Azithromycin, 500 mg 3 pcs

Pharmacotherapeutic group

Azolid antibiotic

ATCode

J01FA10

Pharmacodynamics:

Azithromycin is a broad-spectrum bacteriostatic antibiotic of the macrolide-azalid group. It has a broad spectrum of antimicrobial action.

The mechanism of action of azithromycin is associated with inhibition of microbial cell protein synthesis. Binding to 50S-subunit of ribosome, it inhibits peptide translocase on the translation stage and inhibits protein synthesis, slowing down the growth and reproduction of bacteria. In high concentrations it has bactericidal action.

It has activity against a number of Gram-positive Gram-negative anaerobic intracellular and other microorganisms.

Microorganisms can be initially resistant to the antibiotic or can become resistant to it.

The sensitivity scale for microorganisms to azithromycin (Minimum Inhibitory Concentration (MIC) mt/L):

.

In most cases, susceptible microorganisms

1. Gram-positive aerobes

Staphylococcus aureus methicillin-sensitive

Streptococcus pneumoniae penicillin-sensitive

Streptococcus pyogenes

2. Gram-negative aerobes

Haemophilus influenzae

Haemophilus parainfluenzae

Legionella pneumophila

Moraxella catarrhalis

Pasteurella multocida

Neisseria gonorrhoeae

3. Anaerobes

Clostridium perffingens

Fusobacterium spp.

Prevotella spp.

Porphyriomonas spp.

4. Other microorganisms

Chlamydia trachomatis

Chlamydia pneumoniae

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Chlamydia psittaci

Mycoplasma pneumoniae

Mycoplasma hominis

Borrelia burgdorferi

Microorganisms that can develop resistance to azithromycin

Gram-positive aerobes

Streptococcus pneumoniae penicillin-resistant

Initially resistant microorganisms

Gram-positive aerobes

Enterococcus faecalis

Staphylococci (methicillin-resistant staphylococci have a very high frequency of acquired resistance to macrolides).

Gram-positive bacteria resistant to erythromycin.

Anaerobes

Badneides fragilis

Pharmacokinetics:

Azithromycin is well absorbed and rapidly distributed in the body after oral administration. After a single administration of 500 mg bioavailability is 37% (first pass effect) maximum concentration (04 mg/l) in blood is created after 2-3 hours apparent volume of distribution – 311 l/kg Protein binding is inversely proportional to the concentration in blood and is 7-50%. It penetrates through cell membranes (effective in infections caused by intracellular pathogens). It is transported by phagocytes to the site of infection where it is released in the presence of bacteria.

It easily passes through histohematic barriers and enters the tissues. Concentration in tissues and cells is 10-50 times higher than in plasma and 24-34% higher in the focus of infection than in healthy tissues.

Asithromycin has a very long half-life of 35-50 hours. The half-life from tissues is much longer.

The therapeutic concentration of azithromycin is maintained up to 5-7 days after the last dose. Azithromycin is excreted mainly unchanged – 50% by the intestine 6% by the kidneys. In the liver it is demethylated losing activity.

Indications

Infectious inflammatory diseases caused by microorganisms sensitive to azithromycin:

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

– lower respiratory tract infections (acute bronchitis exacerbation of chronic bronchitis pneumonia including that caused by atypical pathogens);

– infections of the skin and soft tissues (rye impetigo secondary infectious dermatosis acne vulgaris of moderate severity);

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

– Lyme disease (borreliosis) in the initial stage (erythema migrans).

Active ingredient

Composition

One tablet contains:

the active substance:

azithromycin – 500 mg (in the form of azithromycin dihydrate – 524.05 mg);

excipients: calcium hydrophosphate dihydrate, hypromellose, corn starch, starch 1500, corn starch partially pregelatinized, sodium lauryl sulfate, magnesium stearate, microcrystalline cellulose, Opadray II (incl.including polyvinyl alcohol, talc, macrogol 3350, lecithin (soy), titanium dioxide E 171, iron oxide yellow E 172, aluminum lacquer on the basis of indigo carm and on E 132).

How to take, the dosage

Overly 1 hour before or 2 hours after a meal once a day without chewing and with plenty of water.

Adults and children over 12 years of age with a body weight of more than 45 kg:

– in infections of the upper respiratory tract and ENT organs (sinusitis tonsillitis pharyngitis otitis media) – 500 mg / day in a single dose for 3 days (course dose – 15 g);

With acne vulgaris of moderate severity – 500 mg/day for 3 days then 500 mg/day once a week for 9 weeks (course dose – 60 g). The first weekly tablet should be used 7 days after taking the first daily tablet (day 8 from the start of treatment) the following 8 weekly tablets – at 7-day intervals;

– In lower respiratory tract infections (acute bronchitis acute exacerbation of chronic bronchitis pneumonia including that caused by atypical pathogens) – 500 mg/day at a single dose for 3 days (course dose – 15 g);

Infections with lower respiratory tract infectionsp> – in infections of the skin and soft tissues (rye impetigo secondary infectious dermatoses) – 500 mg/d by single administration for 3 days (course dose – 15 g);

– in infections of the urogenital tract caused by Chlamydia trachomatis (urethritis cervicitis) – 10 g once;

In Lyme disease (borreliosis) in the initial stage (erythema migrans) – 10 g on the first day and 500 mg daily from the second to the fifth day (cumulative dose – 30 g).

In patients with impaired renal function: In patients with a GFR of 10-80 ml/min, no dose adjustment is required.

In patients with hepatic impairment: No dose adjustment is required in patients with mild to moderate hepatic impairment.

Elderly patients: No dose adjustment is required. Because elderly people may already have current proarrhythmogenic conditions, caution should be exercised with Azithromycin due to the high risk of cardiac arrhythmias, including pirouette arrhythmias.

Interaction

Antacids do not affect bioavailability of azithromycin, but decrease maximum blood concentrations by 30%; therefore, the drug should be taken at least one hour before or two hours after taking these drugs and meals.

Cetirizine

Concomitant use of azithromycin with cetirizine (20 mg) for 5 days in healthy volunteers did not result in pharmacokinetic interaction or significant QT interval changes.

Didanosine (didezoxinosine)

The concomitant use of azithromycin (1200 mg/day) and didanosine (400 mg/’day) in 6 HIV-infected patients showed no change in the pharmacokinetic readings of didanosine compared with the placebo group.

Digoxin (P-glycoprotein substrates)

The concomitant use of macrolide antibiotics including azithromycin with P-glycoprotein substrates. such as digoxin results in higher serum P-glycoprotein substrate concentrations. Thus, when concomitant use of azithromycin and digoxin it is necessary to consider the possibility of increasing the concentration of digoxin in blood serum.

Zidovudine

The concomitant use of azithromycin (single administration of 1000 mg and multiple administration of 1200 mg or 600 mg) has little effect on the pharmacokinetics including renal excretion of zidovudine or its glucuronide metabolite. However, azithromycin administration caused an increase in the concentration of phosphorylated zidovudine clinically active metabolite in peripheral blood mononuclear cells. The clinical significance of this fact is unclear.

Asithromycin interacts weakly with cytochrome P450 isoenzymes. Azithromycin has not been found to be involved in pharmacokinetic interactions similar to erythromycin and other macrolides. Azithromycin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes.

Due to the theoretical possibility of ergotism, concomitant use of azithromycin with ergot alkaloid derivatives is not recommended.

Pharmacokinetic studies have been performed with azithromycin concomitantly with drugs metabolized by cytochrome P450 isoenzymes.

Atorvastatin

Concomitant administration of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not change concentration of atorvastatin in plasma (on the basis of HMK-CoA reductase inhibition test). However, in post-registration period there were separate reports about cases of rhabdomyolysis in patients receiving azithromycin and statins concomitantly.

Carbamazepine

Pharmacokinetic studies with healthy volunteers showed no significant effect on plasma concentrations of carbamazepine and its active metabolite in patients receiving azithromycin concomitantly.

Cimetidine

In pharmacokinetic studies of the effect of a single dose of cimetidine on the pharmacokinetics of azithromycin no changes in the pharmacokinetics of azithromycin were found if cimetidine was used 2 hours before azithromycin.

Indirect anticoagulants (coumarin derivatives)

In pharmacokinetic studies azithromycin had no effect on the anticoagulant effect of a single dose of 15 mg warfarin taken by healthy volunteers. Potentiation of the anticoagulant effect has been reported after concomitant use of azithromycin and indirect-acting anticoagulants (coumarin derivatives). Despite the fact that the causal relationship has not been established, frequent prothrombin time monitoring should be considered when using azithromycin in patients receiving oral anticoagulants of indirect activity (coumarin derivatives).

Cyclosporine

. In a pharmacokinetic study with healthy volunteers who received oral azithromycin {500 mg/day once daily) for 3 days and then cyclosporine (10 mg/kg/day once daily) a significant increase in maximum plasma concentration (Cmax) and area under the “concentration-time” curve (AUC0-5) of cyclosporine was found. Caution should be exercised when concomitant use of these drugs. In case of necessity of concomitant use of these drugs it is necessary to monitor plasma concentrations of cyclosporine and adjust the dose accordingly.

Efavirenz

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

Fluconazole

Concomitant use of azithromycin (1200 mg once daily) did not alter the pharmacokinetics of fluconazole (800 mg once daily). Total exposure and half-life of azithromycin did not change with concomitant use of fluconazole, but there was a decrease in Cmax of azithromycin (by 18%) which had no clinical significance.

Indinavir

The concomitant use of azithromycin (1200 mg once daily) had no statistically significant effect on the pharmacokinetics of indinavir (800 mg three times daily for 5 days).

Methylprednisolone

Asithromycin has no significant effect on the pharmacokinetics of methylprednisolone.

Nelfinavir

The simultaneous use of azithromycin (1200 mg) and nelfinavir (750 mg 3 times daily) causes increased equilibrium serum concentrations of azithromycin. No clinically significant adverse effects have been observed and no dose adjustment of azithromycin is required when used concomitantly with nelfinavir.

Rifabutin

The concomitant use of azithromycin and rifabutin has no effect on the serum concentrations of either drug. Neutropenia has sometimes been observed with concomitant use of azithromycin and rifabutin. Although neutropenia has been 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.

Sildenafil

There is no evidence of an effect of azithromycin (500 mg/day daily for 3 days) on the AUC and Cmax of sildenafil or its major circulating metabolite when used in healthy volunteers.

Terfenadine

There has been no evidence in pharmacokinetic studies of interactions between azithromycin and terfenadine. There have been some isolated cases where the possibility of such an interaction could not be ruled out completely, but there has not been any concrete evidence that this interaction has occurred.

It has been found that concomitant use of terfenadine and macrolides can cause arrhythmias and prolongation of the QT interval.

Theophylline

There have been no identified interactions between azithromycin and theophylline.

Triazolam/midazolam

There are no significant changes in pharmacokinetic parameters when azithromycin is used concomitantly with triazolam or midazolam in therapeutic doses.

Trimethoprim/sulfamethoxazole

The concomitant use of trimethoprim/sulfamethoxazole with azithromycin showed no significant effect on Cmax total exposure or renal excretion of trimethoprim or sulfamethoceazole. Serum azithromycin concentrations were consistent with those found in other studies.

Special Instructions

If a dose of Azithromycin is missed, the missed dose should be taken as soon as possible and subsequent doses should be taken 24 hours apart.

Azithromycin should be taken at least one hour before or two hours after taking antacids.

The drug Azithromycin should be used with caution in patients with mild to moderate hepatic impairment because of the possibility of fulminant hepatitis and severe hepatic impairment.

In cases of hepatic impairment: If there are symptoms of hepatic impairment such as: rapidly increasing asthenia jaundice darkened urine bleeding tendency hepatic encephalopathy, therapy with Azithromycin should be discontinued and liver function testing should be performed.

In patients with impaired renal function: In patients with a GFR of 10-80 ml/min, no dose adjustment is required.

As with other antibacterial agents during therapy with Azithromycin, patients should be regularly examined for the presence of non-susceptible microorganisms and signs of superinfections, including fungal infections.

Azithromycin should not be used over longer periods than directed, since the pharmacokinetic properties of azithromycin suggest a short and simple dosing regimen.

There are no data on possible interactions between azithromycin and derivatives of ergotamine and dihydroergotamine, but because of the development of ergotism when using macrolides with derivatives of ergotamine and dihydroergotamine simultaneously, this combination is not recommended.

The development of pseudomembranous colitis caused by Clostridium difficile in the form of both mild diarrhea and severe colitis is possible with prolonged use of Azithromycin. If antibiotic-associated diarrhea develops against the background of Azithromycin therapy, as well as 2 months after therapy termination, clostridial pseudomembranous colitis should be excluded. Drugs inhibiting intestinal peristalsis are contraindicated.

Treatment with macrolides including azithromycin has been associated with prolongation of cardiac repolarization and QT interval increasing risk of cardiac arrhythmias including pirouette arrhythmias.

We should use azithromycin with caution in patients with the presence of proarrhythmogenic factors (especially in elderly patients) including congenital or acquired prolongation of QT interval; in patients receiving class IA antiarrhythmic drugs (quinidine procainamide) III (dofetilide amiodarone and sotalol) cisapride terfenadine antipsychotic drugs (pimozide) antidepressants (citalopram) fluoroquinolones (moxifloxacin and levofloxacin) in patients with disorders of water and electrolyte balance, especially in case of irregularities of water andelectrolyte balance especially in case of hypokalemia or hypomagnesemia clinically significant bradycardia arrhythmia or severe heart failure.

The use of azithromycin may provoke myasthenic syndrome or worsen myasthenia gravis.

Rare cases of serious allergic reactions including angioedema and anaphylaxis (rarely fatal) skin reactions including acute generalized exanthematous pustulosis Stevens-Jones syndrome toxic epidermal necrolysis (rarely fatal) drug rash with ezinophilia and systemic manifestations (DRESS syndrome) have also been reported with erythromycin and other macrolides. Some of these reactions developed during azithromycin use were recurrent and required long-term treatment and monitoring. If an allergic reaction develops, the drug should be withdrawn and an appropriate treatment started. It should be borne in mind that after withdrawal of symptomatic therapy the symptoms of allergic reaction may recur.

When using the drug, care must be taken when driving vehicles and engaging in other potentially dangerous activities that require increased concentration and rapid psychomotor reactions. In case of undesirable effects on the nervous system (dizziness, somnolence, syncope) and eyesight (visual disturbances) one should abstain from the above activities.

Contraindications

– Hypersensitivity to azithromycin and other components of the drug to erythromycin other macrolides to ketolides to soy and peanuts;

– severe hepatic impairment (Child-Pugh class C);

– children under 12 years of age with body weight less than 45 kg;

– concomitant use with ergotamine and dihydroergotamine.

Terminal renal insufficiency with a GFR (glomerular filtration rate) less than 10 ml/min; mild to moderate liver function impairment (Child-Pugh class A and B); in patients with proarrhythmogenic factors (especially in older patients): with congenital or acquired prolongation of the QT interval; in patients receiving therapy with class IA (quinidine procainamide) class III (dofetilide amiodarone and sotalol) cisapride terfenadine antipsychotics (pimozide) antidepressants (citalopram) fluoroquinolones (moxifloxacin and levofloxacin) with the disorders of water-electrolyte balance especially in case of hypokalemia or hypomagnesemia; with clinically significant cardiac bradycardia arrhythmia or severe heart failure; concomitant use of digoxin warfarin cyclosporine; myasthenia.

Side effects

The frequency of side effects is classified in accordance with the World Health Organization recommendations: very common – at least 10%; common – at least 1% but less than 10%; infrequent – at least 01% but less than 1%; rare – at least 001% but less than 01%; very rare – less than 001%; unknown frequency – cannot be estimated based on available data.

Infectious diseases: infrequent – candidiasis including oral mucosa vaginal infection pneumonia fungal infection bacterial infection pharyngitis gastroenteritis respiratory diseases rhinitis; unknown frequency pseudomembranous colitis.

Blood and lymphatic system disorders:infrequent – leukopenia neutropenia eosinophilia; very rare – thrombocytopenia hemolytic anemia.

Metabolism and nutrition: infrequent – anorexia.

Allergic reactions: infrequent – angioedema hypersensitivity reaction; unknown frequency – anaphylactic reaction.

Nervous system disorders:Frequent-headache; infrequent- dizziness impaired sense of taste paresthesia somnolence insomnia nervousness; rare- agitation; unknown frequency- synesthesia anxiety aggression fainting convulsions psychomotor hyperactivity loss of smell perversion loss of sense of taste myasthenia delirium hallucinations.

An organ of vision: infrequent – visual impairment.

Hearing organ and labyrinth disorders: infrequent – hearing disorder vertigo; unknown frequency – hearing disorder including deafness and/or tinnitus.

Cardiovascular system disorders: infrequent – palpitations “rush” of blood to the face; unknown frequency – decreased blood pressure increased QT interval on electrocardiogram arrhythmia type “pirouette” ventricular tachycardia.

Respiratory system disorders: infrequent – dyspnea nasal bleeding.

Gastro-intestinal tract: very frequently – diarrhea; frequently – nausea vomiting abdominal pain; infrequently – flatulence dyspepsia constipation gastritis dysphagia abdominal bloating dry mouth mucosa belching oral mucosa ulcers increased salivary gland secretion; very rarely – discoloration of tongue pancreatitis.

Hepatic and biliary tract disorders: infrequent – hepatitis; rare – hepatic impairment cholestatic jaundice; unknown frequency – hepatic failure (in rare cases – with fatal outcome mainly due to severe liver impairment); fulminant hepatitis liver necrosis.

Skin and subcutaneous tissue disorders: infrequent – skin rash itching urticaria dermatitis dry skin sweating; rare – photosensitization reaction; Unknown frequency – Stevens-Johnson syndrome toxic epidermal necrolysis erythema multiforme drug rash with eosinophilia and systemic manifestations (DRESS syndrome) acute generalized exanthematous pustulosis (OGEP)

Motor system disorders: infrequent – osteoarthritis myalgia back pain neck pain; unknown frequency – arthralgia.

Renal and urinary tract disorders: infrequent dysuria kidney pain; unknown frequency – interstitial nephritis acute renal failure.

Gender and mammary gland disorders: infrequent – metrorrhagia impaired testicular function.

Others: infrequent – oedema asthenia malaise feeling of fatigue facial edema chest pain fever peripheral edema.

Laboratory findings: frequent – decreased lymphocyte count increased eosinophil count increased basophil count increased monocyte count increased neutrophil count decreased plasma bicarbonate concentration; infrequent – increased aspartataminotransferase activity alanine aminotransferase increased plasma bilirubin concentration increased plasma urea concentration increased plasma creatinine concentration changed plasma potassium increased plasma alkaline phosphatase activity increased

Overdose

Symptoms: temporary hearing loss nausea vomiting diarrhea.

Treatment: symptomatic (no specific antidote).

Pregnancy use

Prenatal use of the drug is possible only when the estimated benefit to the mother outweighs the potential risk to the fetus.

Breastfeeding should be discontinued if the drug has to be used during lactation.

Similarities