Klaz 250/Klaz Suspension

Klaz 250/Klaz Suspension Mechanism of Action

clarithromycin

Manufacturer:

Amherst Lab

Distributor:

Pediatrica
Full Prescribing Info
Action
Pharmacology: Pharmacodynamics: Clarithromycin, a semi-synthetic 14-membered ring macrolide, exerts its antibacterial activity by binding to the donor site on the 50s subunit of the bacterial ribosome thus inhibiting protein synthesis. Like other macrolides, clarithromycin penetrates intracellularly and is highly concentrated in the polymorphonuclear leukocytes and tissue macrophages. There is no evidence, however, that clarithromycin has in vivo pharmacologic effect on mammalian cells.
Pharmacokinetics: Film-coated Tablet and Suspension: Clarithromycin is rapidly absorbed and reaches peak serum concentrations approximately 2 hours after oral administration.
Clarithromycin has non-linear, dose-dependent pharmacokinetics due to saturation of metabolic pathways. This nonlinearity is minimal with usual dosages (250 to 500 mg every 8 to 12 hours) but increases disproportionately with single high doses (e.g., 1.2 g) or with multiple clarithromycin doses.
Food delays the onset of clarithromycin absorption and increases peak time (tmax) from 2 to 2.5 hours; the extent of absorption is unaffected.
Administration of a 250 mg clarithromycin dose, either as tablet or suspension to fasting healthy adults, results in average peak serum clarithromycin concentration (Cmax) of 0.6 mcg/mL reached within 1 to 4 hours. After oral administration of clarithromycin 250 mg tablet every 12 hours or clarithromycin 500 mg tablet every 8 to 12 hours, peak steady-state clarithromycin concentrations were achieved within 3 days and averaged about 1 to 2 or 3 to 4 mcg/mL, respectively, while peak steady-state 14-hydroxy (OH) clarithromycin concentrations were achieved within 3 to 4 days and averaged about 0.6 to 1 mcg/mL for both doses. The active metabolite of clarithromycin is 14-hydroxy (OH) clarithromycin.
The overall bioavailability of clarithromycin suspension was equivalent to or slightly greater than the tablet in a single 250 mg dose study in adults. Administration of clarithromycin suspension with food led to a slight delay in the onset of absorption but did not affect the overall bioavailability of clarithromycin. The Cmax, area under the plasma concentration time curve (AUC), and half-life (t1/2) for clarithromycin suspension (non-fasted state) were 0.95 mcg/mL, 6.5 mcg.hr/mL, and 3.7 hours, respectively, and for clarithromycin tablet (fasted state) were 1.1 mcg/mL, 6.3 mcg.hr/mL, and 3.3 hours, respectively.
In a single-dose study in children under fed conditions, clarithromycin suspension 7.5 mg/kg resulted in an increase in Cmax from 3.6 ± 1.5 mcg/mL to 4.6 ± 2.8 mcg/mL and the AUC from 10 ± 5.5 mcg.hr/mL to 14.2 ± 9.4 mcg.hr/mL.
In a multiple dose study in adults, administration of clarithromycin suspension 250 mg every 12 hours resulted in steady state after the fifth dose: Cmax 1.98 mcg/mL, AUC 11.5 mcg.hr/mL, tmax 2.8 hours and t1/2 3.2 hours for clarithromycin, and 0.67 mcg/mL, 5.33 mcg.hr/mL, 2.9 hours and 4.9 hours, respectively, for 14-OH clarithromycin. When a similar formulation was administered in children requiring oral antibiotic treatment, steady-state pharmacokinetic parameters reached after the ninth dose on treatment day 5 were: Cmax 4.6 mcg/mL, AUC 15.7 mcg.hr/mL, tmax 2.8 hours and t1/2 2.2 hours for clarithromycin, and 1.64 mcg/mL, 6.69 mcg.hr/mL, 2.7 hours and 4.3 hours, respectively, for 14-OH clarithromycin.
Data on the penetration of clarithromycin into the middle ear fluid in patients with secretory otitis media were obtained in a study in children receiving clarithromycin 7.5 mg/kg every 12 hours. The mean concentrations of clarithromycin and 14-OH clarithromycin in the middle ear fluid were 2.53 mcg/mL and 1.27 mcg/mL, respectively. These concentrations were generally twice as high as the corresponding concentrations in serum (i.e., 1.7 mcg/mL for clarithromycin and 0.8 mcg/mL for 14-OH clarithromycin).
Clarithromycin and 14-OH clarithromycin are distributed into most body tissues and fluids including lung, tonsil and nasal tissues. Tissue concentrations are higher than serum concentrations because of the drug's high intracellular concentrations. Clarithromycin is also distributed into the cerebrospinal fluid after oral administration but there is no evidence regarding its use in the treatment of meningitis.
At usual therapeutic concentrations, clarithromycin's protein binding is approximately 42% to 72%. It has a high affinity for α1-glycoprotein.
Clarithromycin's t1/2 after a 250 mg dose as conventional tablet given twice a day is about 3 to 4 hours; the t1/2 is 5 to 7 hours with 500 mg twice a day. The elimination t1/2 at steady-state is similar with equivalent clarithromycin doses as tablet or oral suspension. The t1/2 of clarithromycin ER tablet was 6.64 hours.
Clarithromycin is metabolized primarily in the liver via the cytochrome P450 3A (CYP3A) isoenzyme. Although seven metabolites of clarithromycin have been identified, 14-OH clarithromycin is the principal metabolite in the serum and is the only one with substantial antibacterial activity.
About 20-30%, or 40% of a given clarithromycin dose is excreted unchanged in the urine within 12 hours after administration of clarithromycin 250 mg or 500 mg tablet, or 250 mg (125 mg/5 mL) suspension every 12 h ours, respectively. Urinary excretion of clarithromycin ER accounts for about 40% of the clarithromycin dose. Fecal elimination accounts for approximately 30%.
Extended-release Tablet: Administration of clarithromycin extended-release (ER) tablets provides extended absorption of clarithromycin from the gastrointestinal (GI) tract. Although the 24-hour AUCs for clarithromycin and 14-OH clarithromycin following administration of clarithromycin ER tablets are equivalent to the 24-hour AUCs of an equal total daily dose as clarithromycin tablets, clarithromycin ER tablets result in lower and later Cmax of clarithromycin and 14-OH clarithromycin. While the extent of formation of 14-OH clarithromycin following oral administration of clarithromycin 500 mg ER tablets is not affected by food, administration under fasting conditions is associated with approximately 30% lower clarithromycin AUC. Therefore, clarithromycin ER tablets should be taken with meals.
In healthy human subjects under fed conditions, the mean Cmax of 1.797 mcg/mL was achieved 5.58 hours (tmax) following oral administration of clarithromycin 500 mg ER tablet once a day for five consecutive days. The AUC (0-τ) was 20.406 mcg.hr/mL and the AUC(0-∞) was 22.214 mcg.hr/mL.
Clarithromycin and 14-OH clarithromycin are distributed into most body tissues and fluids including lung, tonsil and nasal tissues. Tissue concentrations are higher than serum concentrations because of the drug's high intracellular concentrations. Clarithromycin is also distributed into the cerebrospinal fluid after oral administration but there is no evidence regarding its use in the treatment of meningitis.
At usual therapeutic concentrations, clarithromycin's protein binding is approximately 42% to 72%. It has a high affinity for α1-glycoprotein.
Clarithromycin's t1/2 after a 250 mg dose as conventional tablet given twice a day is about 3 to 4 hours; the t1/2 is 5 to 7 hours with 500 mg twice a day. The elimination t1/2 at steady-state is similar with equivalent clarithromycin doses as tablet or oral suspension. The t1/2 of clarithromycin ER tablet was 6.64 hours.
Clarithromycin is metabolized primarily in the liver via the cytochrome P450 3A (CYP3A) isoenzyme. Although seven metabolites of clarithromycin have been identified, 14-OH clarithromycin is the principal metabolite in the serum and is the only one with substantial antibacterial activity.
About 20-30%, or 40% of a given clarithromycin dose is excreted unchanged in the urine within 12 hours after administration of clarithromycin 250 mg or 500 mg tablet, or 250 mg (125 mg/5 mL) suspension every 12 hours, respectively. Urinary excretion of clarithromycin ER accounts for about 40% of the clarithromycin dose. Fecal elimination accounts for approximately 30%.
Microbiology: Antimicrobial Spectrum of Activity: Clarithromycin has demonstrated activity in vitro and in clinical infections against most strains of the following microorganisms: See Table 1.

Click on icon to see table/diagram/image

Beta-lactamases have no effect on clarithromycin activity.
Most strains of methicillin-resistant and oxacillin-resistant staphylococci are resistant to clarithromycin.
Omeprazole/clarithromycin dual therapy, ranitidine bismuth citrate/clarithromycin dual therapy, omeprazole/clarithromycin/amoxicillin triple therapy and lansoprazole/clarithromycin/amoxicillin triple therapy have been shown to be active against most strains of Helicobacter pylori in vitro and in clinical infections.
Clarithromycin has demonstrated in vitro activity against most strains of the following microorganisms; however, clinical significance is unknown: See Table 2.

Click on icon to see table/diagram/image

It is suggested to carry out susceptibility tests.
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Sign up for free
Already a member? Sign in