Clarithromycin - Macrolides

CLARITHROMYCIN

Clarithromycin is derived from erythromycin by addition of a methyl group and has improved acid stability and oral absorption compared with erythromycin. Its mechanism of action is the same as that of erythromycin. Clarithromycin and erythromycin are similar with respect to antibacterial activity except that clarithro-mycin is more active against Mycobacterium avium complex . Clarithromycin also has activity against Mycobacteriumleprae, Toxoplasma gondii, and H influenzae. Erythromycin-resistantstreptococci and staphylococci are also resistant to clarithromycin.

A 500-mg dose of clarithromycin produces serum concentra-tions of 2–3 mcg/mL. The longer half-life of clarithromycin (6 hours) compared with erythromycin permits twice-daily dosing. The recommended dosage is 250–500 mg twice daily or 1000 mg of the extended-release formulation once daily. Clarithromycin penetrates most tissues well, with concentrations equal to or exceeding serum concentrations.

Clarithromycin is metabolized in the liver. The major metabolite is 14-hydroxyclarithromycin, which also has antibacterial activity. Portions of active drug and this major metabolite are eliminated in the urine, and dosage reduction (eg, a 500-mg loading dose, then 250 mg once or twice daily) is recommended for patients with creatinine clearances less than 30 mL/min. Clarithromycin has drug interactions similar to those described for erythromycin.

The advantages of clarithromycin compared with erythromycin are lower incidence of gastrointestinal intolerance and less frequent dosing.