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PubMed1993

Comparative safety and efficacy of clarithromycin and amoxicillin/clavulanate in the treatment of acute otitis media in children.

Clarithromycin is a new macrolide antibiotic with a wide spectrum of activity that includes the pathogens commonly causing pediatric otitis media. This randomized, investigator-blinded, multicenter trial compared the safety and efficacy of clarithromycin and amoxicillin/clavulanate in the treatment of acute otitis media in patients ages 6 months to 12 years. A total of 338 patients with acute otitis media diagnosed by otoscopy were randomized to receive clarithromycin 7.5 mg/kg twice daily, maximum 500 mg twice daily (n = 161), or amoxicillin/clavulanate 13.3 mg/kg three times daily, maximum 500 mg three times daily (n = 177), for 10 days. Treatment groups were comparable with respect to demographics, severity of infection and number of previous episodes. Efficacy was assessed by clinical examination performed within 48 hours of finishing study medication. A successful clinical response was seen in 90% (121 of 135) of evaluable clarithromycin patients vs. 92% (133 of 145) of evaluable amoxicillin/clavulanate patients (P = 0.681). Clinical failure or relapse (Posttreatment Days 0 to 4) occurred in 10% (14 of 135) of clarithromycin-treated patients vs. 8% (12 of 145) of amoxicillin/clavulanate-treated patients. Gastrointestinal adverse events were the most commonly reported in both groups. Of these events diarrhea was the most frequent, occurring in 12% (19 of 161) of clarithromycin and 32% (57 of 177) of amoxicillin/clavulanate-treated patients (P < 0.001). These results indicate that the efficacy of clarithromycin oral suspension was comparable with amoxicillin/clavulanate oral suspension in the treatment of acute otitis media in children. Clarithromycin was better tolerated than amoxicillin/clavulanate with a lower incidence of gastrointestinal side effects.

Acute Disease↗
PubMed1993

Comparison of clarithromycin and penicillin VK suspensions in the treatment of children with streptococcal pharyngitis and review of currently available alternative antibiotic therapies.

In a randomized investigator-blinded study, 506 children ages 6 months to 12 years with positive rapid direct antigen tests for Group A beta-hemolytic Streptococcus (GABHS) received treatment with either clarithromycin suspension, 7.5 mg/kg twice daily, or penicillin VK suspension, 13.3 mg/kg three times per day for 10 days. Signs and symptoms of pharyngitis or tonsillitis were evaluated and throat cultures were obtained before treatment, once during treatment and 4 to 6 days and 19 to 25 days posttreatment. All GABHS isolates were susceptible in vitro to clarithromycin. Successful clinical responses at the end of treatment were demonstrated in 169 of 176 (96%) evaluable clarithromycin-treated patients and 179 of 191 (94%) evaluable penicillin-treated patients. GABHS was successfully eradicated at end of treatment in 168 of 183 (92%) evaluable clarithromycin-treated patients compared with 162 of 199 (81%) evaluable penicillin-treated patients (P = 0.004). There were no significant changes in hematologic or serum chemistry parameters in either group. Both drugs were well-tolerated. The incidence and nature of adverse events were similar in the clarithromycin and penicillin groups, except for gastrointestinal complaints reported in 35 of 250 (14%) clarithromycin recipients compared with 12 of 256 (5%) penicillin recipients (P < or = 0.001). The results indicate that twice daily clarithromycin was as safe and effective as three times daily penicillin VK in the treatment of children with streptococcal pharyngitis or tonsillitis. Clarithromycin was statistically superior to penicillin VK in the eradication of GABHS.

Child↗
PubMed1997

Penetration of clarithromycin into middle ear fluid of children with acute otitis media.

OBJECTIVE: To determine the steady state plasma and middle ear fluid concentrations of clarithromycin and its metabolite, 14(R)-hydroxyclarithromycin in 32 pediatric patients with acute otitis media. METHODS: After the sixth dose of a 7.5-mg/kg every-12-h regimen of clarithromycin suspension, tympanocentesis was performed at 2, 4, 8 or 12 hours postdose. Plasma and middle ear fluid samples were assayed for concentrations of clarithromycin and its 14-hydroxy metabolite. RESULTS: Mean middle ear fluid concentrations ranged from 3.0 to 8.3 micrograms/g during the dosing interval for clarithromycin and from 1.5 to 3.8 micrograms/g for 14(R)-hydroxyclarithromycin. The mean middle ear fluid concentrations were consistently greater than corresponding mean plasma concentrations, which ranged from 0.7 to 3.4 micrograms/ml for clarithromycin and from 0.8 to 1.8 micrograms/ml for 14(R)-hydroxyclarithromycin. The ratios of middle ear fluid to plasma concentration appeared to increase during the dosing interval and were 8.8 and 3.8 for clarithromycin and 14(R)-hydroxyclarithromycin, respectively, 12 h after dosing. CONCLUSIONS: Multiple oral doses of clarithromycin suspension produced sustained middle ear fluid concentrations of clarithromycin and 14(R)-hydroxyclarithromycin which exceed the minimum inhibitory concentrations of most otic pathogens.

Acute Disease↗
PubMed2007

Effects of clarithromycin and grapefruit juice on the pharmacokinetics of glibenclamide.

AIMS: Case reports suggest that clarithromycin can increase the glucose-lowering effect of glibenclamide which is metabolized mainly by CYP2C9 and is a substrate for P-glycoprotein and OATP2B1. Our objective was to evaluate whether the P-glycoprotein inhibitor, clarithromycin, increases and the putative OATP2B1 inhibitor, grapefruit juice, decreases plasma concentrations of glibenclamide. METHODS: In a randomized three-phase crossover study, 12 subjects ingested 250 mg clarithromycin or placebo twice daily or 200 ml grapefruit juice three times daily for 2 days. On day 3, they ingested 0.875 mg glibenclamide with sugar water or grapefruit juice. Concentrations of glibenclamide and clarithromycin in plasma, glucose in blood, and excretion of hydroxy-glibenclamide into urine were measured up to 12 h. RESULTS: Clarithromycin increased the peak concentration (C(max)) of glibenclamide to 1.25-fold (95% confidence interval (CI) 1.12, 1.40; P < 0.01) and the area under the plasma concentration-time curve to 1.35-fold (95% CI 1.21, 1.50; P < 0.01) compared with the placebo phase. The time to C(max), the half-life of glibenclamide, and the amount of hydroxy-glibenclamide excreted into urine remained unaltered. Grapefruit juice did not change the pharmacokinetics of glibenclamide. Clarithromycin concentrations implied a good compliance. Blood glucose did not deviate between the phases. CONCLUSIONS: Clarithromycin increased plasma concentrations of glibenclamide, possibly by inhibiting P-glycoprotein in the intestinal wall. Although not seen with the present study design, clarithromycin may enhance the effect of glibenclamide by increasing plasma glibenclamide concentrations, which warrants close monitoring of blood glucose during their co-administration. Grapefruit juice had no effect on glibenclamide pharmacokinetics.

Adult↗
PubMed1992

Activity of clarithromycin against Mycobacterium avium complex infection in beige mice.

The activity of clarithromycin alone and in combination with other antimycobacterial agents was evaluated in the beige (C57BL/6J bgj/bgj) mouse model of disseminated Mycobacterium avium complex (MAC) infection. A dose-response experiment was performed with clarithromycin at 50, 100, 200, or 300 mg/kg of body weight administered daily by gavage to mice infected with approximately 10(7) viable MAC. A dose-related reduction in spleen and liver cell counts was noted with treatment at 50, 100, and 200 mg/kg. The difference in cell counts between treatment at 200 and 300 mg/kg was not significant. Clarithromycin at 200 mg/kg of body weight was found to have activity against three additional MAC isolates (MICs for the isolates ranged from 1 to 4 micrograms/ml by broth dilution). Clarithromycin at 200 mg/kg in combination with amikacin, ethambutol, temafloxacin, or rifampin did not result in increased activity beyond that seen with clarithromycin alone. Clarithromycin in combination with clofazimine or rifabutin resulted in an increase in activity beyond that seen with clarithromycin alone. The combination of clarithromycin with clofazimine or rifabutin should be considered for evaluation in the treatment of human MAC infections.

Amikacin↗
PubMed1992

Pharmacokinetics of clarithromycin, a new macrolide, after single ascending oral doses.

The pharmacokinetics and safety of single ascending doses of clarithromycin (6-0-methylerythromycin A) were assessed in a placebo-controlled, double-blind, randomized trial with 39 healthy male volunteers. Subjects were randomized to receive single doses of either placebo or 100, 200, 400, 600, 800, or 1,200 mg of clarithromycin. Blood and urine collections were performed over the 24 h following administration of the test preparation. Biological specimens were analyzed for clarithromycin and 14(R)-hydroxyclarithromycin content by a high-performance liquid chromatographic technique. The pharmacokinetics of clarithromycin appeared to be dose dependent, with terminal disposition half-life ranging from 2.3 to 6.0 h and mean +/- standard deviation area under the concentration-versus-time curve from time 0 to infinity for plasma ranging from 1.67 +/- 0.48 to 3.72 +/- 1.26 mg/liter.h per 100-mg dose over the 100- to 1,200-mg dose range. Similar dose dependency was noted in the pharmacokinetics of the 14(R)-hydroxy metabolite. Mean urinary excretion of clarithromycin and its 14(R)-hydroxy metabolite ranged from 11.5 to 17.5% and 5.3 to 8.8% of the administered dose, respectively. Urinary excretion data and plasma metabolite/parent compound concentration ratio data suggested that capacity-limited formation of the active metabolite may account, at least in part, for the nonlinear pharmacokinetics of clarithromycin. No substantive dose-related trend was observed for the renal clearance of either compound. There were no clinically significant drug-related alterations in laboratory and nonlaboratory safety parameters. In addition, there was no significant difference between placebo and clarithromycin recipients in the incidence or severity of adverse events. Clarithromycin appears to be safe and well tolerated.

Administration, Oral↗
PubMed1992

Activity of clarithromycin alone or in combination with other drugs for treatment of murine toxoplasmosis.

The activity of the macrolide antibiotic clarithromycin was examined alone or in combination with other drugs for the treatment of acute or chronic infections with Toxoplasma gondii in mice. A dose of 300 mg of clarithromycin per kg per day administered alone for 10 days, beginning 24 hours after infection, protected 10 to 30% of mice infected with lethal inocula of tachyzoites or tissue cysts of different strains of T. gondii, including some strains isolated from patients with both AIDS and toxoplasmosis. Although clarithromycin was protective, a wide variation in its activity against different strains was observed. Survival of infected mice was increased significantly by treatment with clarithromycin in combination with pyrimethamine or with sulfadiazine. Treatment of chronically infected mice with clarithromycin at 300 mg/kg/day administered alone for 8 weeks resulted in significant reduction in the numbers of T. gondii cysts in their brains. The combination of clarithromycin and minocycline resulted in an activity against T. gondii cysts that was significantly greater than the activity of clarithromycin or minocycline administered alone. These results indicate a role for clarithromycin in the treatment of human toxoplasmosis, particularly when this antibiotic is used in combination with other drugs with activity against T. gondii.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Efficacy of granulocyte colony-stimulating factor and RU-40555 in combination with clarithromycin against Mycobacterium avium complex infection in C57BL/6 mice.

We compared the activities of two different biological-response modifiers with that of clarithromycin against Mycobacterium avium complex infection in C57BL/6 mice. Mice were pretreated daily with clarithromycin (50 mg/kg of body weight subcutaneously [s.c.]), RU-40555 (100 mg/kg s.c.), or granulocyte colony-stimulating factor (G-CSF) at low dose (15 micrograms/kg intraperitoneally [i.p.]) or high dose (300 micrograms/kg i.p.) 3 days before intravenous challenge with 2.5 x 10(7) CFU of the MO-1 strain of M. avium complex. Mice were treated daily until sacrifice at day 1, 8, 15, or 21 after challenge, and the numbers of CFU were measured per gram of tissue in lung and spleen. Compared at day 21 with control treatment, clarithromycin significantly decreased the level of infection in spleen (P < 0.0001) and lungs (P < 0.0001). Compared with control treatment, G-CSF at low dose had no activity, but G-CSF in combination with clarithromycin was more effective than clarithromycin alone in spleen (P < 0.05) and lungs (P < 0.015). The high dose of G-CSF was as effective as the low dose. RU-40555 alone had no beneficial activity. The RU-40555-clarithromycin combination was more effective than control treatment in spleen (P = 0.0001) and lungs (P < 0.0005) and more effective than clarithromycin alone in spleen (P < 0.009) but not in lungs. Thus, our experiments suggest that clarithromycin alone or in combination with G-CSF should be further evaluated for the prophylaxis of M. avium complex infection.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Steady-state pharmacokinetics and electrocardiographic pharmacodynamics of clarithromycin and loratadine after individual or concomitant administration.

To evaluate the potential for an interaction between clarithromycin and loratadine, healthy male volunteers (n = 24) received each of the following regimens according to a randomized crossover design: 500 mg of clarithromycin orally every 12 h (q12h) for 10 days, 10 mg of loratadine orally q24h for 10 days, and the combination of clarithromycin and loratadine. A washout interval of 14 days separated regimens. The addition of loratadine did not statistically significantly affect the steady-state pharmacokinetics of clarithromycin or its active metabolite, 14(R)-hydroxy-clarithromycin. However, the addition of clarithromycin statistically significantly altered the steady-state maximum observed plasma concentration and the area under the plasma concentration-time curve over a dosing interval for loratadine (+36 and +76%, respectively) and for descarboethoxyloratadine (DCL), the active metabolite of loratadine (+69 and +49%, respectively). Clarithromycin probably inhibits the oxidative metabolism of loratadine and DCL by the cytochrome P-450 3A subfamily. Electrocardiograms (n = 12) were obtained over 24-h periods at baseline and steady state (day 10). The mean maximum QTc interval and area under the QTc interval-time curve on day 10 were modestly increased (<3%) from baseline for all three regimens, but no QTc interval exceeded 439 ms for any subject. Elevated steady-state concentrations of loratadine and DCL do not appear to be associated with adverse cardiovascular effects related to prolongation of the QTc interval. Loratadine and clarithromycin were well tolerated, alone and in combination.

Adolescent↗
PubMed1998

Dynamics of clarithromycin and azithromycin efficacies against experimental Haemophilus influenzae pulmonary infection.

The dynamics of clarithromycin and azithromycin efficacy against pulmonary Haemophilus influenzae infection in rats were evaluated. Efficacy was measured by reduction in pulmonary H. influenzae burden on days 3 and 7 postinoculation. Clarithromycin therapy was effective on day 3 or 7 of therapy, while azithromycin was effective on day 7 but not on day 3 of therapy. Both macrolides produced marked efficacy against all six strains of H. influenzae tested, including four strains for which MICs were above the susceptible breakpoint (8 microgram/ml) concentration of clarithromycin. The two macrolides demonstrated markedly different pharmacokinetic characteristics, with clarithromycin present in both blood and tissue, while azithromycin was concentrated primarily in tissue. During pulmonary infection in rats, H. influenzae was found in both intracellular locations and an extracellular location in the lung. Blood concentrations of clarithromycin and azithromycin approximated human pharmacokinetics, and the blood concentrations for either macrolide rarely exceeded MICs for H. influenzae. At dosages producing blood concentrations similar to values achieved clinically, clarithromycin produced efficacy on day 3 of therapy, while both clarithromycin and azithromycin were equally effective on day 7. The different dynamics of clarithromycin and azithromycin suggest that length of therapy should be considered as a key parameter in evaluations of drug efficacy.

Animals↗
PubMed2006

Clarithromycin in the treatment of RSV bronchiolitis: a double-blind, randomised, placebo-controlled trial.

Respiratory syncytial virus (RSV) bronchiolitis is the most common lower respiratory tract infection in infancy. To date, there is no effective therapy for RSV bronchiolitis. In order to investigate the efficacy of clarithromycin in the treatment of RSV bronchiolitis, the present authors conducted a randomised, double-blind, placebo-controlled trial comparing clarithromycin with placebo in 21 infants with a diagnosis of RSV bronchiolitis. The infants were randomised to receive clarithromycin or placebo daily for 3 weeks. Levels of interleukin (IL)-4, IL-8, eotaxin, and interferon-gamma were determined in plasma, before and after treatment, using ELISA. Six months after treatment, parents were surveyed as to whether their child had experienced wheezing within the previous 6 months. Treatment with clarithromycin was associated with a statistically significant reduction in the length of hospital stay, the duration of need for supplemental oxygen and the need for beta(2)-agonist treatment. There were significant decreases in plasma IL-4, IL-8 and eotaxin levels after 3 weeks of treatment with clarithromycin. Readmission to the hospital within 6 months after discharge was significantly lower in the clarithromycin group. In conclusion, clarithromycin has statistically significant effects on the clinical and laboratory findings in respiratory syncytial virus bronchiolitis. Therefore, clarithromycin treatment may be helpful in reducing the short-term effects of respiratory syncytial virus bronchiolitis.

Anti-Bacterial Agents↗
PubMed1990

Comparison of the clinical and bacteriological efficacy of clarithromycin and erythromycin in the treatment of streptococcal pharyngitis.

The efficacy and tolerability of clarithromycin and erythromycin stearate in the treatment of documented Group A beta-haemolytic streptococcal pharyngitis were compared in a single-centre, open, out-patient study. One hundred and twenty patients were randomly assigned to each treatment group. Dosage of clarithromycin and erythromycin was 250 mg twice daily and 500 mg twice daily, respectively; each patient was given a 10-day supply of medication. Clinical success (cured or improved) was observed in 111 (96.5%) of 115 and in 108 (93.9%) of 115 clinically-evaluable patients treated with clarithromycin and erythromycin, respectively. Eradication of the pathogen occurred in 108 (97.3%) of 111 and in 98 (92.5%) of 106 bacteriologically-evaluable clarithromycin and erythromycin patients, respectively. Adverse events reported by 7 (5.8%) of the clarithromycin-treated and by 12 (10%) of the erythromycin-treated patients included epigastritis and nausea and vomiting. In general, the severity of adverse events was greater for the patients treated with erythromycin, necessitating the discontinuation of therapy in 8 (6.7%) patients treated with erythromycin as opposed to 1 (0.8%) patient treated with clarithromycin. Although clarithromycin and erythromycin were comparable in terms of efficacy, clarithromycin was better tolerated.

Administration, Oral↗
PubMedDate not supplied

Concomitant digoxin toxicity and warfarin interaction in a patient receiving clarithromycin.

OBJECTIVE: To report a case of a clarithromycin-associated warfarin interaction and digoxin toxicity in a patient. CASE SUMMARY: A 72-year-old white woman with chronic atrial fibrillation receiving long-standing therapy with digoxin 0.25 mg/d and warfarin 22.5 mg/wk was prescribed clarithromycin 500 mg three times daily for eradication of Helicobacter pylori. The patient presented to the emergency department with gastrointestinal symptoms, weakness, dizziness, and visual changes 12 days after initiation of clarithromycin. Laboratory results revealed a serum digoxin concentration of 4.6 ng/mL (normal 1.0-2.6) and an international normalized ratio of 7.3 (2.0-3.0). Digoxin, warfarin, and clarithromycin were discontinued and the patient was admitted to the hospital for treatment to resolve the symptoms and to return laboratory values to a safe range. Reduced dosages of digoxin (0.125 mg/d) and warfarin (17.5 mg/wk) were restarted on day 7 of hospitalization. The patient was discharged on day 11 in good condition. DISCUSSION: Several reports of clarithromycin-induced drug interactions with digoxin and with warfarin have been published. Previously, case reports of macrolide-associated interactions mainly involved erythromycin, but more recently have implicated clarithromycin. The interaction between clarithromycin and warfarin is thought to occur from an inhibition of the cytochrome P450 drug metabolizing system. Clarithromycin is thought to cause digoxin toxicity by an alteration of the digoxin-metabolizing gut flora, thereby causing an increase in the digoxin concentration in susceptible individuals. Drug interactions can occur by different mechanisms in the same patient. CONCLUSIONS: Potential drug interactions can occur between commonly prescribed medications. It is important to monitor patients for symptoms and alterations in laboratory values to prevent not only serious complications, but also unnecessary hospitalizations.

Aged↗
PubMed2004

The effect of clarithromycin on inflammatory markers in chronic obstructive pulmonary disease: preliminary data.

BACKGROUND: Clarithromycin is an antimicrobial agent that can be used for treatment of chronic obstructive pulmonary disease (COPD) exacerbations with bronchodilator therapy. However, it has also been shown that clarithromycin has antiinflammatory effects by the inhibition of cytokine production. OBJECTIVE: To evaluate the antiinflammatory effect of clarithromycin on serum and sputum interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), and leukotriene B4 levels in patients with COPD. METHODS: Thirty men with mild to moderate COPD were enrolled in this prospective, single-center, double-blind, placebo-controlled study. None of the patients was receiving systemic or inhaled corticosteroids during the study. Subjects received either clarithromycin or placebo for 14 days. Before and after this treatment period, spirometric tests and arterial blood gas analysis were performed, blood was drawn for measurement of serum inflammatory markers, and sputum was induced. RESULTS: There were no statistically significant differences in baseline clinical or laboratory parameters between the groups. After the treatment, the induced sputum total cell counts, and IL-8 and TNF-alpha levels decreased significantly in the clarithromycin group compared with pretreatment levels (mean +/- SD IL-8 1606 +/- 367.3 vs 882 +/- 143.6 pg/mL, p = 0.001; TNF-alpha 638.2 +/- 287.5 vs 390 +/- 235 pg/mL, p = 0.001). Similarly, decreases in serum inflammatory markers were found in the clarithromycin group while there was no significant change in the placebo group. CONCLUSIONS: This study demonstrated that the decrease in IL-8 and TNF-alpha levels might be related to the antiinflammatory effect of clarithromycin. Thus, we suggest that the use of clarithromycin in COPD exacerbations may either treat the infection or help control the inflammation. Future studies are needed to determine the clinical significance of these findings.

Aged↗
PubMed2005

Five-day telithromycin once daily is as effective as 10-day clarithromycin twice daily for the treatment of acute exacerbations of chronic bronchitis and is associated with reduced health-care resource utilization.

STUDY OBJECTIVES: To demonstrate equivalence in the clinical efficacy of telithromycin vs clarithromycin treatment of outpatients with acute exacerbations of chronic bronchitis (AECB), and to compare the tolerability and respiratory-related health-care resource utilization associated with these treatment regimens. DESIGN AND PATIENTS: A randomized, double-blind, multicenter, clinical study was conducted at 105 centers in 14 countries. Adult outpatients (age > or = 30 years) received oral telithromycin, 800 mg qd for 5 days (n = 270), or oral clarithromycin, 500 mg bid for 10 days (n = 282), for the treatment of AECB. Clinical and bacteriologic outcomes were assessed at the posttherapy/test-of-cure (TOC) visit (days 17 to 24; per-protocol population). Health-care resource utilization data were collected for each patient by investigators blinded to study medication up to the late posttherapy visit (days 31 to 36). RESULTS: Clinical cure rates at the posttherapy/TOC visit were comparable between the groups (telithromycin, 193 of 225 patients [85.8%]; clarithromycin, 206 of 231 patients [89.2%]); bacteriologic outcome was satisfactory for 59 of 72 telithromycin-treated patients (81.9%) vs 63 of 76 clarithromycin-treated patients (82.9%). Health-care resource utilization assessed up to the late posttherapy visit was lower in the telithromycin treatment group than the clarithromycin treatment group, with significantly fewer hospitalizations for respiratory-related causes (one hospitalization vs eight hospitalizations for a total of 4 inpatient days vs 39 inpatient days, respectively), significantly fewer AECB-related emergency department visits (0 vs 8), and fewer unscheduled outpatient visits (11 vs 18). Fewer telithromycin-treated patients reported days lost from work (21 of 91 patients [23.1%]; 133 days) compared with those receiving clarithromycin (30 of 98 patients [30.6%]; 141 days). Telithromycin was well tolerated; adverse events considered possibly related to study medication were reported by 61 of 269 patients (22.7%) and 100 of 280 patients (35.7%) receiving telithromycin and clarithromycin, respectively. CONCLUSIONS: In this study, 5-day telithromycin treatment was as effective and well tolerated as 10-day clarithromycin treatment for patients with AECB, and was associated with a reduced utilization of health-care resources.

Acute Disease↗
PubMed1999

Review and comparison of advanced-generation macrolides clarithromycin and dirithromycin.

We reviewed English-language clinical studies, abstracts, and review articles identified from MEDLINE searches from January 1966-August 1998, and bibliographies of identified articles to compare advanced-generation macrolides dirithromycin and clarithromycin and their use for respiratory tract infections. Both agents have superior adverse effect profiles compared with erythromycin, the original macrolide. Both have broad antibacterial coverage, but clarithromycin usually has a lower MIC90 to susceptible organisms than dirithromycin; for most isolates this difference is not clinically significant. Clarithromycin has better in vitro coverage of Haemophilus influenzae, but this activity varies with formation of its bioactive metabolite, 14-hydroxyclarithromycin. Neither agent is ideal for H. influenzae eradication. The agents differ markedly in terms of pharmacokinetics, pharmacodynamics, metabolism, and cost, and thus with respect to drug interaction profiles and dosages. Dirithromycin's drug interaction profile is markedly better than clarithromycin's. Clarithromycin is dosed twice/day; dirithromycin's pharmacokinetics allow once/day dosing. Dirithromycin is less expensive with regard to both cost/day and cost/treatment regimen. Clarithromycin has been studied and approved for administration to children. In adults with respiratory tract infections who are receiving drugs that would interact with clarithromycin, and in those with renal dysfunction with or without coexisting hepatic dysfunction, dirithromycin appears to be superior in terms of safety and equivalent to clarithromycin in terms of efficacy.

Animals↗
PubMed1993

Clarithromycin clinical pharmacokinetics.

Clarithromycin is a semisynthetic macrolide antibiotic, structurally related to erythromycin. It has a more favourable pharmacokinetic profile than erythromycin, thus allowing twice-daily administration and possibly increasing compliance among outpatients. Clarithromycin is well absorbed from the gastrointestinal tract and its systemic bioavailability (about 55%) is reduced because of first-pass metabolism. It undergoes rapid biodegradation to produce the microbiologically active 14-hydroxy-(R)-metabolite. The maximum serum concentrations of clarithromycin and its 14-hydroxy metabolite, following single oral doses, are dose proportional and appear within 3 hours. With multiple doses, steady-state concentrations are attained after 5 doses and the maximal serum concentrations of clarithromycin and of the 14-hydroxy derivative appear within 2 hours after the last dose. Clarithromycin is well distributed throughout the body and achieves higher concentrations in tissues than in the blood. Also, the 14-hydroxy metabolite exhibits high tissue concentrations, with values about one-third of the parent compound concentrations. The presence of food appears to have no clinically significant effect on clarithromycin pharmacokinetics. The main metabolic pathways are oxidative N-demethylation and hydroxylation, which are saturable and result in nonlinear pharmacokinetics. The primary metabolite (14-hydroxy derivative) is mainly excreted in the urine with the parent compound. A reduction in urinary clearance in the elderly and in patients with renal impairment is associated with an increase in area under the plasma concentration-time curve, peak plasma concentrations and elimination half-life. Mild hepatic impairment does not significantly modify clarithromycin pharmacokinetics. In conclusion, clarithromycin, because of its antibacterial activity and pharmacokinetic properties, appears to be a useful alternative to other macrolides in the treatment of community acquired infections.

Absorption↗
PubMed2006

Efficacy and safety of Helicobacter pylori eradication therapy with omeprazole, amoxicillin and high- and low-dose clarithromycin in Japanese patients: a randomised, double-blind, multicentre study.

OBJECTIVE: Seven-day administration of omeprazole 40 mg/day + amoxicillin 1500 mg/day + clarithromycin 800 mg/day is currently approved in Japan for the eradication of Helicobacter pylori infection. We investigated the efficacy and safety of an omeprazole-based triple therapy regimen in combination with amoxicillin and low-dose clarithromycin in Japanese patients. METHODS: Patients were randomly assigned to either the low-dose group (omeprazole 40 mg/day + amoxicillin 1500 mg/day + clarithromycin 400 mg/day) or the high-dose group (omeprazole 40 mg/day + amoxicillin 1500 mg/day + clarithromycin 800 mg/day). A total of 288 patients were allocated to the low-dose (143) and high-dose (145) groups and were treated twice daily for 1 week. RESULTS: For the full-analysis set, H. pylori eradication rates were 81.1% (116/143 patients, 90% confidence interval [CI] 74.9, 86.3) in the low-dose group and 80.0% (116/145 patients, 90% CI 73.7, 85.3) in the high-dose group. Per-protocol eradication rates were 81.7% (103/126 patients, 90% CI 75.1, 87.2) and 84.1% (90/107 patients, 90% CI 77.1, 89.6), respectively. When patients with non-susceptibility to clarithromycin were excluded, eradication rates were >80% for both gastric and duodenal ulcers in the two groups. The results suggested that eradication rates were affected more by susceptibility to clarithromycin than to amoxicillin. Both regimens were well tolerated. CONCLUSION: This study demonstrated that an omeprazole-based triple-therapy regimen with clarithromycin 400 mg/day was as effective as that with clarithromycin 800 mg/day for H. pylori eradication.

Adult↗