Ketek

telithromycin

Ketek

Pharmacologic class: Ketolide antibiotic

Therapeutic class: Anti-infective

Pregnancy risk category C

FDA Box 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.

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.

telithromycin

(te-lith-roe-mye-sin) ,

Ketek

(trade name)

Classification

Therapeutic: anti infectives
Pharmacologic: ketolides
Pregnancy Category: C

Indications

Community-acquired pneumonia.

Action

Blocks bacterial protein synthesis at the level of the 50S ribosomal subunit.

Therapeutic effects

Resolution of infection.
Active against the following organisms: Staphylococcus aureus (methicillin and erythromycin susceptible strains only), Streptococcus pneumoniae (including multidurg-resistant strains), Haemophilus influenzae, Moraxella catarrhalis, Chlamydophila pneumoniae, and Mycoplasma pneumoniae.

Pharmacokinetics

Absorption: 57% absorbed following oral administration; unaffected by food.
Distribution: Concentrates in bronchial mucosa, epithelial lining fluid and alveolar macrophages.
Metabolism and Excretion: 70% metabolized by the liver (50% by CYP3A4), 13% excreted unchanged in urine, 7% excreted unchanged via biliary/intestinal elimination.
Half-life: 10 hr.

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
POrapid1 hr24 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity; History of hepatitis or jaundice associated with use of telithromycin; Hypersensitivity to macrolides (erythromycin, azithromycin, clarithromycin); Concurrent use of pimozide, ergot alkaloids, simvastatin, lovastatin, atorvastatin, or rifampin; Congenital QTc prolongation, uncorrected hypokalemia or hypomagnesemia, bradycardia, concurrent use of Class IA (quinidine, procainamide) or Class III antiarrhythmics (dofetilide); Concurrent use of colchicine in patients with renal or hepatic impairment; Myasthenia gravis; Lactation: Excreted in breast milk; consider alternative to breastfeeding.
Use Cautiously in: CCr <30 mL/min (dosage not established); Concurrent use of midazolam and other benzodiazpines; Obstetric: Use only if benefits outweigh risks to fetus; Pediatric: Safety not established.

Adverse Reactions/Side Effects

Central nervous system

  • confusion
  • hallucinations
  • loss of consciousness

Ear, Eye, Nose, Throat

  • visual disturbances

Cardiovascular

  • arrhythmias
  • QTc interval prolongation

Gastrointestinal

  • pseUdomembranous colitis (life-threatening)
  • diarrhea (most frequent)
  • hepatitis
  • HEPATotoxicity (life-threatening)
  • nausea

Neurologic

  • exacerbation of myasthenia gravis

Interactions

Drug-Drug interaction

Blood levels are ↑ by ketoconazole and itraconazole.↑ levels and risk of myopathy from simvastatin, lovastatin, and atorvastatin ; avoid concurrent use.↑ levels and risk of toxicity with colchicine ; avoid concurrent use in patients with renal or hepatic impairment; ↓ dose of colchicine if patients have normal renal and hepatic function.↑ levels and risk of excessive sedation with midazolam ; careful titration is required. Similar effects may occur with triazolam.↑ levels of metoprolol ; use caution in patients with HF.May also ↑ levels, effects and risk of toxicity from ergot derivatives (ergotamine, dihydroergotamine ); concurrent use not recommended; similar effects may occur with carbamazepine, cyclosporine, tacrolimus, sirolimus, hexobarbital, or phenytoin.Rifampin ↓ levels and effectiveness; avoid concurrent use. Similar effects may occur with phenytoin, carbamazepine, or phenobarbital.

Route/Dosage

Oral (Adults) community-acquired pneumonia—800 mg once daily for 7–10 days.

Availability

Tablets: 300 mg, 400 mg

Nursing implications

Nursing assessment

  • Assess for infection (vital signs; sputum, WBC) at beginning of and during therapy.
  • Obtain specimens for culture and sensitivity before initiating therapy. First dose may be given before receiving results.
  • Determine any family history of QTc prolongation or proarrythmic conditions (hypokalemia, bradycardia).
  • Monitor for signs or symptoms of hepatitis (fatigue, malaise, anorexia, nausea, jaundice, bilirubinuria, acholic stools, liver tenderness or hepatomegaly). If these occur, discontinue telithromycin immediately and monitor liver function; do not re-administer telithromycin.
  • Lab Test Considerations: May cause ↑ platelet count.
    • Monitor liver function periodically during therapy and if signs of hepatitis occur.

Potential Nursing Diagnoses

Risk for infection (Indications)
Noncompliance (Patient/Family Teaching)

Implementation

  • Oral: Administer with or without food. Swallow tablets whole; do not crush, break, or chew.

Patient/Family Teaching

  • Instruct patient to take medication as directed and to finish medication completely, even if feeling better. Take missed doses as soon as remembered, but do not take more than one dose in a 24–hr period. Advise patient to read Patient Information Sheet prior to starting therapy.
  • May cause visual disturbances (blurred vision, difficulty focusing, diplopia). Caution patient to avoid driving or other activities requiring visual acuity until response to medication is known. Advise patient to notify health care professional if visual disturbances interfere with daily activities.
  • Instruct patient to notify health care professional if fainting occurs.
  • Advise patient to report the signs of superinfection (black, furry overgrowth on the tongue; vaginal itching or discharge; loose or foul-smelling stools).
  • Instruct patient to notify health care professional if fever and diarrhea develop, especially if stool contains blood, pus, or mucus. Advise patient not to treat diarrhea without consulting health care professional.
  • Advise patient to discontinue telithromycin and notify health care professional immediately if signs of liver injury (nausea, fatigue, anorexia, jaundice, dark urine, light-colored stools, pruritus, or tender abdomen) occur.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
  • Advise patient to notify health care professional if pregnancy is planned or suspected or if breast feeding.

Evaluation/Desired Outcomes

  • Resolution of the signs and symptoms of infection. Length of time for complete resolution depends on the organism and site of infection.

Ketek

a trademark for telithromycin.
Mentioned in ?
References in periodicals archive ?
For antibiotics is very high, partly due to a scandal over the approval of Sanofi's drug Ketek in 2004, which US officials said later should be reserved for serious diseases due to the risk of side effects.
After 13 weeks of dosing, multinucleated hepatocytes were reported for clarithromycin while Ketek elicited increased LFTs, increased NAGs (3x) in urine and phospholipidosis (FDA Briefing Package, 2001).
Other drugs deemed too unsafe for marketing-yet approved--include the type 2 diabetes drag Avandia (linked to heart attack by FDA Medical Reviewer Robert Misbin and likewise so identified in a meta-analysis published in the New England Journal of Medicine); the antibiotic Ketek (inked to liver damage by FDA Medical Reviewer David Ross, who testified that the drug "could kill people from liver damage"); and the antidepressant drugs Paxil, Zoloft, and Effex or (linked to increased risk of suicidality by FDA Medical Reviewer Andrew Mosholder).
The most prominent example, of course, would be Vioxx, but other drugs come to mind, such as the Avandia diabetes pill and the Ketek antibiotic.
McGarity, Corporate Accountability for Scientific Fraud: Ketek and the Perils of Aggressive Agency Preemption, 58 EMORY L.
David Ross, a former Food and Drug Administration (FDA) scientist, described a pattern of political interference in his work that culminated in his resignation after the approval of the antibiotic drug Ketek.
The committee's oversight subcommittee is investigating whether FDA Commissioner Andrew von Eschenbach gave misleading testimony on Sanofi-Aventis SA's antibiotic Ketek during a committee hearing in March.
FDA has determined that the balance of benefits and risks for Ketek do not support continued approval of Ketek for these generally nonserious and often self-limited illnesses," Dr.
Ketek has been linked to rare reports of acute liver failure that have resulted in several deaths and several patients needing a liver transplant.
More recently we have learned about the potential problems with Ketek, an antibiotic used to treat chronic bronchitis, acute bacterial sinusitis and community acquired pneumonia, including pneumonia caused by resistant strep infections.
Telithromycin, which is marketed by Sanofi-Aventis as Ketek, is no longer approved to treat acute bacterial sinusitis or acute bacterial exacerbation of chronic bronchitis.