Clarithromycin Extended-release Research Articles

Pharmacokinetics of extended-release clarithromycin in patients with Mycobacterium ulcerans infection

Clarithromycin extended-release (CLA-ER) was used as companion drug to rifampicin (RIF) for Mycobacterium ulcerans infection in the intervention arm of a WHO drug trial. RIF enhances CYP3A4 metabolism, thereby reducing CLA serum concentrations, and RIF concentrations might be increased by CLA co-administration. We studied the pharmacokinetics of CLA-ER at a daily dose of 15 mg/kg combined with RIF at a dose of 10 mg/kg in a subset of trial participants, and compared these to previously obtained pharmacokinetic data. Serial dried blood spot samples were obtained over a period of ten hours, and analyzed by LC–MS/MS in 30 study participants—20 in the RIF-CLA study arm, and 10 in the RIF-streptomycin study arm. Median CLA Cmax was 0.4 mg/L—and median AUC 3.9 mg*h/L, following 15 mg/kg CLA-ER. Compared to standard CLA dosed at 7.5 mg/kg previously, CLA-ER resulted in a non-significant 58% decrease in Cmax and a non-significant 30% increase in AUC. CLA co-administration did not alter RIF Cmax or AUC. Treatment was successful in all study participants. No effect of CLA co-administration on RIF pharmacokinetics was observed. Based on our serum concentration studies, the benefits CLA-ER over CLA immediate release are unclear.

Effects of Citric Acid and Sodium Alginate on the Stability and Dissolution of Clarithromycin Extended-Release Tablet

The pharmacokinetics of clarithromycin (CLR) conventional tablets (T1/2: 5-7 h) demand 2 or 3 doses per day, which is inconvenient for patients. Therefore, a sustained-release CLR tablet is necessary. Based on Klacid MR tablets (AbbVie) composed of citric acid and sodium alginate (Na-ALG), we developed a 24-hour extended-release CLR tablet. Although citric acid had a significant effect on the CLR release profile, the incompatibility of citric acid and CLR was reported (via FT-IR and stability study). Based on the function of Na-ALG in controlling the release and reducing the incompatibility of citric acid and CLR, a process (CLR and citric acid were granulated separately) was proposed. The final tablet formulation showed 1-month stability and dissolution similarity to standard tablets in pH 6.8 medium (f2 > 50).

Generic versus Non-Generic Formulation of Extended-Release Clarithromycin in Patients with Community-Acquired Respiratory Tract Infections

There is a general concern about the use of multisource (generic) antibacterials in the clinical setting with registration based solely on bioequivalence data. In order to address this concern, two modified-release formulations of clarithromycin (i.e. the originator Klacid XL and the generic Klarithran MR) were compared in patients with acute community-acquired respiratory tract infections. Patients presenting with tonsillopharyngitis, sinusitis or pneumonia were randomized to receive either of the test drugs provided they clinically qualified for empirical clarithromycin treatment. The study endpoints were clinical and bacteriological cure rates, tolerability and safety. The study was designed to test for non-inferiority with regard to cure rates. The main outcome of this study was that both agents had similar clinical (non-inferior) and bacteriological cure rates and demonstrated no difference in tolerability in patients. The study also demonstrated the clinical efficacy of clarithromycin when used as empirical treatment in patients with respiratory tract infections in community practice (i.e. 95% clinical cure rate). The clarithromycin extended-release multisource product (Klarithran MR) does not differ significantly from the originator (Klacid XL) and the clinical cure rate of the generic formulation is non-inferior to that of the originator. The two formulations are tolerated similarly.

Utilisation de la clarithromycine à libération modifiée en traitement court des exacerbations aiguës d’une BPCO peu grave en pratique médicale courante

Objective This study was designed to confirm, in routine clinical practice conditions, the success rates and safety of extended-release clarithromycin tablets in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD), according to the usual empirical criteria in routine clinical practice. Patients and methods An open-label, pharmacoepidemiological, clinical study in community practice was performed with 180 practitioners. The bacterial origin was suspected when sputum was obviously purulent. Results Seven hundred and nineteen adult patients with acute exacerbation of mild or moderately severe COPD were included. A favorable clinical course of the exacerbation was observed in 92.5% of cases, with resolution of frankly purulent sputum in 99% of cases, associated with good tolerance. Conclusion These results confirm the value of extended-release clarithromycin tablets as first-line treatment for presumed bacterial exacerbation of mild or moderately severe, stable COPD according to the Société de pathologie infectieuse de langue française consensus.

P842 An open-label, randomised, comparative study of the patient compliance, efficacy and safety of treatment with clarithromycin extended-release versus clarithromycin immediate-release for the treatment of acute bacterial exacerbation of chronic bronchitis

P842 An open-label, randomised, comparative study of the patient compliance, efficacy and safety of treatment with clarithromycin extended-release versus clarithromycin immediate-release for the treatment of acute bacterial exacerbation of chronic bronchitis

Role for 5‑day, once-daily extended-release clarithromycin in acute bacterial exacerbation of chronic bronchitis

ABSTRACTBackground: Clarithromycin is commonly dosed for 7 or more days in patients with acute bacterial exacerbation of chronic bronchitis (ABECB). Studies with other antibiotics have shown equivalent efficacy, reduced/similar frequency of adverse events, improved adherence and patient satisfaction, and lower treatment costs with a shorter treatment course.Patients and methods: The study population was derived from two multicenter, randomized, double-blind (North America)/single-blind (France) comparative trials in which outpatients at least 35 years old with a presumptive diagnosis of obstructive ABECB were randomized to receive clarithromycin extended-release (ER) 1000 mg once daily for 5 days or a comparator agent – clarithromycin immediate-release (IR) 500 mg twice daily for 7 days (in North America) or telithromycin 800 mg once daily for 5 days (in France).Results: A total of 818 patients were randomized (411 to clarithromycin ER and 407 to a comparator agent). The clinical cure rate in clinically evaluable patients at the follow-up visit was 90% each for the clarithromycin ER group (318/353) and the comparator group (318/355). The patient bacteriological cure rate and the overall target pathogen eradication rate in clinically and bacteriologically evaluable patients were each 92% for the clarithromycin ER group (155/168 and 189/205, respectively) and 93% for the comparator group (147/158 and 183/197, respectively) at the follow-up visit. The study drugs were generally well tolerated, with < 2% of patients discontinuing their treatment prematurely due to a drug-related adverse event. The incidence of drug-related adverse events was 18% (73/411) in the clarithromycin ER group and 24% (97/407) in the comparator group. Clarithromycin ER-treated patients reported statistically significantly fewer episodes of abdominal pain than did patients treated with a comparator agent (0.2% vs. 1.7%, respectively; p = 0.037). This combined analysis is limited by differing blinding methods, comparator agents, and their duration of administration. Furthermore, many patients were excluded from the clinically and bacteriologically evaluable group due to lack of a pretreatment target pathogen.Conclusion: A once daily, 5‑day clarithromycin ER regimen appears to be a suitable choice for treating patients with ABECB.

Comparative Tolerability, Safety and Efficacy of Tablet Formulations of Twice-Daily Clarithromycin 250 mg versus Once-Daily Extended-Release Clarithromycin 500 mg in Pediatric and Adolescent Patients

Clarithromycin is widely used to treat respiratory tract and superficial skin infections in pediatric and adult populations. Using clinical endpoints and 7-day therapy, we compared the efficacy of clarithromycin 250 mg tablets given twice daily versus clarithromycin 500 mg extendedrelease tablets given once daily in ambulatory children and adolescents 6 to 16 years old. Of the 199 evaluable patients, 124 were infected with group A streptococcal pharyngitis, 39 with sinusitis, 21 with ambulatory pneumonia, and 15 with superficial skin infections. The overall cure rate exceeded 90% for each treatment group. Discontinuation rates and adverse events were 4.5% and 24.6%, respectively.

Clarithromycin extended-release in community-acquired respiratory tract infections

Clarithromycin extended-release (ER) is a second-generation macrolide with bactericidal activity against a broad group of pathogens. It allows for convenient once-daily dosing (2 x 500 mg/day), and has less severe adverse effects than the immediate-release (IR) formulation of the drug, which may result in improved patient compliance. Clarithromycin ER has been approved for the treatment of community-acquired pneumonia, acute maxillary sinusitis and acute bacterial exacerbation of chronic bronchitis. In comparison to the IR formulation, clarithromycin ER demonstrates prolonged absorption from the gastrointestinal tract, allowing for once-daily dosing with improved gastrointestinal tolerability. Various double-blind, randomised clinical trials and group studies have found clarithromycin ER to be an efficacious treatment option, comparable with clarithromycin IR, or its other competitors.

Pharmacokinetics of Clarithromycin Extended-Release (ER) Tablets in Patients with AIDS

Background: Clarithromycin is a key agent in effective antimycobacterial therapy and prophylaxis for AIDS-related disseminated Mycobacterium avium complex (dMAC) infection. Immediate-release (IR) clarithromycin tablets are dosed at 500 mg bid for these indications. A new extended-release (ER) tablet of clarithromycin has been developed and approved at a dosing interval of once every 24 hours for treatment of respiratory tract bacterial infections. However, the pharmacokinetics of clarithromycin ER in AIDS patients with or at risk for dMAC has not been previously investigated. Method: We conducted a randomized, crossover trial in which 14 AIDS patients received clarithromycin ER, 1000 mg once daily, and clarithromycin IR, 500 mg bid, each for 1 week, with pharmacokinetic sampling at the end of each week. Results: The mean of the individual AUC ratios for clarithromycin ER vs. IR was 1.09 (90% CI, 0.94-1.24). Adverse events were no more severe or frequent with clarithromycin ER than IR. Conclusion: Clarithromycin ER is a once-daily regimen that is as well tolerated as standard bid IR clarithromycin dosing and has average bioequivalence to the IR formulation in patients with AIDS.

Single-Dose Azithromycin Microspheres vs Clarithromycin Extended Release for the Treatment of Mild-to-Moderate Community-Acquired Pneumonia in Adults

Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality worldwide. The inability or failure of many subjects to adhere to standard antibiotic regimens, which may last up to 10 days, results in suboptimal antibiotic treatment. Treatment with a single-dose antibiotic regimen may improve compliance with prescribed therapy. A novel microsphere formulation of azithromycin provides a single-dose regimen while maintaining tolerability. To compare the efficacy and safety of a single 2.0-g dose of azithromycin microspheres to that of an extended-release formulation of clarithromycin (1.0 g/d for 7 days) for the treatment of adults with mild-to-moderate CAP. A phase III, multinational, multicenter, randomized, double-blind, double-dummy study, comparing single-dose azithromycin microspheres to extended-release clarithromycin, both administered orally. Subjects with mild-to-moderate CAP (Fine class I and II) were included. The primary end point was clinical response at the test-of-cure (TOC) visit (days 14 to 21) in the clinical per protocol (CPP) population. The bacteriologic response at the TOC visit was assessed in subjects with a baseline pathogen. A total of 501 subjects were randomized, and 499 were treated. Clinical cure rates at the TOC visit in the CPP population were 92.6% (187 of 202 subjects) for azithromycin microspheres and 94.7% (198 of 209 subjects) for extended-release clarithromycin. Overall pathogen eradication rates were 91.8% (123 of 134 subjects) for azithromycin microspheres and 90.5% (153 of 169 subjects) for extended-release clarithromycin. Both agents were well tolerated. The incidence of treatment-related adverse events was 26.3% with azithromycin microspheres and 24.6% with extended-release clarithromycin. Most adverse events were mild to moderate in severity. A single 2.0-g dose of azithromycin microspheres was as effective and well tolerated as a 7-day course of extended-release clarithromycin in the treatment of adults with mild-to-moderate CAP.

Costs and Outcomes of Extended-Release vs. Immediate-Release Clarithromycin for Lower Respiratory Tract Infections

Costs and Outcomes of Extended-Release vs. Immediate-Release Clarithromycin for Lower Respiratory Tract Infections

Comparative efficacy of once daily, 5-day short-course therapy with clarithromycin extended-release versus twice daily, 7-day therapy with clarithromycin immediate-release in acute bacterial exacerbation of chronic bronchitis

ABSTRACTObjective: The objective of this study was to compare the efficacy, tolerability, and safety of two clarithromycin regimens, extended-release (ER) 1000 mg once daily for 5 days and immediate-release (IR) 500 mg twice daily for 7 days, in the treatment of acute bacterial exacerbation of chronic bronchitis (ABECB).Patients and methods: This was a double-blind, randomized, parallel-group, multicenter study of ambulatory patients at least 40 years old with a presumptive diagnosis of ABECB, purulent sputum, and documented evidence of chronic obstructive pulmonary disease (COPD), including forced expiratory volume in one second (FEV1) < 70% of predicted value. Clinical cure, bacteriological cure, and target pathogen eradication rates were determined at a test-of-cure visit (study days 14–40). Safety was assessed based on the incidence of study drug-related adverse events.Results: A total of 485 patients were randomized (240 to ER and 245 to IR). Clinical cure rates were similar for evaluable patients treated with ER (84%, 157/187) and those treated with IR (84%, 172/204) (95% CI –7.9, 7.2). The bacteriological cure rates were 87% (82/94) and 89% (91/102), and the overall target pathogen eradication rates were 88% (107/122) and 89% (117/131) for the respective treatment groups. The incidence of adverse events was 13% (31/240) in the ER group and 18% (45/245) in the IR group. The rate of gastrointestinal adverse events was lower with ER (8%, 19/240) compared to IR (11%, 26/245). Clarithromycin ER-treated patients reported statistically significantly fewer adverse events due to abnormal taste than did clarithromycin IR-treated patients (3% and 8%, respectively, p = 0.012).Conclusion: Both once-daily, 5-day, short-course therapy with clarithromycin ER and 7-day, twice-daily therapy with clarithromycin IR were effective in resolving clinical signs/symptoms of ABECB and eradicating the causative pathogens, with no statistically significant difference in clinical cure rate between the treatment groups. Clarithromycin ER was better tolerated, causing fewer gastrointestinal adverse events and statistically significantly fewer reports of abnormal taste as compared with clarithromycin IR.

Costs and Outcomes of Extended-Release vs. Immediate-Release Clarithromycin for Lower Respiratory Tract Infections

We used decision-analysis modeling to compare costs and outcomes of clarithromycin extended-release (Biaxin XL, Abbott Laboratories, Abbott Park, Illinois, USA) and clarithromycin immediate-release (Biaxin®) for outpatients with lower respiratory tract infections (LRTI). More patients achieved clinical cure with extended-release (83.9%) versus immediate-release (72.8%); fewer discontinued due to adverse events. Total costs with extended-release were $32 (16%) less; incorporating greater adherence for extended-release (once-daily) therapy resulted in greater savings. Results indicate that clarithromycin extended-release is cost-saving compared with immediate-release for LRTI.

Once daily clarithromycin extended-release vs twice-daily amoxicillin/clavulanate in patients with acute bacterial sinusitis: a randomized, investigator-blinded study

ABSTRACTObjective: To compare the efficacy and tolerability of clarithromycin extended-release (ER) to amoxicillin/clavulanate in patients diagnosed with acute bacterial sinusitis.Research design and methods: In a controlled, multicenter, investigator-blinded study, 437 ambulatory patients at least 12 years old with signs/symptoms and radiographic findings of acute sinusitis were randomized to receive clarithromycin ER 1000 mg once daily or amoxicillin/clavulanate 875 mg/125 mg twice daily for 14 days.Main outcome measures: Clinical and bacteriological response rates were determined at a test-of-cure visit, which was conducted up to 10 days following the completion of treatment. Radiological response was assessed at a follow-up visit.Results: The clinical cure rate in clinically evaluable patients was 98% (184/188) in the clarithromycin ER group and 97% (179/185) in the amoxicillin/clavulanate group (95% CI for the difference in rates [–2.4%, 4.7%]). Clinical cure was sustained at the follow-up visit (96% for each treatment group). The pathogen eradication rates were 94% (61/65) in the clarithromycin ER group and 98% (61/62) in the amoxicillin/clavulanate group (95% CI for difference in rates [–12.0%, 2.9%]). The radiological success rate was 94% (172/183) in both the clarithromycin ER and amoxicillin/clavulanate groups (95% CI for difference in rates [–4.9%, 4.9%]). Symptomatic improvement or relief was observed as early as 2 days–5 days after the initiation of study drug, with a statistically significantly higher resolution rate of sinus pressure ( p = 0.027) and improvement/resolution rate of nasal congestion ( p = 0.035) during treatment with clarithromycin ER. The resolution/improvement rate at the test-of-cure visit for each treatment group was ≥ 94% for the primary acute sinusitis signs/symptoms, with a statistically significantly higher resolution/improvement rate of purulent nasal discharge with clarithromycin ER ( p = 0.010). Both study drugs had a positive and rapid impact on quality of life. Patients reported a high level of satisfaction and probability of using either study antibiotic again, and health care resource use was low, with slightly fewer sinusitis-related physician and outpatient visits required by patients in the clarithromycin ER group ( p = 0.055). The treatment groups were comparable with respect to incidence of drug-related adverse events.Conclusion: In this multinational population of patients with acute bacterial sinusitis, clarithromycin ER was comparable, and for selected measures superior, to amoxicillin/clavulanate based on clinical, bacteriological, and radiological responses as well as quality of life measures, satisfaction with antibiotic therapy, and health care resource utilization.

Overview of newer antimicrobial formulations for overcoming pneumococcal resistance

The pharmacokinetic (PK) and pharmacodynamic (PD) profile of an antimicrobial agent provides important information that can be used to maximize bacteriologic and clinical efficacy, minimize selective pressure for the development of antimicrobial resistance, and determine an optimal dosing regimen. Judicious selection of an antimicrobial based on local susceptibility data and PK and PD parameters is imperative in this era of increasing resistance among Streptococcus pneumoniae, a leading cause of community-acquired respiratory tract infections. The β-lactam antimicrobials display time-dependent bacterial killing with minimal to no persistent effects. Ketolides and fluoroquinolones display concentration-dependent bacterial killing, and tetracyclines and macrolides display time-dependent killing. All have prolonged persistent effects (e.g., postantibiotic effect) that retard or prevent bacterial regrowth when free drug levels fall below the minimum inhibitory concentration (MIC). New high-dose and/or extended-release formulations of traditional antimicrobials have been added to the current armamentarium for treatment of community-acquired respiratory tract infections. These formulations include amoxicillin-clavulanate potassium powder for oral suspension 90/6.4 mg/kg per day divided every 12 hours (Augmentin ES-600; GlaxoSmithKline, Research Triangle Park, NC), amoxicillin-clavulanate potassium extended-release tablets 2 × 1,000 mg/62.5 mg every 12 hours (Augmentin XR; GlaxoSmithKline), clarithromycin extended-release tablets 2 × 500 mg once daily (Biaxin XL; Abbott Laboratories, North Chicago, IL), and cefaclor extended-release tablets 375 mg or 500 mg every 12 hours (Ceclor CD; Eli Lilly Pharmaceuticals, Indianapolis, IN). Of these agents, only amoxicillin-clavulanate potassium powder for oral suspension and amoxicillin-clavulanate potassium extended-release tablets were designed to treat infections caused by penicillin-resistant pneumococci (penicillin MIC ≤2 μg/mL). Extended-release clarithromycin does not provide higher daily doses than its immediate-release counterpart; rather, it allows for once-daily dosing of this agent because of its slower absorption following oral administration. Extended-release cefaclor is considered clinically equivalent to 250 mg of immediate-release cefaclor pulvules administered 3 times daily; it cannot be used interchangeably with 500 mg 3-times-daily dosages of other cefaclor formulations. Thus, despite providing a similar or higher total daily dose than its immediate-release counterpart, extended-release cefaclor is indicated only for the treatment of patients with mild to moderate infections caused by susceptible strains of certain organisms.

Comparison of 5 days of extended-release clarithromycin versus 10 days of penicillin V for the treatment of streptococcal pharyngitis/tonsillitis: results of a multicenter, double-blind, randomized study in adolescent and adult patients

SUMMARYObjective: This study compared a short-course of clarithromycin with a standard course of penicillin V in patients with tonsillopharyngitis caused by Streptococcus pyogenes.Research design and methods: A total of 539 patients, aged 12–75 years, were randomized to receive either clarithromycin extended-release (ER) 500 mg once daily for 5 days or penicillin V 500 mg three times daily for 10 days in this multicenter, double-blind, parallel-group trial. Eligibility required a positive antigen test for group A beta-hemolytic streptococcus (GABHS) followed by confirmatory culture.Main outcome measures: Bacteriological and clinical assessments were conducted at each study visit (visit 1: study day 1; visit 2: study day 3; visit 3: study days 8–12; visit 4: study days 13–20; and visit 5: study days 40–50).Results: At the test-of-cure visit (visit 3 for clarithromycin ER patients and visit 4 for penicillin V patients) in per-protocol patients, 5 days of clarithromycin ER was comparable to 10 days of penicillin V in eradicating S. pyogenes (89% (157/177) vs 90% (139/154) respectively; 95% CI for difference (−8.2, 5.1)). Bacterial eradication was sustained in both treatment groups at the follow-up visit (88% (135/153) vs 91% (112/123) respectively; 95% CI for difference (−10.0, 4.4)). Clinical cure was achieved in > 94% of patients in each treatment group. The most commonly reported study drug-related adverse events (< 3% in either treatment group) were abdominal pain, diarrhea, dyspepsia and nausea.Conclusion: Clarithromycin ER 500 mg once daily for 5 days is equally effective as penicillin V 500 mg three times daily for 10 days in the treatment of adolescent and adult patients with streptococcal tonsillopharyngitis.

Short-course therapy of acute bacterial exacerbation of chronic bronchitis: a double-blind, randomized, multicenter comparison of extended-release versus immediate-release clarithromycin

SUMMARYObjective: The objective of this study was to compare the efficacy and safety of two clarithromycin formulations given for 5 days to patients with acute bacterial exacerbation of chronic bronchitis (ABECB).Patients and methods:This was a double-blind, randomized, multicenter study of ambulatory patients between 40 and 75 years of age with a medical history of chronic bronchitis, chronic obstructive pulmonary disease and a presumptive diagnosis of ABECB who met Anthonisen Type 1 criteria (increased dyspnea, increased sputum volume and increased sputum purulence). Eligible patients received a 5-day course of clarithromycin extended-release (ER) 500 mg once daily or clarithromycin immediate-release (IR) 250 mg twice daily. Clinical cure, bacteriological cure and pathogen eradication rates were determined at the end of therapy and at a follow-up visit.Results: Clinical cure rates were similar at the test-of-cure visit for evaluable patients in the clarithromycin ER group (97%, 298/307) and clarithromycin IR group (98%, 300/307) (95% CI (−3.2,1.9)). The bacteriological cure rate was 89% and the pathogen eradication rate was 90% in both treatment groups. Resolution or improvement in cough, sputum production, sputum volume and sputum appearance was observed in >90% of evaluable patients in each treatment group. The incidence of study drug-related adverse events was 6.6% (23/351) in the clarithromycin ER group and 5.4% (19/352) in the clarithromycin IR group. The most frequently occurring study drug-related adverse events were abdominal pain, diarrhea and taste perversion.Conclusion: Clarithromycin ER 500 mg once daily for 5 days is equivalent to clarithromycin IR 250 mg twice daily for 5 days in treating adults with ABECB. Both regimens were effective in resolving clinical signs and symptoms of ABECB and eradicating the target pathogens, and were well tolerated.

An open-label, randomized, multicenter, comparative study of the efficacy and safety of 7 days of treatment with clarithromycin extended-release tablets versus clarithromycin immediate-release tablets for the treatment of patients with acute bacterial exacerbation of chronic bronchitis

Objective: The aim of this study was to compare the efficacy and safety of clarithromycin extended-release (ER) tablets and immediate-release (IR) tablets. Methods: This was a Phase III, open-label, randomized, multicenter, comparative study in ambulatory patients with a diagnosis of acute exacerbation of chronic bronchitis (AECB). Eligible patients were randomized 1:1 to receive either 1 clarithromycin ER 500-mg tablet QD for 7 days or 1 clarithromycin IR 250-mg tablet BID for 7 days. Clinical and bacteriologic responses were assessed within 48 hours after the last dose of study drug and at a test-of-cure visit 21 ± 2 days posttreatment. Results: Of 233 patients randomized, 162 (86/117 [73.5%] in the ER group and 76/115 [66.1%] in the IR group) completed the study protocol. Compliance did not differ significantly between the treatment groups; however, significantly fewer patients in the ER group reported missing doses of study medication than in the IR group (7/118 [5.9%] vs 16/115 [13.9%]; P = 0.04). The clinical cure rates for the clarithromycin ER and IR groups were 81.0% (68/84) and 82.1% (64/78) and the clinical success (clinical cure plus clinical improvement) rates were 94.0% [79/84] and 89.7% [70/78], respectively. There were insufficient data for analysis of bacteriologic efficacy. However, bacteria were eradicated or presumed eradicated in 71.4% (10/14) and 79.2% (19/24) of patients in the ER and IR groups, respectively. The number of adverse events (AEs) considered to be possibly or probably related to study drug (23.4% [52/222] of patients receiving clarithromycin ER and 24.4% [43/176] of patients receiving clarithromycin IR) was similar between groups, as was the severity of these events (94.2% [49/52] in the ER group classified as mild or moderate vs 93.0% [40/43] in the IR group). Overall, the most commonly reported AEs were diarrhea, nausea, abdominal pain, headache, and taste disturbance. Conclusion: Clarithromycin ER 500-mg tablets QD for 7 days were as effective and well tolerated as clarithromycin IR 250-mg tablets BID for 7 days in treating adults with AECB.

A controlled, double-blind, multicenter study comparing clarithromycin extended-release tablets and levofloxacin tablets in the treatment of community-acquired pneumonia

Background: Macrolides and fluoroquinolones are frequently used for the empiric treatment of community-acquired pneumonia (CAP).Objective: The aim of the study was to compare the safety profile and efficacy of clarithromycin extended-release (ER) tablets with those of levofloxacin tablets for the treatment of CAP in ambulatory adult patients.Methods: In a Phase III, double-blind, randomized, parallel-group, multicenter study, ambulatory adult patients (≥18 years) with signs and symptoms of CAP received a 7-day course of treatment with either clarithromycin ER (two 500-mg tablets once daily) or levofloxacin (two 250-mg tablets once daily). A diagnosis of CAP was confirmed by radiography of the chest and physical examination, and sputum samples were analyzed to identify etiologic pathogen(s). Tolerability was assessed through subjective reports of adverse events and through changes in physical findings, concomitant medications, and laboratory values.Results: There were no statistically significant differences between treatment groups in terms of sex, age, race, or body weight. The mean age was 50 years (range, 18–91 years). Of 299 patients randomized and treated, 252 were clinically evaluable (128 clarithromycin ER, 124 levofloxacin). The 95% CI for the difference between cure rates demonstrated equivalence of the 2 treatments. Among clinically evaluable patients at the test-of-cure visit, clinical cure rates were 88% (113/128) and 86% (107/124), and radiographic success rates were 95% (117/123) and 88% (104/118) for clarithromycin ER and levofloxacin, respectively. Both treatment regimens were effective in resolving and improving clinical signs and symptoms of CAP. Among clinically and bacteriologically evaluable patients, bacteriologic cure rates were 86% (80/93) and 88% (85/97) for clarithromycin ER and levofloxacin, respectively. No statistically significant differences were observed between the 2 treatment groups in the overall incidence of adverse events.Conclusions: Clarithromycin ER demonstrated equivalent efficacy and tolerability to the fluoroquinolone levofloxacin in a group of ambulatory adult patients with CAP. Clarithromycin ER also appeared to be safe in the population studied.

Serum Bactericidal Activity of Extended‐Release Clarithromycin Against Macrolide‐Resistant Strains of Streptococcus pneumoniae

To investigate the serum bactericidal activity (SBA) over time of extended-release clarithromycin against moderately resistant strains of Streptococcus pneumoniae. Prospective, single-dose pharmacodynamic study. University-affiliated research center. Eleven healthy male volunteers. All volunteers received a single dose of extended-release clarithromycin as two 500-mg tablets, and blood samples were obtained at 0, 2, 6, 12, and 24 hours after administration of the dose. For each blood sample, a serum bactericidal titer (SBT) was determined against S. pneumoniae strains with minimum inhibitory concentrations (MICs) of 0.5, 1.0, 2.0, 4.0, and 8.0 microg/ml to clarithromycin. The median SBT was determined for each time period. The extended-release formulation of clarithromycin exhibited SBA for 24 hours against pneumococcal strains with MICs of 0.5, 1.0, and 2.0 microg/ml. No SBA was observed against isolates with MICs of 4.0 or 8.0 microg/ml. The extended-release formulation of clarithromycin, taken once/day, will provide SBA for 24 hours against strains of S. pneumoniae with MICs of 2.0 microg/ml or less.