Ketek

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.

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.