telithromycin


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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.
References in periodicals archive ?
The global market for Macrolide Antibiotics is segmented on the basis of Treatment Type, End User and geography: Macrolide Antibiotics Market Segment by Drug Type Azithromycin Clarithromycin Erythromycin Fidaxomicin Telithromycin Request Free Sample Report@ https://www.factmr.com/connectus/sample?flag=S&rep_id=3224 Macrolide Antibiotics Market Segment by Route of Administration Oral Parenteral Macrolide Antibiotics Market Segment by Distribution Channel Hospital Pharmacy Retail Pharmacy Mail Order Pharmacy The global Macrolide Antibiotics market is segmented by drug type, route of administration, distribution channel and geography.
Eighteen outbreak isolates (10 human and eight puppy) representing all three clades were selected for antibiotic susceptibility testing, and all were resistant to azithromycin, ciprofloxacin, clindamycin, erythromycin, nalidixic acid, telithromycin, and tetracycline.
Common drugs metabolized by CYP3A46 Group of drugs Drug name Antidepressants (SSRIs; Citalopram, escitalopram, SNRIs; tricyclics; others) paroxetine, fluoxetine; venalafaxine, trazodone; amitriptyline, imipramine, clomipramine; buspirone nefazodone, mirtazapine Antipsychotics (first Haloperidol, perphenazine; generations; second aripiprazole, quetiapine, generations) risperidone, ziprasidone Benzodiazepines Alprazolam, diazepam, medazolam, temazepam, lorazepam, clonazepam Opiates Codeine, methadone, fentanyl, buprenorphine Hypnotics Zopiclone, zaleplon, zolpidem Antibiotics Erythromycin, clarithromycin, telithromycin Phosphodiesters Sildenafil, tadalafil inhibitors Table 2.
The clinical efficacy and side effects of cefuroxime axetil, telithromycin, amoxicillin/ potassium clavulanate, levofloxacin, moxifloxacin and metronidazole in the treatment of sinusitis.
The platform differentiates the semi-synthetic ketolides telithromycin and solithromycin, which have been associated with significant liver injury, from the commercially marketed macrolides azithromycin and clarithromycin.
Mutations in the genes encoding ribosomal proteins L4 and L22 have been associated with in vitro resistance to pristinamycin and telithromycin, respectively, in M.
Clinical and bacteriological efficacy and safety of 5 and 7 day regimens of telithromycin once daily compared with a 10 day regimen of chlarithromycin twice daily in patients with mild to moderate community-acquired pneumonia.
pneumoniae, and Ureaplasma urealyticum to GAR-936, dalfopristin, dirithromycin, evernimicin, gatifloxacin, linezolid, moxifloxacin, quinupristin-dalfopristin, and telithromycin compared to their susceptibilities to reference macrolides, tetracyclines, and quinolones.
A case report to highlight the above statement; one in which an individual case report identified the hepatotoxicity of telithromycin - an FDA approved drug - and underpinned poor drug testing practices.
Unlike other macrolides such as telithromycin and clarithromycin, the presence of nitrogen within the lactone ring structure of azithromycin grants resistance to pH changes in phagocytic vesicles, which facilitates delivery and concentration sustaining of azithromycin at sites of infection by host chemotaxis and contributes to antibacterial property by host macrophages [78].
Indeed, antimicrobial efficacy of Vancomycin, Clindamycin, and Telithromycin is related to [C.sub.max]/MIC or [AUC.sub.0-24]/mic.