Clarithromycin dosage

Clarithromycin (0.75-2 g/day), minocycline (200 mg/ day), and clofazimine (100 mg/day) for 15 months were investigated as treatment of MAC lung disease in 30 HIVnegative patients. Eight patients did not complete the study owing to deviations from protocol or adverse effects. Persistently negative cultures were found in 14 of the other patients. There were three cases of hepatic disturbances and three of ototoxicity, which required a reduction in clarithromycin dosage after a short interruption of treatment (10). 

Clarithromycin is a derivative of erythromycin (macrolide). Advantages over erythromycin include lower frequency of gastrointestinal side-effects and lower dosage frequency. Clarithromycin is administered every 12 hours. As with all macrolides it should be used with caution in patients who are at risk of developing QT interval prolongation caused either by electrolyte imbalances or the concomitant use of other drugs. 

Clarithromycin - In the presence of severe renal impairment (Ccr less than 30 mL/min) with or without coexisting hepatic impairment, decreased dosage or prolonged dosing intervals may be appropriate. 

Clarithromycin - Studies show age-related decreases in renal function. Consider dosage adjustment in elderly patients with severe renal impairment. 

A 500-mg dose of clarithromycin produces serum concentrations 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. A portion of active drug and this major metabolite is 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. 

Excretion Erythromycin and azithromycin are primarily concentrated and excreted in an active form in the bile. Partial reabsorption occurs through the enterohepatic circulation. In contrast, clarithromycin and its metabolites are eliminated by the kidney as well as the liver and it is recommended that dosage be adjusted in patients with compromised renal function. 

Clarithromycin is indicated for the treatment of mild to moderate upper and lower respiratory tract infections as well as skin infections caused by susceptible strains of Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, H. influenzae, Legionella pneumophila, and Mycoplasma pneumoniae. The usual dosage is 250 to 500 mg twice a day for 7 to 14 days. 

Verapamil is both a snbstrate and an inhibitor of CYP3A4, which is inhibited by clarithromycin and erythromycin. Giving these macrolide antibiotics dnring verapamil therapy is likely to rednce the first-pass metabolism of verapamil, increase its systemic availability, and impair its elimination. In patients taking this combination, verapamil should be started in a low dosage and its hemodynamic effects should be monitored closely. 

In addition to being available in a variety of dosage forms as the hydrochloride salt, ranitidine is also available us a bismuth citrate salt for use with the macrolide antibiotic clarithromycin in treating patients with an active duodenal ulcer... 

When single doses of 100, 200, 400, 600, 800, and 1200 mg of clarithromycin were compared in healthy subjects, the pharmacokinetics of the parent drug and metabolite were nonlinear [51], with apparent capacity-limited formation of the 14-(i )-hydroxy metabolite at doses of >600 mg. Nonlinear kinetics were also seen in studies of single and multiple doses of clarithromycin, where increases in C ,ax and AUC of the parent drug were more than proportionate with the dosages [52]. In another study, the AUC for clarithromycin increased 13-fold, with a 4.8-fold increase in dose. Pharmacokinetic data suggest that nonlinearity was due predominantly to a decrease in the apparent metabolic clearance, which fell from 913 to 289 ml/min (Table II) [50]. 

Periti, P., and Mazzei, T. (1999). Clarithromycin Pharmacokinetic and pharmacodynamic interrelationships and dosage regimen. / Chemother. 11, 11-27. 

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