Clerimed, 500 mg 14 pcs

Clarithromycin is a semi-synthetic broad-spectrum macrolide antibiotic. It disrupts protein synthesis of microorganisms by binding to 50S-subunit of microbial cell ribosome membrane. Primarily bacteriostatic action, but in high doses it is bactericidal.

It has antibacterial action against a wide range of sensitive microorganisms. It acts upon extra- and intracellularly located pathogens.

Clarithromycin activity against most strains of the following microorganisms has been proved both in vitro and in clinical practice – Aerobic Gram-positive microorganisms: Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes; Aerobic Gram-negative microorganisms: Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Legionella pneumophila; other microorganisms: Mycoplasma pneumoniae, Chlamydia pneumoniae; mycobacteria: Mycobacterium avium complex (MAC) – complex including: Mycobacterium avium, Mycobacterium intracellulare; Helicobacter pylori.

Beta-lactamases do not affect clarithromycin activity.

Clarithromycin activity in vitro – aerobic gram-positive microorganisms: Listeria monocytogenes; Streptococcus agalactiae; Streptococci groups C, F, G; Streptococci group viridans; aerobic gram-negative microorganisms: Neisseria gonorrhoeae, 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; mycobacteria: Mycobacterium leprae, Mycobacterium chelonae; Campylobacter: Campylobacter jejuni.

Against Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Campylobacter jejuni, Helicobacter pylori clarithromycin exhibits bactericidal activity.

Microbiologically active metabolite of clarithromycin – 14(R)-hydroxyclarithromycin, twice as active as the parent compound against Haemophilus influenza. Against other susceptible microorganisms, the minimum suppressive concentration (MSC) of 14(R)-hydroxyclarytromycin is equal to or 1-2 times weaker than the MSC of the parent substance.

Most strains of staphylococci, resistant to methicillin and oxacillin, are resistant to clarithromycin.

MAC of clarithromycin against most sensitive microorganisms is 2 times lower than MAC of erythromycin.

Clarithromycin is superior to roxithromycin in activity against Streptococcus and Haemophilus influenzae. The antibacterial activity of clarithromycin is several times greater in mildly alkaline or neutral media than in acidic.

Pharmacokinetics:

After oral administration, it is rapidly and completely absorbed from the gastrointestinal tract. Food slows down absorption without significantly affecting bioavailability. The bioavailability of 250 mg tablets is 50%. Binding with plasma proteins is 70-80%.

Two peaks of maximum concentration (Cmax) are registered after a single dose. The second peak is caused by the ability of the drug to accumulate in the gallbladder with subsequent gradual or rapid intestinal absorption. TCmax when taking 250 mg is 1-3 hours. In therapeutic concentrations it is accumulated in lungs, skin and soft tissues (the tissue concentration in them is 10 times higher than in blood serum).

Detected in tonsils, liver, and middle ear fluid. Clarithromycin penetrates the gastric wall well, with higher levels in smooth muscle and gastric mucosa when combined with omeprazole than without it. No more than 1-2% of the drug level in blood plasma penetrates through the intact blood-brain barrier. It penetrates well into breast milk.

It is biotransformed in the liver (first pass effect). After oral intake 20% of administered dose is rapidly hydroxylated in liver by cytochrome Р450 isoenzymes (CYP3A4, CYP3A5 and CYP3A7) with formation of main metabolite – 14(R)-hydroxyclarithromycin, marked antimicrobial activity against Haemophilus influenza. It is an inhibitor of CYP3A4, CYP3A5 and CYP3A7 isoenzymes.

Equilibrium concentration (Css) of clarithromycin and its main metabolite is established within 2 days after starting the drug. At regular use of 250 mg per day Css for unchanged drug and its metabolite is 1.0 and 0.6 mcg/ml, respectively; half-life (T1/2) is 3-4 hours and 5-6 hours respectively.

When the dose is increased to 500 mg/day Css of unchanged drug and its metabolite in plasma is 2.7-2.9 and 0.83-0.88 µg/ml, respectively; T1/2 is 4.8-5 h and 6.9-8.7 h, respectively. Plasma concentrations of clarithromycin when administered 500 mg three times daily are higher than those when administered 500 mg twice daily.

Excreted by the kidneys and intestines: 20-30% unchanged, the rest as metabolites. In a single dose of 250 mg 37.9% is excreted by the kidneys, the intestine – 40.2%, respectively. The share of the main metabolite – 14-hydroxyclarithromycin in the urine is 10-15% of the ingested dose.

In chronic renal failure increased Tmax, Cmax and AUC of clarithromycin and its metabolite.

In impaired liver function, the equilibrium concentration of clarithromycin did not differ from that of patients with normal liver function, whereas the equilibrium concentration of 14(R)-hydroxyclarithromycin was significantly lower in patients with impaired liver function.

The decreased excretion of the drug as 14(R)-hydroxyclarithromycin in impaired hepatic function is partially compensated by increased renal excretion of clarithromycin, resulting in little change in the Css value of clarithromycin and no dose adjustment is required.

In elderly patients the pharmacokinetics do not change significantly.

Indications

Infectious and inflammatory diseases caused by susceptible microflora.

Adults:

– pharyngitis, tonsillitis, acute maxillitis;

– chronic bronchitis in the acute stage, community-acquired pneumonia (including those caused by atypical pathogens: Mycoplasma pneumoniae, Chlamydia pneumonia, Legionella pneumophila);

– uncomplicated skin and subcutaneous tissue infections;

– disseminated infection caused by Mycobacterium avium and Mycobacterium intracellulare;

– in combination with amoxicillin and omeprazole/lansoprazole as triple therapy in infections caused by Helicobacter pylori, including gastric and duodenal ulcer. In combination with omeprazole or ranitidine bismuth citrate as triple therapy for the treatment of acute duodenal ulcers caused by Helicobacter pylori.

Children over 12 years of age (or with body weight over 33 kg):

– pharyngitis, tonsillitis, acute maxillary sinusitis, acute otitis media;

– community-acquired pneumonia;

– uncomplicated skin and subcutaneous tissue infections;

– disseminated infection caused by Mycobacterium avium and Mycobacterium intracellulare.

Active ingredient

Composition

Active ingredient:

excipients:

microcrystalline cellulose 178.5 mg,

colloidal silica 2.0 mg,

croscarmellose sodium salt 74.0 mg,

povidone 35.0 mg,

stearic acid 12.5 mg,

talc 15.0 mg,

magnesium stearate 7.5 mg;

coating: Hypromellose 13.0 mg, propylene glycol 8.6 mg, sorbitan monooleate 1.0 mg, vanilla flavoring 0.550 mg, titanium dioxide E171 3.0 mg, quinoline yellow varnish E104 1.1 mg, hydroxypropyl cellulose 1.0 mg, sorbitic acid 0.55 mg.

How to take, the dosage

Interaction

Special Instructions

In the presence of chronic liver disease, regular monitoring of the activity of “hepatic” serum enzymes is necessary.

With caution, prescribe against the background of drugs that are metabolized by the liver (it is recommended to measure their blood concentrations). In case of co-administration with warfarin and other indirect anticoagulants the prothrombin time should be monitored.

In case of development of secondary infection, adequate therapy should be prescribed.

If severe or prolonged diarrhea occurs during or after treatment, the diagnosis of pseudomembranous colitis should be excluded, which requires immediate withdrawal of the drug and appropriate treatment.

The development of cross-resistance between clarithromycin and other antibiotics from the macrolide group, as well as lincosamides (lincomycin and clindamycin) is possible. With prolonged therapy, development of drug resistance of the microflora is possible.

With regard to the possibility of side effects on the central nervous system, during treatment, caution should be exercised when driving motor vehicles and during potentially dangerous activities that require increased concentration and rapid psychomotor reactions.

Contraindications

Side effects

Central nervous system: headache, dizziness, anxiety, insomnia, nightmares, seizures, depression, disorientation, hallucinations, psychosis, depersonalization, confusion.

Digestive system disorders: Dyspepsia (decreased appetite,bloating),nausea,vomiting,gastralgia (abdominal pain),diarrhea (diarrhea),flatulence,stomatitis,glossitis,oral mucosal candidiasis,discoloration of tongue or teeth (noted when used together with omeprazole), acute pancreatitis, transient increase in “hepatic” transaminase activity, hepatocellular and cholestatic hepatitis, intrahepatic cholestasis, cholestatic jaundice;

Rarely – pseudomembranous colitis, liver failure with fatal outcome, mainly against the background of severe comorbidities and/or concomitant drug therapy. Discoloration of the teeth is reversible and is usually restored with professional tooth cleaning by a dentist.

Cardiovascular system disorders: ventricular tachycardia, including “pirouette” type, ventricular flutter or fibrillation, prolongation of Q-T interval on ECG.

Sense organs: noise, tinnitus, distortion of the sense of taste (dysgeusia), decreased hearing; in single cases – hearing loss transient after drug withdrawal, impaired sense of smell (insomnia).

Hematopoietic and hemostatic system disorders: thrombocytopenia (unusual bleeding, hemorrhage).

Urinary system disorders: interstitial nephritis, renal failure.

Motor system disorders: arthralgia, myalgia.

Laboratory measures: leukopenia, eosinophilia, hypercreatininemia, hypoglycemia (including with simultaneous use of hypoglycemic agents). Allergic reactions: skin rash, pruritus, urticaria, skin hyperemia, erythema malignant exudative (Stevens-Johnson syndrome), toxic epidermal necrolysis, anaphylactic reactions; rarely – anaphylactic shock, angioedema, bronchospasm.

Others: increase in body temperature, superinfections (development of resistance of microorganisms), candidiasis.

In case of an adverse reaction, the drug should be stopped and a doctor should be seen as soon as possible. If any of the side effects listed in the instructions worsen, or if you notice any other adverse reactions not listed in the instructions, tell your doctor.

Overdose

Symptoms: abdominal pain, nausea, vomiting, diarrhea, headache, confusion. A case of overdose in a patient (with a history of bipolar disorder) after taking 8 g of clarithromycin has been described – mental disorders, paranoid behavior, hypokalemia and hypoxemia occurred.

Treatment: gastric lavage and symptomatic therapy are recommended. It is not removed by hemodialysis or peritoneal dialysis. There is no specific antidote.

Pregnancy use

Clarithromycin is contraindicated in the first trimester of pregnancy.

In the second and third trimesters the drug is prescribed only if there are clear indications and if the expected benefit to the mother exceeds the potential risk to the fetus.

If it is necessary to prescribe during lactation, discontinuation of breastfeeding should be considered.

Similarities