KETEK 400 mg tablets are supplied as light-orange, oval, film-coated tablets, imprinted "H3647" on one side and "400" on the other side. These are packaged in bottles and blister cards (Ketek Pak���and unit dose) as follows: Bottles of 60 (NDC 0088-2225-41) Ketek Pak���, 10-tablet cards (2 tablets per blister cavity) (NDC 0088-2225-07) Unit dose package of 100 (blister pack) (NDC 0088-2225-49) KETEK 300 mg tablets are supplied as light-orange, oval, film-coated tablets, imprinted "38AV" on one side and blank on the other side. These are packaged in bottles as follows: Bottles of 20 (NDC 0088-2223-20) Store at 25��C (77��F); excursions permitted to 15���30��C (59���86��F) [see USP Controlled Room Temperature]. | lld:dailymed |
| dailymed-drugs:1044 | dailymed-instance:genericDr... | http://www4.wiwiss.fu-berli... | lld:dailymed |
| dailymed-drugs:1044 | dailymed-instance:boxedWarn... | 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. | lld:dailymed |
| dailymed-drugs:1044 | dailymed-instance:activeMoi... | dailymed-ingredient:telithr... | lld:dailymed |
| dailymed-drugs:1044 | dailymed-instance:inactiveI... | dailymed-ingredient:magnesi... | lld:dailymed |
| dailymed-drugs:1044 | dailymed-instance:inactiveI... | dailymed-ingredient:microcr... | lld:dailymed |
| dailymed-drugs:1044 | dailymed-instance:inactiveI... | dailymed-ingredient:povidon... | lld:dailymed |
| dailymed-drugs:1044 | dailymed-instance:inactiveI... | dailymed-ingredient:hyprome... | lld:dailymed |
| dailymed-drugs:1044 | dailymed-instance:inactiveI... | dailymed-ingredient:titaniu... | lld:dailymed |
| dailymed-drugs:1044 | dailymed-instance:inactiveI... | dailymed-ingredient:talc | lld:dailymed |
| dailymed-drugs:1044 | dailymed-instance:inactiveI... | dailymed-ingredient:polyeth... | lld:dailymed |
| dailymed-drugs:1044 | dailymed-instance:inactiveI... | dailymed-ingredient:red_fer... | lld:dailymed |
| dailymed-drugs:1044 | dailymed-instance:inactiveI... | dailymed-ingredient:croscar... | lld:dailymed |
| dailymed-drugs:1044 | dailymed-instance:inactiveI... | dailymed-ingredient:yellow_... | lld:dailymed |
| dailymed-drugs:1044 | dailymed-instance:overdosag... | In the event of acute overdosage, the stomach should be emptied by gastric lavage. The patient should be carefully monitored (e.g., ECG, electrolytes) and given symptomatic and supportive treatment. Adequate hydration should be maintained. The effectiveness of hemodialysis in an overdose situation with KETEK is unknown. | lld:dailymed |
| dailymed-drugs:1044 | dailymed-instance:genericMe... | telithromycin | lld:dailymed |
| dailymed-drugs:1044 | dailymed-instance:fullName | Ketek (Tablet, Film Coated) | lld:dailymed |
| dailymed-drugs:1044 | dailymed-instance:adverseRe... | In Phase III clinical trials, 4,780 patients (n=2702 in controlled trials) received daily oral doses of KETEK 800 mg once daily for 5 days or 7 to 10 days. Most adverse events were mild to moderate in severity. In the combined Phase III studies, discontinuation due to treatment-emergent adverse events occurred in 4.4% of KETEK-treated patients and 4.3% of combined comparator-treated patients. Most discontinuations in the KETEK group were due to treatment-emergent adverse events in the gastrointestinal body system, primarily diarrhea (0.9% for KETEK vs. 0.7% for comparators), nausea (0.7% for KETEK vs. 0.5% for comparators). All and possibly related treatment-emergent adverse events (TEAEs) occurring in controlled clinical studies in���2.0% of all patients are included below: The following events judged by investigators to be at least possibly drug related were observed infrequently (���0.2% and<2%), in KETEK-treated patients in the controlled Phase III studies. Gastrointestinal system: abdominal distension, dyspepsia, gastrointestinal upset, flatulence, constipation, gastroenteritis, gastritis, anorexia, oral candidiasis, glossitis, stomatitis, watery stools. 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 the upper limit of normal were observed in 1.6%, and 1.7% of patients treated with KETEK and comparators, respectively. Hepatitis, with or without jaundice, occurred in 0.07% of patients treated with KETEK, and was reversible. (See PRECAUTIONS, General .) Nervous system: dry mouth, somnolence, insomnia, vertigo, increased sweating Body as a whole: abdominal pain, upper abdominal pain, fatigue Special senses: Visual adverse events most often included blurred vision, diplopia, or difficulty focusing. Most events were mild to moderate; however, severe cases have been reported. Some 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 following the first or second dose. Visual events lasted several hours and recurred upon subsequent dosing in some patients. For patients who continued treatment, some resolved on therapy while others continued to have symptoms until they completed the full course of treatment. (See WARNINGS and PRECAUTIONS, Information for patients.) Females and patients under 40 years old experienced a higher incidence of telithromycin-associated visual adverse events. Urogenital system: vaginal candidiasis, vaginitis, vaginosis fungal Skin: rash Hematologic: increased platelet count Other possibly related clinically-relevant events occurring in<0.2% of patients treated with KETEK from the controlled Phase III studies included: anxiety, bradycardia, eczema, elevated blood bilirubin, erythema multiforme, flushing, hypotension, increased blood alkaline phosphatase, increased eosinophil count, paresthesia, pruritus, urticaria.<br/>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 reactions, including angioedema and anaphylaxis. Cardiovascular: atrial arrhythmias, palpitations Gastrointestinal system: pancreatitis Liver and biliary system: Hepatic dysfunction has been reported. Severe and in some cases fatal hepatotoxicity, including fulminant hepatitis, hepatic necrosis and hepatic failure have been reported in patients treated with KETEK. These hepatic reactions were observed during or immediately after treatment. In some of these cases, liver injury progressed rapidly and occurred after administration of only a few doses of KETEK. . Severe reactions, in some but not all cases, have beenassociated with serious underlying diseases or concomitant medications. Data from post-marketing reports and clinical trials show that most cases of hepatic dysfunction were mild to moderate. Musculoskeletal: muscle cramps, rare reports of exacerbation of myasthenia gravis. Nervous system: loss of consciousness, in some cases associated with vagal syndrome. | lld:dailymed |
| dailymed-drugs:1044 | dailymed-instance:indicatio... | KETEK tablets are indicated for the treatment of community-acquired pneumonia (of mild to moderate severity) due to Streptococcus pneumoniae, (including multi-drug resistant isolates [MDRSP*]), Haemophilus influenzae, Moraxella catarrhalis, Chlamydophila pneumoniae, or Mycoplasma pneumoniae, for patients 18 years old and above. *MDRSP, Multi-drug resistant Streptococcus pneumoniae includes isolates known as PRSP (penicillin-resistant Streptococcus pneumoniae), and are isolates resistant to two or more of the following antibiotics: penicillin, 2generation cephalosporins, e.g., cefuroxime, macrolides, tetracyclines and trimethoprim/sulfamethoxazole. 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 suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. | lld:dailymed |
| dailymed-drugs:1044 | dailymed-instance:represent... | http://www4.wiwiss.fu-berli... | lld:dailymed |
| dailymed-drugs:1044 | dailymed-instance:routeOfAd... | http://www4.wiwiss.fu-berli... | lld:dailymed |
| dailymed-drugs:1044 | dailymed-instance:name | Ketek | lld:dailymed |
| http://www4.wiwiss.fu-berli... | dailymed-instance:producesD... | dailymed-drugs:1044 | lld:dailymed |