Zitrolid forte

General characteristics. Structure:

Active agent: azithromycin a dihydrate of 500 mg, (in terms of azithromycin) 
 
Excipients: MKTs — 64,3 mg; magnesium stearate — 5,7 mg 
 
Solid gelatin capsule  
Case: titanium dioxide (E171) — 2%; gelatin — to 100%  
Lid: titanium dioxide (E171) — 1,7434%; Sunset dye yellow (E110) — 0,4183%; gelatin — to 100%.

Pharmacological properties:

Pharmacodynamics. Azithromycin — a bacteriostatic antibiotic of a broad spectrum of activity from group of macroleads, azaleads. Possesses a wide range of antimicrobic action. The mechanism of effect of azithromycin is connected with suppression of synthesis of protein of a microbic cell. Contacting ribosome 50S-subunit, oppresses to a peptidtranslokaz at a stage of broadcasting and suppresses protein synthesis, slowing down growth and reproduction of bacteria. In high concentration has bactericidal effect.
Has activity concerning a row gram-positive, gram-negative, anaerobe bacterias, intracellular and other microorganisms.
Microorganisms can be initial steady against action of an antibiotic or gain resistance to it.

Scale of sensitivity of some microorganisms to azithromycin (the minimum inhibiting concentration — MIK)

Microorganisms	MIK, mg/l
	Sensitive	Steady
Staphylococcus	≤1	> 2
Streptococcus A, B, C, G	≤0,25	> 0,5
S. pneumoniae	≤0,25	> 0,5
H. influenzae	≤0,12	> 4
M. catarrhalis	≤0,5	> 0,5
N. gonorrhoeae	≤0,25	> 0,5

List of the microorganisms sensitive to azithromycin, in most cases

Gram-positive aerobes — Staphylococcus aureus metitsillinchuvstvitelny; Streptococcus pneumoniae is penitsillinchuvstvitelny; Streptococcus pyogenes.

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

Anaerobe bacterias — Clostridium perfringens; Fusobacterium spp.; Prevotella spp.; Porphyromonas spp.

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

The list of the microorganisms capable to develop azithromycin resistance

Gram-positive aerobes — Streptococcus pneumoniae penitsillinustoychivy.

Initially steady microorganisms

Gram-positive aerobes — Enterococcus faecalis; Staphylococci (metitsillinustoychivy staphylococcus show very high degree of resistance to macroleads).

Gram-positive bacteria steady against erythromycin.

Anaerobe bacterias — Bacteroides fragilis.

Pharmacokinetics. Absorption is high, кислотоустойчив, липофилен. Bioavailability after a single dose of 500 mg — 37% (effect of the first passing through a liver), Cmax after oral administration of 500 mg — 0,4 mg/l, Tmax — 2,5–2,9 h; in fabrics and cells concentration is 10-50 times higher, than in blood serum, Vd — 31,1 l/kg. Easily passes gistogematichesky barriers. Well gets into respiratory tracts, urinogenital bodies, including a prostate gland, skin and soft tissues; collects in the environment with a low rn, in lysosomes (that is especially important for an eradikation of intracellularly located activators). It is transported also by phagocytes, polymorphonuclear leukocytes and macrophages. Gets through membranes of cells and creates high concentration in them. Concentration in the centers of an infection it is reliable above (for 24–34%), than in healthy fabrics, and correlates with expressiveness of inflammatory hypostasis. In the center of an inflammation remains in effective concentration within 5–7 days after reception of the last dose. Communication with proteins of plasma — 7–50% (it is inversely proportional concentration in blood).
In a liver it demetilirutsya, the formed metabolites are inactive. Isoenzymes of CYP3A4, CYP3A5, CYP3A7 which inhibitor it is participate in metabolism of drug. Plasma clearance — 630 ml/min.; T1/2 between 8 and 24 h after reception makes 14–20 h, T1/2 in the range from 24 to 72 h — is removed with bile in not changed look, 6% 41 h 50% — kidneys.
Meal significantly changes pharmacokinetics: Cmax decreases by 52%, AUC — for 43%.
At elderly men (65–85 years) pharmacokinetic parameters do not change, at women Cmax increases (by 30–50%).

Indications to use:

- The infectious and inflammatory diseases caused by microorganisms, sensitive to azithromycin:
- infections of upper parts of respiratory tracts and ENT organs (sinusitis, pharyngitis, tonsillitis, average otitis);
- infections of lower parts of respiratory tracts: pneumonia (including atypical, exacerbation of chronic pneumonia), bronchitis (including acute, aggravation of chronic);
- infections of skin and soft tissues: the eels ordinary (moderate severity), an ugly face, impetigo for the second time infected a dermatosis;
- infections of urinary tract: gonorrheal and not gonorrheal urethritis, cervicitis;
- an initial stage of a disease Laima (borreliosis) — the migrating erythema (erythema migrans).

Route of administration and doses:

Inside, for 1 h to or in 2 h after food of 1 times a day.
Adults and children are more senior than 12 years with body weight more than 45 kg
Infections of upper and lower parts of respiratory tracts, ENT organs, skin and soft tissues: 500 mg/days for 1 reception within 3 days (a course dose — 1,5 g).
Eels ordinary: 500 mg/days for 1 reception within 3 days, then on 500 mg/days once a week during 9 weeks. The first weekly dose should be accepted in 7 days after reception of the first daily dose (the 8th day from an initiation of treatment), the subsequent 8 weekly doses — at an interval of 7 days.
Acute infections of urinogenital bodies (uncomplicated urethritis or cervicitis): once 1 g.
Lyme's disease: for treatment of the I stage (erythema migrans) — 1 g in the first day and 500 mg/days from the 2nd to the 5th day (a course dose — 3 g).
Pneumonia: appoint on 500 mg/days within 7–10 days; reception is begun right after the end of use in/in a dosage form.

Features of use:

In case of the admission of reception of a dose it is necessary to accept the passed dose as soon as possible, and the subsequent — at an interval of 24 h.

Azithromycin should be taken for 1 h to or in 2 h after reception of antiacid HP.

To take with caution to patients with a moderate liver failure (because of a possibility of development of fulminantny hepatitis and a heavy liver failure). In the presence of symptoms of an abnormal liver function (quickly accruing adynamy, jaundice, urine darkening, tendency to bleedings, hepatic encephalopathy) therapy by azithromycin it is necessary to stop and conduct a research of a functional condition of a liver.

At a moderate renal failure (creatinine Cl more than 40 ml/min.) use of azithromycin should be carried out under control of function of kidneys.

The concomitant use of azithromycin with derivatives of ergotamine and dihydroergotamine is contraindicated (because of possible development of an ergotism).

At drug use, both against the background of reception, and in 2–3 weeks after the treatment termination, development of the diarrhea caused by Clostridium difficile (pseudomembranous colitis) is possible. In mild cases there is enough cancellation of treatment and use of ion-exchange resins (Colestyraminum, колестипол), in hard cases compensation of loss of liquid, electrolytes and protein, purpose of Vancomycinum, bacitracin or metronidazole is shown.

It is impossible to apply the HP braking an intestines peristaltics during treatment by azithromycin.

As lengthening of an interval of QT at the patients receiving macroleads including azithromycin is possible, at azithromycin use, it is necessary to be careful at patients with the known risk factors of lengthening of an interval of QT: advanced age; disturbance of electrolytic balance (hypopotassemia, hypomagnesiemia); syndrome of inborn lengthening of an interval of QT; heart diseases (heart failure, myocardial infarction, bradycardia); a concomitant use of the HP capable to extend QT interval (including antiarrhytmic HP of Ia and the III classes, tricyclic and tetracyclic antidepressants, neuroleptics, ftorkhinolona).

At use of azithromycin development of a myasthenic syndrome or an aggravation of a myasthenia is possible.

Influence on ability to manage vehicles and to work with mechanisms. During treatment it is necessary to be careful at control of vehicles and the occupations other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

- From the alimentary system: diarrhea, nausea, an abdominal pain, a meteorism, vomiting, a melena, cholestatic jaundice, increase in activity of hepatic transaminases, a lock, anorexia, gastritis, a candidiasis of a mucous membrane of an oral cavity, dyspepsia, a hyperbilirubinemia, hepatitis, pancreatitis, pseudomembranous colitis, an abnormal liver function, a liver failure (in rare instances — with a lethal outcome, generally against the background of an abnormal liver function), a liver necrosis, fulminantny hepatitis.
- From CCC: a heart consciousness, thorax pain, decrease in the ABP, increase in an interval of QT, arrhythmia like "pirouette", ventricular tachycardia.
- From a nervous system: dizziness, headache, вертиго, drowsiness, paresthesia, disturbance of flavoring feelings, hypesthesia, aggression, syncope, spasms, psychomotor hyperactivity, loss of sense of smell, flavoring feelings, myasthenia; children have a headache (at therapy of average otitis), a hyperkinesia, alarm, neurosis, sleeplessness.
- From sense bodys: disturbance of clearness of visual perception, conjunctivitis, deafness, sonitus.
- From urinogenital system: increase in residual nitrogen of urea, a vaginal candidiasis, increase in concentration of creatinine in a blood plasma, intersticial nephrite, an acute renal failure.
- From bodies of a hemopoiesis: leukopenia, neutropenia, thrombocytopenia, lymphopenia, eosinophilia, hemolitic anemia.
- Allergic reactions: rash, urticaria, skin itch, Quincke's disease, mnogoformny erythema, Stephens-Johnson's syndrome, toxic epidermal necrolysis, hypersensitivity reaction, anaphylactic reaction.
- Other: hyperglycemia, arthralgia, adynamy, photosensitization, weakness, peripheral hypostases, indisposition.

Interaction with other medicines:

Antacids (aluminum - and magniysoderzhashchy) do not influence bioavailability, but reduce concentration, azithromycin in blood by 30% therefore azithromycin should be taken for 1 h to or in 2 h after reception of the specified drugs.

At simultaneous use with derivatives of ergotamine and dihydroergotamine strengthening of toxic action (a vasospasm, a dizesteziya) of the last is possible.

At combined use of anticoagulants of indirect action of a coumarinic row (warfarin) and azithromycin (in usual doses) at patients careful control of PV is necessary.

It is necessary to be careful at combined use of a terfenadin and azithromycin as it was established that the concomitant use of a terfenadin and macroleads causes arrhythmia and lengthening of an interval of QT. Proceeding from it, it is impossible to exclude the above-stated complications at joint reception of a terfenadin and azithromycin.

At simultaneous use with cyclosporine it is necessary to control concentration of cyclosporine in blood.

At simultaneous use with digoxin control of concentration of digoxin in blood is necessary (possibly increase in absorption of digoxin in intestines).

At simultaneous use with nelfinaviry increase in frequency of side reactions of azithromycin (decrease in hearing, increase in activity of hepatic transaminases) is possible.

At simultaneous use with a zidovudine azithromycin does not influence its pharmacokinetic parameters in a blood plasma or on removal by kidneys of both the zidovudine, and its glucuronide, but increases concentration of an active metabolite — a fosforilirovanny zidovudine in mononuclear cells of peripheral vessels. Clinical value of this fact is not defined.

It is necessary to consider a possibility of inhibition of an isoenzyme of CYP3A4 azithromycin at simultaneous use with cyclosporine, terfenadiny, ergot alkaloids, tsizapridy, Pimozidum, quinidine, astemizoly and other HP which metabolism happens to participation of this enzyme.

Azithromycin does not influence concentration of carbamazepine, Cimetidinum, didanozin, efavirenz, flukonazol, indinavir, midazolam, theophylline, a triazolam, Trimethoprimum/sulfamethoxazole, a tsetirizin, sildenafil, atorvastatin, rifabutin and Methylprednisolonum in blood at simultaneous use.

Contraindications:

- hypersensitivity to azithromycin (including to other macroleads), to drug components;
- heavy renal failure (creatinine Cl less than 40 ml/min.);
- a heavy liver failure (a class B above on a scale of Chayld-Pyyu);
- lactation period;
- the age up to 12 years, body weight is less than 45 kg;
- concomitant use of ergotamine and dihydroergotamine.

With care: pregnancy; arrhythmia, including predisposition to development of arrhythmia and lengthening of an interval of QT (risk of development of ventricular arrhythmias and lengthening of an interval of QT); renal failure (creatinine Cl more than 40 ml/min.); a liver failure (below a class B on a scale of Chayld-Pyyu); myasthenia; concomitant use of a terfenadin, warfarin, digoxin.

Use at pregnancy and feeding by a breast
Azithromycin gets through a placenta. Use at pregnancy is possible only if the estimated advantage for mother exceeds potential risk for a fruit. In need of use of azithromycin in the period of a lactation it is necessary to stop breastfeeding.

Overdose:

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

Treatment: drug withdrawal, gastric lavage, purpose of absorbent carbon, symptomatic therapy.

Storage conditions:

In the place protected from light, at a temperature not above 25 °C.
To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Capsules, 500 mg. In a blister strip packaging from the film of PVC and printing aluminum foil varnished on 3 pieces 1 or 2 blister strip packagings in a pack from a cardboard.