Ketek

Ketek,

a trademark for telithromycin.

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telithromycin

Ketek

Pharmacologic class: Ketolide antibiotic

Therapeutic class: Anti-infective

Pregnancy risk category C

FDA Boxed Warning

• Drug is contraindicated in myasthenia gravis because life-threatening or fatal respiratory failure has occurred in these patients.

Action

Blocks protein synthesis by binding to domains II and V of 23S rRNA of 50S ribosomal subunit. Binding at domain II enables drug to retain activity against gram-positive cocci in resistance mediated by methylases that alter domain-V binding site.

Availability

Tablets (film-coated): 300 mg, 400 mg

⊘Indications and dosages

➣ Mild to moderate community-acquired pneumonia caused by Streptococcus pneumoniae (including multidrug-resistant isolates), Haemophilus influenzae, Moraxella catarrhalis, Chlamydophila pneumoniae, or Mycoplasma pneumoniae

Adults age 18 and older: 800 mg P.O. daily for 7 to 10 days

Dosage adjustment

• Severe renal impairment, with or without coexisting hepatic impairment

Contraindications

• Hypersensitivity to drug, its components, or macrolide antibiotics
• History of hepatitis or jaundice with previous use of telithromycin or macrolide antibiotics
• Concurrent use of cisapride or pimozide
• Myasthenia gravis

Precautions

Use cautiously in:
• severe renal impairment, hepatic dysfunction, congenital prolongation of QT interval, ongoing proarrhythmic conditions (such as uncorrected hypokalemia or hypomagnesemia), clinically significant bradycardia (use should be avoided)
• concurrent use of some HMG-CoA reductase inhibitors (atorvastatin, lovastatin, simvastatin), rifampin, and Class IA or Class III antiarrhythmics (use should be avoided)
• concurrent use of midazolam and other benzodiazepines metabolized by CYP3A4 that undergo high first-pass effect (such as triazolam)
• concurrent use of ergot alkaloid derivatives, metoprolol, or rifampin (use not recommended)
• pregnant or breastfeeding patients
• children younger than age 18 (safety and efficacy not established).

Administration

• Administer tablets whole with or without food.
• Give at least 1 hour before or after theophylline (if prescribed).
☞ Don't give currently with cisapride or pimozide.

Route	Onset	Peak	Duration
P.O.	Unknown	1 hr	Unknown

Adverse reactions

CNS: headache, dizziness, fatigue, loss of consciousness

CV: prolonged QT interval with increased risk of ventricular arrhythmias and torsades de pointes

EENT: visual disturbances, poor visual accommodation

GI: nausea, vomiting, diarrhea, loose stools, light-colored stools, dysgeusia, anorexia, pseudomembranous colitis (possibly caused by Clostridium difficile)

GU: dark urine

Hepatic: abnormal hepatic function, fulminant hepatitis, hepatic necrosis, hepatic failure

Skin: pruritus

Other: superinfection, hypersensitivity reactions including angioedema and anaphylaxis (rare), acute myasthenia gravis exacerbation

Interactions

Drug-drug. Atorvastatin, lovastatin, simvastatin: increased blood levels of these drugs, increased myopathy risk

Benzodiazepines metabolized by CYP3A4 (such as midazolam, triazolam): increased blood levels of these drugs

Cisapride, pimozide: increased blood levels of these drugs, increasing risk of significantly prolonged QT interval

Class IA antiarrhythmics (such as procainamide, quinidine), Class III antiarrhythmics (such as dofetilide): interference with antiarrhythmic efficacy

Colchicine: increased serum colchicine blood level and toxicity risk

Cyclosporine, sirolimus, tacrolimus: increased blood levels of these drugs, with increased toxicity risk

CYP3A4 inducers (such as carbamazepine, phenobarbital, phenytoin, rifampin): subtherapeutic telithromycin blood level

CYP3A4 inhibitors (such as itraconazole, ketoconazole): increased telithromycin blood level

Digoxin: increased peak and trough digoxin levels

Ergot alkaloid derivatives (such as dihydroergotamine, ergotamine): acute ergot toxicity

Hexobarbital: increased hexobarbital blood level and toxicity risk

Metoprolol: increased metoprolol effect

Oral anticoagulants: possible potentiation of these drugs

Sotalol: decreased sotalol absorption

Theophylline: increased theophylline blood level, with exacerbated adverse GI reactions

Verapamil: increased verapamil blood level, causing increased risk of cardiotoxicity

Drug-diagnostic tests. Alanine aminotransferase, aspartate aminotransferase: increased levels

Patient monitoring

• Monitor liver function tests frequently.
☞ Discontinue drug permanently if patient develops clinical hepatitis or transaminase elevations and other systemic symptoms.
• Monitor patient closely for adverse GI reactions, especially diarrhea.
• In patients receiving drug concurrently with anticoagulants, stay alert for potentiation of anticoagulant effects.
• In patients receiving drug concurrently with midazolam, stay alert for need to adjust midazolam dosage.
• In patients receiving drug concurrently with digoxin, monitor peak and trough digoxin levels periodically, and stay alert for adverse reactions to digoxin.

Patient teaching

• Ensure that patient has received and read medication guide that comes with drug.
• Instruct patient to take tablet whole with or without food.
• Advise patient to take drug at least 1 hour before or after theophylline (if prescribed).
• Stress importance of completing full course of therapy, even if patient feels better.
☞ Urge patient to immediately stop taking drug and report signs and symptoms of liver damage, such as nausea, fatigue, appetite loss, yellowing of skin or eyes, dark urine, light-colored stools, itching, and tender abdomen.
☞ Instruct patient to immediately report fainting episodes or signs of heartbeat irregularities.
☞ Urge patient to immediately report watery or loose stools even as late as several months after taking the last dose.
☞ Advise patient to immediately report itching, throat swelling, and other signs or symptoms of allergic reaction.
• Inform patient that drug may cause visual disturbances.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects vision and alertness.
• Advise patient to consult prescriber before taking other prescription or over-the-counter drugs or dietary supplements.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.