Zitrolide forte - instructions for use, dose, side effects, contraindications

Description:Capsules № 00, the case is white, the lid is orange. The contents of the capsules are white to white powder with a yellowish hue of color, prone to clumping.

Pharmacotherapeutic group:Antibiotic-azalide

ATX: & nbsp

J.01.F.A.10 Azithromycin

Pharmacodynamics:

Azithromycin is a bacteriostatic broad-spectrum antibiotic from the group of macrolides-azalides. It has a wide spectrum of antimicrobial action. The mechanism of action of azithromycin is associated with the suppression of protein synthesis of a microbial cell. Communicating with 50S-subunit of the ribosome, inhibits peptidranslokase at the stage of translations and suppresses protein synthesis, slowing the growth and multiplication of bacteria. In high concentrations has a bactericidal effect.

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

Microorganisms may initially be resistant to the action of the antibiotic or may acquire resistance to it.

The sensitivity scale of microorganisms to azithromycin (Minimum inhibitory concentration (MIC), mg / l):

Microorganisms		MIC, mg / l
		Sensitive		Sustainable
Staphylococcus		≤1		>2
Streptococcus A, B, C, G		≤0,25		>0,5
S. pneumonia		≤0,25		>0,5
N. influenzae		≤0,12		>4
M. caiarrhalis	≤0,5		>0,5
N. gonorrhoeae	≤0,25		>0,5

In most cases, sensitive microorganisms:

1. Gram-positive aerobes

Staphylococcus aureus Methicillin-sensitive

Streptococcus pneumoniae Penicillin-sensitive

Streptococcus pyogenes

2. Gram-negative aerobes

Haemophilus influenza

Haemophilus parainjluenzae

Legionella pneumophila

Moraxella caiarrhalis

Pasteurella muliocida

Neisseria gonorrhoeae

3. Anaerobes

Clostridium perfringens

Fusobacterium spp.

Prevotella spp.

Porphyriomonasspp.

4. Other microorganisms

Chlamydia trachomatis

Chlamydia pneumonia

Chlamydia psittaci

Mycoplasma pneumonia

Mycoplasma hominis

Borrelia burgdorferi

Microorganisms that can develop resistance to azithromycin:

Gram-positive aerobes

Streptococcus pneumoniae Penicillin-stable

Initially, resistant microorganisms:

Gram-positive aerobes

Enterococcus faecalis

Staphylococci (methicillin-resistant staphylococci exhibit a very high degree of resistance to macrolides)

Gram-positive bacteria resistant to erythromycin.

Anaerobes

Bacteroides fragilis

Pharmacokinetics:

Absorption is high, acid-fast, lipophilic. Bioavailability after a single dose of 500 mg - 37% (the effect of "first pass" through the liver), the maximum concentration (Cmah) after oral intake of 500 mg - 0.4 mg / l, the time to reach the maximum concentration (TCmah) - 2,5-2,9 hours; in tissues and cells the concentration is 10-50 times higher than in serum, the volume of distribution is 31.1 l / kg. Easily passes gistogematicheskie barriers. It penetrates well into the respiratory tract, urino-genital organs and tissues, into the prostate gland, into the skin and soft tissues; accumulates in a medium with low pH, in lysosomes (which is especially important for the eradication of intracellularly located pathogens); is also transported by phagocytes, polymorphonuclear leukocytes and macrophages. It penetrates the membranes of cells and creates high concentrations in them. The concentration in the foci of infection is significantly higher (by 24-34%) than in healthy tissues, and correlates with the severity of the inflammatory edema.In the focus of inflammation persists in effective concentrations within 5-7 days after taking the last dose. The connection with plasma proteins is 7-50% (inversely proportional to the concentration in the blood).

In the liver demethylated, the metabolites formed are not active. In the metabolism of the drug, isozymes participate CYP3A4, CYP3A5, CYP3A7, of which it is an inhibitor. Plasma clearance - 630 ml / min; half-life (T1 / 2) between 8 and 24 hours after admission is 14-20 hours, T1 / 2 in the interval from 24 to 72 hours - 41 hours. 50% is excreted with bile in unchanged form, 6% - in kidneys.

Eating significantly changes the pharmacokinetics. FROMmah decreases by 52%, the area under the pharmacokinetic curve "concentration-time" (AUC) - by 43%.

In elderly men (65-85 years) the pharmacokinetic parameters do not change, in women C increasesmah (by 30-50%).

Indications:Infectious-inflammatory diseases caused by microorganisms susceptible to azithromycin:

- infections of the upper respiratory tract and ENT organs: pharyngitis, tonsillitis, sinusitis, otitis media;

- Infections of the lower respiratory tract: pneumonia (including atypical, exacerbation of chronic pneumonia), bronchitis (including acute, exacerbation of chronic);

- skin and soft tissue infections: acne vulgaris (medium severity), erysipelas, impetigo, secondarily infected dermatoses;

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

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

Contraindications:

- Hypersensitivity to azithromycin (including other macrolides), components of the drug;

- severe renal failure (creatinine clearance (CK) less than 40 ml / min);

- severe hepatic insufficiency (class B and higher on the Child-Pugh scale);

- lactation period;

- children under 12 years of age and weighing less than 45 kg;

- simultaneous reception with ergotamine and dihydroergotamine.

Carefully:

Pregnancy, arrhythmia, including predisposition to the development of arrhythmia and lengthening of the interval Q-T (risk of ventricular arrhythmia and lengthening of the interval Q-T), renal insufficiency (CC more than 40 ml / min), liver failure (lower class B, Child-Pugh scale), myasthenia gravis, simultaneous reception with terfenadine, warfarin, digoxin.

Pregnancy and lactation:

Azithromycin penetrates the placenta.Use during pregnancy is possible only if the intended benefit to the mother exceeds the potential risk to the fetus. If azithromycin is to be used during lactation, breastfeeding should be stopped.

Dosing and Administration:

Inside, 1 hour before or 2 hours after meals 1 time per day.

Adults and children over 12 years of age with a body weight of more than 45 kg:

- with infections of the upper and lower respiratory tract, ENT organs, skin and soft tissues - 500 mg per day for 1 reception for 3 days (exchange dose - 1.5 g).

- acne vulgaris - 500 mg per day for 1 reception for 3 days, then 500 mg per day once a week for 9 weeks. The first weekly dose should be taken 7 days after the first daily dose (8 days from the start of treatment), followed by 8 weekly doses at intervals of 7 days.

- with acute infections of the urogenital organs (uncomplicated urethritis or cervicitis) - once 1 g.

- In case of illness. Lyme - for the treatment of stage I (erythema migrans) -1 g on the first day and 500 mg daily from 2 to 5 days (course dose - 3 g).

- In the treatment of pneumonia, 500 mg daily are prescribed for 7-10 days; reception begin immediately after the end of the use of the intravenous dosage form (the recommended dose for intravenousadministration of 500 mg once a day for at least 2 days).

Side effects:

From the digestive system: diarrhea, nausea, abdominal pain, flatulence, vomiting, melena, cholestatic jaundice, increased activity of "liver" transaminases, constipation, anorexia, gastritis, candidamycosis of the oral mucosa, dyspepsia, hyperbilirubinemia, hepatitis, pancreatitis, pseudomembranous colitis, hepatic dysfunction , liver failure (in rare cases with a fatal outcome, mainly on the background of a violation of liver function), liver necrosis, fulminant hepatitis.

From the cardiovascular system: heart palpitations, chest pain, lowering blood pressure, increasing the interval Q-T, arrhythmia such as "pirouette", ventricular tachycardia.

From the nervous system: dizziness, headache, vertigo, drowsiness, paresthesia, taste disorders, hypoesthesia, aggression, fainting, convulsions, psychomotor hyperactivity, loss of smell, taste sensations, myasthenia gravis; children - headache (with the treatment of otitis media), hyperkinesia, anxiety, neurosis, insomnia.

From the sense organs: impaired clarity of visual perception, deafness, noise in the ears.

From the genitourinary system: increased residual urea nitrogen, vaginal candidiasis, increased serum creatinine concentration, interstitial nephritis, acute renal failure.

From the hematopoiesis: leukopenia, neutropenia, thrombocytopenia, lymphopenia, eosinophilia, hemolytic anemia.

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

Other: hyperglycemia, arthralgia, asthenia, photosensitivity, conjunctivitis, taste change, weakness, peripheral edema, malaise.

Overdose:

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

Treatment: cancellation of the drug, gastric lavage, the reception of activated charcoal, symptomatic therapy.

Interaction:

Antacids (aluminum and magnesium-containing) do not affect bioavailability, but reduce the concentration of azithromycin in the blood by 30%, so the interval between their intake should be 1 hour before or 2 hours after taking these drugs.

With simultaneous use with derivatives of ergotamine and dihydroergotamine, toxic effects (vasospasm, dysesthesia) of the latter are possible. When combined with anticoagulants indirect effect of the coumarin series (warfarin) and azithromycin (in usual doses) patients need careful monitoring of prothrombin time.

Caution should be exercised in the joint use of terfenadine and azithromycin, since it was found that the simultaneous administration of terfenadine and macrolides causes arrhythmia and lengthening Q-T interval. Proceeding from this, it is impossible to exclude the aforementioned complications in the joint administration of terfenadine and azithromycin. When used simultaneously with cyclosporine, it is necessary to monitor the concentration of cyclosporine in the blood.

With simultaneous use with digoxin, it is necessary to control the concentration of digoxin in the blood (there may be an increase in absorption of digoxin in the intestine).

At simultaneous application with nelfinavir it is possible to increase the incidence of adverse reactions of azithromycin (decrease in hearing, increase of activity of "liver" transaminases).

When combined with zidovudine azithromycin does not affect the pharmacokinetic parameters of zidovudine in blood plasma or on the excretion of his and his metabolite glucuronide by the kidneys, but the concentration of the active metabolite of phosphorylated zidovudine in mononuclear cells of peripheral vessels increases. The clinical significance of this fact is not determined.

The possibility of inhibiting the isoenzyme should be considered CYP3A4 azithromycin with simultaneous application with cyclosporine, terfenadine, ergot alkaloids, cisapride, pimozide, quinidine, astemizole and other drugs, the metabolism of which occurs with the participation of this enzyme.

Azithromycin does not affect the concentration of carbamazepine, cimetidine, didanosine, efavirenz, fluconazole, indinavir, midazolam, theophylline, triazolam, trimethoprim / sulfamethoxazole, cetirizine, sildenafil, atorvastatin, rifabutin and methylprednisolone in the blood together.

Special instructions:

In case of missed dose, the missed dose should be taken as soon as possible, and the subsequent dose should be taken at intervals of 24 hours.

Azithromycin should be taken 1 hour before or 2 hours after taking antacid medicines.

Take with caution patients with moderate hepatic impairment because of the possibility of developing fulminant hepatitis and severe hepatic insufficiency in such patients: in the presence of symptoms of impaired liver function (rapidly increasing asthenia, jaundice, darkening of the urine, propensity to bleed, hepatic encephalopathy), azithromycin therapy should be discontinued and conduct a study of the functional state of the liver.

With moderate renal failure (CC greater than 40 ml / min), azithromycin should be administered under the control of kidney function.

Contraindicated simultaneous administration of azithromycin with derivatives of ergotamine and dihydroergotamine because of the possible development of ergotism.

When using the drug, both on the background of taking and 2-3 weeks after discontinuation of treatment, it is possible to develop diarrhea caused by Clostridium difficile (pseudomembranous colitis). In mild cases, it is sufficient to cancel the treatment and apply ion-exchange resins (colestramine, colestipol), in severe cases, compensation for loss of fluid, electrolytes and protein, the appointment of vancomycin, bacitracin or metronidazole.

Do not use drugs that inhibit the intestinal motility.

Since it is possible to extend the interval Q-T in patients receiving macrolides, including azithromycin, with the use of azithromycin, caution should be exercised in patients with known risk factors for lengthening the interval Q-T: elderly age; violation of electrolyte balance (hypokalemia, hypomagnesemia); congenital lengthening syndrome Q-T; heart disease (heart failure, myocardial infarction, bradycardia); simultaneous reception of drugs that can lengthen the interval Q-T (including antiarrhythmic drugs 1a and III classes, tricyclic and tetracyclic antidepressants, neuroleptics, fluoroquinolones).

With the use of azithromycin, the development of myasthenic syndrome or myasthenia exacerbation is possible.

Effect on the ability to drive transp. cf. and fur:

During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:

Capsules 500 mg.

Packaging:

3 capsules per contour cell packaging made of polyvinylchloride film and aluminum foil printed lacquered.

1 or 2 contour squares, together with instructions for use, are placed in a pack of cardboard.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N003955 / 01

Date of registration:01.12.2009 / 28.06.2017

Expiration Date:Unlimited

The owner of the registration certificate:VALENTA PHARM, PAO VALENTA PHARM, PAO Russia

Manufacturer: & nbsp

VALENTA PHARMACEUTICS, JSC Russia

Information update date: & nbsp14.10.2017

Illustrated instructions

Instructions

Sietrolide® forte (Zitrolid® forte)