Azivok - instructions for use, doses, side effects, contraindications

capsules hard gelatinous No. 0, body and lid: dye quinoline yellow, dye sunset yellow, titanium dioxide, gelatin, purified water, sodium lauryl sulfate, propyl parahydroxybenzoate (propylparaben), methyl parahydroxybenzoate (methylparaben);

black ink: (shellac, ethanol anhydrous, isopropanol, isobutanol, propylene glycol, ammonium sulfate concentrated solution, iron dye oxide black, sodium hydroxide, purified water).

Description:Hard gelatin capsules № 0, with the inscription in black ink "AZIWOK" and "WOCKHARDT". The body and the lid are yellowish white in color. The contents of the capsules are white or almost white powder.

Pharmacotherapeutic group:Antibiotic - azalide

ATX: & nbsp

J.01.F.A.10 Azithromycin

Pharmacodynamics:

Antibacterial agent of a wide spectrum of action, azalide, acts bacteriostatically. Communicating with 50S 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.

Azithromycin acts on extra- and intracellular pathogens.

Sensitive: aerobic Gram-positive microorganisms: Streptococcus pneumoniae (penicillin-sensitive), Streptococcus pyogenes, Staphylococcus aureus (methicillin-sensitive);

aerobic gram-negative microorganisms: Haemophilus influenzae, Moraxella catarrhalis, Legionella pneumophila, Haemophilus parainfluenzae, Pasteurella multocida, Neisseria gonorrhoeae;

anaerobic microorganisms: Prevotella spp., Clostridium perfringens, Fusobacterium spp., Porphyromonas spp .;

other - Chlamydia trachomatis, Chlamydia pneumoniae, Chlamydia psittaci, Mycoplasma pneumoniae, Mycoplasma hominis, Borrelia burgdorferi.

Moderately sensitive or insensitive: aerobic gram-positive microorganisms - Streptococcus pneumoniae (moderately sensitive or resistant, to penicillin).

Stable: aerobic Gram-positive microorganisms - Enterococcus faecalis, Staphylococcus spp., (methicillin-resistant); anaerobes - Group Bacteroides fragilis, Streptococcus pneumoniae, beta-hemolytic Streptococcus spp. groups A, Enterococcus faecalis and Staphylococcus aureus (including methicillin-resistant strains), resistant to erythromycin and other macrolides, lincosamides, are resistant to azithromycin.

Pharmacokinetics:

Absorption is high, acid-fast, lipophilic. Bioavailability after a single dose of 0.5 g - 37% (the effect of "first passage" through the liver), maximum concentration after oral administration 0.5 g - 0.4 mg / l, time to reach the maximum concentration - 2.5-2.9 h; in tissues and cells the concentration is 10-50 times higher than in blood plasma, the volume of distribution is 31.1 l / kg. Easily passes through the histohematological barriers.

It penetrates well into the respiratory tract, genito-urinary organs and tissues, incl. prostate, in the skin and soft tissues.

It penetrates through cell membranes and creates high concentrations in them, accumulates in lysosomes (which is especially important for the eradication of intracellularly located pathogens). It is also transported by phagocytes: polymorphonuclear leukocytes and macrophages.

Concentration in the foci of infection is significantly higher (by 24-34%) than in healthy tissues, and correlates with severity of inflammatory edema. It remains in effective concentrations for 5-7 days after the last dose. The connection with plasma proteins is 7-50% (inversely proportional to the concentration in the blood).

In the liver, demethylated, inactive metabolites are formed.In the metabolism of the drug isozymes participate CYP3A4, CYP3A5, CYP3A7, of which it is an inhibitor.

Plasma clearance - 630 ml / min. The half-life between 8 and 24 hours after admission is 14-20 hours, the half-life in the interval from 24 to 72 hours is 41 hours.

50% is excreted with bile in unchanged form, 6% - with kidneys.

Eating significantly changes the pharmacokinetics: the maximum concentration and area under the "concentration-time" curve (AUC) decreases by 52 % and 43%, respectively.

In elderly men (65-85 years) pharmacokinetic parameters do not change, in women the maximum concentration (by 30-50%) increases.

Indications:

Infectious-inflammatory diseases caused by microorganisms sensitive to the preparation:

- infections of the upper respiratory tract and ENT organs (pharyngitis, tonsillitis, sinusitis, otitis media);

- infection of the lower respiratory tract (pneumonia (in the city caused by atypical pathogens), bronchitis);

- infections of the skin and soft tissues (acne vulgaris (mean severity), erysipelas, impetigo, secondarily infected dermatoses);

- urinary tract infections caused by Chlamydia trachomatis (urethritis, cervicitis);

- Lyme disease (initial stage - erythema migrans).

Contraindications:

Hypersensitivity (incl.erythromycin; ketolides and other macrolides, azithromycin, other components of the drug), severe hepatic insufficiency (Child-Pugh class C); severe renal failure (creatinine clearance less than 40 ml / min), simultaneous reception of ergotamine and dihydroergotamine, lactation period, children's age (up to 12 years with a body weight of less than 45 kg, for this dosage form), lactose intolerance, lactase deficiency, Glucose-galactose malabsorption (because the composition of the drug includes lactose).

Carefully:

Disorders of liver function of mild and moderate severity, disturbance of renal function of mild and moderate severity (KC more than 40 ml / min), in patients with proarrhythmogenic factors (especially in elderly patients): with congenital or acquired lengthening of the interval QT, in patients receiving antiarrhythmic drug therapy classes IA (quinidine, procainamide), III (dofetilide, amiodarone and sotalol), cisapride. terfenadine. antipsychotic drugs (pimozide), antidepressants (citalopram), fluoroquinolines (moxifloxacin and levofloxacin), with disturbances of water-electrolyte balance,especially in the case of hypokalemia or hypomagnesemia, with clinically significant bradycardia, cardiac arrhythmia or severe heart failure; simultaneous use of digoxin, warfarin, cyclosporine, in patients with myasthenia and during pregnancy.

Pregnancy and lactation:

In pregnancy, the drug is used only if the intended benefit to the mother exceeds the potential risk to the fetus.

During lactation during the treatment should stop breastfeeding.

Dosing and Administration:

Adults and children over 12 years of age weighing more than 45 kg: inside, 1 hour before or 2 hours after meals once a day: for infections of the upper and lower respiratory tract, ENT organs, skin and soft tissues - 0.5 g / day for 1 reception for 3 days (exchange dose - 1.5 g); when acne vulgaris - 0.5 g / day for 1 reception for 3 days, then 0.5 g / day 1 time per week for 9 weeks. The course dose of 6 g. The first weekly capsule should be taken 7 days after the first daily capsule (8 days from the start of treatment), the next 8 weekly capsules - at intervals of 7 days.

In cases of urinary tract infections caused by Chlamydia trachomatis (urethritis, cervicitis) - once 1 g.

With Lyme disease, for the treatment of I st. (erythema migrans) - 1 g on the first day and 0.5 g daily from 2 to 5 days (course dose - 3 g). When used in patients with impaired renal function of mild and moderate severity (QC greater than 40 ml / min), dose adjustment is not required; when used in patients with impaired liver function of mild and moderate severity, in elderly patients dose adjustment is not required.

Side effects:

From the side of the circulatory system: thrombocytopenia, neutropenia, hemolytic anemia.

From the nervous system: dizziness / vertigo, headache, seizures, drowsiness, paresthesia, fatigue, insomnia, hyperactivity, aggressiveness, anxiety, nervousness, agitation, delirium, hallucinations, hypesthesia, anxiety, fear, loss of smell, loss of taste, smell perversion, myasthenia gravis.

From the sense organs: noise in the ears, reversible hearing loss down to deafness (with high doses for long time), a violation of the perception of taste and smell, impaired vision.

From the cardiovascular system: palpitations, arrhythmias such as pirouettes, lowering of arterial pressure, ventricular tachycardia, increased interval QT, bidirectional ventricular tachycardia, "hot flashes" of blood to individuals.

From the digestive system: gastritis, bloating, pancreatitis, nausea, vomiting, diarrhea, abdominal pain / spasms, flatulence, belching, digestive disorders, anorexia, constipation, discoloration of the tongue, pseudomembranous colitis, cholestatic jaundice, fulminant hepatitis, impaired liver function, hepatic insufficiency, necrosis liver (possibly fatal), gastroenteritis, dysphagia. dryness of the oral mucosa, ulcers of the oral mucosa. increased secretion of the salivary glands.

Allergic reactions: itching, skin rashes, angioedema, hives, eosinophilia, anaphylactic reaction, including Quincke's edema (in rare cases, fatal), erythema multiforme, Stevens-Johnson syndrome, Lyell's syndrome, hypersensitivity reaction.

From the musculoskeletal system: arthralgia, osteoarthritis, myalgia, back pain, neck pain.

From the genitourinary system: interstitial nephritis, acute renal failure, pain in the kidney, metrorrhagia, dysuria, dysuria.

From the respiratory system: pneumonia, pharyngitis, respiratory diseases, rhinitis, shortness of breath, nosebleeds.

From the skin: dermatitis. dry skin, sweating.

Other: vaginitis, candidiasis, photosensitivity, malaise, fatigue, chest pain, peripheral edema, face swelling, fever.

Laboratory indicators: decrease in the number of lymphocytes, increased activity of aspartate aminotransferase, alanine aminotransferase; in the blood plasma: an increase in the number of basophils, monocytes, neutrophils, a decrease or increase in the concentration of bicarbonates, an increase in the activity of alkaline phosphatase, an increase in the chlorine content, an increase in the concentration of glucose, an increase in the number of platelets, an increase in the hematocrit, a change in the sodium content, an increase in the concentration of bilirubin, change in potassium content.

Overdose:

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

Treatment: gastric lavage, symptomatic therapy, hemodialysis is not effective.

Interaction:

- Antacids do not affect the bioavailability of azithromycin.but reduce the maximum concentration in the blood by 30%, so the drug should be taken one hour before or two hours after taking these drugs and food.

- Azithromycin does not affect the concentration of carbamazepine, didanosine, rifabutin and methylprednisolone in the blood in a joint application.

- In pharmacokinetic studies of the effect of a single dose of cimetidine on the pharmacokinetics of azithromycin, no changes in the pharmacokinetics of azithromycin have been observed, provided cimetidine is administered 2 hours before azithromycin.

- Simultaneous use of azithromycin (600 mg / day once) and efavirenz (400 mg / day) daily for 7 days did not cause any clinically significant pharmacokinetic interaction.

- Simultaneous use of azithromycin (1200 mg once) did not change the pharmacokinetics of fluconazole (800 mg once). The total exposure and half-life of azithromycin did not change with the simultaneous use of fluconazole. However, there was a decrease in Cmah azithromycin (by 18%). that had no clinical significance.

- Simultaneous use of azithromycin (1200 mg once) did not cause a statistically significant effect on the pharmacokinetics of indinavir (800 mg three times daily for 5 days).

- Simultaneous use of azithromycin with cetirizine (20 mg) for 5 days in healthy volunteers did not lead to a pharmacokinetic interaction and a significant change in the interval QT.

- When used in healthy volunteers, evidence of the effect of azithromycin (500 mg / day daily for 3 days) on AUC and Cmah sildenafil or its main circulating metabolite.

- Azithromycin has no effect on the bioavailability of co-trimoxazole.

- Significant changes in pharmacokinetic parameters with the simultaneous use of azithromycin with triazolam or midazolam in therapeutic doses are not revealed.

With the simultaneous use of azithromycin and rifabutin, neutropenia was sometimes 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.

- Azithromycin has no effect on the pharmacokinetics of theophylline, however, when co-administered with other macrolides theophylline plasma concentrations may be increased.

- If it is necessary to use together with cyclosporine, it is recommended to monitor the concentration of cyclosporin in the blood plasma and adjust the dose accordingly.

- With the joint administration of digoxin and azithromycin, it is necessary to monitor the concentration of digoxin in the blood, simultaneous application of macrolide antibiotics, including azithromycin, with P-glycoprotein substrates, such as digoxin. leads to an increase in the concentration of the P-glycoprotein substrate in the blood plasma.

- If it is necessary to share with warfarin, careful monitoring of prothrombin time is recommended.

- It was found that the simultaneous administration of terfenadine and antibiotics of the macrolide class causes arrhythmia and lengthening QT interval. Proceeding from this, it is impossible to exclude the aforementioned complications in the joint use of terfenadine and azithromycin.

- Since it is possible to inhibit the isoenzyme CYP3A4 azithromycin in parenteral form when combined with cyclosporine, terfenadine, ergot alkaloids, cisapride, pimozide, quinidine, astemizole and other drugs whose metabolism occurs with the participation of this enzyme, the possibility of such interaction in the administration of azithromycin for oral administration should be considered.

- Given the theoretical possibility of the emergence of ergotism, the simultaneous use of azithromycin with derivatives of ergot alkaloids (ergotamine, and dihydroergotamine) is not recommended.

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

- Azithromycin weakly interacts with cytochrome P450 isoenzymes. It was not 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.

- Simultaneous use of azithromycin (1200 mg) and nelfinavir (750 mg 3 times a day) causes an increase in the equilibrium concentration of azithromycin in the blood plasma, there were no clinically significant side effects and no dosage adjustment of azithromycin is required when used simultaneously with nelfinavir.

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

Special instructions:

In case of missed intake of a single dose of the drug, the missed dose should be taken as soon as possible, and the following - with interruptions of 24 hours.

As with any antibiotic. in the treatment of azithromycin, it is possible to attach superinfection (including fungal).

The drug should be taken at least one hour before or two hours after taking antacid preparations.

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

Azithromycin should be used with caution in patients with impaired hepatic and mild liver function due to the possibility of developing fulminant hepatitis and severe

hepatic insufficiency. In the presence of symptoms of impaired function, such as rapidly increasing asthenia, jaundice, darkening of the urine, a tendency to bleeding, hepatic encephalopathy therapy with Azivok should be discontinued and an examination of the functional state of the liver should be carried out.

In patients with impaired renal function of mild and moderate severity (CC greater than 40 ml / min), Azivok should be administered with caution under the supervision ofthe state of functions of the nights.

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

The drug should not be used for longer courses than indicated in the instructions, since the pharmacokinetic properties of azithromycin allow us to recommend a short and simple dosing regimen. The use of the drug may trigger the development of myasthenic syndrome or cause an exacerbation of myasthenia gravis.

Effect on the ability to drive transp. cf. and fur:Given the side effects of the drug from the central nervous system, it is necessary to be careful when driving vehicles and working with mechanisms that require concentration of attention.

Form release / dosage:

Capsules 250 mg.

Packaging:

6 capsules per alum / PVC blister, 1 blister each, along with instructions for use in a cardboard box.

Storage conditions:

In the dark place at a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N014850 / 01

Date of registration:24.03.2009

Expiration Date:Unlimited

The owner of the registration certificate:Vokhard LtdVokhard Ltd India

Manufacturer: & nbsp

WOCKHARDT, Ltd. India

Representation: & nbspVokhard Ltd., IndiaVokhard Ltd., India

Information update date: & nbsp04.02.2017

Illustrated instructions

Instructions

Azivok (Aziwok)