Cethromycin

Gram-positive bacteria, mycoplasma pneumoniae, chlamydia pneumoniae, ureaplasma urealyticum, legionella pneumophila, H. influenzae, M. catarrhalis, Neisseria, Bordatella Pertussis, Clostridium perfringens.

Mechanism of Action:

Inhibits bacterial protein synthesis by interacting close to the peptidyl transferase site of the 50S ribosomal subunit. The main binding sites are within domains II and V of the 23S rRNA.

Pharmacodynamics:

Ketolides display concentration dependent killing.

Pharmacokinetics: (100mg dose)

Cmax: 140mg/L; Half-life: 3.6 hours;Volume of distribution: 940L; Table 4

Adverse Effects:

Note: preliminary data for cethromycin suggests that adverse effects are dose-related and similar to those seen for telithromycin. These include:

Gastrointestinal: nausea, vomiting, diarrhea
Cardiovascular System: atrial arrhythmias, flushing, hypotension, bradycardia
Central Nervous System: headache, dizziness, somnolence, insomnia, vertigo
Endocrine: increased sweating
Hepatic: reversal hepatitis, abnormal LFTs
Ocular: blurred vision, diplopia
Respiratory: respiratory failure in myasthenia gravis patients
Musculoskeletal: worsening of myasthenia gravis symptoms
Hematologic: thrombocytosis
Dermatologic: skin rashes

Dosage:

No data available-investigational

Disease state based dosing:

Renal Failure: Unknown

Hepatic failure: Unknown

Contraindications/Warnings/Precautions:

Contraindications: hypersensitivity to cethromycin, telithromycin or macrolides.

Precautions: cethromycin might potentially prolong the QT interval; avoid with drugs known to be associated with cardiac toxicities

Drug Interactions:

Note: Although clinical trials are not available for cethromycin, it is expected that the drug acts similarly to other ketolides with respect to toxicity and drug interactions:

Interactions of major severity include drugs that have additive effects on QT prolongation. These drugs are contraindicated in patients taking telithromycin and not recommended in patients taking cethromycin. Examples include: antipsychotics, arsenic trioxide,.astemizole, bepedril, chloral hydrate, chloroquine, cisapride, clarithromycin, antiarrhythmic agents, cotrimoxazole, dolesetron, droperidol, enflurane, erythromycin, fluconazole, fluoxetine, foscarnet, halfantrine, halothane, isradipine, isoflurane, phenothiazines, and pimozide, along with many others.

Interactions of major severity include drugs that are substrates of CYP-3A4. Telithromycin (and possibly cethromycin) inhibits this enzyme, resulting in increased serum levels of the following drugs and others metabolized by CYP-3A4: atorvastatin, dihydroergotamine, ergot derivatives.

Pregnancy:

N/A; Cethromycin is in phase III trials

Monitoring Requirements:

=Therapeutic: WBC, culture and sensitivity, temperature

Toxicity: EKG, signs of hypersensitivity, loose stools, dizziness

Brand names/Manufacturer:

USAN, rINN/Investigational