medicalmeds.eu Medicines Macroleads, linkozamida and streptogramina. Azitro Sandoz®

Azitro Sandoz®

Препарат Азитро Сандоз®. Sandoz Gmbh (Сандоз Гмбх) Германия

Producer: Sandoz Gmbh (Sandoz Gmbh) Germany

Code of automatic telephone exchange: J01FA10

Release form: Firm dosage forms. Tablets.

Indications to use: Tonsillitis. Pharyngitis. Average otitis. Bronchitis. Sinusitis. Upper respiratory tract infections. Lower respiratory tract infections. Infections of urinogenital system. Pneumonia.

General characteristics. Structure:

Active ingredient: azithromycin;
1 tablet contains azithromycin 250 mg or 500 mg in the form of dihydrate azithromycin;
excipients: cellulose microcrystallic, starch corn, starch sodium (type A), silicon dioxide colloid anhydrous, magnesium stearate, sodium lauryl sulfate;
cover: lactose, gipromelloza, titanium dioxide (E171), macrogoal 4000.

Pharmacological properties:

Pharmacodynamics. Active ingredient of drug Azitro Sandoz — azithromycin — is the representative of group of makrolidny antibiotics — azaleads, possesses a wide range of antimicrobic action. The mechanism of effect of azithromycin consists in inhibition of synthesis of bacterial protein due to linkng with 50S-subunit of ribosomes and prevention of a translocation of peptides in the absence of influence on synthesis of polynucleotides (bacteriostatic effect).
Resistance to azithromycin can be inborn or acquired. There is a full cross resistance between erythromycin, azithromycin, other macroleads and linkozamida for Streptococcus pneumoniae, a β-hemolitic streptococcus of group A, Enterococcus faecalis and Staphylococcus aureus, including metitsillinrezistentny S. aureus (MRSA).
Sensitive to azithromycin:
• aerobic gram-positive bacteria: Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes (гр. A);
• aerobic gram-negative bacteria: Haemophilus influenzae, Haemophilus parainfluenzae, Neisseria gonorrhoeae, Moraxella catarrhalis, Pasteurella multocida;
• anaerobic bacteria: Clostridium perfringens, Fusobacterium spp., Prevotella spp., Porphyromonas spp.;
• other bacteria: Chlamydia trachomatis, Chlamydophila pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae.

The types gaining resistance in some cases:
• aerobic gram-positive bacteria: Streptococcus pneumoniae (with intermediate sensitivity to penicillin, penitsillinrezistentny).

Vrozhdennorezistentny microorganisms:
• aerobic gram-positive bacteria: Enterococcus faecalis, staphylococcus of MRSA, MRSE (metitsillinrezistentny golden and epidermal staphylococcus);
• aerobic gram-negative bacteria: Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa.

Pharmacokinetics. Bioavailability of azithromycin after oral administration makes about 37%. Cmax in blood serum is reached in 2–3 h after administration of drug.
After intake azithromycin is quickly distributed in fabrics and liquids of an organism. Well gets into respiratory tracts, bodies and fabrics of an urogenital path, into skin and soft tissues. Accumulates intracellularly at the expense of what concentration of drug in fabrics are much higher (by 50 times), than in plasma that testifies to high affinity of drug to fabrics and it is connected with low linkng of azithromycin with proteins of a blood plasma.
Concentration of azithromycin in target organs (lungs, a throat, a prostate gland) exceed MIK90 for pathogenic microorganisms after reception of a single dose of drug of 500 mg. Azithromycin in a large number collects in phagocytes and fibroblasts. Phagocytes transport drug to the place of an inflammation. Azithromycin collects in bactericidal concentration in the place of an inflammation for 5–7 days after reception of the last dose that allows to carry out short (3-and 5-day) courses of treatment.
The final period of plasma semi-removal completely answers Т½ from fabrics for 2–4 days.
About 12% in/in doses of azithromycin are removed with urine in not changed look for the next 3 days. Especially high concentration of not changed azithromycin were revealed in bile. 10 metabolites which are formed by means of N-and O-demethylation, a hydroxylation and other metabolic transformations are identified. The corresponding researches confirmed that they metabolites of azithromycin do not show antimicrobic action.

Indications to use:

the infections caused by the microorganisms sensitive to azithromycin:
• infections of ENT organs (sinusitis, pharyngitis, tonsillitis);
• lower respiratory tract infections (bronchitis, pneumonia weak and moderately severe);
• inflammation of a middle ear;
• infections of skin and soft tissues;
• the uncomplicated urogenital infections caused by Chlamydia trachomatis.

Route of administration and doses:

Azitro Sandoz, tablets
Dosing and duration of use are defined by the doctor. Tablets, film coated, it is necessary to accept without chewing together with liquid of 1 times a day. Tablets need to be applied for an hour to or in 2 h after food as the concomitant use with food can break azithromycin absorption.
Adults, including patients of advanced age and children with body weight> 45 kg:
• at infections of ENT organs, respiratory tracts, skin and soft tissues (except the migrating erythema): 500 mg of 1 times a day for 3 days or 500 mg of 1 times a day in the 1st day of treatment and on 250 mg of 1 times a day in the next 4 days. The general course dose of azithromycin makes 1500 mg;
• at the migrating erythema: the adult — 1 time a day for 5 days (the 1st day — 1 g, the 2-5th day — 500 mg);
• at the uncomplicated urogenital infections caused by Chlamydia trachomatis — 1 g of drug of 1 times a day. A course dose — 1 g.

In case of the admission of administration of drug it is necessary to accept the passed dose as soon as possible, and the following — bucketed in 24 h.
Renal failure
Patients with insignificant dysfunction of kidneys (clearance of creatinine> of 40 ml/min.) do not have need to change dosing. Did not conduct any researches at patients with clearance of creatinine <40 ml/min. Respectively, such patients need to appoint azithromycin with care.
Liver failure
As azithromycin is metabolized in a liver and removed with bile, drug should not be used at patients with a serious illness of a liver.
Azitro Sandoz, suspension
The adult appoint 500 mg of 1 times a day within 3 days or on 500 mg in the 1st day and then on 250 mg from the 2nd to the 5th day.
At an uncomplicated urethritis / cervicitis dosing for adults makes 1 g in the form of a single peroral dose.
At the urethritis/cervicitis complicated a long current caused by Chlamidia trachomatis — on 1 g 3 times at an interval of 7 days (1-7-14-y). A course dose — 3 g.
Children: appoint 1 time a day on 10 mg/kg of body weight within 3 or 5 days, since a single dose of 10 mg/kg in the 1st day, then — in a dose of 5 mg/kg the next 4 days according to the table given below.

                                        Azithromycin of 100 mg / 5 ml
                              3-day therapy                          5-day therapy
Body weight, kg      1-3rd day of 10 mg/kg/days      1st day of 10 mg/kg/days      2-5th day of 5 mg/kg/days
       10                                  5                                                                  ml 5 ml 2,5 ml
       12                                  6                                                                     ml 6 ml 3 ml

                                         Azithromycin of 200 mg / 5 ml
                              3-day therapy                          5-day therapy
Body weight, kg      1-3rd day of 10 mg/kg/days      1st day of 10 mg/kg/days      2-5th day of 5 mg/kg/days
                                          10 2,5                                                           ml 2,5 ml 1,25 ml
      12                                       3                                                                ml 3 ml 1,5 ml
                                          14 3,5                                                            ml 3,5 ml 1,75 ml
      16                                       4                                                                   ml 4 ml 2 ml
    17–25                                    5                                                                ml 5 ml 2,5 ml
                                      26-35 7,5                                                           ml 7,5 ml 3,75 ml
    36–45                                   10                                                                ml 10 ml 5 ml
    > 45                                                                                       kg 12,5 ml 12,5 ml 6,25 ml

Exception is the dosage for treatment of the pharyngitis caused by Streptococcus pyogenes: efficiency of azithromycin at treatment of the pharyngitis caused by Streptococcus pyogenes when it was entered to children in a single dose of 10 or 20 mg/kg of body weight within 3 days at the maximum daily dose of 500 mg is proved.
(100 mg / 5 ml or 200 mg / 5 ml) it is necessary for preparation of 20 ml of suspension:
• to carefully stir up dry powder in a bottle;
• to open a cover of a bottle and to place the adapter in a bottle neck;
• to gain in the syringe (the volume of 10 ml with a marking on 0,25 ml) 10 ml of drinking water;
• to place a syringe tip in the adapter;
• to add from the syringe 10 ml of water to a bottle with powder. It is good to stir up before receiving homogeneous suspension.

By means of the syringe which is applied it is necessary for measuring off of necessary amount of suspension:
• to stir up a bottle;
• to place a syringe tip in the adapter;
• to turn a bottle upside down;
• to gain necessary amount of suspension in the syringe;
• to turn a bottle in the correct situation, to remove the syringe and to close a bottle a cover.

Flavoring feelings after reception of suspension can be improved, having washed down it with fruit juice. Suspension can be accepted together with food.
If reception of 1 dose of drug was missed, the following dose should be accepted as soon as possible, and to accept the subsequent with an interval of 24 h /

Features of use:

The liver is the main body of metabolism and removal of azithromycin therefore patients with heavy pathology of a liver should not accept drug.
At patients with a heavy renal failure (clearance of creatinine <10 ml/min.) it is necessary to apply with care azithromycin as at such patients noted increase in its concentration in a blood plasma for 33%.
Allergic reactions: it was in some cases reported that after reception of azithromycin there were serious allergic reactions, such as a Quincke's disease and an anaphylaxis. Some of these reactions predetermined development of recurrent symptoms and needed long observation and treatment.
The lengthening of cordial repolarization and interval of Q-T increasing risk of development of cardiac arrhythmia and trembling/fibrillation of ventricles was revealed at treatment by other makrolidny antibiotics. The similar effect of azithromycin cannot be excluded completely at patients with the increased risk of lengthening of a phase of cordial repolarization.
Data on possible interaction between alkaloids of an ergot and azithromycin are absent, however in connection with theoretical possibility of an ergotism it is not necessary to appoint derivatives of an ergot and azithromycin at the same time.
Streptococcal infections: azithromycin is not drug of the first choice at treatment of pharyngitis and tonsillitis, the caused Streptococcus pyogenes. There are no data which show efficiency of azithromycin in prevention of acute rhematoid polyarthritis.
Azithromycin is not shown for treatment of the infected burn wounds.
At treatment of uncomplicated urogenital infections, sexually transmitted, it is necessary to exclude simultaneous infection of Treponema pallidum.
As well as in a case with other antibacterial drugs, there is a possibility of superinfection (for example mycoses).
At use of makrolidny antibiotics there were messages on possibility of pseudomembranous colitis. Therefore this diagnosis should be considered when developing diarrhea at patients in an initiation of treatment azithromycin. At pseudomembranous colitis antiperistaltic means are contraindicated.
Tablets contain lactose therefore patients with the most rare hereditary forms of intolerance have galactoses, deficit of lactase and disturbances of absorption of glucose galactose it is not necessary to use this drug.
Use during pregnancy and feeding by a breast
Azithromycin gets through a placenta, however the adverse effect of drug on a fruit was not revealed. The corresponding and well controlled researches with participation of pregnant women are absent. Therefore azithromycin can be applied during pregnancy in that case when the expected advantage for mother exceeds potential risk for a fruit. Azithromycin gets into breast milk therefore it is recommended during treatment and 2 more days after its termination to stop breastfeeding.
Children. Children with the body weight of ≤45 kg are recommended to appoint azithromycin drugs in the form of suspension. There are no uses of drug given relatively in the form of suspension at children aged up to 6 months.
Ability to influence speed of response at control of vehicles or work with other mechanisms. During treatment by drug it is necessary to consider a possibility of development of undesirable effects from TsNS. At emergence of similar reactions it is necessary to refrain from control of vehicles and occupations other potentially dangerous types of activity which need the increased concentration of attention and speed of psychomotor reactions.

Side effects:

Assessment of by-effects is based on classification taking into account the frequency of reactions: very often (≥ 1/10), it is frequent (≥1/100, <1/10), sometimes (≥1/1000, <1/100), is rare (≥1/10 000, <1/1000), is very rare (<1/10 000), isolated cases:
• from system of blood: seldom — thrombocytopenia. In clinical trials there were separate messages on the periods of the tranzitorny poorly expressed neutropenia. However the causal relationship with treatment by azithromycin was not confirmed;
• mental disorders: seldom — aggression, a hyperactivity, alarm and nervousness;
• from TsNS: sometimes — dizziness / вертиго, drowsiness, syncopal states, a headache, spasms (it was established that they are also caused by other makrolidny antibiotics), change of taste and feeling of smells; seldom — paresthesia, an adynamy, sleeplessness;
• from an acoustic organ: seldom — a hearing disorder, approach of deafness and/or a ring in ears. The majority of these cases is connected with prolonged use of azithromycin in high doses during clinical trials. Usually these symptoms had reversible character;
• from cardiovascular system: it was seldom reported about strong heartbeat, arrhythmia (including ventricular tachycardia) (it was established that these symptoms arise under the influence of other makrolidny antibiotics). There were single messages on lengthening of an interval of Q-T and trembling/fibrillation of ventricles, arterial hypotension;
• from a GIT: often — nausea, vomiting, diarrhea, unpleasant feelings in a stomach (pains/spasms); sometimes — a liquid chair, a meteorism, digestion disturbance, anorexia; seldom — a lock, language discoloration. It was reported about pseudomembranous colitis, pancreatitis;
• gepatobiliarny disturbances: it was seldom reported about hepatitis and cholestatic jaundice, including pathological indicators of a functional trial of a liver, and also about separate cases of necrotic hepatitis and dysfunction of a liver which extremely seldom led to a lethal outcome;
• from skin: sometimes — allergic reactions, including an itch and rash; seldom — allergic reactions, including a Quincke's disease, a small tortoiseshell and a photosensitivity; heavy skin reactions, namely — a poliformny erythema, Stephens's syndrome — Johnson and a toxic epidermal necrolysis;
• from a musculoskeletal system: sometimes — an arthralgia;
• from an urinary system: seldom — intersticial nephrite and an acute renal failure;
• from reproductive system: sometimes — a vaginitis;
• system disturbances: seldom — an anaphylaxis, including hypostasis, candidiasis;
• laboratory researches: often — reduction of quantity of lymphocytes, increase in quantity of eosinophils and decrease in bicarbonates in blood; sometimes — increase in level of bilirubin, urea, creatinine in a blood plasma, increase in activity of ASAT, ALAT, change of amount of potassium in blood. These changes had reversible character.

Interaction with other medicines:

It is necessary to appoint with care azithromycin to patients along with medicines which extend Q–T interval (for example quinidine, cyclophosphamide, кетоконазол, терфенадин, a haloperidol, lithium).
Antacids: when studying influence of the combined use of antacids on pharmacokinetics of azithromycin bioavailability changes are not revealed though plasma peak concentration of azithromycin decreased by 25%. Azithromycin needs to be taken for 1 h to or in 2 h after reception of an antacid.
Tsetirizin: at healthy volunteers simultaneous use of azithromycin from 20 mg of a tsetirizin for 5 days did not lead to pharmacokinetic interaction in an equilibrium state, but considerably changed Q–T interval.
Ergot alkaloids: at the combined use of azithromycin and dihydroergotamine or alkaloids of an ergot it is impossible to exclude vasopressor effect with perfusion disturbance that leads to damage of fingers of hands and legs. Therefore it is necessary to avoid their simultaneous use.
Carbamazepine: azithromycin did not exert considerable impact on amount of carbamazepine or its active metabolites in a blood plasma.
Cyclosporine: some of makrolidny antibiotics influence cyclosporine metabolism. Therefore at co-administration of azithromycin and cyclosporine it is necessary to carry out careful monitoring of level of cyclosporine and to respectively regulate dosing.
Coumarin anticoagulants: at simultaneous use of azithromycin and warfarin strengthening of anti-coagulative effect therefore at such use it is necessary to control a prothrombin time is possible.
Digoxin: it was reported that makrolidny antibiotics influence metabolism of digoxin in intestines. Respectively, in case of simultaneous use of azithromycin and digoxin it is necessary to carry out monitoring of level of digoxin.
Terfenadin: in pharmacokinetic researches it was not reported about interaction between azithromycin and terfenadiny. As well as in a case with other makrolidny antibiotics, it is necessary to appoint azithromycin with care in a combination with terfenadiny.
Theophylline: azithromycin did not influence theophylline pharmacokinetics at a concomitant use. The combined use of theophylline and other makrolidny antibiotics sometimes led to increase in level of theophylline in blood serum.
Zidovudine: 1000 mg of azithromycin as a single dose, and 600 mg or 1200 mg of azithromycin as reusable doses did not influence pharmacokinetics and removal with urine of a zidovudine or its glyukuronidny metabolites. However reception of azithromycin increased concentration of a fosforilirovanny zidovudine in mononukleara of peripheric circulation. The clinical importance of these data is unknown, but they can be useful to patients.
Didanozin: simultaneous use of daily doses of azithromycin of 1200 mg with didanoziny at 6 volunteers led to increase in Cmax of a didanozin by 44% and AUC by 14%.
Rifabutin: simultaneous use of azithromycin and a rifabutin did not influence plasma concentration of these drugs. At persons who accepted at the same time azithromycin and рифабутин, noted a neutropenia. Though the neutropenia was connected using a rifabutin, the causal relationship was not established with a concomitant use of azithromycin.
Tsizaprid: simultaneous use of a tsizaprid can cause lengthening of an interval of Q-T, ventricular arrhythmia and a syndrome of trembling/fibrillation of auricles therefore they should not be applied at the same time.
Astemizol, alfentanit: at their simultaneous use it is necessary to be careful with azithromycin as for erythromycin strengthening of its action was established.
Azithromycin significantly does not interact with system of P450 cytochrome in a liver therefore for it it is not necessary to expect manifestation of the pharmacokinetic interaction characteristic of erythromycin and other macroleads.
Nelfinavir: use of a nelfinavir causes increase in equilibrium concentration of azithromycin in blood serum. Though dose adjustment of azithromycin at its simultaneous use with nelfinaviry is not recommended, note justified careful monitoring of the known side effects of azithromycin.
Other antibiotics: it is necessary to consider possible cross resistance between azithromycin and makrolidny antibiotics (such as erythromycin), and also lincomycin and clindamycin.

Contraindications:

Hypersensitivity to active ingredient or to any other of components of drug or to other makrolidny antibiotics; the expressed abnormal liver functions; disturbance of electrolytic balance, especially at a hypopotassemia and a hypomagnesiemia; clinically expressed bradycardia, arrhythmia or heavy heart failure. In view of theoretical possibility of an ergotism it is not necessary to appoint azithromycin along with ergot derivatives.
For drug in the form of suspension also: feeding period breast; children up to 6 months.

Overdose:

Symptoms: reversible hearing disorder, nausea, vomiting, diarrhea.
Treatment: symptomatic, directed to maintenance of vital signs of an organism, a gastric lavage, use of absorbent carbon.

Storage conditions:

Azitro Sandoz in the form of tablets — at a temperature not above 25 °C. Azitro Sandoz in the form of powder for preparation of suspension it is necessary to store at a temperature not above 30 °C. Ready suspension is stored at a temperature not above 25 °C within 5 days.