Description: Clarithromycin is a semi-synthetic macrolide antibiotic. Chemically, it is 6-O-methylerythromycin. Clarithromycin is a white to off-white crystalline powder. It is soluble in acetone, slightly soluble in methanol, ethanol, and acetonitrile, and practically insoluble in water.

Pharmacological effects: Clarithromycin is rapidly and well-absorbed with dose-linear kinetics, low protein binding, and a high volume of distribution. Plasma half-life ranged from 1 to 6 hours and was species dependent. High tissue concentrations were achieved, but negligible accumulation was observed. Fecal clearance predominated. Hepatotoxicity occurred in all species tested (i.e., in rats and monkeys at doses 2 times greater than and in dogs at doses comparable to the maximum human daily dose, based on mg/m2). Renal tubular degeneration (calculated on a mg/m2 basis) occurred in rats at doses 2 times, in monkeys at doses 8 times, and in dogs at doses 12 times greater than the maximum human daily dose. Testicular atrophy (on a mg/m2 basis) occurred in rats at doses 7 times, in dogs at doses 3 times, and in monkeys at doses 8 times greater than the maximum human daily dose. Corneal opacity (on a mg/m2 basis) occurred in dogs at doses 12 times and in monkeys at doses 8 times greater than the maximum human daily dose. Lymphoid depletion (on a mg/m2 basis) occurred in dogs at doses 3 times greater than and in monkeys at doses 2 times greater than the maximum human daily dose. These adverse events were absent during clinical trials.

Pharmacokinetics:  Clarithromycin is rapidly absorbed from the gastrointestinal tract after oral administration. The absolute bioavailability of 250 mg Clarithromycin Capsules was approximately 50%. For a single 500 mg dose of Clarithromycin, food slightly delays the onset of Clarithromycin absorption, increasing the peak time from approximately 2 to 2.5 hours. Food also increases the Clarithromycin peak plasma concentration by about 24%, but does not affect the extent of Clarithromycin bioavailability. Food does not affect the onset of formation of the antimicrobially active metabolite, 14-OH-Clarithromycin or its peak plasma concentration but does slightly decrease the extent of metabolite formation, indicated by an 11% decrease in area under the plasma concentration-time curve (AUC). Therefore, Clarithromycin Capsules may be given without regard to food.
In nonfasting healthy human subjects (males and females), peak plasma concentrations were attained within 2 to 3 hours after oral dosing. Steady-state peak plasma Clarithromycin concentrations were attained within 3 days and were approximately 1 to 2 mcg/mL with a 250 mg dose administered every 12 hours and 3 to 4 mcg/mL with a 500 mg dose administered every 8 to 12 hours. The elimination half-life of Clarithromycin was about 3 to 4 hours with 250 mg administered every 12 hours but increased to 5 to 7 hours with 500 mg administered every 8 to 12 hours. The nonlinearity of Clarithromycin pharmacokinetics is slight at the recommended doses of 250 mg and 500 mg administered every 8 to 12 hours. With a 250 mg every 12 hours dosing, the principal metabolite, 14-OH-Clarithromycin, attains a peak steady-state concentration of about 0.6 mcg/mL and has an elimination half-life of 5 to 6 hours. With a 500 mg every 8 to 12 hours dosing, the peak steady-state concentration of 14-OH-Clarithromycin is slightly higher (up to 1 mcg/mL), and its elimination half-life is about 7 to 9 hours. With any of these dosing regimens, the steady-state concentration of this metabolite is generally attained within 3 to 4 days.
After a 250 mg Capsule every 12 hours, approximately 20% of the dose is excreted in the urine as Clarithromycin, while after a 500 mg Capsule every 12 hours, the urinary excretion of Clarithromycin is somewhat greater, approximately 30%. In comparison, after an oral dose of 250 mg (125 mg/5 mL) suspension every 12 hours, approximately 40% is excreted in urine as Clarithromycin. The renal clearance of Clarithromycin is, however, relatively independent of the dose size and approximates the normal glomerular filtration rate. The major metabolite found in urine is 14-OH-Clarithromycin, which accounts for an additional 10% to 15% of the dose with either a 250 mg or a 500 mg Capsule administered every 12 hours.
Steady-state concentrations of Clarithromycin and 14-OH-Clarithromycin observed following administration of 500 mg doses of Clarithromycin every 12 hours to adult patients with HIV infection were similar to those observed in healthy volunteers. In adult HIV-infected patients taking 500 or 1000 mg doses of Clarithromycin every 12 hours, steady-state Clarithromycin Cmaxvalues ranged from 2 to 4 mcg/mL and 5 to 10 mcg/mL, respectively.
The steady-state concentrations of Clarithromycin in subjects with impaired hepatic function did not differ from those in normal subjects; however, the 14-OH-Clarithromycin concentrations were lower in the hepatically impaired subjects. The decreased formation of 14-OH-Clarithromycin was at least partially offset by an increase in renal clearance of Clarithromycin in the subjects with impaired hepatic function when compared to healthy subjects.The pharmacokinetics of Clarithromycin was also altered in subjects with impaired renal function .
Clarithromycin and the 14-OH-Clarithromycin metabolite distribute readily into body tissues and fluids. There are no data available on cerebrospinal fluid penetration. Because of high intracellular concentrations, tissue concentrations are higher than serum concentrations. Examples of tissue and serum concentrations are presented below.
CONCENTRATION (after 250 mg q12h)
Tissue Type Tissue
(mcg/g) Serum
(mcg/mL)
Tonsil 1.6 0.8
Lung 8.8 1.7

Clarithromycin 500 mg every 8 hours was given in combination with omeprazole 40 mg daily to healthy adult males. The plasma levels of Clarithromycin and 14-hydroxy-Clarithromycin were increased by the concomitant administration of omeprazole. For Clarithromycin, the mean Cmaxwas 10% greater, the mean Cmin was 27% greater, and the mean AUC0-8 was 15% greater when Clarithromycin was administered with omeprazole than when Clarithromycin was administered alone. Similar results were seen for 14-hydroxy-Clarithromycin, the mean Cmax was 45% greater, the mean Cmin was 57% greater, and the mean AUC0-8 was 45% greater. Clarithromycin concentrations in the gastric tissue and mucus were also increased by concomitant administration of omeprazole.
Clarithromycin Tissue Concentrations 2 Hours After Dose (mcg/mL)/(mcg/g)
Treatment N antrum fundus N mucus
Clarithromycin 5 10.48 ± 2.01 20.81 ± 7.64 4 4.15 ± 7.74
Clarithromycin + Omeprazole 5 19.96 ± 4.71 24.25 ± 6.37 4 39.29 ± 32.79


Indications: Clarithromycin Capsules USP are indicated for the treatment of mild to moderate infections caused by susceptible isolates of the designated bacteria in the conditions as listed below:
Adults: Pharyngitis/Tonsillitis due to Streptococcus pyogenes (The usual drug of choice in the treatment and prevention of streptococcal infections and the prophylaxis of rheumatic fever is penicillin administered by either the intramuscular or the oral route. Clarithromycin is generally effective in the eradication of S. pyogenes from the nasopharynx; however, data establishing the efficacy of Clarithromycin in the subsequent prevention of rheumatic fever are not available at present). Acute maxillary sinusitis due to Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae. Acute bacterial exacerbation of chronic bronchitis due to Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, or Streptococcus pneumoniae. Community-Acquired Pneumonia due to Haemophilus influenzae, Mycoplasma pneumoniae,Streptococcus pneumoniae, or Chlamydophila pneumoniae (TWAR). Uncomplicated skin and skin structure infections due to Staphylococcus aureus, or Streptococcus pyogenes. Disseminated mycobacterial infections due to Mycobacterium avium, or Mycobacterium intracellulare. Clarithromycin Capsules USP in combination with amoxicillin and lansoprazole or omeprazole delayed-release capsules, as triple therapy, are indicated for the treatment of patients withHelicobacter pylori infection and duodenal ulcer disease (active or five-year history of duodenal ulcer) to eradicate H. Pylori. Clarithromycin Capsules USP in combination with omeprazole capsules or ranitidine bismuth citrate Capsules are also indicated for the treatment of patients with an active duodenal ulcer associated with H. pylori infection. However, regimens which contain Clarithromycin as the single antimicrobial agent are more likely to be associated with the development of Clarithromycin resistance among patients who fail therapy. Clarithromycin-containing regimens should not be used in patients with known or suspected Clarithromycin resistant isolates because the efficacy of treatment is reduced in this setting. In patients who fail therapy, susceptibility testing should be done if possible. If resistance to Clarithromycin is demonstrated, a non-Clarithromycin-containing therapy is recommended The eradication of H. pylori has been demonstrated to reduce the risk of duodenal ulcer recurrence.
Children:Pharyngitis/Tonsillitis due to Streptococcus pyogenes. Community-Acquired Pneumonia due to Mycoplasma pneumoniae, Streptococcus pneumoniae, or Chlamydophila pneumoniae.Acute maxillary sinusitis due to Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae Acute otitis media due to Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae

Precautions: Prescribing Clarithromycin Capsules in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Clarithromycin is principally excreted via the liver and kidney. Clarithromycin may be administered without dosage adjustment to patients with hepatic impairment and normal renal function. However, in the presence of severe renal impairment with or without coexisting hepatic impairment, decreased dosage or prolonged dosing intervals may be appropriate. Clarithromycin in combination with ranitidine bismuth citrate therapy is not recommended in patients with creatinine clearance less than 25 mL/min. Clarithromycin in combination with ranitidine bismuth citrate should not be used in patients with a history of acute porphyria. Exacerbation of symptoms of myasthenia gravis and new onset of symptoms of myasthenic syndrome has been reported in patients receiving Clarithromycin therapy.

Adverse reaction: The most frequent and common adverse reactions related to Clarithromycin therapy for both adult and pediatric populations are abdominal pain, diarrhea, nausea, vomiting and dysgeusia. These adverse reactions are consistent with the known safety profile of macrolide antibiotics. There was no significant difference in the incidence of these gastrointestinal adverse reactions during clinical trials between the patient population with or without preexisting mycobacterial infections. Adverse Reactions Observed During Clinical Trials of Clarithromycin,The following adverse reactions were observed in clinical trials with Clarithromycin at a rate greater than or equal to 1%: Gastrointestinal Disorders/Diarrhea, vomiting, dyspepsia, nausea, abdominal pain/ Hepatobiliary Disorders/Liver function test abnormal/Immune System Disorders/ Anaphylactoid reaction/Infection and Infestations/Candidiasis/Nervous System Disorders/ Dysgeusia, headache/Psychiatric Disorders/Insomnia/Skin and Subcutaneous Tissue Disorders/Rash.