Telithromycin

812

812.00

1533716-785-6

DTXSID3046455

White to off-white crystalline powder|Crystals from ether

J01FA15|J - Antiinfectives for systemic use

171.85000

4.52

1.26±0.1 g/cm3(Predicted)

176-188 C

966℃

>110°(230°F)

1.589

Sparingly soluble in water

-20°C Freezer

0mmHg at 25°C

9

36/37/38

26-36

KF4674500

Xi

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl telithromycin, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

|Danger|H318 (100%): Causes serious eye damage [Danger Serious eye damage/eye irritation]|P201, P260, P263, P264, P270, P273, P280, P305+P351+P338, P308+P313, P310, P391, and P501|Aggregated GHS information provided by 2 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

As with other macrolide antibiotics, telithromycin has been associated with a low rate (1% to 2%) of transient serum enzyme elevations during therapy. These elevations, however, are usually transient and resolve even with drug continuation and a similar rate of serum enzyme elevations can occur with comparator agents. More importantly, telithromycin has been linked to severe forms of acute, clinically apparent hepatotoxicity, first reported within a short time of its general approval for use in the United States. The typical latency to onset of liver injury is rapid, some cases presenting within a day or two of initiation of therapy, the average latency being 1 week. The liver injury is often abrupt in onset with fatigue, weakness, jaundice and fever. The pattern of enzyme elevations is typically hepatocellular and serum aminotransferase levels can be quite high (>1000 U/L). Mild and anicteric cases of liver injury attributed to telithromycin have been reported, but some cases are very severe and associated with rapid development of hepatic failure with ascites and hepatic encephalopathy. Eosinophilia and rash can occur, but are not common. Recurrence of injury with reexposure has been described.

/Use of telithromycin with pimozide/ is contraindicated; risk of increased pimozide levels.|/Use of telithromycin with phenobarbital, phenytoin, or St. John's wort/ may result in subtherapeutic levels of telithromycin and loss of effect.|When telithromycin is administered with benzodiazepine which are metabolized by CYP 3A4 and undergo a high first-pass effect, serum levels of the other benzodiazepines may increase.|May increase midazolam AUC /when used concurrently with telithromycin/; patients should be monitored and dosage adjustments of midazolam should be considered if necessary.|For more Interactions (Complete) data for TELITHROMYCIN (20 total), please visit the HSDB record page.

While data specific to telithromycin were not located(SRC, 2005), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2). Studies have indicated that several polar pharmaceutically active compounds can leach through subsoils into aquifers(1).

Telithromycin may also be distributed in human milk.

Telithromycin is distributed into the breast milk of rats. Telithromycin may also be distributed in human milk.

When prescribing Ketek, consideration should be given to official guidance on the appropriate use ofantibacterial agents and the local prevalence of resistance.Ketek is indicated for the treatment of the following infections:In patients of 18 years and oldercommunity-acquired pneumonia, mild or moderate.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:acute exacerbation of chronic bronchitis;acute sinusitis;In patients of 12 years and oldertonsillitis / 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.|When prescribing Levviax 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).Levviax 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 sinusitisIn 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).

Telithromycin is a ketolide, a novel form of macrolide antibiotic that is recommended for treatment of community acquired pneumonia. Telithromycin was approved for use in the United States in 2004 and subsequently linked to several cases of severe drug induced liver injury.

Antiinfective Agents

Antibacterial|Telithromycin in indicated in the treatment of acute bacterial exacerbation of chronic bronchitis due to Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis. /Included in US product labeling/|Telithromycin is indicated for the treatment of group A-beta Hemolytic Streptococcus as an alternative when beta-lactam antibiotics are not appropriate. /NOT included in US product labeling/|Telithromycin is indicated in the treatment of community-acquired pneumonia due to Streptococcus pneumoniae (including multi-drug resistant isolates (MDRSP)), Haemophilus influenzae, Chlamydophila pneumoniae, Mycoplasma pneumoniae, or Moraxella catarrhalis. /NOT included in US product labeling/|Telithromycin is indicated in the treatment of acute bacterial sinusitis due to Steptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, or Staphylococcus aureus. /Included in US product labeling/

Pseudomembranous colitis has been reported with nearly all antibacterial agents, including telithromycin, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of any antibacterial agents.|FDA Pregnancy Risk Category: C /RISK CANNOT BE RULED OUT. Adequate, well controlled human studies are lacking, and animal studies have shown risk to the fetus or are lacking as well. There is a chance of fetal harm if the drug is given during pregnancy; but the potential benefits may outweigh the potential risk./|Treatment with anti-infectives, including telithromycin, may permit overgrowth of clostridia. Consider Clostridium difficile-associated diarrhea and colitis (antibiotic-associated pseudomembranous colitis) if diarrhea develops and manage accordingly. Some mild cases of C. difficile-asssociated diarrhea and colitis may respond to discontinuance alone. Manage moderate to severe cases with fluid, electrolyte, and protein supplementation; appropriate anti-infective therapy (e.g., oral metronidazole or vancomycin) recommended if colitis is severe|To reduce development of drug-resistant bacteria and maintain effectiveness of telithromycin and other antibacterials, use only for treatment of infections proven or strongly suspected to be caused by susceptible bacteria. When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing. In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.|For more Drug Warnings (Complete) data for TELITHROMYCIN (14 total), please visit the HSDB record page.

Substances that inhibit the growth or reproduction of BACTERIA. (See all compounds classified as Anti-Bacterial Agents.)

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 ug/mL at 6 hours, and remained at 14.1 ug/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 ug/mL 48 hours after the last dose.|Volume of distribution - 2.9 L/kg following an intervenous infusion. Widely distributed throughout the body. Telithromycin is distributed into breast milk of rats.|Rapidly absorbed, absolute bioavailability is 57% in both young and elderly patients. The rate and extent of absorption are unaffected by food. The AUC following a single dose is 8.25 ug h/mL and 12.5 ug h/mL following multiple dosing.|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.|For more Absorption, Distribution and Excretion (Complete) data for TELITHROMYCIN (11 total), please visit the HSDB record page.

About 70% (33% presystemic and 37% systemic) of an oral dose is metabolized about equally by cytochrome P450 (CYP) 3A4 and non-CYP3A4 isoenzymes to 4 major metabolites. The systemically available telithromycin is eliminated in the feces as unchanged drug (7%), in urine as unchanged drug (13%), and 37% is metabolized in the liver.|Biotransformation: Hepatic; 37% of the dose is metabolized by the liver. Metabolism accounts for approximately 70% of the dose. The main metabolite represented 12.6% of the AUC while three other metabolites quantified represented 3% or less of the AUC of telithromycin.|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.

Elimination: 10 hours following oral dosing.

Telithromycin may be bacteriostatic or bactericidal in action. Like conventional macrolides, telithromycin inhibits protein synthesis in susceptible organisms by binding to the 50S ribosomal subunit. Telithromycin binds to domains II and V of the 23S rRNA of the 50S subunit and has a higher affinity for these ribosomal targets than conventional macrolides, apparently because of additional interactions and increased binding at domain II. This allows telithromycin to retain activity against some gram-positive cocci (e.g., some strains ofS. pneumoniae) that have methylase-mediated resistance (erm genes) that alter the domain V binding site. In addition to inhibiting protein synthesis, telithromycin may inhibit assembly of nascent ribosomal units.|Telithromycin blocks protein synthesis by binding to two sites on the 50S ribosomal subunit: domain II and V of the 23S rRNA. The greater affinity in binding strength can be attributed to the C11-C12 carbamate side chain.

...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 /telithromycin/ is unknown.|Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

/CASE REPORTS/ Exacerbations of myasthenia gravis have been reported in patients with myasthenia gravis treated with telithromycin. This has sometimes occurred within a few hours after intake of the first dose of telithromycin. Reports have included life-threatening acute respiratory failure with a rapid onset in patients with myasthenia gravis treated for respiratory tract infections with telithromycin. Telithromycin is not recommended in patients with myasthenia gravis unless no other therapeutic alternatives are available. If other therapeutic alternatives are not available, patients with myasthenia gravis taking telithromycin must be closely monitored. Patients must be advised that if they experience exacerbation of their symptoms, they should discontinue treatment of ketek and immediately seek medical attention.

HMR 3647

Oral: Tablets 400 mg (Ketek), (Aventis).|Tablets are light-orange, oval, film-coated

Human drugs -> Ketek -> EMA Drug Category|Antibacterials for systemic use -> Human pharmacotherapeutic group|Human drugs -> Levviax -> EMA Drug Category|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients