Claryn

Clarithromycin (Claryn) 125 mg per 5 mL granules for suspension. Bottles of white to off-white clarithromycin spheroidal particles. The reconstituted suspension is a white to off-white suspension with white particles and has an orange flavor and sweet fruit taste.
Each film-coated tablet contains: Clarithromycin 500 mg.
Each 5 mL (1 teaspoonful) contains: Clarithromycin, USP 125 mg.
Clarithromycin is a macrolide derived from erythromycin with similar actions and uses. It is given in the treatment of respiratory-tract infections including otitis media and in skin and soft-tissue infections.

Pharmacology: Pharmacodynamics: Granules for suspension: Clarithromycin is a macrolide antibiotic whose spectrum of activity includes many gram-positive (Staphylococcus aureus, S. pneumonia, and S. pyogenes) and gram-negative aerobic bacteria (Haemophilus influenzae, H. parainfluenzae, and Moraxella catarrhalis), many anaerobic bacteria, some mycobacteria, and some other organism including Mycoplasma, Ureaplasma, Chlamydia, Toxoplasma, and Borrelia. Other aerobic bacteria that clarithromycin has activity against include C. pneumoniae and M. pneumoniae, Clarithromycin has an in-vitro activity that is similar or greater than that of erythromycin against erythromycin-susceptible organisms. Clarithromycin is usually bacteriostatic, but may be bactericidal depending on the organism and the drug concentration.
Pharmacokinetics: Film-coated tablet: Clarithromycin is rapidly absorbed from the gastrointestinal tract following oral administration, and undergoes first-pass metabolism; the bioavailability of the parent drug is about 55%. The extent of absorption is relatively unaffected by the presence of food. Peak concentrations of clarithromycin and its principal active metabolite 14-hydroxyclarithromycin are reported to be about 600 and 700 nanograms per mL respectively following a single 250-mg dose by mouth; at steady state the same dose given every 12 hours as tablets produces peak concentrations of clarithromycin of about 1 μg per mL. The same dose given as suspension produces a steady-state plasma concentration of about 2 μg per mL.
The pharmacokinetics of clarithromycin are non-linear and dose dependent; high doses may produce disproportionate increases in peak concentration of the parent drug, due to saturation of the metabolite pathways.
Granules for suspension: Clarithromycin is rapidly absorbed from the gastrointestinal tract and undergoes first-pass metabolism; the bioavailability of the parent drug is about 55%. The extent of absorption is relatively unaffected by the presence of food. Peak plasma concentrations occur 2 to 3 hours after an oral dose. At steady state, peak plasma concentrations of clarithromycin, and its principal active metabolite, 14-hydroxyclarithromycin, are about 1 and 0.6 microgram/mL, respectively, after 250 mg orally every 12 hours as tablets. The same dose given as a suspension to fasting subjects produces steady-state plasma concentrations of about 2 micrograms/mL of clarithromycin and about 0.7 microgram/mL of 14-hydroxyclarithromycin. Steady-state concentrations are reached within 3 to 4 days. The pharmacokinetics of clarithromycin are non-linear and dose dependent; high closes may produce disproportionate increases in peak concentrations of the parent drug, due to saturation of the metabolite pathways. However, the non-linearity is slight at the recommended doses of 250 to 500 mg every 8 to 12 hours.

For the treatment of respiratory tract infections, mild to moderate skin and soft tissue infections, otitis media, and Helicobacter pylori eradication.

Film-coated tablet: The usual recommended dosage of clarithromycin in adults is one 250 mg tablet twice daily. In severe infections, the dosage can be increased to 500 mg twice daily or as prescribed by the physician.
Children 15 mg/kg/day in 2 divided doses maximum of 500 mg every 12 hour. The usual duration of therapy is 5 to 14 days excluding treatment of community acquired pneumonia and sinusitis which require 6 to 14 days of therapy.
Granules for suspension: Children: 15 mg/kg/day in two (2) divided doses maximum of 500 mg every 12 hours.
7-12 years: 7.5 mL-10 mL (1½ tsp-2 tsp).
2-6 years: 5 mL (1 tsp).
6 months-1 year: 2.5 mL (½ tsp.)
To be taken every 12 hours or as prescribed by the physician.
The usual duration of therapy is 5 to 14 days excluding treatment of community acquired pneumonia and sinusitis which require 6 to 14 days therapy.
Direction for Reconstitution: To make 50 mL reconstituted suspension, add approximately 40 mL of water. Shake well until the granules are evenly suspended. The suspension is stable for one week at temperatures not exceeding 30°C and two weeks under refrigeration (2-8°C).

Overdosage of clarithromycin can cause gastrointestinal symptoms such as abdominal pain, vomiting, nausea, and diarrhea.
Adverse reactions accompanying over dosage should be treated by the prompt elimination of unabsorbed drug and supportive measures. As with other macrolides, clarithromycin serum concentrations are not expected to be appreciably affected by hemodialysis or peritoneal dialysis.

Film-coated tablet: Clarithromycin is contraindicated in patient with known hypersensitivity to macrolide antibiotic drugs.
Granules for suspension: Clarithromycin is contraindicated in patients with a known hypersensitivity to clarithromycin, erythromycin, or any of the macrolide antibiotics. Clarithromycin is contraindicated in patients with a history of cholestatic jaundice/hepatic dysfunction associated with prior use of clarithromycin. Concomitant administration of clarithromycin and any of the following drugs is contraindicated: cisapride, pimozide, astemizole, terfenadine, and ergotamine or dihydroergotamine. There have been postmarketing reports of drug interactions when clarithromycin and/or erythromycin are co-administered with cisapride, pimozide, astemizole, or terfenadine resulting in cardiac arrhythmias (QT prolongation, ventricular tachycardia, ventricular fibrillation, and torsades de pointes most likely due to inhibition of metabolism of these drugs by erythromycin and clarithromycin. Fatalities have been reported. Concomitant administration of clarithromycin and colchicine is contraindicated in patients with renal or hepatic impairment.

Use in Pregnancy: Clarithromycin should not be used in pregnant women except in clinical circumstances where no alternative therapy is appropriate. If pregnancy occurs while taking this drug, the patient should be apprised of the potential hazard to the fetus. Clarithromycin has demonstrated adverse effects of pregnancy outcome and/or embryo-fetal development in monkeys, rats, mice, and rabbits at doses that produced plasma levels 2 to 17 times the serum levels achieved in humans treated at the maximum recommended human doses.
Hepatotoxicity: Hepatic dysfunction including increased liver enzymes and hepatocellular and/or cholestatic hepatitis, with or without jaundice, has been reported with clarithromycin. This hepatic dysfunction may be severe and is usually reversible. In some instances, hepatic failure with fatal outcome has been reported and generally has been associated with serious underlying diseases and/or concomitant medications. Discontinue clarithromycin immediately if signs and symptoms of hepatitis occur.
Clostridium difficile Associated Diarrhea: Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents including clarithromycin and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality as these infections can be refractory to antimicrobial therapy and may require colectomy, CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

Caution is required in patients with impaired renal or hepatic function and cases should be reduced in those with severe renal impairment.

It should not be used during pregnancy if possible high doses have been associated with embryotoxicity in animal studies.
Granules for suspension: Pregnancy: The safety of clarithromycin use during pregnancy has not been established. Therefore, use during pregnancy is not advised without carefully weighing the benefits against risk.
Lactation: The safety of clarithromycin use during breast-feeding of infants has not been established. Clarithromycin is excreted into human breast milk.

Gastrointestinal disturbances are the most frequent adverse effect but are usually mild and less frequent than with erythromycin. Smell and taste disturbances, stomatitis, glossitis, tongue and tooth discoloration, and headache have occurred. Transient elevations of liver enzyme value, cholestatic jaundice, and hepatitis have been reported. Headache and rashes from mild skin eruption to, rarely, Steven-Johnson Syndrome have occurred. There have also been reports of transient central nervous system effects such as anxiety, dizziness, insomnia, hallucinations, and confusion. Hearing loss has been reported occasionally and is usually reversible. Other adverse effects include arthralgia, myalgia, hypoglycemia, leucopenia, and thrombocytopenia, interstitial nephritis and renal failure have been reported rarely.

Cytochrome P450 interactions data available to date indicate Clarithromycin is metabolized primarily by the hepatic cytochrome P450 3A isoenzyme. This is an important mechanism determining many drug interactions. The metabolism of other drugs by this system may be inhibited by concomitant administration with Clarithromycin and may be associated with elevation in serum levels of these other drugs.
The following drugs or drug classes are known or suspected to be metabolized by the same CYP3A isoenzyme: alprazolam, astemizole, carbamazepine, cilostazol, cisapride, cyclosporine, disopyramide, ergot alkaloids, lovastatin, methylprednisolone, midazolam, omeprazole, oral anticoagulants (e.g. warfarin) pimozide, quinidine, rifabutin, sildenafil, simvastatin, tacrolimus, terfenadine, triazolam and vinblastine. Drugs interacting by similar mechanisms through other isoenzymes within the cytochrome P450 system include phenytoin, theophylline and valproate.

Store at temperatures not exceeding 30°C.

Macrolides

J01FA09 - clarithromycin ; Belongs to the class of macrolides. Used in the systemic treatment of infections.

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