Telithromycin

Pronunciation: tel-ITH-roe-MYE-sin
Class: Ketolide

Trade Names

Ketek
- Tablets 300 mg
- Tablets 400 mg

Pharmacology

Interferes with microbial protein synthesis.

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Pharmacokinetics

Absorption

Bioavailability 57%. C _max approximately 2 mcg/mL after an 800 mg oral dose; peak level is reached in about 1 h. Steady-state plasma level reached in 2 to 3 days.

Distribution

Protein binding is 60% to 70%. Vd is 2.9 L/kg.

Metabolism

Approximately 70% of dose is metabolized. About 50% of metabolism is mediated by CYP3A4.

Elimination

Terminal elimination t _½ is about 10 h. Elimination consists of 7% unchanged in feces, 13% unchanged in the urine, and 37% metabolized by the liver.

Indications and Usage

Treatment of community-acquired pneumonia of mild to moderate severity caused by Streptococcus pneumoniae (including multi-drug resistant isolates), Haemophilus influenzae , Moraxella catarrhalis , Chlamydophila pneumoniae , or Mycoplasma pneumoniae .

Contraindications

Coadministration of cisapride or pimozide; history of hepatitis, jaundice, or hypersensitivity to any macrolide antibiotic or any component of this product; myasthenia gravis.

Dosage and Administration

PO 800 mg daily for 7 to 10 days.

PO In severe renal function impairment (CrCl less than 30 mL/min), including patients on dialysis, reduce the dosage to 600 mg once daily. In patients undergoing hemodialysis, give the drug after the dialysis session on dialysis days. In severe renal function impairment with coexisting hepatic function impairment, reduce the dosage to 400 mg once daily.

Storage/Stability

Store tablets at controlled room temperature (59° to 86°F).

Drug Interactions

Telithromycin may elevate plasma levels of these agents, increasing the risk of adverse reactions (eg, myopathy).

Telithromycin may elevate plasma levels of these agents, increasing the pharmacologic and adverse reactions.

May decrease telithromycin plasma concentrations, resulting in subtherapeutic levels and loss of efficacy.

Concurrent use of these agents with telithromycin is contraindicated.

Because telithromycin has the potential to prolong the QTc interval, avoid coadministration of telithromycin and agents in these classes.

Digoxin peak plasma concentrations may be elevated.

Acute ergot toxicity characterized by severe peripheral vasospasm and dysesthesia may occur.

May increase telithromycin plasma concentrations.

Elevated plasma concentrations of these drugs may occur, increasing the therapeutic and adverse reactions.

Sotalol plasma levels may be decreased by telithromycin.

Theophylline plasma concentrations may be elevated, increasing the risk of adverse reactions.

Risk of cardiotoxicity may be increased.

There have been postmarketing reports of potentiation of the effects of oral anticoagulants.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Atrial arrhythmias, palpitations (postmarketing).

CNS

Headache (6%); dizziness (4%); fatigue, insomnia, somnolence, vertigo (less than 2%); loss of consciousness (sometimes associated with vagal syndrome), syncope (postmarketing).

Dermatologic

Increased sweating, rash (less than 2%).

EENT

Visual adverse reactions, including blurred vision, difficulty focusing, and diplopia (less than 2%).

GI

Diarrhea (11%); nausea (8%); vomiting (3%); dysgeusia, loose stools (2%); abdominal distension, abdominal pain, anorexia, constipation, dry mouth, dyspepsia, flatulence, gastritis, gastroenteritis, GI upset, glossitis, oral candidiasis, stomatitis, upper abdominal pain, watery stools (less than 2%); pancreatitis (postmarketing).

Genitourinary

Vaginal candidiasis, vaginal fungal infection, vaginitis (less than 2%).

Hematologic

Increased platelet count (less than 2%).

Hepatic

Abnormal LFTs, increased liver enzymes (eg, ALT, AST), increased transaminases (less than 2%); hepatic function impairment, including fulminent hepatitis, hepatic failure, and hepatic necrosis (postmarketing).

Musculoskeletal

Exacerbation of myasthenia gravis, muscle cramps (postmarketing).

Miscellaneous

Allergy, including anaphylaxis, angioedema, and face edema (postmarketing).

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Renal Function

Dosage reduction required in severe renal function impairment.

Superinfection

Prolonged use of antibiotics may result in bacterial or fungal overgrowth of nonsusceptible microorganisms.

Hepatotoxicity

Acute hepatic failure and severe liver injury, sometimes fatal, may occur. Do not administer to patients with a history of hepatitis and/or jaundice associated with telithromycin use.

Loss of consciousness

Has been reported and in some cases has been associated with vagal syndrome.

Pseudomembranous colitis

Consider possibility in patients who develop diarrhea.

QT interval

May be prolonged in some patients.

Visual disturbances

Ability to accommodate and ability to release accommodation may be slowed.

Overdosage

Symptoms

Carefully monitor ECG and electrolytes.

Patient Information

• Caution patient that the drug may cause fainting and impact the ability to drive, especially if patient is experiencing severe nausea, vomiting, or lightheadedness. Caution patient to avoid driving, operating heavy machinery, and engaging in hazardous tasks if these symptoms are experienced.
• Instruct patient to take exactly as prescribed and not to change the dose or discontinue therapy unless advised by health care provider.
• Instruct patient to take prescribed dose at the same time once daily. Advise patient that medication can be taken without regard to meals, but to take with food if stomach upset occurs.
• Instruct patient to complete entire course of therapy, even if symptoms of infection have disappeared.
• Instruct patient to notify health care provider if infection does not appear to be improving or appears to be getting worse.
• Advise patient to discontinue therapy and contact health care provider immediately if fainting, hives, itching, palpitations, shortness of breath, or skin rash occur.
• Advise patient to discontinue therapy and contact health care provider immediately if signs or symptoms of liver disease (eg, dark urine, itchy skin, light-colored stools, nausea, stomach pains, yellowing of skin or eyes) occur.
• Advise patient to report the following signs of superinfection to health care provider: black, “furry” tongue; foul-smelling stools; vaginal itching or discharge; white patches in mouth.
• Warn patient that diarrhea containing blood or pus may be a sign of a serious disorder and to seek medical care if noted and to not treat at home. Caution patient that this may occur even weeks after completing therapy.
• Caution patient that drug may cause visual disturbances (eg, blurred vision, difficulty focusing, double vision) and to use caution while driving or performing other potentially hazardous activities until tolerance is determined. If visual problems develop, advise patient that avoiding quick changes in viewing distant and nearby objects may help decrease the effects. Advise patient to contact health care provider if visual difficulties interfere with daily activities.
• Advise patient to report any other bothersome adverse reactions to health care provider.

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