Zetamax retard - instructions for use, dose, side effects, contraindications

Sucrose 19.360 g, sodium phosphate anhydrous 0.352 g, magnesium hydroxide 0.250 g, giprolase 0.067 g, xanthan gum 0.067 g, colloidal colloidal silicon 0.110 g, titanium dioxide 0.400 g, cherry flavor 0.140 g, banana flavor - 0.230 g.

Description:

White or almost white non-uniform powder, including microspheres.

The suspension is white, almost white or light yellow with a fruity odor.

Pharmacotherapeutic group:Antibiotic - azalide

ATX: & nbsp

J.01.F.A.10 Azithromycin

Pharmacodynamics:

Azithromycin is the first representative of a subclass of macrolide antibiotics, known as azalides.

Azithromycin binds to the 50S subunit of ribosomes of sensitive microorganisms and breaks their synthesis of proteins, without affecting the synthesis of nucleic acids. Azithromycin accumulates in fibroblasts, epithelial cells, macrophages and circulating neutrophils and monocytes. After 1 hour incubation, the ratio of intra- and extracellular concentrations in vitro exceeded 30.

The results of in vivo studies suggest that the accumulation of the drug in macrophages and circulating leukocytes can contribute to the distribution of the antibiotic in inflamed tissues.

Azithromycin showed activity against most strains of the following microorganisms, both in vitro and in clinical infections (see section "Indications for use"):

Aerobic and facultative Gram-positive microorganisms

Streptococcus pneumoniae

Note: gram-positive microorganisms resistant to erythromycin and penicillin may exhibit cross-resistance to azithromycin.

Aerobic and facultative gram-negative microorganisms

Haemophilus influenzae

Moraxella catarrhalis

Other microorganisms

Chlamydia pneumoniae

Mycoplasma pneumoniae

The production of beta-lactamases by the microorganism does not affect the activity of azithromycin. In experiments in vitro, at least 90% of the strains of the following microorganisms were marked with minimal inhibitory concentrations (MICs), indicating a sensitivity to azithromycin.However, the safety and efficacy of azithromycin in the treatment of infections caused by these microorganisms have not been established in adequate controlled studies.

Aerobic and facultative Gram-positive microorganisms

Staphylococcus aureus

Streptococcus pyogenes

Streptococcus agalactiae

Streptococcus spp. (groups C, F and G, other than those resistant to erythromycin)

Streptococcus spp. group viridans

Aerobic and facultative gram-negative microorganisms

Bordetella pertussis,

Legionella pneumophila

Anaerobic microorganisms

Peptostreptococcus species

Prevotella bivia

Other microorganisms

Ureaplasma urealyticum.

Inactive against Gram-positive bacteria, resistant to erythromycin.

Pharmacokinetics:

Zetamax retard is a microsphere that provides a sustained release of the active substance. In healthy volunteers, the maximum concentration of azithromycin (Cma) in the serum and the area under the concentration-time curve (AUC0-24) after a single dose of Zetamax retard oral dose at a dose of 2.0 g was higher than with azithromycin in tablets at a total dose of 1.5 g for 3 days (500 mg / day) or 5 days (500 mg on the first day and then 250 mg / day) (see Table 1). Given the difference in pharmacokinetics, the Zetamax retard drug is not interchangeable with azithromycin in the form of tablets (3- and 5-day regimens).

Table 1.The average pharmacokinetic parameters of azithromycin on the first day after a single dose of Zetamax retard at a dose of 2.0 g and after the use of azithromycin in tablets in a total dose of 1.5 g for 3 days (500 mg / day) or 5 days (500 mg in the first day, and then 250 mg / day) in healthy adult volunteers.

	Azithromycin
Pharmacokinetic parameters	Zetamax	3 days ŧ	5 days ŧ
	retard [n = 41] ţ	[n=12]	[n=12]
FROM_max* (ICG / ML)	0.821	0.441	0.434
	(0.281)	(0.223)	(0.202)
Tmah g (h)	5.0	2.5	2.5
	(2.0-8.0)	(1.0-4.0)	(1.0-6.0)
AUC₀-24	8.62	2.58	2.60
(mg* h / ml)	(2.34)	(0.84)	(0.71)
AUC_0-8 (mg* h / ml)	20.0	17.4	14.9
	(6.66)	(6.2)	(3.1)
t1/2 (h)	58.8	71.8	68.9
	(6.91)	(14.7)	(13.8)

* Pharmacokinetic parameters of Zetamax retard and azithromycin in the form of tablets (for 3 and 5 days) were obtained in different studies,

ţ n = 21 for AUC_0-8and t₁/₂;

ŧ C_max, T_m_Oh and AUC₀-24 only on the first day;

§ average value (range);

¶ General AUC for a single admission, admission for 3 and 5 days;

SD = standard deviation;

FROM_m_Oh = maximum serum concentration;

Tmax = time to reach CmOh;

AUC = area under the concentration-time curve;

t1/2 = terminal half-life of serum.

Suction

In a cross-sectional study, 16 healthy adult volunteers received a single dose of 2.0 g of Zetamax retard (powder for suspension with sustained release for oral administration) and azithromycin in the form of a powder for the preparation of an oral suspension (PIC) (2 sachets of 1.0 g). Average Cmah and AUC₀-t azithromycin, when taken with Zetamax retard, were 57% and 17% lower respectively than with pituitary azithromycin.

The bioavailability of the Zetamax retard drug in relation to PIC was 83%. After taking Zetamax retard, the maximum serum azithromycin concentrations were achieved on average 2.5 hours later than after taking azithromycin PIC. Thus, doses of Zetamax retard and azithromycin PIC, which are 2.0 g once, are not bioequivalent and interchangeable.

When taking Zetamax retard in a dose of 2.0 g after fatty foods (150 kcal proteins, 250 kcal carbohydrates and 500-600 kcal fat) in 15 healthy volunteers the average Cmah azithromycin increased by 115%, and the average AUCo-4 - by 23% compared with those on an empty stomach. When using Zetamax retard in a dose of 2.0 g after a standard meal (56 kcal proteins, 316 kcal carbohydrates and 207 kcal fat) in 88 adults the average Cmah azithromycin increased by 119%, and the average AUC0-72 hours - by 12% compared with those when administered on an empty stomach.

Distribution

The degree of binding of azithromycin to serum proteins depends on the concentration and decreases from 51% at a concentration of 0.02 μg / ml to 7% at 2.0 μg / ml. After oral administration azithromycin is actively distributed into tissues, while the equilibrium volume of distribution is 31.1 l / kg. The concentrations of azithromycin in tissues exceeded those in plasma and serum. The active distribution of the drug in the tissue may be important for its clinical effectiveness.

Antimicrobial the activity of azithromycin depends on pH and decreases when it decreases. Therefore, high tissue concentrations may not be quantitatively correlated with clinical efficacy. The active distribution in tissues was confirmed by additional study of tissues and liquids, such as bones, ejaculate, prostate, ovaries, uterus, appendages, stomach, liver and gallbladder. However, the clinical significance of the drug concentration in these tissues is not established, since the effectiveness of azithromycin in the treatment of infections of this localization in adequate controlled studies has not been studied.

After a 5-day course of using azithromycin in tablets (500 mg on the first day and 250 mg / day for the remaining 4 days), the concentrations of the drug in the cerebrospinal fluid were very low (less than 0.01 μg / ml) in the absence of inflammation of meningeal membranes.

Metabolism

Metabolism is carried out in the liver by the process of demethylation with the formation of inactive metabolites.

Excretion

Serum azithromycin concentrations after a single dose of Zetamax retard at a dose of 2.0 g decrease in several phases with a half-life of 59 hours. A long half-life is considered a consequence of a large volume of distribution. Azithromycin is output mainly in unchanged form with bile (50%). After a week of therapy in unchanged form, about 6% of the dose taken is excreted in the urine.

Special Groups

Renal insufficiency

The pharmacokinetics of azithromycin was studied in 42 adults (21-85 years) with impaired renal function of varying severity. After a single intake of 1.0 g azithromycin (4 capsules of 250 mg) in patients with a glomerular filtration rate (GFR) 10-80 ml / min average Cmah and AUC_0-120were respectively 5 and 4.2% higher than in patients with normal renal function (GFR> 80 ml / min). In patients with terminal renal disease deficiency (GFR <10 ml / min) C_max and AUC_0-120were 61% and 35%, respectively, higher than in patients with normal kidney function (GFR> 80 mL / min). Based on data on the study of the pharmacokinetics of azithromycin in patients with renal insufficiency, dose adjustment of Zetamax retard in patients with GFR> 10 ml / min is not required.

Liver failure

The pharmacokinetic parameters of azithromycin in patients with impaired liver function have not been studied.

Floor

The effect of sex on the pharmacokinetics of the Zetamax retard drug has not been studied. However, in previous studies, no significant difference in the pharmacokinetics of azithromycin in men and women has been identified. In this regard, dose adjustment of azithromycin for patients of different sex is not recommended.

Aged people

The pharmacokinetics of Zetamax retard in elderly people has not been studied.

Children

With a single application of 60 mg / kg azithromycin in children aged 3 months to 16 years, there was a high variability in each patient. Nevertheless, the pharmacokinetics (Cmah and AUC) in the whole group of patients were comparable or higher than in adults with 2 g of Zetamax retard.

Indications:

Treatment of mild to moderate severity of infections of a specific location caused by sensitive strains of these microorganisms:

- acute bacterial sinusitis in adults, caused by Haemophilus influenzae, Moraxella catarrhalis or Streptococcus pneumoniae, light and moderate severity;

- Community-acquired pneumonia in adults and children over the age of 6 months caused by Chlamydophila pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae or Streptococcus pneumoniae, light and moderate severity (if oral therapy is possible);

- exacerbation of chronic bronchitis in adults caused by Streptococcus pneumoniae, Haemophilus influenzae or Moraxella catarrhalis',

- pharyngitis / tonsillitis in adults and children over the age of 6 months caused by Streptococcus pyogenes;

- acute otitis media in children over 6 months of age caused by Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis or Streptococcus pyogenes.

Contraindications:

Hypersensitivity to azithromycin, erythromycin and any macrolide or ketolide antibiotic.

Hypersensitivity to the components of the drug.

Severe hepatic insufficiency.

Previous episodes of jaundice or impaired liver function with a history of azithromycin.

The efficacy and safety of the Zetamax retard drug when used in children under 6 months of age have not been studied.

Simultaneous reception of ergotamine and dihydroergotamine.

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

Carefully:

Violation of the function of the liver (t. azithromycin is output mainly by the liver); terminal renal failure with GFR <10 ml / min (experience of using the drug in such patients is limited); arrhythmia (ventricular arrhythmias and Q-T interval elongation possible); myasthenia gravis; simultaneous reception with terfenadine, digoxin, warfarin, cyclosporine.

Caution should be exercised when using azithromycin in patients:

- with congenital or recorded lengthening of Q-T interval;

- in patients who are currently receiving therapy with other drugs that can lead to prolongation of the Q-T interval (for example, antiarrhythmic drugs of classes IA and III, antipsychotics, antidepressants, fluoroquinolones);

- in patients with electrolyte imbalance, mainly in cases of hypokalemia and hypomagnesemia;

- in patients with clinically significant bradycardia, arrhythmia or heart failure;

- in elderly patients (elderly patients may be more susceptible to medication on the Q-T interval).

Pregnancy and lactation:

Adequate controlled studies in pregnant women have not been conducted, therefore azithromycin in pregnancy apply only if the intended benefit to the mother exceeds the potential risk to the fetus.

There is evidence of excretion of azithromycin with breast milk, however, studies of the pharmacokinetics of excretion of azithromycin with breast milk have not been carried out, therefore, when using azithromycin, it is recommended to stop breastfeeding.

Dosing and Administration:

A full course of antibacterial therapy with Zetamax retard in adults and children weighing 34 kg or more suggests taking it once inwards at a dose of 2.0 g. The contents of the vial are diluted in 60 ml of water, resulting in a 75 ml suspension. Before use, shake well and take it once inside. The drug should be taken on an empty stomach (at least 1 hour before or 2 hours after meals).

For children 6 months and older, but with a body weight of less than 34 kg, Zetamax retard should be taken once in a dose of 60 mg / kg body weight. At a child's body weight of less than 34 kg, the volume of the suspension (in ml) is calculated as follows: for each kilogram of the child's body weight, 60 mg of the Zetamax retard preparation is required, which is equivalent to 2.2 ml of the suspension.To calculate the volume of the suspension, the weight of the child's body in kilograms is multiplied by 2.2 ml. To measure the volume of the suspension, use a 10 ml or 20 ml syringe, which can be purchased at a pharmacy.

Elderly patients

Do not require dose adjustment in elderly patients (see section "Special instructions").

Impaired renal function

In patients with impaired renal function of mild and moderate severity (GFR 10-80 ml / min), dose adjustment is not required.

Caution should be exercised when using Zetamax retard in patients with severe renal impairment (GFR <10 mL / min).

Impaired liver function

Patients with a mild or moderate liver function disorder do not require dose adjustment (see section "Special instructions").

Side effects:

When taking Zetamax retard once in a dose of 2.0 g, the most often observed are mild or moderate unwanted reactions from the gastrointestinal tract: diarrhea / unstable stool (12%), nausea (4%), abdominal pain (3% ), headache (1%) and vomiting (1%). The incidence of gastrointestinal disorders associated with Zetamax retard and comparator drugs was 17% and 10%, respectively.The incidence of other adverse events associated with therapy in patients receiving Zetamax retard did not exceed 1%. Adverse events occurring with a frequency of less than 1% in patients taking Zetamax retard are listed below.

From the cardiovascular system: heart palpitations, chest pain, arrhythmias * (including ventricular tachycardia and hypotension), lengthening of the interval Q-T* and extrasystole by the type of "pirouette" *, "tides".

On the part of the digestive system: constipation, dyspepsia, flatulence, gastritis, candidiasis of the oral mucosa *, dysphagia, unstable stools, anorexia, nausea, vomiting *, diarrhea *, rarely leading to dehydration, abdominal discomfort (pain / spasms), bloating, pseudomembranous colitis *, pancreatitis *, a change in the color of the tongue *, a decrease in appetite, dryness of the oral mucosa, belching, ulceration of the oral mucosa, hypersalivation.

From the genitourinary system: vaginitis *, interstitial nephritis *, acute renal failure *, vaginal candidiasis *, dysuria, pain in the kidney, metrorrhagia, dysfunction of the testicles.

From the side of the central nervous system and the peripheral nervous system: dizziness, convulsions *, headache *, drowsiness *, hyperactivity *, nervousness *, agitation * and fainting *, aggressive reactions * and anxiety *, emotional lability, paresthesia, hyposthenia *, insomnia.

From the sense organs: perversion / loss of taste, hearing impairment (including hearing loss, deafness and / or tinnitus), impaired vision, vertigo, anosmia *.

From the liver and bile ducts: impaired liver function (including hepatitis and cholestatic jaundice), cases of liver necrosis * and liver failure *, which sometimes led to death.

From the musculoskeletal system: exacerbation of myasthenia gravis gravis, arthralgia *, osteoarthritis, myalgia, back pain, neck pain.

Allergic reactions: allergic reactions, rash, itching, hives, angioedema, anaphylaxis * (in rare cases with fatal outcome).

From the skin: dermatitis, dry skin, hyperhidrosis, swelling *, photosensitivity reactions *, severe skin reactions * (including erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis).

On the part of the hematopoiesis system: thrombocytopenia *, mild neutropenia.

Common violations: edema (including facial edema and peripheral edema), fatigue, pain of uncertain location, fatigue *, malaise, fungal infections, bacterial infections, fever, chills, flu-like symptoms.

On the part of the respiratory system: pneumonia, pharyngitis, rhinitis, bronchitis, respiratory failure, dyspnea, epistaxis, increased cough, otitis media.

Laboratory indicators:

In clinical studies, the drug Zetamaks retard following clinically significant abnormalities have been reported in laboratory parameters (regardless of relationship to treatment) at their normal baseline values: decrease the number of lymphocytes, increase the number of eosinophils, monocytes, neutrophils, decrease or increase in concentration of bicarbonates, leukopenia, neutropenia, increased concentration of bilirubin, chlorides, increased activity of alanine aminotransferase (ALT), aspartate aminotransferase (ACT), alkaline phosphatase, an increase in the concentration of creatinine, residual urea nitrogen, changes in the concentration of potassium, sodium, glucose and platelets,reduction of hematocrit and white blood cells.

In those cases where the results of the observation were known, laboratory abnormalities were reversible.

undesirable phenomena registered in postmarketing research.

Overdose:

In case of overdose, it is possible to expect the development of the above-mentioned dose-dependent side effects (except allergic reactions) in a more pronounced form.

Treatment: symptomatic and supportive therapy.

Interaction:

In pharmacokinetic studies, the interaction of azithromycin in the form of capsules and tablets (in doses of 500 to 1200 mg) was studied with preparations that could be used simultaneously with it. The effects of azithromycin on the pharmacokinetics of other drugs are given in Table. 3, and the effects of other drugs on the pharmacokinetics of azithromycin - in Table. 4.

The use of azithromycin in capsules and tablets at therapeutic doses had an insignificant effect on the pharmacokinetics of the drugs listed in Table. 3. Although the interaction of Zetamax retard with other drugs has not been studied, it can be assumed that there is no potential interaction,since the values of the total azithromycin AUC with the use of Zetamax retard and other forms of azithromycin are comparable. In this regard, the correction of the doses of the drugs listed in Table. 3, with their simultaneous use with the preparation Zetamax retard is not recommended. Efavirenz and fluconazole had little effect on the pharmacokinetics of azithromycin, used in the form of tablets. Nelfinavir Caused a significant increase in Cmah and azithromycin AUC. Similar results can be expected with the use of Zetamax retard. Although the correction of doses of Zetamax retard with its simultaneous use with the drugs listed in Table. 4 is not recommended, however, when combined with nelfinavir, it is advisable to carefully monitor known side effects of azithromycin, such as increased hepatic enzyme activity and hearing impairment. Azithromycin did not influence the change in prothrombin time with a single admission of warfarin. However, with the simultaneous use of azithromycin with warfarin, it is advisable to carefully monitor prothrombin time.The simultaneous use of macrolides and warfarin in clinical practice was accompanied by an increase in the anticoagulant effect.

In pharmacokinetic studies, it has been found that in therapeutic doses azithromycin It has little influence on the pharmacokinetics of atorvastatin, carbamazepine, cetirizine, didanosine, efavirenz, fluconazole, indinavir, midazolam, rifabutin, sildenafil, theophylline (intravenously and orally), triazolam, trimethoprim / sulfamethoxazole, zidovudine and methylprednisolone. The simultaneous use of efavirenz or fluconazole had little effect on the pharmacokinetics of azithromycin. There are also reports of the development of rhabdomyolysis with simultaneous use of azithromycin and statins.

At simultaneous application with rifabutin development of a neutropenia was observed. Despite the fact that this effect is associated with the use of rifabutin, a clear connection with the administration of this drug in combination with azithromycin has not been established.

Correction of doses of these drugs with their simultaneous use with azithromycin is not required.

In a cross-sectional study 39Healthy adult volunteers received only Zetamaks retard in a dose of 2.0 g Zetamaks retard and combined with 20 ml Antacids containing aluminum hydroxide and magnesium at standard doses. The use of antacids did not affect the rate and extent of absorption of azithromycin. Do not use azithromycin and antacid at the same time.

In the application of cimetidine for 2 hours before receiving azithromycin no marked effect on the pharmacokinetics of azithromycin cimetidine.

Table 3. Pharmacokinetic parameters of drugs used simultaneously with azithromycin.

Dose

azithromycin *

Ratio (with / without azithromycin)

Preparations

Doses

pharmacokinetic parameters of drugs used

simultaneously (90% lack of effect

DI);

=1,00

Average

Cmax

Average

AUC

Atorvastatin

10 mg / day 8 days

500 mg / day orally on the 6th-8th day

0.83

(0.63-1.08)

1,01

(0.81- 1,25)

Carbamazepine

200 mg / day 2 days, then 200 mg twice daily 18 days

500 mg / day on the 16-18th day

0.97

(0.88-1.06)

0.96

(0.88-1.06)

Cetirizine

20 mg / day 11 days

500 mg orally on the 7th day, then 250 mg / day (days 8-11)

1.03

(0.93-1.14)

1.02

(0.92-1.13)

Didanosine

200 mg orally 2 times a day 21 days

1200 mg / day orally on the 8th-21st day

1.44

(0.85-2.43)

1.14

(0.83-

1.57)

Efavirenz

400 mg / day 7 days

600 mg orally on the 7th day

1.04ţ

0.95ţ

Fluconazole

200 mg orally once

1200 mg orally once

1.04

(0.98-1.11)

(0.97-

1,01

1.05)

Indinavir

800 mg 3 times a day 5 days

1200 mg orally on the 5th day

0.96

(0.86-1.08)

0.90

(0.81-1.00)

Midazolam

15 mg orally on the 3rd day

500 mg / day inside 3 days

1.27

(0.89-1.81)

1.26

(1.01-1.56)

Nelfinavir

750 mg 3 times a day 11 days

1200 mg orally on the 9th day

0.90

(0.81-1.01)

0.85

(0.78-0.93)

Rifabutin

300 mg / day 10 days

500 mg orally on the first day, then 250 mg (days 2-10)

No data

Sildenafil

100 mg on days 1 and 4

500 mg / day 3 days

1.16

(0.86-1.57)

0.92

(0.75-1.12)

Theophylline

4 mg / kg IV days 1, 11.25

500 mg orally on the 7th day, then 250 mg / day (days 8-11)

1.19

(1.02-1.40)

1.02

0,86-1.22)

Theophylline

300 mg orally 2 times a day 15 days

500 mg orally on the 6th day, and then 250 mg / day (days 7-10)

1.09

(0.92-1.29)

1.08

(0.89-1.31)

Triazolam

0.125 mg on day 2

500 mg orally on the first day, and then 250 mg / day on the second day

1.06ţ

1.02ţ

Trimethoprim /

sulfamethoxazole

160 mg / 800 mg orally 7 days

1200 mg orally on the 7th day

0.85

(0.75-0.97)/

0.90

(0.78-1.03)

0.87

(0.80-0.95)/

0.96

(0.88-1.03)

Zidovudine

500 mg orally 21 days

600 mg orally for 14 days

1.12

(0.42-3.02)

0.94

(0.52-1.70)

Zidovudine

500 mg orally 21 days

1,200 mg / day inside 14 days

1.31

(0.43-3.97)

1.30

(0.69-2.43)

* capsules and tablets of azithromycin, unless otherwise specified;

ţ 90% confidence interval is not specified;

ŧ mean concentrations of rifabutin 12 hours after the last dose of rifabutin were 60 ng / ml with simultaneous use with azithromycin and 71 ng / ml with simultaneous application with placebo.

Table 4. Pharmacokinetic parameters of azithromycin when used simultaneously with other drugs

Preparations	Doses	Dose azithromycin *	n	Ratio (with / without concomitantly used drugs) of pharmacokinetic parameters of azithromycin, (90% CI); no effect = 1.00
Preparations	Doses	Dose azithromycin *	n	Average FROMmOh	Average AUC
Efavirenz	400 mg / day 7 days	600 mg orally on the 7th day	14	1.22 (1.04-1.42)	0.92t
Fluconazole	200 mg once in	1200 mg once in	18	0.82 (0.66-1.02)	1.07 (0.94-1.22)
Nelfinavir	750 mg 3 times a day 11 days	1200 mg orally on the 9th day	14	2.36 (1.77-3.15)	2.12 (1.8-2.50)
Rifabutin	300 mg / day 10 days	500 mg orally on the first day, then 250 mg / day (days 2-10)	6	ŧ	No data
Aluminum and magnesium hydroxide	20 ml once in usual doses	2.0 g of Zetamax once	39	0.99 (0.93-1.06)	0.99 (0.92-1.08)

* capsules and tablets of azithromycin, unless otherwise specified;

ţ 90% confidence interval is not specified;

ŧ The average concentrations of azithromycin 1 day after the last dose were 53 ng / ml with simultaneous application with rifabutin at a dose of 300 mg / day and 49 ng / ml with simultaneous application with placebo.

With the simultaneous use of chloroquine (1000 mg) and azithromycin (500 mg, 1000 mg, 1500 mg once daily), there was an increase in the QTc interval depending on the dose and concentration. With the simultaneous use of azithromycin in doses of 500 mg, 1000 mg, 1500 mg once a day, the QTcF interval was increased by 5 (10) ms, 7 (12) ms and 9 (14) ms, respectively, as compared with the administration of chloroquine as monotherapy.

In clinical studies of the interaction of the medicines listed below with azithromycin is not established, however, no special studies of their interaction have been conducted.Nevertheless, the cases of interaction were recorded when they were applied simultaneously with other macrolides. Before receiving additional data on the interaction with azithromycin, while taking the following medicines at the same time, careful monitoring of patients is recommended:

- Digoxin - reported cases of increased concentrations of P-glycoprotein substrates, such as digoxin, in blood plasma with their simultaneous use with azithromycin. Therefore, with simultaneous use of azithromycin and P-glycoprotein substrates, such as digoxin, possible increase in digoxin concentration in the blood plasma should be considered.

- Ergotamine and dihydroergotamine - acute toxicity, characterized by severe peripheral vasospasm or dysesthesia.

- Monitoring of concentrations of terfenadine, hexobarbital and phenytoin.

When azithromycin was used by healthy volunteers, a significant increase in Cmax and AUCo-5 of azithromycin was observed for three days at a dose of 500 mg / day inwards, and then cyclosporine once at a dose of 10 mg / kg. In this regard, care should be taken with the simultaneous use of these drugs and it is necessary to monitor the concentration of cyclosporine with possible dose adjustment.

Caution should be exercised when using simultaneously with medications that extend the Q-T interval.

Special instructions:

To prevent the formation of resistant strains of bacteria and ensure the preservation of the effectiveness of Zetamax retard, as well as other antibacterial means, the drug should be used only to treat confirmed or suspected with a high probability of bacterial infections caused by sensitive bacteria. When selecting or modifying antibacterial therapy, the results of inoculation and sensitivity assessment should be taken into account. If such data are not available, regional information on the distribution of pathogens and their sensitivity may provide some assistance in choosing empirical therapy.

Before starting treatment, bacteriological tests should be performed to identify the pathogen and determine its sensitivity to the Zetamax retard drug. Therapy with the Zetamax retard drug can be started before the test results are obtained. When they become known, antimicrobial therapy should be adjusted accordingly.

As with any antibiotics, it is recommended that patients with azithromycin be monitored for the development of superinfection of insensitive microorganisms, including fungi.

There are reports of impaired liver function, the development of hepatitis, cholestatic jaundice, liver necrosis and liver failure, in some cases fatal, with the administration of azithromycin. In case of development of signs of hepatitis should immediately stop taking Zetamax retard.

In the treatment with macrolides, including azithromycin, prolongation of repolarization of the heart and interval Q-T, which increases the risk of arrhythmias, in particular extrasystoles like "pirouette." In this regard, the risk of lengthening the interval Q-T, including those with a fatal outcome and to assess the risk / benefit ratio when using azithromycin in patients at risk:

- with congenital or recorded lengthening of the interval Q-T;

- in patients who are currently receiving therapy with other drugs that can lead to lengthening of the interval Q-T (for example, antiarrhythmic drugs classes IA and III, antipsychotic drugs, antidepressants, fluoroquinolones);

- in patients with electrolyte imbalance, mainly in cases of hypokalemia and hypomagnesemia;

- in patients with clinically significant bradycardia, arrhythmia or cardiac failure;

- in elderly patients (elderly patients may be more sensitive to the effect of drugs on the interval Q-T).

Zetamax retard contains 19.36 g of sucrose. This drug can not be administered to patients with fructose intolerance, glucose-galactose malabsorption or insufficiency of isomaltase sucrose.

In rare cases, patients receiving other forms of azithromycin developed serious allergic reactions, including angioedema, anaphylaxis and skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis. Although rare, there have been fatal cases (see the section "Contraindications"), despite the effectiveness of primary symptomatic therapy, after its cessation in some patients, the allergy symptoms soon reappeared, although patients did not receive azithromycin. Such patients need longer follow-up and symptomatic treatment. The relationship between such undesirable phenomena and the long half-life of azithromycin from tissues with subsequent exposure to the antigen is not established.

If any signs of an allergic reaction appear, patients should immediately consult a doctor. If the allergic reaction develops, the drug should be withdrawn and adequate therapy prescribed. The physician should consider that after the termination of symptomatic treatment it is possible to resume allergy symptoms.

In the treatment of almost all antibacterial agents, cases of pseudomembranous colitis are described, the severity of which can range from mild to life-threatening. Therefore, when diarrhea occurs after prescribing antibacterial agents, the possibility of such a disease should be considered.

Treatment with antibacterial drugs leads to a change in the normal microflora of the large intestine and can cause an excessive growth of clostridia. Studies indicate that the primary cause of "colitis associated with antibiotics" is toxin Clostridium difficile. Strains C. difficile, which produce hypertoxin, lead to an increase in morbidity and mortality, since these infections can be resistant to antimicrobial therapy and colectomy may be necessary for treatment. The patient's history should be carefully analyzed, as it has been reported about the development of "colitis associated with antibiotics" within two months after taking antibacterial drugs.

If a diagnosis of pseudomembranous colitis is established, appropriate measures must be taken. In mild cases it is usually enough to cancel the antibacterial drug. In the medium-heavy and severe cases, the introduction of fluid and electrolytes, proteins and the appointment of antibacterial agents effective in colitis caused by Clostridium difficile.

If within 5 minutes after taking the drug the patient develops vomiting, the doctor should consider the advisability of prescribing additional antibiotic therapy, since the absorption of azithromycin in this case will be minimal. Information on the absorption of azithromycin in the case of vomiting in the range of 5-60 minutes after its intake is not enough, so the doctor should evaluate the need for alternative therapy.If vomiting develops for more than 60 minutes after taking the drug in patients with normal gastric motility, taking a second dose of Zetamax retard or another antibiotic is not required.

Patients treated with ergotamine derivatives experienced a more rapid development of ergotism symptoms with the simultaneous use of certain macrolide antibiotics. There is no information on the interaction of ergotamine and azithromycin. Nevertheless, in view of the theoretical possibility of the development of ergotism, one should not jointly apply azithromycin and derivatives of ergotamine.

It is necessary to monitor the concentration of digoxin in the blood plasma during and after treatment with azithromycin.

Zetamax retard suspension contains 148 mg of sodium.

Effect on the ability to drive transp. cf. and fur:During treatment with Zetamax retard, caution should be exercised when driving vehicles or controlling other complex mechanisms due to the possibility of developing dizziness.

Form release / dosage:

Powder for the preparation of a suspension of prolonged action for oral administration of 2 g.

Packaging:

2 g azithromycin in a plastic bottle of high-density polyethylene with a plastic screw cap providing protection from opening by children.

1 bottle with instructions for use in a cardboard box.

Storage conditions:

At a temperature not exceeding 30 ° C.

Shelf life:

3 years.

Do not use after the expiration date printed on the package.

Cellular suspension should be used within 12 hours.

Terms of leave from pharmacies:On prescription

Registration number:LS-001823

Date of registration:28.09.2011

Date of cancellation:2017-08-21

The owner of the registration certificate:Pfizer Pharmaceuticals ELELSiPfizer Pharmaceuticals ELELSi Puerto Rico

Manufacturer: & nbsp

PFIZER PHARMACEUTICALS, LLC Puerto Rico

Representation: & nbspPfizer H. Si. Pi. CorporationPfizer H. Si. Pi. Corporation

Information update date: & nbsp21.08.2017

Illustrated instructions

Instructions

Zetamax retard (Zetamax retard)