Zytrolide forte, 500 mg capsules 3 pcs

Pharmacological action Pharmacological action – antibacterial.

Pharmacodynamics

Azithromycin is a bacteriostatic broad spectrum antibiotic of macrolide group, azalid. It has a broad spectrum of antimicrobial action. Azithromycin mechanism of action is associated with inhibition of microbial cell protein synthesis. Binding to 50S-subunit of ribosome, it inhibits peptide translocase at the translation stage and inhibits protein synthesis, slowing down the growth and reproduction of bacteria. In high concentrations it has a bactericidal effect.

It has activity against a number of Gram-positive, Gram-negative, anaerobes, intracellular and other microorganisms.

Microorganisms can be initially resistant to the action of the antibiotic or become resistant to it.

Table

The sensitivity scale for some microorganisms to azithromycin (minimum inhibitory concentration – MIC)

List of microorganisms sensitive to azithromycin in most cases

Gram-positive aerobes – Staphylococcus aureus methicillin-sensitive; Streptococcus pneumoniae penicillin-sensitive; Streptococcus pyogenes.

Gram-negative aerobes – Haemophilus influenzae; Haemophilus parainfluenzae; Legionella pneumophila; Moraxella catarrhalis; Pasteurella multocida; Neisseria gonorrhoeae.

The anaerobes are Clostridium perfringens; Fusobacterium spp.; Prevotella spp.; Porphyromonas spp.

Other microorganisms – Chlamydia trachomatis; Chlamydia pneumoniae; Chlamydia psittaci; Mycoplasma pneumoniae; Mycoplasma hominis; Borrelia burgdorferi.

List of microorganisms capable of developing resistance to azithromycin

Gram-positive aerobes – Streptococcus pneumoniae penicillin-resistant.

Initially resistant microorganisms

Gram-positive aerobes – Enterococcus faecalis; Staphylococci (methicillin-resistant staphylococci show very high resistance to macrolides).

Gram-positive bacteria that are resistant to erythromycin.

The anaerobes are Bacteroides fragilis.

Pharmacokinetics

Absorption is high, acid resistant, lipophilic. Bioavailability after a single dose of 500 mg is 37% (effect of first passage through the liver); Cmax after oral administration of 500 mg – 0.4 mg/l, Tmax – 2.5-2.9 hours; in tissues and cells concentration is 10-50 times higher than in blood serum, Vd – 31.1 l/kg. Easily passes histohematic barriers. It penetrates into respiratory tract, urogenital organs, including prostate, skin and soft tissues; it accumulates in low pH environment, in lysosomes (which is especially important for eradication of intracellularly located pathogens). It is also transported by phagocytes, polymorphonuclear leukocytes and macrophages.

It penetrates through cell membranes and generates high concentrations in cells. The concentration in the foci of infection is significantly higher (24-34%) than in healthy tissues and correlates with the severity of inflammatory edema. In the focus of inflammation it is maintained in effective concentrations for 5-7 days after the last dose. Binding with plasma proteins is 7-50% (inversely proportional to the concentration in blood).

The drug is demethylated in the liver, the resulting metabolites are inactive. CYP3A4, CYP3A5, CYP3A7 isoenzymes are involved in metabolism of the drug. Plasma clearance is 630 ml/min; T1/2 between 8 and 24 hours after intake is 14-20 hours, T1/2 from 24 to 72 hours – 41 hours. 50% is excreted unchanged in the bile, 6% – by the kidneys.

Eating significantly changes pharmacokinetics: Cmax decreases by 52%, AUC – by 43%.

In elderly men (65-85 years old) pharmacokinetic parameters do not change, in women Cmax increases (by 30-50%).

Indications

Infectious and inflammatory diseases caused by microorganisms sensitive to azithromycin:

Infections of the upper respiratory tract and ENT (sinusitis, pharyngitis, tonsillitis, otitis media);

Lower respiratory tract infections: pneumonia (including atypical, exacerbation of chronic pneumonia), bronchitis (including acute, exacerbation of chronic);

infections of the skin and soft tissues: common acne (moderate severity), rye, impetigo, secondary infected dermatoses;

infections of the urinary tract: gonorrheal and non-gonorrheal urethritis, cervicitis;

the initial stage of Lyme disease (borreliosis) – erythema migrans (erythema migrans).

Active ingredient

Composition

One capsule contains:
active substance: azithromycin dihydrate – 525.8 mg * (in terms of azithromycin) – 500.0 mg;
excipients: microcrystalline cellulose, lactose monohydrate, magnesium stearate, sodium lauryl sulfate;
Solid gelatin capsules:
Body: titanium dioxide E 171, gelatin;
Lid: titanium dioxide E 171, sunset yellow dye E 110, gelatin.
*Quantity is based on the theoretical activity of azithromycin 95.1%

How to take, the dosage

Overly, 1 h before or 2 h after a meal once a day.

Adults and children over 12 years of age with body weight over 45 kg

Infections of upper and lower respiratory tract, ENT organs, skin and soft tissues: 500 mg/day 1 course for 3 days (course dose – 1.5 g).

Common acne: 500 mg/d at 1 dose for 3 days, then 500 mg/d once a week for 9 weeks. The first weekly dose should be taken 7 days after the first daily dose (day 8 from the start of treatment); the next 8 weekly doses should be taken 7 days apart.

Acute urinary tract infections (uncomplicated urethritis or cervicitis): 1 g once.

Lyme disease: to treat stage I (erythema migrans) – 1 g on the first day and 500 mg/day from day 2 to day 5 (course dose – 3 g).

Pneumonia: prescribed at 500 mg/day for 7-10 days; administration starts immediately after the end of the IV dosage form.

Interaction

Antacids (aluminum- and magnesium-containing) do not affect bioavailability, but decrease azithromycin concentration in blood by 30%, therefore azithromycin should be taken 1 hour before or 2 hours after taking these drugs.

Concomitant use with ergotamine and dihydroergotamine derivatives may increase the toxic effects (vasospasm, dysesthesia) of the latter.

When concomitant use of coumarin-type indirect anticoagulants (warfarin) and azithromycin (in usual doses) in patients a careful monitoring of PV is necessary.

Caution should be exercised when concomitant use of terfenadine and azithromycin, because concomitant use of terfenadine and macrolides has been found to cause arrhythmias and prolongation of the QT interval. Therefore, these complications cannot be excluded when terfenadine and azithromycin are taken together.

When concomitant use with cyclosporine it is necessary to monitor the blood concentration of cyclosporine.

Concomitant use with digoxin requires monitoring of digoxin concentrations in the blood (digoxin absorption in the intestine may be increased).

Concomitant use with nelfinavir may increase the incidence of adverse reactions to azithromycin (decreased hearing, increased liver transaminase activity).

In concomitant use with zidovudine azithromycin does not affect its pharmacokinetic parameters in blood plasma or renal excretion of both zidovudine itself and its glucuronide, but increases concentration of active metabolite – phosphorylated zidovudine in mononuclear cells of peripheral vessels. The clinical significance of this fact has not been determined.

Possible inhibition of CYP3A4 isoenzyme by azithromycin when used concomitantly with cyclosporine, terfenadine, ergot alkaloids, cisapride, pimozide, quinidine, astemizole and other drugs metabolized with this enzyme should be considered.

Asithromycin does not affect blood concentrations of carbamazepine, cimetidine, didanosine, efavirenz, fluconazole, indinavir, midazolam, theophylline, triazolam, trimethoprim/sulfamethoxazole, cetirizine, sildenafil, atorvastatin, rifabutin and methylprednisolone when administered simultaneously.

Special Instructions

If a dose is missed, the missed dose should be taken as soon as possible, and subsequent doses should be taken 24 hours apart.

Azithromycin should be taken 1 h before or 2 h after taking antacid drugs.

Take with caution in patients with moderate hepatic impairment (because of the possibility of fulminant hepatitis and severe hepatic failure). In case of symptoms of liver function abnormality (rapidly increasing asthenia, jaundice, darkened urine, bleeding tendency, hepatic encephalopathy) azithromycin therapy should be discontinued and liver function tests should be performed.

In moderate renal insufficiency (creatinine Cl over 40 ml/min) azithromycin should be used under monitoring of renal function.

The concomitant use of azithromycin with ergotamine and dihydroergotamine derivatives is contraindicated due to the possible development of ergotism.

When using the drug both against and 2-3 weeks after discontinuation of treatment, development of diarrhea caused by Clostridium difficile (pseudomembranous colitis) is possible. In mild cases withdrawal of treatment and use of ion exchange resins (colestyramine, colestipol) is sufficient, in severe cases compensation of loss of fluid, electrolytes and protein, prescription of vancomycin, bacitracin or metronidazole is indicated.

Prevent use of drugs that inhibit intestinal peristalsis during treatment with azithromycin.

Because QT interval prolongation is possible in patients treated with macrolides, including azithromycin, caution should be exercised when using azithromycin in patients with known risk factors for QT interval prolongation: Elderly age; electrolyte imbalance (hypokalemia, hypomagnesemia); congenital QT interval prolongation syndrome; heart disease (heart failure, myocardial infarction, bradycardia); concurrent use of drugs that can prolong the QT interval (includingAntiarrhythmic drugs of classes Ia and III, tricyclic and tetracyclic antidepressants, neuroleptics, fluoroquinolones).

When using azithromycin it is possible to develop myasthenic syndrome or exacerbation of myasthenia gravis.

Impact on the ability to drive vehicles and operate machinery. During treatment, caution must be exercised when driving motor vehicles and engaging in other potentially hazardous activities requiring increased concentration and rapid psychomotor reactions.

Contraindications

With caution: pregnancy; arrhythmia, including predisposition to arrhythmias and QT interval prolongation (risk of ventricular arrhythmias and QT interval prolongation); renal insufficiency (creatinine Cl over 40 ml/min); hepatic insufficiency (below Child-Pugh class B); myasthenia; simultaneous use of terfenadine, warfarin, digoxin.

Side effects

Digestive system disorders: Diarrhea, nausea, abdominal pain, flatulence, vomiting, melena, cholestatic jaundice, increased liver transaminase activity, constipation, anorexia, gastritis, candida mucosa, dyspepsia, hyperbilirubinemia, hepatitis, pancreatitis, pseudomembranous colitis, liver dysfunction, liver failure (rarely fatal, mostly against the background of liver dysfunction), liver necrosis, fulminant hepatitis.

Particularly cardiac disorders: palpitations, chest pain, decreased blood pressure, increased QT interval, pirouette-type arrhythmia, ventricular tachycardia.

Nervous system disorders: dizziness, headache, vertigo, somnolence, paraesthesia, impaired sense of taste, hypoesthesia, aggression, fainting, convulsions, psychomotor hyperactivity, loss of sense of smell and taste, myasthenia; in children – headache (in otitis media therapy), hyperkinesia, anxiety, neurosis, insomnia.

Sensory organs: impairment of clarity of vision, conjunctivitis, deafness, tinnitus.

Urogenital system disorders: increased residual urea nitrogen, vaginal candidiasis, increased concentration of creatinine in blood plasma, interstitial nephritis, acute renal failure.

Hematopoietic organs: leukopenia, neutropenia, thrombocytopenia, lymphopenia, eosinophilia, hemolytic anemia.

Allergic reactions: rash, urticaria, skin itching, angioedema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, hypersensitivity reaction, anaphylactic reaction.

Others: hyperglycemia, arthralgia, asthenia, photosensitization, weakness, peripheral edema, malaise.

Overdose

Symptoms: severe nausea, temporary hearing loss, vomiting, diarrhea.

Treatment: withdrawal of the drug, gastric lavage, administration of activated charcoal, symptomatic therapy.

Pregnancy use

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