Azithromycin Sandoz - instructions for use, dose, side effects, contraindications

	100 mg / 5 ml	200 mg / 5 ml
Active substance
Azithromycin monohydrate (corresponds azithromycin)	102.4 mg ¹(100 mg)	204.8 mg ¹(200 mg)
Excipients
Sucrose (powder))²	2665.13 mg	2593.33 mg
Sucrose (powder)	1142.10 mg	1111.50 mg
Xanthan gum	6.66 mg	6.66 mg
Hydroxypropylcellulose	6.66 mg	6.66 mg
Trisodium phosphate anhydrous	18.395 mg	18.395 mg
Silica dioxide colloidal anhydrous	4.00 mg	4.00 mg
Aspartame	30.00 mg	30.00 mg
Aromatizer creamy caramel	13.00 mg	13.00 mg
Titanium dioxide	11.66 mg	11.66 mg

¹the content is adjusted if the result of quantification on an "as-is" basis is not more than 99%.

² the amount is adjusted according to or initial mass of the poured active substance (mass correction).

Description:

Powder from white to white with a yellowish tint of color with a specific caramel flavor.

Ready-to-use suspension: a homogeneous suspension from white to white with a yellowish tint of color with a specific caramel flavor.

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. Communicating with 50S-a subunit of ribosomes, inhibits peptidranslokase at the stage of translation, suppresses protein synthesis, slows the growth and multiplication of bacteria, has a bactericidal effect at high concentrations.

Has activity against a number of gram-positive, gram-negative, intracellular and other microorganisms.

Gram-positive aerobes: Staphylococcus aureus (methicillin-sensitive), Streptococcus pneumonia (penicillin-sensitive), Streptococcus pyogenes, Streptococcus agalactiae, Mycobacterium avium complex.

Gram-negative aerobes: Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Pasteurella multocida, Neisseria gonorrhoeae.

Anaerobic microorganisms: kinds kind Prevotella, Clostridium perfringens. Intracellular: kinds kind Chlamydia psittacci, Chlamydia trachomatis, Chlamydophila pneumonia, kinds kind Mycoplasma, Legionella pneumophila, Borrelia burgdorferi.

Microorganisms, capable of to develop sustainability to azithromycin: Streptococcus pneumonia (penicillin-resistant), sustainable microorganisms: Enterococcus faecalis, Staphylococcus spp. (methicillin-resistant staphylococci with very high frequency have acquired resistance to macrolides), Gram-positive bacteria resistant to erythromycin, Bacteroides fragilis.

Cases of cross-resistance between Streptococcus pneumoniae, Streptococcus pyogenes (beta-hemolytic group streptococcus A), Enterococcus faecalis and Staphylococcus aureus, including Staphylococcus aureus (methicillin-resistant strains) to erythromycin, azithromycin, other macrolides and lincosamides.

Pharmacokinetics:

Suction

Absorption is high, acid-fast, lipophilic. Bioavailability after a single dose of 0.5 g - 37% (the effect of "first passage" through the liver). The maximum concentration in the blood plasma (C_m_Oh) after oral administration is achieved after 2-3 hours and is 0.4 mg / l. Bioavailability is 37.5%.

Distribution

After oral administration azithromycin quickly distributed throughout the body. In pharmacokinetic studies, a higher level of azithromycin concentration in tissues is observed than in plasma and serum. The association with blood plasma proteins varies depending on the serum concentration: from 52% at 0.05 mg / L to 12 % at 0.5 mg / l.The volume of distribution in the equilibrium state is 31.1 l / kg.

Easily passes the histohematological 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 low pH, in lysosomes (which is especially important for the eradication of intracellular pathogens). It 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 blood plasma proteins is 7-50% (inversely proportional to the concentration in the blood).

Excretion

Excretion of azithromycin from the blood plasma takes place in two stages: the half-life (T_1/2) is 14-20 hours in the interval from 8 to 24 hours after taking the drug and 41 hours in the range of 24 to 72 hours, which allows the drug to be used once a day.

The drug is produced mainly with bile in the unchanged form, a small part is excreted by the kidneys.

Pharmacokinetics in special cases

Patients with renal insufficiency: after administration of a single dose of 1 g azithromycin in patients with mild and moderate renal insufficiency (glomerular filtration rate (GFR) - 10-80 ml / min) C_m_Oh and the area under the "concentration-time" curve AUC_0-120increased by 5.1% and 4.2%, respectively, compared with the group of patients with normal renal function (GFR-> 80 ml / min). In patients with severe renal insufficiency, the mean C_m_Oh and AUC_0-₁₂₀increased by 61% and 33%, respectively.

At the terminal stage of renal failure (CC less than 10 ml / min), the concentration of azithromycin in the blood plasma is increased by 33%.

Patients with hepatic insufficiency: in patients with hepatic insufficiency of mild or moderate severity, there was no evidence of significant changes in the pharmacokinetics of azithromycin in the blood serum as compared to patients with normal liver function.

Elderly patients: the pharmacokinetics of azithromycin in elderly male patients was close to the pharmacokinetics observed in young patients.

In elderly female patients, significant cumulation of azithromycin did not occur.

Indications:

Infectious 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 caused by atypical pathogens), acute bronchitis, exacerbation of chronic bronchitis;

- skin and soft tissue infections: chronic migrainea of erythema (Lyme disease) - initial stage, erysipelas, impetigo, secondarily infected dermatoses.

Contraindications:

- increased sensitivity to azithromycin, erythromycin, other macrolides or ketolides, as well as other components of the drug;

- impaired renal function (CC less than 40 ml / min);

- severe hepatic dysfunction (no data on efficacy and safety);

- the period of breastfeeding;

- children's age (up to 6 months);

- phenylketonuria;

- simultaneous administration of ergotamine and dihydroergotamine;

- deficiency of sugar / isomaltase, intolerance to fructose, glucose-galactose malabsorption.

Carefully:

Pregnancy, myasthenia gravis, liver dysfunction of mild to moderate severity, renal dysfunction of mild and moderate severity (creatinine clearance more than 40 ml / min), elderly patients; the patients with congenital or acquired lengthening of the interval QT, receiving antiarrhythmic drugs classes IA, III, cisapride, hypokalemia or hypomagnesemia, clinically significant bradycardia, arrhythmia or severe heart failure; simultaneous use of terfenadine, warfarin, digoxin, diabetes mellitus; simultaneous use with cyclosporine, antipsychotics such as pimozide; antidepressants, such as citalopram; and fluoroquinolones, such as moxifloxacin and levofloxacin.

Pregnancy and lactation:

The use of the drug during pregnancy is possible only if the intended benefit for the mother exceeds the potential risk to the fetus.

If it is necessary to prescribe the drug during lactation, breastfeeding should be stopped (it is excreted in breast milk).

Dosing and Administration:

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

After taking the drug, the child must necessarily offer to drink a few sips of water so that he can swallow the remains of the suspension.

Before each intake of the drug, the contents of the vial are shaken carefully until a homogeneous suspension is obtained. If the required volume of the suspension has not been removed from the vial within 20 minutes after shaking, the suspension should be shaken again, take the necessary volume and give the baby.

The required dose is measured with a syringe for dosing with a 1 ml division price, enclosed in a cardboard package together with a vial.

After use, the syringe (previously disassembled) is washed with running water. Dry and store in a dry place until the next dose.

In infections of the upper and lower respiratory tract and ENT organs. skin and soft tissues: at the rate of 10 mg / kg body weight 1 time per day for 3 days (course dose 30 mg / kg).

For accurate dosing according to the child's body weight, the following tables should be used.

Suspension (00 mg) / 5 ml

Body weight, kg	The volume of suspension (ml) at 1 reception
5	2.5 ml (50 mg of azithromycin)
6	3.0 ml (60 mg of azithromycin)
7	3.5 ml (70 mg of azithromycin)
8	4.0 ml (80 mg of azithromycin)
9	4.5 ml (90 mg of azithromycin)
10	5 ml (100 mg of azithromycin)

Suspension 200 mg / 5 ml

Body weight, kg	The volume of suspension (ml) at 1 reception
10-14	2.5 ml (100 mg of azithromycin)
15-24	5.0 ml (200 mg of azithromycin)
25-34	7.5 ml (300 mg of azithromycin)
35-44	10.0 ml (400 mg of azithromycin)
ns less than 45	12.5 ml (500 mg azithromycin) corresponds to the dose for adult patients

With pharyngitis / tonsillitis, caused by Streptococcus pyogenes, the drug is used at a dose of 20 mg / kg / day for 3 days (exchange dose of 60 mg / kg). The maximum daily dose is 500 mg.

With Lyme disease (the initial stage of borreliosis) - migratory erythema (Erythema migrans): In the first day at a dose of 20 mg / kg / day, then from 2nd to 5th day in a dose of 10 mg / kg / day (a course dose 60 mg / kg).

Patients with impaired renal function: when used in patients with impaired renal function of mild and moderate severity (CC greater than 40 ml / min), dose adjustment is not required.

Patients with impaired hepatic function: when used in patients with impaired liver function of mild to moderate severity, dose adjustment is not required.

In elderly patients, dose adjustment is not required.

Method of preparing the suspension

Suspension 100 mg / 5 ml: should be thoroughly shaken dry powder. 10.0 ml of purified water is added to the powder.For injection, the tip of the syringe is placed in the neck of the vial, while the plug must be open.

To the contents of the vial intended for preparation 20 ml of suspension (nominal volume), 10 ml of water is added using a syringe for dosing. Shake until a homogeneous suspension is obtained. The volume of the resulting suspension is about 25 ml, which exceeds the nominal volume by approximately 5 ml. This is provided to compensate for the inevitable loss of the suspension when the drug is dosed. The prepared suspension can be stored at a temperature of no higher than 30 ° C for not more than 5 days.

Suspension 200 mg / 5 ml: should be thoroughly shaken dry powder.

To the contents of the vial intended for preparation 15 ml of suspension (nominal volume), 7.5 ml of water is added using a syringe for dosing. Shake until a homogeneous suspension is obtained. The volume of the resulting suspension is about 20 ml, which exceeds the nominal volume by approximately 5 ml. This is provided to compensate for the inevitable loss of the suspension when the drug is dosed. The prepared suspension can be stored at a temperature of no higher than 30 ° C for not more than 5 days.

The amount of water indicated below is added to the powder:

for 15 ml (600 mg) (reconstituted suspension): 7.5 ml of water are added; for 20 ml (800 mg) (reconstituted suspension): 10.0 ml of water are added;

- for 22.5 ml (900 mg) (reconstituted suspension): 11.0 ml of water are added; for 30 ml (1200 mg) (reconstituted suspension): 15.0 ml of water are added;

- for 37.5 ml (1500 mg) (reconstituted suspension): 18.5 ml of water are added.

Side effects:

According to the World Health Organization (WHO), adverse reactions are classified according to their developmental frequency as follows: very often (> 1/10), often (> 1/100, <1/10), infrequently (> 1/1000, < 1/100), rarely (> 1/10000, <1/1000) and very rarely (<1/10000); frequency is unknown - according to available data, it was not possible to establish the frequency of occurrence.

Infectious diseases

infrequently: Candidiasis, including oral and genital mucosa, pneumonia, fungal infections, bacterial infections, pharyngitis, gastroenteritis, respiratory diseases, rhinitis, vaginal infections;

rarely: pseudomembranous colitis.

From the side of metabolism and nutrition

infrequently: anorexia.

Allergic reactions

often: skin itching, skin rash;

infrequently: hypersensitivity reactions, photosensitization reaction, urticaria, Stevens-Johnson syndrome, angioedema;

rarely: anaphylactic reaction, erythema multiforme, toxic epidermal necrolysis.

On the part of the blood and lymphatic system

infrequently: eosinophilia, leukopenia, neutropenia;

frequency is unknown: thrombocytopenia, hemolytic anemia.

From the nervous system

often: headache, dizziness, paresthesia, a violation of taste, nervousness;

infrequently: hypoesthesia, drowsiness, insomnia;

rarely: agitation;

rarely: anxiety, aggression, fainting, convulsions, psychomotor hyperactivity, loss of smell (anosmia) and taste sensations, myasthenia gravis, anxiety;

frequency is unknown: delirium, hallucinations.

From the sense organs

infrequently: impaired vision, hearing impairment, vertigo;

frequency is unknown: hearing impairment, including deafness and / or ringing in the ears.

From the side of the cardiovascular system

infrequently: sensation of a palpitation, sensation of heat and "tides" of a blood to a skin of the face;

rarely: lowering blood pressure, increasing the interval QT, arrhythmia such as "pirouette", ventricular tachycardia.

From the gastrointestinal tract

Often: diarrhea, nausea, flatulence, abdominal pain;

often: dyspepsia, vomiting;

infrequently: constipation, gastritis, dysphagia, bloating;

rarely: dryness of the oral mucosa, belching, ulcers of the oral mucosa, hypersecretion of the salivary glands, discoloration of the tongue, pancreatitis.

From the liver and biliary tract

infrequently: increased activity of "hepatic" transaminases, increased bilirubin concentration, hepatitis;

rarely: abnormal liver function;

rarely: cholestatic jaundice, hepatic insufficiency (in rare cases with a legal outcome, mainly against a background of severe impairment of liver function), liver necrosis, fulminant hepatitis.

From the musculoskeletal system and connective tissue

often: arthralgia;

infrequently: osteoarthritis, myalgia, back pain, neck pain;

From the side of the kidneys and urinary tract

infrequently: increase in the concentration of urea and creatinine in the blood plasma; rarely: interstitial nephritis, acute renal failure, dysuria, kidney pain;

From the genitals and breast

infrequently: metrorrhagia, dysfunction of testicles.

Other

infrequently: swelling, chest pain, peripheral edema, facial swelling, asthenia, malaise, weakness, pain at the injection site, fever, dermatitis, dry skin, sweating, shortness of breath, nosebleed.

Impact on the results of laboratory and instrumental studies

often: a decrease in the number of lymphocytes, an increase in the number of eosinophils, a decrease in the concentration of bicarbonates in the blood plasma, an increase in the number of basophils, an increase in the number of monocytes, an increase in the number of neutrophils;

infrequently: change in potassium concentration, increase in concentration alkaline phosphatase in the blood plasma, an increase in the chloride content, an increase in the concentration of glucose, an increase in the number of platelets, a decrease in hematocrit, an increase in the concentration of bicarbonates, a change in the sodium content.

Overdose:

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

Treatment: carry out gastric lavage and other emergency measures, to reduce the absorption of azithromycin, to appoint Activated carbon, magnesium or calcium-containing antacids, to ensure a sufficient supply of fluid with adequate diuresis.

Interaction:

Antacid preparations do not affect the bioavailability of azithromycin, but decrease the maximum concentration (C_m_Oh) in blood plasma by 30%, so azithromycin should be taken at least 1 hour before or 2 hours after taking these drugs or food.

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

When used simultaneously with indirect anticoagulants (warfarin, other anticoagulants of the coumarin type) azithromycin (in usual doses) no changes in prothrombin time have been revealed, however, considering that the interaction of macrolides and warfarin may enhance the anticoagulation effect, patients need careful monitoring of prothrombin time.

When simultaneous application with cyclosporin it is recommended to monitor the concentration of cyclosporine in the blood plasma, it is necessary to correct the dose of cyclosporine.

With simultaneous application digoxin and azithromycin, it is necessary to monitor the concentration of digoxin in the blood plasma, many macrolides increase absorption of digoxin in the intestine.

When combined with zidovudine azithromycin has little effect on the pharmacokinetics, including kidney excretion, zidovudine or its glucuronide metabolite.

However, the use of azithromycin increases the concentration phosphorylated zidovudine, a clinically active metabolite, in peripheral blood mononuclear cells. The clinical significance of this observation is unclear, but it can be useful for patients.

Simultaneous use of azithromycin (1200 mg) and nelfinavir (750 mg three times a day) causes an increase in the concentrations of azithromycin. Clinically significant adverse events were not observed, dose adjustment is not required.

Azithromycin weakly interacts with cytochrome P450 isoenzymes, it was revealed that azithromycin participates in pharmacokinetic interactions similar to erythromycin and other macrolides, azithromycin It is not an inducer and inhibitor of cytochrome P450 isoenzymes.

Ergotamine and dihydroergotamine: increased toxic effect (vasospasm, dysesthesia).

Macrolides slow down excretion, increase plasma concentrations and toxicity of cycloserine, indirect anticoagulants, methylprednisolone, felodipine, as well as drugs undergoing microsomal oxidation (cyclosporine, hexobarbital, ergot alkaloids, valproic acid, disopyramide, bromocriptine, phenytoin, hypoglycemic drugs for oral administration), However, with the use of azalides (including azithromycin), this type of interaction was not noted.

Lincosamides weaken, and tetracycline and chloramphenicol increase the effectiveness of azithromycin.

Separate reports of cases of rhabdomyolysis in patients concomitantly receiving azithromycin and statins.

With the simultaneous use of azithromycin and rifabutin Sometimes neutropenia was observed, despite the fact that neutropenia was associated with the use of rifabutin, a causal relationship between the use of a combination of azithromycin and rifabutin and neutropenia has not been established.

Special instructions:

When using the drug in patients with diabetes mellitus, as well as with a low-calorie diet, it is necessary to take into account that the suspension contains sucrose (0.32 XE / 5 ml).

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.

It is necessary to observe a break of 2 hours with simultaneous use of antacids.

The drug should be used with caution in patients with moderate impairment of liver function due to the possibility of developing fulminant hepatitis and severe hepatic insufficiency.

There have been reports of rare serious allergic reactions such as angioedema and anaphylaxis (rarely fatal), as in cases with erythromycin and other macrolides. Some of these reactions to azithromycin became the cause of recurrent symptoms and needed long-term observation and treatment.

In the presence of symptoms of liver dysfunction, such as rapidly increasing asthenia, jaundice, darkening of the urine, a tendency to bleeding, hepatic encephalopathy, drug therapy should be discontinued and a study of the functional state of the liver should be carried out.

For moderate renal dysfunction (CC greater than 40 mL / min), drug therapy should be performed with caution under the control of the kidney function.

As with the use of other antibacterial drugs, the drug should be regularly monitored for susceptible microorganisms and signs of development of superinfections, including fungal ones.

The drug should be used with longer courses than indicated in the instructions, since the pharmacokinetic properties of azithromycin allow us to recommend a short and convenient dosage regimen.

It was reported that the symptoms of severe myasthenia and the development of myasthenic syndrome in patients receiving azithromycin treatment increased. There is no data on the possible interaction between azithromycin and derivatives of ergotamine and dihydroergotamine, but due to the development of ergotism with the simultaneous use of macrolides with derivatives of ergotamine and dihydroergotamine, this combination is contraindicated.

With prolonged use of the drug, the development of pseudomembranous colitis caused by Clostridium difficile, both in the form of mild diarrhea, and severe colitis.With the development of diarrhea against the background of taking azithromycin, and also within 2 months after the end of therapy, clostridial pseudomembranous colitis should be excluded. Drugs that inhibit the intestinal peristalsis are contraindicated.

After the withdrawal of the treatment, hypersensitivity reactions in some patients may persist, which requires specific therapy under the supervision of a physician.

Azithromycin should be used with caution in patients with impaired liver function of mild to moderate severity; in patients with impaired renal function of mild and moderate severity.

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

During treatment, care should be taken when driving a car and practicing potentially dangerous activities that require increased attention and speed of psychomotor reactions.

Form release / dosage:Powder for the preparation of a suspension for ingestion 100 mg / 5 ml, 200 mg / 5 ml.

Packaging:

Primary packaging for 100 mg / 5 ml:

By 16.5 g (a suspension of 20 ml) of the powder of the preparation into bottles (HDPE) with screw caps (PP / PE), which are unscrewed when pressed, with a ring indicator of the first opening (PE).

Primary packaging for 200 mg / 5 ml:

12.4 g (15 ml slurry), 16.5 g (20 ml slurry), 18.6 g (22.5 ml suspension), 24.8 g (30 ml slurry) or 31.0 g g (a suspension of 37.5 ml) of the preparation into bottles (HDPE) with screw caps (PP / PE), which are unscrewed when pressed, with an annular first opening indicator (PE).

Secondary packaging:

1 bottle together with the instructions for use and a plastic syringe (PE / PP) enclosed in a plastic bag, a syringe cap (PE) and a stopper (G1E) with an opening for connecting a syringe into a cardboard pack.

Storage conditions:

At a temperature not exceeding 30 ° C

The reconstituted suspension is stored at a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

2 years

Shelf life of the reconstituted suspension is 5 days.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002934

Date of registration:31.03.2015

The owner of the registration certificate:Sandoz d.Sandoz d. Slovenia

Manufacturer: & nbsp

S.C. SANDOZ Romania

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp14.08.2015

Illustrated instructions

Instructions

Azithromycin Sandoz (Azithromycin Sandoz)