Sumalak

General characteristics. Structure:

Active ingredient: 125 mg, 250 mg or 500 mg of azithromycin.

Excipients: starch corn, gipromelloza, starch prezhelatinizirovanny, sodium lauryl sulfate, magnesium stearate, cellulose microcrystallic, calcium hydrophosphate anhydrous.

Structure of a cover: gipromelloza, titanium dioxide, talc, E 132 indigo carmine, macrogoal 400.

Antibacterial agent of group of macroleads of a broad spectrum of activity, the rendering bactericidal and bacteriostatic effect.

Pharmacological properties:

Pharmacodynamics. Antibacterial agent of a broad spectrum of activity azithromycin, the first representative of a subclass of azaleads, works bacteriostatically. Communicating with 50S in subunit of ribosomes, oppresses to a peptidtranslokaz at a broadcasting stage, suppresses protein synthesis, slows down growth and reproduction of bacteria, in high concentration renders bactericidal effect.

Scale of sensitivity of microorganisms to azithromycin (MIK, mg/l):

Microorganisms	MIK (mg/l)
	Sensitive	Steady
Staphylococcus spp.	≤1	> 2
Streptococcus A, B, C, G	≤0.25	> 0.5
S. pneumoniaе	≤0.25	> 0.5
H. influenzae	≤0.12	> 4
M. catarrhalis	≤0.5	> 0.5
N. gonorrhoeae	≤0.25	> 0.5

In most cases azithromycin is active concerning aerobic gram-positive bacteria: Staphylococcus aureus (Methicillinum - sensitive strains), Streptococcus pneumoniae (penicillin - sensitive strains), Streptococcus pyogenes; aerobic gram-negative bacteria: Haemophilus influenzae, Haemophilus parainfluenzae, Legionella pneumophila, Moraxella catarrhalis, Pasteurella multocida, Neisseria gonorrhoeae; anaerobic bacteria: Clostridium perfringens, Fusobacterium spp., Prevotella spp., Porphyromonas spp; other microorganisms: Chlamydia trachomatis, Chlamydia pneumoniae, Chlamydia psittaci, Mycoplasma pneumoniae, Mycoplasma hominis, Borrelia burgdorferi.

Microorganisms can be initial steady against action of an antibiotic or can gain resistance to it. Thus, distinguish the natural and acquired azithromycin resistance. The acquired stability is developed quickly, but after the termination of contact with azithromycin over time sensitivity to it is recovered. Azithromycin resistance of microorganisms is intra group and cross. The long persistirovaniye of azithromycin in an organism in low concentration which do not suppress growth of microorganisms, but is caused by mutations, promotes stability development. The main mechanisms of development of stability are: modification of a target (microorganism) due to methylation of adenine in 23S-ribosomalny RNA, pushing out of an antibiotic from a microbic cell and an antibiotic inactivation microbic esterases.

The microorganisms capable to develop azithromycin resistance: gram-positive aerobes - Streptococcus pneumoniae (penicillin - resistant strains).

Initially steady microorganisms: gram-positive aerobes - Enterococcus faecalis, Staphylococcus spp. (Methicillinum - resistant strains of staphylococcus show very high degree of resistance to macroleads); gram-positive bacteria steady against erythromycin; anaerobe bacterias - Bacteroides fragilis.

For optimization of antimicrobic chemotherapy azithromycin it is rational to be guided by local information on sensitivity to this antibiotic.

Pharmacokinetics. Azithromycin is characterized by higher, than at other macroleads, acid resistance (by 300 times bigger, than at erythromycin) which collapse under the influence of hydrochloric acid of a stomach. However in acid medium its ionization increases and activity decreases. Absorption of azithromycin increases in the alkalescent environment: optimum value рН for absorption of azithromycin and other macroleads is 7,5. Drugs of azithromycin are well dissolved in lipids, applied generally orally and well absorbed from intestines.

At intake azithromycin is well soaked up and quickly redistributed from plasma in fabrics and bodies, however its bioavailability makes about 37% that is connected with intensive presistemny metabolism in a liver. After a single dose in 500 mg of azithromycin from 7 to 50 its % contacts blood proteins (linkng with proteins in inverse proportion to concentration in a blood plasma) and in 2–3 h in plasma Cmax of drug — 300-450 ng/ml is noted. The seeming Vd makes 31.1 l/kg. Azithromycin gets through membranes of cells (it is effective at the infections caused by intracellular activators). It is transported by phagocytes to the place of an infection where it is released in the presence of bacteria. Easily gets through gistogematichesky barriers and comes to fabrics. Concentration in fabrics and cells 10-50 times higher, than in plasma, and in the infection center - is 24-34% more, than in healthy fabrics.

Azithromycin is metabolized in a liver, mainly by N-and O-demethylation, with the participation of R-450 cytochrome (CYP3A4 isoform) with formation of the metabolites which do not have antibacterial property. Metabolites are allocated preferential with bile and further with excrements. Renal excretion makes 5-10%. At a renal failure the elimination half-life does not change therefore correction of the mode of dosing is not required.

T1/2 long - 35-50 p. T1/2 from fabrics much more. Therapeutic concentration of azithromycin remains up to 5-7 days after reception of the last dose. Azithromycin is removed, generally in not changed look - 50% through intestines, 6% by kidneys.

Indications to use:

The infectious and inflammatory diseases caused by microorganisms, sensitive to drug:
- upper respiratory tract infection and ENT organs (bacterial pharyngitis / tonsillitis, sinusitis, average otitis);
- lower respiratory tract infections (an acute bronchitis, an exacerbation of chronic bronchitis, pneumonia, including caused by atypical activators);
- infections of skin and soft tissues (the moderately severe acne rash, an ugly face, impetigo for the second time infected a dermatosis);
- an initial stage of a disease Laima (borreliosis) - the migrating erythema (erythema migrans);
- the infections of urinogenital ways caused by Chlamydia trachomatis (an urethritis, a cervicitis).

Route of administration and doses:

SUMALEK should take 1 time a day for 1 h to or in 2 h after food as the concomitant use with food can reduce absorption of active ingredient (azithromycin) though in an organism meal does not influence its bioavailability. A pill is taken without chewing.

The adult (including elderly) and to children 12 years with body weight are more senior more than 45 kg appoint drug in the form of tablets on 500 mg. Children aged from 6 years and can appoint more senior drug in the form of tablets on 125 mg. Drug in the form of tablets of 125 mg is dosed taking into account the body weight of the child as it is presented in the table:

Body weight	Amount of azithromycin (in tablets of 125 mg)
18-30 kg	2 tablets (250 mg)
31-44 kg	3 tablets (375 mg)
45kg	appoint the doses recommended for adults

At infections of upper and lower respiratory tracts, ENT organs, skin and soft tissues (except for the chronic migrating erythema and an acne вульгарис):
- to adults and children 12 years with body weight are more senior more than 45 kg drug appoint in a dose 500 mg of 1 times a day within 3 days, a course dose - 1.5 g;
- to children at the age of 6 years is also more senior appoint at the rate of 10 mg/kg of body weight of 1 times a day within 3 days, a course dose - 30 mg/kg.

At the chronic migrating erythema drug is appointed 1 time a day within 5 days:
- to adults and children 12 years with body weight more than 45 kg are more senior appoint in the 1st day - 1 g, then from 2 to 5 days - 500 mg, a course dose - 3 g;
- to children at the age of 6 years is also more senior appoint in the 1st day in a dose 20 mg/kg of body weight and then from 2 to 5 days - daily in a dose of 10 mg/kg of body weight, a course dose - 60 mg/kg.

At an acne вульгарис moderate severity:
- to adults and children 12 years with body weight are more senior more than 45 kg appoint 500 mg in the first 3 days once a day, then on 500 mg once a week within 9 weeks, a course dose - 6 g. Attention!!! 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 should be accepted at an interval of 7 days.

At infections, sexually transmitted (urethritis/cervicitis):
The uncomplicated urogenital infection caused by Chlamydia trachomatis - once 1 g.
Complicated, it is long the proceeding urogenital infection caused by Chlamydia trachomatis - on 1 g in bucketed days between three receptions in 7 days (the 1st, 7th and 14th days), a course dose - 3 g.

For patients with moderate renal failures (KK> of 40 ml/min.) dose adjustment is not required.

Features of use:

 In case of the admission of reception of one dose of drug it is necessary to accept the passed dose as soon as possible, and the subsequent – with breaks in 24 h.

Also as when performing any antibiotic treatment, at treatment by azithromycin, accession of superinfection is possible (including fungal). 

Azithromycin also as well as penicillin is active concerning a streptococcal infection, however is inefficient for prevention of development of acute rheumatic fever.

The patient should be warned about need to report to the doctor about emergence of any side effect. At some patients of reaction of hypersensitivity can remain also after treatment cancellation that demands specific therapy under observation of the doctor.

Management of transport and mechanisms. Drug does not influence ability to driving of motor transport and other activity demanding high concentration of attention and speed of psychomotor reactions.

Pregnancy and lactation. At pregnancy use of drug is possible only if the potential advantage of therapy for mother surpasses possible risk for a fruit. In need of use of drug in the period of a lactation breastfeeding should be stopped.

Side effects:

From the alimentary system: often (<5%) - nausea, vomiting, diarrhea, abdominal pains and spasms; sometimes (<1%) - a meteorism, digestive disturbances, anorexia; seldom (<0,1%) - a lock, language discoloration, pseudomembranous colitis, cholestatic jaundice, hepatitis, change of values of laboratory indicators of function of a liver; very seldom (<0,01%) - abnormal liver functions and a necrosis of a liver (it is possible from the death).

Allergic reactions: sometimes (<1%) - an itch, skin rashes; seldom (<0,1%) - a Quincke's disease, a small tortoiseshell, a photosensitization, anaphylactic reaction (in rare instances from the death), a mnogoformny erythema, Stephens-Johnson's syndrome, a toxic epidermal necrolysis.

From TsNS and peripheral nervous system: sometimes (<1%) - dizziness / вертиго, a headache, drowsiness, spasms; seldom (<0,1%) - paresthesias, an adynamy, sleeplessness, a hyperactivity, aggression, concern, nervousness.

From a musculoskeletal system: sometimes (<1%) - an arthralgia.         

From system of a hemopoiesis: seldom (<0,1%) - thrombocytopenia, a neutropenia, an eosinophilia. 

From sense bodys: seldom (<0,01%) - a sonitus, a reversible hearing disorder up to deafness (at reception in high doses for a long time), disturbance of perception of taste and a smell.

From cardiovascular system: seldom (<0,1%) - heartbeat, arrhythmia, including ventricular tachycardia, increase in an interval of QT, bidirectional ventricular tachycardia.

From an urinary system: seldom (<0,1%) - intersticial nephrite, an acute renal failure.

Others: seldom (<0,1%) - a vaginitis, candidiasis

Interaction with other medicines:

Antiacid means do not influence bioavailability of azithromycin, but reduce Cmax in blood by 30% therefore drug SUMALEK should be taken, at least, for 1 h to or in 2 h after reception of these drugs and food.

At simultaneous use azithromycin does not influence concentration of carbamazepine, a didanozin, rifabutin and Methylprednisolonum in blood.

At parenteral use azithromycin does not influence concentration in a blood plasma of Cimetidinum, an efavirenz, a flukonazol, an indinavir, midazolam, theophylline, a triazolam, Trimethoprimum/sulfamethoxazole in case of a combination therapy, however it is not necessary to exclude possibilities of such interaction at purpose of SUMALEKA inside.

Azithromycin does not influence theophylline pharmacokinetics, however at joint reception with other macroleads concentration of theophylline in a blood plasma can increase. At simultaneous use of an atorvastatin, on the contrary, its concentration can decrease slightly.

In need of combined use with cyclosporine, it is recommended to control the content of cyclosporine in blood. In spite of the fact that there are no data on influence of azithromycin on change of concentration of cyclosporine in blood, other representatives of a class of macroleads are capable to change its concentration in a blood plasma.

At joint reception of digoxin and azithromycin it is necessary to control concentration of digoxin in blood since many macroleads increase absorption of digoxin from intestines, increasing that its concentration in a blood plasma.
In need of joint reception with warfarin it is recommended to carry out careful control of a prothrombin time.

It was established that the concomitant use of a terfenadin and antibiotics of a class of macroleads causes arrhythmia and lengthening of QT of an interval. Proceeding from it, it is impossible to exclude development of these complications at joint reception of a terfenadin and azithromycin.

As there is a possibility of inhibition azithromycin in a parenteral form of an isoenzyme CYP3A4 at joint appointment with cyclosporine, terfenadiny, ergot alkaloids, tsizapridy, Pimozidum, quinidine, astemizoly and other drugs which metabolism happens to participation of this isoenzyme it is necessary to consider a possibility of such interaction at purpose of azithromycin for intake.

At joint reception of azithromycin and a zidovudine, azithromycin does not influence pharmacokinetic parameters of a zidovudine in a blood plasma or on removal by kidneys of its and its metabolite of a glucuronide. Nevertheless, concentration of an active metabolite - a fosforilirovanny zidovudine in mononuclear cells of peripheral vessels increases. Clinical value of this fact is not clear.

At a concomitant use of macroleads with ergotamine and dihydroergotamine manifestation of their toxic action is possible.

Contraindications:

- heavy abnormal liver functions and kidneys;
- period of a lactation (breastfeeding);
- a concomitant use with ergotamine and dihydroergotamine;
- hypersensitivity to azithromycin and other components of drug;
- hypersensitivity to antibiotics of group of macroleads;
- the children's age up to 12 years and body weight is less than 45 kg (for tablets of 500 mg);
- children's age up to 6 years (for tablets).

With care it is necessary to appoint preparatpr moderate abnormal liver functions and kidneys, to patients with disturbances or predisposition to arrhythmias and lengthening of an interval of QT, together with terfenadiny, warfarin, digoxin.

Overdose:

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

Treatment: symptomatic therapy.

Storage conditions:

To store in the place protected from moisture at a temperature from +15 °C to +25 °C. To store in the place, unavailable to children. Period of validity 2 years.

Issue conditions:

According to the recipe

Packaging:

- tablets, coated, 125 mg in a blister strip packaging No. 6×1, No. 6×2 and in banks No. 6, No. 40 in packaging No. 1;
- tablets, coated, 250 mg in a blister strip packaging No. 6×1, No. 6×2 and in banks No. 3, No. 6, No. 20 in packaging No. 1;
- tablets, coated, 500 mg in a blister strip packaging No. 3×1 and in banks No. 3, No. 10 in packaging No. 1;

Together with a leaf insert strip packagings (one or two) or bank, the containing corresponding dosages of SUMALEKA, are located in packs from a cardboard.