Klacid/Klacid MR

Klacid/Klacid MR

clarithromycin

Manufacturer:

Abbott

Distributor:

Zuellig Pharma
Full Prescribing Info
Contents
Clarithromycin.
Action
Clarithromycin is an antibiotic of the macrolide family.
Pharmacokinetics: Initial pharmacokinetic data were obtained with clarithromycin tablet formulations. These data indicated the drug is rapidly absorbed from the gastrointestinal tract and the absolute bioavailability of a clarithromycin 250-mg tab was approximately 50%. Both the onset of absorption and the formation of the antimicrobially active metabolite, 14-OH-clarithromycin, were slightly delayed by food, but the extent of bioavailability was not affected by administration of drug in the non-fasting state. In fasting healthy human subjects, peak serum concentrations were attained within 2 hrs after oral dosing. With twice-daily dosing using a 250-mg tab every 12 hrs, steady-state peak serum concentrations of clarithromycin were attained in 2-3 days and were approximately 1 mcg/mL. Corresponding peak serum concentrations were 2-3 mcg/mL with a 500-mg dose administered every 12 hrs. The elimination half-life of clarithromycin was about 3-4 hrs with a 250-mg tab administered every 12 hrs but increased to 5-7 hrs with 500 mg administered every 12 hrs. 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 5-6 hrs after a dose of 250 mg every 12 hrs. With a dose of 500 mg every 12 hrs, the peak steady-state concentrations of 14-OH-clarithromycin are slightly higher (up to 1 mcg/mL), and its elimination half-life is about 7 hrs. With either dose, the steady-state concentration of this metabolite is generally attained within 2-3 days. The steady-state concentrations of clarithromycin in subjects with impaired hepatic function did not differ from those of 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 were also altered in subjects with impaired renal function who received multiple 500-mg oral doses. The plasma levels, half-life, Cmax and Cmin for both clarithromycin and its 14-OH metabolite were higher and the AUC was larger in subjects with renal impairment than in normal subjects. The extent to which these parameters differed was correlated with the degree of renal impairment; the more severe the renal impairment, the more significant the difference. (See Dosage & Administration.) Clarithromycin and its 14-OH metabolite distribute readily into body tissues and fluids. Concentrations in tissues are usually several folds higher than serum concentrations. The bioavailability and pharmacokinetics of clarithromycin paediatric suspensions were investigated in adult subjects and in paediatric patients. A single-dose study in adult subjects found the overall bioavailability of the paediatric formulation to be equivalent to or slightly greater than that of the tablet (dosage with each was 250 mg). As with the tablet, administration of the paediatric formulation with food leads to a slight delay in the onset of absorption, but does not affect the overall bioavailability of clarithromycin. The comparative clarithromycin Cmax, AUC and T½ for the paediatric formulation (nonfasted state) were 0.95 mcg/mL, 6.5 mcg hr/mL and 3.7 hrs, respectively, and for the 250-mg tab (fasted state) were 1.1 mcg/mL, 6.3 mcg hr/mL and 3.3 hrs, respectively. In a multiple dose study in which adult subjects were administered 250 mg of the clarithromycin paediatric suspension every 12 hrs, steady state blood levels were nearly reached by time of the 5th dose. Pharmacokinetic parameters after the 5th dose for clarithromycin paediatric suspension were: Cmax 1.98 mcg/mL, AUC 11.5 mcg hr/mL, Tmax 2.8 hrs and T½ 3.2 hrs for clarithromycin, and 0.67, 5.33, 2.9 and 4.9, respectively, for 14-OH-clarithromycin. In paediatric patients requiring oral antibiotic treatment, clarithromycin demonstrated good bioavailability with pharmacokinetic profile, consistent with previous results from adult subjects using the same suspension formulation. The results indicated rapid and extensive drug absorption in children and, except for a slight delay in onset of absorption, food seemed to have no significant effect on drug bioavailability or pharmacokinetic profiles. Steady-state pharmacokinetic parameters obtained after the 9th dose on treatment day 5 were as follows for the parent drug: Cmax 4.6 mcg/mL, AUC 15.7 mcg hr/mL and Tmax 2.8 hrs; the corresponding values for the 14-OH metabolite were: 1.64 mcg/mL, 6.69 mcg hr/mL and 2.7 hrs, respectively. Elimination half-life was estimated to be approximately 2.2 and 4.3 hrs for the parent compound and metabolite, respectively. In another study, information was obtained regarding the penetration of clarithromycin in middle ear fluid in patients with otitis media. Approximately 2.5 hrs after receiving the 5th dose (dosage was 7.5 mg/kg twice daily), the mean concentration of clarithromycin was 2.53 mcg/g fluid in the middle ear and for the 14-OH metabolite was 1.27 mcg/g. The concentrations of parent drug and 14-OH metabolite were generally twice as high as the corresponding concentrations in serum.
Microbiology: Clarithromycin exerts its antibacterial activity by inhibiting the synthesis of proteins, by means of a link with the 50S sub-unit of the cellular ribosome. Clarithromycin has demonstrated excellent in vitro activity against both standard strains of bacteria and clinical isolates. It is highly potent against a wide variety of aerobic and anaerobic gram-positive and gram-negative organisms. The in vitro antibacterial spectrum of clarithromycin is as follows: Usually Sensitive Bacteria: Streptococcus agalactiae, Streptococcus pyogenes, Streptococcus viridans, Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Neisseria gonorrheae, Listeria monocytogenes, Legionella pneumophila, Pasteurella multocida, Mycoplasma pneumoniae, Helicobacter (Campylobacter) pylori, Campylobacter jejuni, Chlamydia trachomatis, Chlamydia pneumoniae (TWAR), Moraxella (Branhaemella) catarrhalis, Bordetella pertussis, Borrelia burgdorferi, Staphylococcus aureus, Clostridium perfringens, Peptococcus niger, Propionibacterium acnes, Bacteroides melaninogenicus, Mycobacterium avium, Mycobacterium leprae, Mycobacterium kansasii, Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium intracellulare.
Nonsensitive Bacteria: Enterobacteriaceae, Pseudomonas sp.
The principal metabolite of clarithromycin in man and other primates is a microbiologically active metabolite, 14-OH-clarithromycin. This metabolite is as active or 1- to 2-fold less active than the parent compound for most organisms, except for H. influenzae against which it is twice as active. The parent compound and the 14-OH-metabolite exert either an additive or synergistic effect on H. influenzae in vitro and in vivo, depending on bacterial strains.
Indications/Uses
Treatment of infections due to susceptible organisms of the upper respiratory infections (eg, streptococcal pharyngitis), lower respiratory infections (eg, bronchitis, pneumonia), acute otitis media, skin and skin structure infections (eg, impetigo, folliculitis, cellulitis, abscesses).
Disseminated or localized mycobacterial infections due to Mycobacterium avium or Mycobacterium intracellulare. Localized infections due to Mycobacterium chelonae, Mycobacterium fortuitum, or Mycobacterium kansasii.
Dosage/Direction for Use
Klacid Tablet: Clarithromycin recommended dosage in adults is one 500-mg tab every 12 hrs.
Administration must be continued, according to severity of infection, up to 6-14 days.
In patients with renal impairment with creatinine clearance <30 mL/min, the dosage should be reduced by ½. Dosage should not be continued beyond 14 days in these patients.
Klacid Granules For Oral Suspension 250 mg/5 mL: Children >8-12 years; 30-40 kg: 5 mL twice daily, >5-8 years; 20-29 kg: 3.75 mL twice daily.
Klacid Granules For Oral Suspension 125 mg/5 mL: Children 2-5 years; 12-19 kg: 5 mL twice daily, 6 months-2 years; 8-11 kg: 2.5 mL twice daily.
The recommended daily dosage of clarithromycin paediatric suspension (125 mg/5 mL) in children is given in the following table and is based on a 7.5 mg/kg twice daily regimen. Doses up to 500 mg twice daily have been used in the treatment of serious infections. (See table.)

Click on icon to see table/diagram/image

Patients with Renal Impairment: In children with creatinine clearance <30 mL/min, the dosage of clarithromycin should be reduced by ½ ie, up to 250 mg once daily, or 250 mg twice daily in more severe infections. Dosage should not be continued beyond 14 days in these patients.
The usual duration of treatment is 5-10 days, depending on the pathogen involved and the severity of the condition. Treatment for streptococcal pharyngitis should be at least 10 days.
Suspension Preparation: To prepare Klacid suspension, add water to the granules contained in the bottle until the line impressed on it. Shake well. Add more water up to the line. The prepared suspension can be taken with or without meals, and can be taken with milk.
Klacid MR: 500 mg once daily with food.
Severe Infections: 1000 mg (2 x 500 mg) once daily with food.
Duration of Treatment: 6-14 days.
Overdosage
Reports indicate that the ingestion of large amounts of clarithromycin can be expected to produce gastrointestinal symptoms. One patient who had a history of bipolar disorder ingested clarithromycin 8 g and showed altered mental status, paranoid behaviour, hypokalemia and hypoxemia. Allergic reactions accompanying overdosage should be treated by the prompt elimination of unabsorbed drug and supportive measures. As with other macrolides, clarithromycin plasma levels are not expected to be appreciably affected by hemodialysis or peritoneal dialysis.
Contraindications
Patients hypersensitive to macrolides. Clarithromycin is contraindicated in patients receiving terfenadine therapy who have preexisting cardiac abnormalities (arrhythmia, bradycardia, QT interval prolongation, ischemic heart disease, congestive heart failure, etc) or electrolyte disturbances. (See Precautions.)
Warnings
It has been demonstrated that clarithromycin can interfere with carbamazepine plasma levels which can significantly increase. Patients administered with such a combination must be clinically monitored and, if necessary, relevant posology modifications must be made.
Clarithromycin can cause an increase of theophylline plasma concentrations, slight enough to not justify a modification of theophylline usual posology.
Special Precautions
Clarithromycin is principally excreted by the liver. Therefore, caution should be exercised in administering the antibiotic to patients with impaired hepatic function. Caution should also be exercised when administering clarithromycin to patients with moderate to severe renal failure. Attention should also be paid to the possibility of cross-resistance between clarithromycin and other macrolide drugs, as well as lincomycin and clindamycin.
Use in pregnancy: If clarithromycin paediatric suspension is considered for patients of post-pubertal age, the physician should carefully weigh the benefits against the risk when pregnancy is either suspected or confirmed.
Use In Pregnancy & Lactation
Use in pregnancy: If clarithromycin paediatric suspension is considered for patients of post-pubertal age, the physician should carefully weigh the benefits against the risk when pregnancy is either suspected or confirmed.
Adverse Reactions
The safety profile of the paediatric formulation is similar to that of the 250-mg tab in adult patients. The majority of adverse events reported were of the gastrointestinal system, eg diarrhea, vomiting, abdominal pain, dyspepsia and nausea. Other adverse events included headache, altered taste and transient elevations of liver enzymes. Allergic reactions ranging from urticaria and mild skin eruptions to anaphylaxis have occurred with orally administered clarithromycin. There have been reports with oral clarithromycin of transient CNS side effects including anxiety, dizziness, insomnia, hallucinations, bad dreams and confusion; however, a cause and effect relationship has not been established.
Side Effects
After oral administration of clarithromycin, some cases of gastrointestinal disturbances (nausea, heartburns, abdominal pain, diarrhea), headache and skin rashes have been reported.
Using macrolides, transient increases of SGOT-SGPT are possible, normally reversible after therapy withdrawal. While during clinical studies with clarithromycin, more severe problems relevant to the liver have not been experienced, it should be taken into account that with antibiotics of this family, episodes of cholestatic hepatitis can exceptionally happen.
Like with other antibiotics, during therapy with clarithromycin superinfections by resistant bacteria or fungi can rarely arise, needing administration withdrawal and adoption of suitable therapies.
Drug Interactions
Results of clinical studies indicate that there was a modest but statistically significant increase (p=0.05) of circulating theophylline or carbamazepine levels when either of these drugs are administered concomitantly with clarithromycin. As with other macrolide antibiotics, the use of clarithromycin in patients concurrently taking drugs metabolized by the cytochrome P-450 system (eg, digoxin, warfarin) may be associated with elevations in serum levels of these other drugs.
Macrolides have been reported to alter the metabolism of terfenadine resulting in increased levels of terfenadine which has occasionally been associated with cardiac arrhythmias. In 1 study in 14 healthy volunteers, the concomitant administration of clarithromycin and terfenadine resulted in 2- to 3-fold increases in the serum level of the acid metabolite of terfenadine and in prolongation of the QT-interval which did not lead to any clinically detectable effect.
MIMS Class
ATC Classification
J01FA09 - clarithromycin ; Belongs to the class of macrolides. Used in the systemic treatment of infections.
Presentation/Packing
Klacid FC tab 500 mg x 28's. Klacid granules for oral susp 125 mg/5 mL x 60 mL. 250 mg/5 mL x 60 mL. Klacid MR tab 500 mg x 5's.
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