BACKGROUND:Macrolide antibiotics have long been used as steroid-sparing agents in patients with severe steroid-dependent asthma. Their efficacy and their propensity to potentiate glucocorticoid adverse effects have been attributed in part to their ability to delay glucocorticoid clearance. OBJECTIVE: We sought to determine whether clarithromycin, a newer macrolide antibiotic, can alter the pharmacokinetic profile of oral glucocorticoids and thereby increase the risk of steroid-induced adverse effects. METHODS: An open-label study in a paired design (before and after treatment) was conducted in a hospital-based outpatient clinic. Participants were 6 adult patients (mean age, 30 years) with mild-to-moderate asthma. Prednisone (40 mg/1.73 m2) and methylprednisolone (40 mg/1.73 m2) were given as single randomized doses on consecutive study days before and on days 8 and 9 of a clarithromycin (500 mg twice daily) course. Twelve-hour pharmacokinetic profiles with measurement of plasma methylprednisolone and prednisolone levels were taken before and after clarithromycin therapy. RESULTS:Clarithromycin therapy resulted in a 65% reduction of methylprednisolone clearance and significantly higher mean plasma methylprednisolone concentrations compared with preclarithromycin concentrations but had no significant effect on prednisolone clearance or mean prednisolone plasma concentrations. CONCLUSIONS: Clinicians must be aware of potential drug interactions that could place patients at increased risk for steroid-induced adverse effects. Such an effect has been demonstrated between clarithromycin and methylprednisolone, two drugs that may be administered concomitantly in asthma. To avoid potential steroid-enhancing effects, prednisone should be substituted for methylprednisolone during prolonged courses of clarithromycin therapy.
RCT Entities:
BACKGROUND:Macrolide antibiotics have long been used as steroid-sparing agents in patients with severe steroid-dependent asthma. Their efficacy and their propensity to potentiate glucocorticoid adverse effects have been attributed in part to their ability to delay glucocorticoid clearance. OBJECTIVE: We sought to determine whether clarithromycin, a newer macrolide antibiotic, can alter the pharmacokinetic profile of oral glucocorticoids and thereby increase the risk of steroid-induced adverse effects. METHODS: An open-label study in a paired design (before and after treatment) was conducted in a hospital-based outpatient clinic. Participants were 6 adult patients (mean age, 30 years) with mild-to-moderate asthma. Prednisone (40 mg/1.73 m2) and methylprednisolone (40 mg/1.73 m2) were given as single randomized doses on consecutive study days before and on days 8 and 9 of a clarithromycin (500 mg twice daily) course. Twelve-hour pharmacokinetic profiles with measurement of plasma methylprednisolone and prednisolone levels were taken before and after clarithromycin therapy. RESULTS:Clarithromycin therapy resulted in a 65% reduction of methylprednisolone clearance and significantly higher mean plasma methylprednisolone concentrations compared with preclarithromycin concentrations but had no significant effect on prednisolone clearance or mean prednisolone plasma concentrations. CONCLUSIONS: Clinicians must be aware of potential drug interactions that could place patients at increased risk for steroid-induced adverse effects. Such an effect has been demonstrated between clarithromycin and methylprednisolone, two drugs that may be administered concomitantly in asthma. To avoid potential steroid-enhancing effects, prednisone should be substituted for methylprednisolone during prolonged courses of clarithromycin therapy.
Authors: E Rand Sutherland; Tonya S King; Nikolina Icitovic; Bill T Ameredes; Eugene Bleecker; Homer A Boushey; William J Calhoun; Mario Castro; Reuben M Cherniack; Vernon M Chinchilli; Timothy J Craig; Loren Denlinger; Emily A DiMango; John V Fahy; Elliot Israel; Nizar Jarjour; Monica Kraft; Stephen C Lazarus; Robert F Lemanske; Stephen P Peters; Joe Ramsdell; Christine A Sorkness; Stanley J Szefler; Michael J Walter; Stephen I Wasserman; Michael E Wechsler; Hong Wei Chu; Richard J Martin Journal: J Allergy Clin Immunol Date: 2010-10 Impact factor: 10.793
Authors: Robert C Strunk; Leonard B Bacharier; Brenda R Phillips; Stanley J Szefler; Robert S Zeiger; Vernon M Chinchilli; Fernando D Martinez; Robert F Lemanske; Lynn M Taussig; David T Mauger; Wayne J Morgan; Christine A Sorkness; Ian M Paul; Theresa Guilbert; Marzena Krawiec; Ronina Covar; Gary Larsen Journal: J Allergy Clin Immunol Date: 2008-10-25 Impact factor: 10.793
Authors: Mark H Gotfried; Rose Jung; Chad R Messick; Israel Rubinstein; Kevin W Garey; Keith A Rodvold; Larry H Danziger Journal: Curr Ther Res Clin Exp Date: 2004-01