Clacid, lyophilizate 500 mg

Pharmacodynamics

Clarithromycin is a semi-synthetic antibiotic of macrolide group and has antibacterial effect by interacting with 50S ribosomal subunit of susceptible bacteria and inhibiting protein synthesis.

Clarithromycin has shown high in vitro activity against standard and isolated cultures of bacteria. It is highly effective against many aerobic and anaerobic gram-positive and gram-negative microorganisms. Clarithromycin in vitro is highly effective against Legionella pneumophila, Mycoplasma pneumoniae and Helicobacter (Campylobacter) pylori. Enterobacteriaceae and Pseudomonas as well as other non-lactose-degrading Gram-negative bacteria are not sensitive to clarithromycin.

Clarithromycin has been shown to have antibacterial activity against the following pathogens: aerobic Gram-positive microorganisms – Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Listeria monocytogenes. Aerobic Gram-negative microorganisms: Haemophilus influenzae, Haemophilus parainftuenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, Legionella pneumophila; other microorganisms – Mycoplasma pneumoniae, Chlamydia pneumoniae (TWAR), Chlamydia trachomatis; Mycobacteria – Mycobacterium leprae, Mycobacterium kansasii, Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium avium complex (MAC) – Mycobacterium avium, Mycobacterium intracellulare.

The production of beta-lactamase has no effect on clarithromycin activity. Most staphylococcal strains resistant to methicillin and oxacillin are also resistant to clarithromycin.

Helicobacter pylori. Sensitivity of H. pylori to clarithromycin was studied in H. pylori isolates isolated from 104 patients before the start of therapy with the drug. Clarithromycin-resistant H. pylori strains were isolated in 4 patients and 2 patients had strains with intermediate resistance; the remaining 98 patients’ H. pylori isolates were sensitive to clarithromycin.

Clarithromycin also has action in vitro against most strains of the following microorganisms (however, the safety and efficacy of clarithromycin in clinical practice has not been confirmed by clinical studies and the practical significance remains unclear) aerobic gram-positive microorganisms – Streptococcus agalactiae, Streptococci (groups C,F,G), Viridans group streptococci; aerobic gram-negative microorganisms – Bordetella pertussis, Pasteurella multocida; anaerobic Gram-positive microorganisms – Clostridium perfringens, Peptococcus niger, Propionibacterium acnes; anaerobic Gram-negative microorganisms – Bacteroides melaninogenicus; spirochetes – Borrelia burgdorferi, Treponema pallidum; Campylobacter – Campylobacter jejuni.

The main metabolite of clarithromycin in humans is the microbiologically active metabolite 14-OH-clarithromycin. The microbiological activity of the metabolite is the same as that of the parent substance, or 1-2 times weaker against most microorganisms. The exception is H. influenzae, against which the efficacy of the metabolite is 2 times higher. The starting substance and its main metabolite have either additive or synergistic effect against H. influenzae under in vitro and in vivo conditions depending on the bacterial culture.

Sensitivity studies

Quantitative methods requiring measurement of the diameter of the microbial growth retention zone provide the most accurate estimates of bacterial sensitivity to antimicrobial agents. One recommended sensitivity testing procedure uses discs soaked in 15 mcg of clarithromycin (Kirby-Bauer diffusion test) and interprets the test results as a function of the diameter of the stasis zone and the minimum suppressive concentration (MSC) of clarithromycin. The MPC value is determined by dilution of the medium or by diffusion into the agar. Laboratory tests give 1 out of 3 results:

1) resistant – it can be considered that the infection is not treatable with this drug;

2) moderately sensitive – the therapeutic effect is ambiguous and possibly increasing the dosage can lead to sensitivity;

3) sensitive – it can be considered that the infection is treatable with clarithromycin.

Pharmacokinetics

Healthy. In clinical trials in healthy volunteers, clarithromycin was administered once in doses of 75, 125, 250, and 500 mg in 100 mL as an infusion for 30 minutes and in doses of 500, 750, or 1000 mg in 250 mL for more than 60 minutes. The equilibrium Cmax of clarithromycin was 5.16 to 9.40 μg/mL after infusion of 500 and 1000 mg of clarithromycin for 60 min, respectively. The Cmax of 14-hydroxyclarithromycin (14-OH-clarithromycin) was 0.66 µg/mL after infusion of 500 mg and 1.06 µg/mL after 1000 mg clarithromycin infusion for 60 min.

In equilibrium, the terminal T1/2 of clarithromycin is dose-dependent and ranges from 3.8 to 4.5 h when doses of 500 to 1000 mg are administered in 60 min, respectively. The T1/2 of 14-OH-clarithromycin after administration of the same doses of 500 and 1000 mg in 60 min is 7.3 and 9.3 h, respectively, confirming approximately the same relationship increasing with increasing clarithromycin dose.

In equilibrium, AUC values changed disproportionately with increasing dose, i.e. there was a nonlinear dependence of AUC values from 22.29 to 53.26 h-μg/ml at doses of 500-1000 mg in 60 min, respectively. AUC data for 14-OH-clarytromycin ranged from 8.16 to 14.76 h-mcg/mL when the same doses were administered in 60 min of infusion.

In the 7-day clinical trial, clarithromycin was administered repeatedly at doses of 125 and 250 mg in 100 mL for more than 30 minutes and at doses of 500 and 750 mg in 250 mL for more than 60 minutes every 12 hours. In this study, equilibrium Cmax values increased from 5.5 mcg/mL at the 500 mg dose to 8.6 mcg/mL at the 750 mg dose. At equilibrium, the terminal T1/2 at the 500 and 750 mg clarithromycin doses after more than 60 minutes of infusion was 5.3 and 4.8 h, respectively. The Cmax of 14-OH clarithromycin at equilibrium after 500 and 750 mg doses increased from 1.02 to 1.37 μg/mL. The terminal phase T1/2 for this metabolite in groups administered 500 or 750 mg was 7.9 h and 5.4 h, respectively. The pharmacokinetics of 14-OH clarithromycin were not dose-dependent.

Indications

Infectious and inflammatory diseases caused by microorganisms sensitive to the drug:

– lower respiratory tract infections (bronchitis, pneumonia);

– upper respiratory tract infections (pharyngitis, tonsillitis and sinusitis);

– skin and soft tissue infections (impetigo, folliculitis, cellulitis, abscesses);

– otitis media;

– disseminated or localized mycobacterial infections caused by Mycobacterium avium or Mycobacterium intracellulare;

– localized infections caused by Mycobacterium kansasii, Mycobacterium fortuitum, Mycobacterium chelonae.

Active ingredient

Composition

How to take, the dosage

Injections are administered in adults in a daily dose of 1 g divided into 2 injections (500 mg 2 times/day). Each injection is given by IV drip for 60 minutes. In case of mycobacterial infections the dose may be doubled.
In elderly patients the drug is administered in the same doses as in adults.

In patients with significant renal dysfunction (CKG less than 30 ml/min) the drug dose should be reduced by 50%.

The dose of clarithromycin should be reduced by 50% in patients with impaired renal function (CKR of 30 to 60 mL/min) and by 75% in patients with CKR of less than 30 mL/min. Do not prescribe clarithromycin at a dose greater than 1 g/day when concomitantly used with ritonavir.

Intravenous and intravenous doses are prohibited!

The drug is administered by injection for 2-5 days, with possible subsequent switch, if necessary, to oral clarithromycin administration.Injections are given to adults in a daily dose of 1 g divided into 2 injections (500 mg 2 times/day). Each injection is given by IV drip for 60 minutes. In mycobacterial infections, the dose may be doubled.

In elderly patients the drug is administered in the same doses as in adults.

In patients with significant renal dysfunction (CKG less than 30 ml/min) the drug dose should be reduced by 50%.

The dose of clarithromycin should be reduced by 50% in patients with impaired renal function (CKR of 30 to 60 mL/min) and by 75% in patients with CKR of less than 30 mL/min. Do not prescribe clarithromycin at a dose greater than 1 g/day when concomitantly used with ritonavir.

Intravenous and intravenous doses are prohibited!

The intravenous drug is administered for 2-5 days, with possible transition to oral clarithromycin if necessary.

Interaction

Special Instructions

Long-term antibiotic treatment can lead to colonies with increased numbers of insensitive bacteria and fungi.

In case of superinfection, appropriate therapy should be prescribed.

Hepatic dysfunction (increased hepatic enzyme activity in the blood, hepatocellular and/or cholestatic hepatitis with or without jaundice) has been reported with clarithromycin.

Hepatic dysfunction can be severe, but is usually reversible. There have been cases of fatal liver failure, usually associated with the presence of serious comorbidities and/or concomitant use of other medications.

In case of signs and symptoms of hepatitis, such as anorexia, jaundice, darkened urine, itching, abdominal pain on palpation, clarithromycin therapy should be stopped immediately.

In the presence of chronic liver disease, serum enzymes should be monitored regularly.

When treated with virtually all antibacterials, including clarithromycin, there have been cases of pseudomembranous colitis, the severity of which may vary from mild to life-threatening.

Cases of Clostridium difficile-associated diarrhea, the severity of which can range from mild to life-threatening colitis, have been described with virtually all antibiotic treatments, including clarithromycin. Antibacterials can change the normal gut microflora, which can lead to growth of C.difficile.

Pseudomembranous colitis caused by Clostridium difficile should be suspected in all patients who develop diarrhea after using antibiotics.

After a course of antibiotic therapy, close medical follow-up of the patient is necessary.

Cases of pseudomembranous colitis have been described 2 months after antibiotic treatment.

When treated with macrolides, including clarithromycin, prolongation of cardiac repolarization and QT interval have been observed, causing risk of cardiac arrhythmias and pirouette-type ventricular tachycardia (see section “Adverse effects”).

Because the following situations may increase the risk of ventricular arrhythmias (including pirouette-type ventricular tachycardia), clarithromycin should not be used in the following patients:

In hospital pneumonia, clarithromycin should be used in combination with appropriate antibiotics. Skin and soft tissue infections of mild to moderate severity are most often caused by Staphylococcus aureus and Streptococcus pyogenes. Both pathogens can be resistant to macrolides. Therefore, it is important to test for sensitivity.

Macrolides can be used for infections caused by Corynebacterium minutissimum, diseases of acne vulgaris and rye, as well as in situations where penicillin cannot be used.

In case of acute hypersensitivity reactions such as anaphylactic reaction, Stevens-Johnson syndrome, toxic epidermal necrolysis and drug rash with eosinophilia and systemic symptoms (DRESS syndrome), clarithromycin should be stopped immediately and appropriate therapy started.

In case of co-administration with warfarin or other indirect anticoagulants, the INR and prothrombin time should be monitored.

Synopsis

Contraindications

Side effects

Overdose

Pregnancy use

Similarities