Sumalak

General characteristics. Structure:

Active ingredients: 100 mg, 200 mg and 500 mg of azithromycin in 20 ml of ready suspension.

Excipients: xanthane gum, silicon dioxide colloid anhydrous, sodium carbonate anhydrous, aspartame (Е 951), tartrazine (Е 102), fragrance PX1496 Vanillin, granulated sugar. Excipients: xanthane gum, silicon dioxide colloid anhydrous, sodium carbonate anhydrous, aspartame (Е 951), tartrazine (Е 102), fragrance PX1496 Vanillin, granulated sugar.

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 medicine:
- 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:

Before medicine use Sumalek it is necessary to prepare suspension from powder. For this purpose in a bottle with powder pour to a tag "60 ml" svezheprokipyacheny and chilled water and intensively shake up. After when the formed foam accumulates, repeatedly to bring suspension volume water to a tag of "60 ml", to shake up carefully. Suspension is ready to the use.

The period of validity of ready suspension at storage it in the refrigerator at a temperature of +2-+8 °C makes 10 days. Before each use the bottle is intensively shaken up and left to stand until the formed foam accumulates.
Drug should be taken surely for 1 h to food or in 2 h after food of 1 times/days.

At an infection of upper and lower respiratory tracts, skin and soft tissues (except for the chronic migrating erythema) a total dose of 30 mg/kg, i.e. 10 mg/kg of body weight once in days within 3 days. To children dose proceeding from weight:

Body weight	The volume of suspension of Sumalak of 100 mg / 20 ml (amount of azithromycin in mg)	The volume of suspension of Sumalak of 200 mg / 20 ml (amount of azithromycin in mg)	The volume of suspension of Sumalak of 500 mg / 20 ml (amount of azithromycin in mg)
5 kg	10 ml (50 mg)	5 ml (50 mg)	/
6 kg	12 ml (60 mg)	/	/
7 kg	14 ml (70 mg)	/	/
8 kg	16 ml (80 mg)	8 ml (80 mg)	/
9 kg	18 ml (90 mg)	9 ml (90 mg)	/
10-14 kg	20 ml (100 mg)	10 ml (100 mg)	4 ml (100 mg)
15-24 kg	40 ml (200 mg)	20 ml (200 mg)	8 ml (200 mg)
25-34 kg	60 ml (300 mg)	30 ml (300 mg)	12 ml (300 mg)
35-44 kg	/	40 ml (400 mg)	16 ml (400 mg)
≥45 kg	/	50 ml (500 mg)	20 ml (500 mg)

At the chronic migrating erythema the total dose of drug makes 60 mg/kg: once in day on 20 mg/kg – in the 1st day and on 10 mg/kg – in the next days from 2 to 5 day.

At the diseases of a stomach and a 12-perstny gut associated with Helicobacter pylori     of 20 mg/kg of body weight once in day in combination with anti-secretory means and other medicines according to the recommendation of the doctor.

If the dose of drug was passed, it needs to be accepted, whenever possible, at once, and then to accept the subsequent doses at an interval of the 24th hour.

At infections, sexually transmitted. An uncomplicated urethritis / cervicitis – 10 mg/kg of body weight once.

Complicated, it is long the proceeding urethritis/cervicitis caused  by Chlamydia trachomatis – on 10 mg/kg of body weight three times at an interval of 7 days (1-7-14).

To measure necessary amount of suspension the glass dosing.

Dosage form	Age	Dosage	Frequency rate of reception	Course duration / course dose
500 mg / 20 ml	At respiratory infections, skin and soft tissues
	Adults	20 ml (0,5 g)	1 time a day	3 days (60 ml – 1,5 g)
	At uncomplicated erythritol and/or a cervicitis
	Adults	40 ml (1 g)	once	Once (40 ml – 1 g)
	For treatment of erythema migrans – an initial stage of borreliosis (Lyme's disease)
	Adults	The 1st day – 40 ml (1 g) The 2-5th days – on 20 ml (0,5 g)	1 time a day	5 days (120 ml – 3,0 g)
	At the diseases of a stomach and duodenum associated with Helicobacter pylori
	Adults	40 ml (1 g)	1 time a day	3 days (120 ml – 3,0 g)
200 mg / 20 ml	Children *	1 ml/kg/days (10 mg/kg/days)	1 time a day	3 days (3 ml / кг-30 mg/kg)
100 mg / 20 ml	Children	2 ml/kg/days (10 mg/kg/days)	1 time a day	3 days (6 ml / кг-30 mg/kg)

* At treatment of erythema migrans to children appoint in a dose 20 mg/kg of body weight in the 1st day and on 10 mg/kg – with 2nd for the 5th days.

In case of the admission of reception of 1 dose of drug it is necessary to accept the passed dose as soon as possible, and the subsequent – with a break in 24 h.

Features of use:

In case of the admission of reception of one drug dose 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 medicine 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 SUMALEK medicine should be taken, at least, for 1 h to or in 2 h after reception of these medicines 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 medicine;
- 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 medicinal sredstvopr 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 at a temperature not above +25 °C. Period of validity 2 years. A period of storage of the prepared suspension of 5 days at a temperature not above +25 °C

Issue conditions:

According to the recipe

Packaging:

On 20 g in the bottles with the glass dosing placed together with a leaf insert in packs from a cardboard.