Brands, Medical Use, Clinical Data
Drug Category
- Anti-infectives
- Macrolides
Dosage Forms
- Tablets (enteric coated, 250mg)
Brands / Synonyms
Dynabac
Indications
For the treatment of the following mild-to-moderate infections caused by susceptible strains of microorganisms: acute bacterial exacerbations of chronic bronchitis, secondary bacterial infection of acute bronchitis, community-acquired pneumonia, pharyngitis/tonsilitis, and uncomplicated skin and skin structure infections.
Pharmacology
Dirithromycin is a pro-drug which is converted non-enzymatically during intestinal absorption into the microbiologically active moiety erythromycylamine. Erythromycylamine exerts its activity by binding to the 50S ribosomal subunits of susceptible mircoorganisms resulting in inhibition of protein synthesis. Dirithromycin/erythromycylamine has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections: Staphylococcus aureus (methicillin-susceptible strains only), Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, Legionella pneumophila, Moraxella catarrhalis, and Mycoplasma pneumoniae.
Mechanism of Action
Dirithromycin prevents bacteria from growing, by interfering with their protein synthesis. Dirithromycin binds to the 50S subunit of the 70S bacterial ribosome, and thus inhibits the translocation of peptides. Dirithromycin has over 10 times higher affinity to the subunit 50S than erythromycin. In addition, dirithromycin binds simultaneously in to two domains of 23S RNA of the ribosomal subunit 50S, where older macrolides bind only in one. Dirithromycin can also inhibit the formation of ribosomal subunits 50S and 30S.
Absorption
Oral dirithromycin is rapidly absorbed, with an absolute bioavailability of approximately 10%. Dietary fat has little or no effect on the bioavailability of dirithromycin.
Toxicity
The toxic symptoms following an overdose of a macrolide antibiotic may include nausea, vomiting, epigastric distress, and diarrhea.
Biotrnasformation / Drug Metabolism
Dirithromycin is converted by nonenzymatic hydrolysis during absorption to the active compound, erythromycylamine. Sixty to 90% of a dose is hydrolyzed to erythromycylamine within 35 minutes after dosing, and conversion is nearly complete after 1.5 hours. Erythromycylamine undergoes little or no hepatic biotransformation. No other metabolites of dirithromycin have been detected in the serum.
Contraindications
Dynabac is contraindicated in patients with known hypersensitivity to dirithromycin, erythromycin, or any other
macrolide antibiotic.
Drug Interactions
Terfenadine In a prospective study involving six-healthy-male volunteers, dirithromycin did not affect the
metabolism of terfenadine. These six volunteers received terfenadine alone (60 mg twice daily) for 8 days, followed
by terfenadine in combination with dirithromycin (500 mg once daily) for 10 days. (Both drugs were thus dosed to
steady state.) The pharmacokinetics of terfenadine and its acid metabolite and the electrocardiographic QT
c interval were measured during both periods: with terfenadine alone, and with terfenadine plus
dirithromycin. In five men, terfenadine levels were undetectable (<5 ng/mL) throughout the study; in one man, the
C max of terfenadine was 8.1 ng/mL with terfenadine alone and 7.2 ng/mL with terfenadine plus
dirithromycin. The mean C max , T max , and AUC of the acid metabolite of terfenadine were not
significantly changed. The mean QT c interval (msec) was 369 with terfenadine alone and 367 with
terfenadine plus dirithromycin.
Also, in vitro experiments demonstrated a lack of interaction between dirithromycin and terfenadine. Thus,
the interaction observed between erythromycin and terfenadine is not expected for dirithromycin.
Serious cardiac dysrhythmias, some resulting in death, have occurred in patients receiving terfenadine
concomitantly with other macrolide antibiotics. In addition, most macrolides are contraindicated in patients
receiving terfenadine therapy who have pre-existing cardiac abnormalities (arrhythmia, bradycardia, QT c
interval prolongation, ischemic heart disease, congestive heart failure, etc.) or electrolyte disturbances.
Theophylline Following co-administration of two 250-mg dirithromycin tablets administered once daily with
200-mg theophylline tablets administered twice daily for 10 days to 14 healthy subjects, the steady-state plasma
concentration of theophylline was not significantly altered. In general, most patients treated with dirithromycin who
are receiving concomitant theophylline therapy may not require empiric adjustment of theophylline dosage or
monitoring of theophylline plasma concentrations. However, theophylline plasma concentrations should be monitored,
with dosage adjustment as appropriate, in patients whose pulmonary disease requires maintaining a given theophylline
plasma concentration for optimal pulmonary function or in patients with theophylline concentrations at the higher end
of the therapeutic range.
Antacids or H 2 receptor antagonists When dirithromycin is administered immediately following
antacids or H 2 -receptor antagonists, the absorption of dirithromycin is slightly enhanced.
The following drug interactions have been reported with erythromycin products. It is presently not known whether
these same drug interactions occur with dirithromycin. Until further data are available regarding the potential
interaction of dirithromycin with these compounds, caution should be used during coadministration.
Triazolam Erythromycin has been reported to decrease the clearance of triazolam and, thus, may increase the
pharmacologic effect of triazolam.
Digoxin Concomitant administration of erythromycin and digoxin has been reported to result in elevated
digoxin serum levels.
Anticoagulants There have been reports of increased anticoagulant effects when erythromycin and oral
anticoagulants were used concomitantly. Increased anticoagulation effects due to a drug interaction with erythromycin
may be more pronounced in the elderly.
Ergotamine Concurrent use of erythromycin and ergotamine or dihydroergotamine has been associated in some
patients with acute ergot toxicity characterized by severe peripheral vasospasm and dysesthesia.
Other drugs Drug interactions have been reported with concomitant administration of erythromycin and other
medications, including cyclosporine, hexobarbital, carbamazepine, alfentanil, disopyramide, phenytoin, bromocriptine,
valproate, astemizole, and lovastatin.
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