Telithromycin

CrCl (mL/min)	Dosage
<30	Alternating daily doses of 800 mg and 400 mg, starting w/ 800 mg.

May be taken with or without food.

Known hypersensitivity to telithromycin and other macrolides, history of hepatitis and/or jaundice associated w/ macrolide therapy, myasthenia gravis. Patient w/ congenital or known history of QT interval prolongation. Patient w/ renal or hepatic impairment receiving colchicine. Concomitant admin w/ drugs that prolong QT interval and are CYP3A4 substrates, HMG-CoA reductase inhibitors metabolised by CYP3A4 or ergot alkaloid derivatives.

Patient w/ CHD, cardiac arrhythmias, hypokalaemia or hypomagnesaemia. Hepatic or renal impairment. Pregnancy and lactation.

Diarrhoea, nausea, vomiting, abdominal pain, flatulence, dizziness, headache, vertigo, insomnia, drowsiness, taste and smell disturbances, paraesthesia, eosinophilia, rash, arrhythmias, hypotension, bradycardia, visual disturbances, syncope, angioedema, anaphylaxis, erythema multiforme, muscle cramps.
Potentially Fatal: Hepatotoxicity including fulminant hepatitis, hepatic necrosis and hepatic failure, acute resp failure in patient w/ myasthenia gravis, Clostridium difficile-associated disease (CDAD).

PO: C

This drug may cause visual disturbances, confusion or hallucination, if affected, do not drive, operate heavy machinery or engage in other hazardous activities.

Perform LFTs. Closely monitor for signs and symptoms of liver failure (e.g. jaundice, fatigue, nausea, acholic stools) and visual acuity.

Additive effect on QT interval prolongation w/ class 1A (e.g. quinidine, procainamide) or class III (e.g. dofetilide) antiarrhythmic agents. Decreased telithromycin concentrations and/or increased anticonvulsant concentrations w/ phenytoin, carbamazepine, phenobarbital. Increased peak plasma concentration and area under the concentration-time curve (AUC) w/ itraconazole and ketoconazole. Decreased peak plasma concentration and AUC w/ rifampicin. Increased AUC of midazolam or levonorgestrel. Increased plasma concentrations of colchicine, digoxin, repaglinide, ciclosporin, sirolimus or tacrolimus. May potentiate effects of oral anticoagulants (e.g. warfarin).
Potentially Fatal: Increased risk of QT interval prolongation and cardiac arrhythmias w/ cisapride, pimozide, astemizole, terfenadine, dronedarone, saquinavir. Increased concentrations of ergot alkaloids (e.g. ergotamine, dihydroergotamine) leading to possible peripheral vasospasm, dysesthesia and acute ergot toxicity. Increased plasma concentrations of CYP3A4 metabolised HMG-CoA reductase inhibitors (e.g. lovastatin, simvastatin, atorvastatin), hence the risk of myopathy and rhabdomyolysis.

St John's wort may reduce therapeutic effect of telithromycin.

Description:
Mechanism of Action: Telithromycin is a semisynthetic ketolide antibiotic that blocks protein synthesis by binding to domains II and V of 23S ribosomal RNA of the 50S ribosome subunit. It may also inhibit the assembly of nascent ribosomal units.
Pharmacokinetics:
Absorption: Rapidly absorbed from the GI tract. Bioavailability: 57%. Time to peak plasma concentration: Approx 1-3 hr.
Distribution: Widely distributed in body fluids and tissues, including the resp tract. Volume of distribution: 2.9 L/kg. Plasma protein binding: 60-70%.
Metabolism: Undergoes hepatic metabolism by CYP3A4 and non-CYP3A4 isoenzymes to 4 major metabolites.
Excretion: Via urine (13% as unchanged drug; remainder as metabolites) and faeces (7%). Elimination half-life: 2-3 hr. Terminal half-life: Approx 10 hr.

Source: National Center for Biotechnology Information. PubChem Database. Telithromycin, CID=3002190, https://pubchem.ncbi.nlm.nih.gov/compound/Telithromycin (accessed on Jan. 23, 2020)

Store at 25°C.

Macrolides

Anon. Telithromycin. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 11/06/2014.

Buckingham R (ed). Telithromycin. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 10/06/2014.

Ketek Tablet, Film Coated (Sanofi-Aventis US LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 10/06/2014.

Ketek Tablets. U.S. FDA. https://www.fda.gov/. Accessed 10/06/2014.

McEvoy GK, Snow EK, Miller J et al (eds). Telithromycin. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 10/06/2014.