Telithromycin (1 brand name, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- KETEK
Boxed Warning
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 .)
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 [MDRSPMDRSP, 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, 2nd generation cephalosporins, e.g., cefuroxime, macrolides, tetracyclines and trimethoprim/sulfamethoxazole.]), Haemophilus influenzae, Moraxella catarrhalis, Chlamydophila pneumoniae, or Mycoplasma pneumoniae, for patients 18 years old and above. 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.
Dosage and Administration
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 (CLCR < 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 (CLCR < 30 mL/min), with coexisting hepatic impairment, the dose should be reduced to KETEK 400 mg once daily. (See CLINICAL PHARMACOLOGY, Multiple insufficiency .)
Contraindications
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 telithromycin. Reports have included fatal and life-threatening acute respiratory failure with a rapid onset and progression. KETEK is contraindicated in patients with previous history of hepatitis and/or jaundice associated with the use of KETEK tablets, or any macrolide antibiotic. KETEK is contraindicated in patients with a history of hypersensitivity to telithromycin and/or any components of KETEK tablets, or any macrolide antibiotic. Concomitant administration of KETEK with cisapride or pimozide is contraindicated. (See CLINICAL PHARMACOLOGY, Drug-drug Interactions and PRECAUTIONS .) Concomitant administration of KETEK and colchicine is contraindicated in patients with renal or hepatic impairment. (See WARNINGS, Drug Interactions and PRECAUTIONS, Drug interactions .)
Adverse Reactions
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: Table 5 All and Possibly Related Treatment-Emergent Adverse Events Reported in Controlled Phase III Clinical Studies (Percent Incidence) Adverse Event All TEAEs Possibly-Related TEAEs KETEKn= 2702 ComparatorIncludes comparators from all controlled Phase III studies. n= 2139 KETEKn= 2702 Comparator n= 2139 Diarrhea 10.8% 8.6% 10.0% 8.0% Nausea 7.9% 4.6% 7.0% 4.1% Headache 5.5% 5.8% 2.0% 2.5% Dizziness (excl. vertigo) 3.7% 2.7% 2.8% 1.5% Vomiting 2.9% 2.2% 2.4% 1.4% Loose Stools 2.3% 1.5% 2.1% 1.4% Dysgeusia 1.6% 3.6% 1.5% 3.6% 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 co
Drug Interactions
Telithromycin is a strong inhibitor of the cytochrome P450 3A4 system. Co-administration of KETEK tablets and a drug primarily metabolized by the cytochrome P450 3A4 enzyme system may result in increased plasma concentration of the drug co-administered with telithromycin that could increase or prolong both the therapeutic and adverse effects. Therefore, appropriate dosage adjustments may be necessary for the drug co-administered with telithromycin. The use of KETEK is contraindicated with cisapride. (See CONTRAINDICATIONS and CLINICAL PHARMACOLOGY, Drug-drug interactions ) The use of KETEK is contraindicated with pimozide. Although there are no studies looking at the interaction between KETEK and pimozide, there is a potential risk of increased pimozide plasma levels by inhibition of CYP 3A4 pathways by KETEK as with macrolides. (See CONTRAINDICATIONS ) In a pharmacokinetic study, simvastatin levels were increased due to CYP 3A4 inhibition by telithromycin. (See CLINICAL PHARMACOLOGY, Drug-drug interactions ) Similarly, an interaction may occur with lovastatin or atorvastatin but not with statins which are not metabolized by CYP3A4. High levels of HMG-CoA reductase inhibitors increase the risk of myopathy and rhabdomyolysis. Use of simvastatin, lovastatin, or atorvastatin concomitantly with KETEK should be avoided. If KETEK is prescribed, therapy with simvastatin, lovastatin, or atorvastatin should be suspended during the course of treatment. Patients concomitantly treated with statins should be carefully monitored for signs and 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 interactions). Monitoring of digoxin side effects or serum levels should be considered during concomitant administra
Overdosage
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.