Sumaсlid® 1000 film-coated tablets 1000 mg

Sumaсlid® 1000 film-coated tablets 1000 mg

International nonproprietary name

Azithromycin

Pharmacological group

Антибактериальные средства

Composition

Active substance:
Azithromycin dihydrate (equivalent to azithromycin 1 g) - 1.048 g
Excipients of the core:
hypromellose (hydroxypropylmethicellulose) - 0.0126 g
sodium lauryl sulfate - 0.0018 g
calcium stearate - 0.0144 g
sodium stearyl fumarate - 0.0144 g
sodium croscarmellose - 0.0432 g
disodium dihydrate calcium phosphate
(calcium hydrogen phosphate dihydrate) - sufficient to obtain the core with weight 1.2 g
Excipients of the coating:
hypromellose (hydroxypropylmethicellulose) - 0.029535 g
titanium dioxide - 0.0025 g
polysorbate-80 (tween 80) - 0.0029 g
ponceau dye “ponceau 4R”, Е 124 - 0.000065 g

Pharmacological action

Antibacterial agent of a broad spectrum of action, azalide, acts bacteriostatically. Binding to the 50S subunit of ribosomes, the drug inhibits peptidranslokase at the stage of translation, suppresses protein synthesis, slows the growth and multiplication of bacteria, at high concentrations has a bactericidal effect. The drug is active against extracorporeal and intracellular pathogens. It is active against Gram-positive aerobic microorganisms: Streptococcus pneumoniae (penicillin-sensitive), Streptococcus pyogenes, Staphylococcus aureus (methicillin-sensitive); Gram-negative aerobic microorganisms: Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Legionella pneumophila, Neisseria gonorrhoeae, Pasteurella multocida; some anaerobic microorganisms: Prevotella spp., Clostridium perfringens, Fusobacterium spp., Porphyriomonas spp.; as well as Chlamydia trachomatis, Chlamydia pneumoniae, Chlamydia psittaci, Mycoplasma pneumoniae, Mycoplasma hominis, Borrelia burgdorferi.
Microorganisms that can develop resistance to azithromycin: Gram-positive aerobes (Strepto-coccus pneumoniae (penicillin-resistant). Initially, resistant microorganisms: gram-positive aerobes (Enterococcus faecalis, Staphylococcus spp. (methicillin-resistant staphylococci exhibit a very high degree of resistance to macrolides), Gram-positive bacteria resistant to erythromycin); anaerobes (Bacteroides fragilis).
The drug is inactive against Gram-positive bacteria, resistant to erythromycin.

Pharmacokinetics

Azithromycin is rapidly absorbed from the gastrointestinal tract, which is due to its stability in an acidic medium and lipophilicity. Bioavailability after the single dose 0.5 g is 37% (the effect of first pass through the liver), the maximum plasma concentration of the drug after oral administration of 0.5 g is 0.4 mg/l, time to the maximum plasma concentration of the drug is 2,5-2.9 h; in tissues and cells the concentration is 10-50 times higher than in serum, the volume of distribution is 31.1 l/kg.
The drug easily crosses the histohematological barriers. The drug pen-etrates well into the respiratory tract, urino-genital organs and tissues, into the prostate gland, into the skin and soft tissues; accumulates in a medium with low pH, in lysosomes (which is es-pecially important for eradication of intracellular pathogens). It is also transported by phagocytes, polymorphonuclear leukocytes and macrophages. It crosses the membranes of cells and creates high concentrations in them. T
he concentration in the infection foci is significantly higher (by 24-34%) than in healthy tissues, and correlates with the inflammatory edema severity. In the inflammation focus the drug persists in effective concentrations within 5-7 days after administration of the last dose. Binding to the plasma proteins is 7-50% (inversely proportional to the concentration in the blood).
The drug is demethylated in the liver, the formed metabolites are inactive. Plasma clearance is 630 ml/min: the half-life of the drug within the period from 8 and 24 hours after administration is 14-20 hours, the half-life of the drug within the period from 24 to 72 hours is 41 hours. 50% is excreted with bile in unchanged form, 6% - by the kidneys.
Food significantly changes the pharmacokinetics: the maximum plasma concentration of the drug increases (by 31%), the area under the "concentration-time" curve does not change. In elderly patients (65-85 years) the pharmacokinetic parameters do not change, in women the maximum plasma concentration of the drug increases (by 30-50%).

Indications for Use

Urinary tract infections caused by Chlamydia trachomatis (urethritis, cervicitis).

Contraindications

Hypersensitivity to azithromycin, other macrolides, other components of the drug, increased sen-sitivity to erythromycin; ketolides; simultaneous administration with ergotamine and dihydroer-gotamine, severe liver dysfunction (Child-Pugh class C); severe renal dysfunction (creatinine clearance less than 40 mL/min); lactation period, children under 18 years old (for this dose).
With care
Myasthenia, mild and moderate liver dysfunction, mild and moderate renal dysfunction (creati-nine clearance more than 40 ml/min), in patients with pro-arrhythmic factors (especially in elderly patients): with congenital or acquired QT interval elongation, in patients receiving antiarrhythmic drugs of classes IA (quinidine, procainamide), III (dofetilide, amiodarone and sotalol), cisapride, terfenadine, antipsychotic drugs (pimozide), antidepressants (citalopram), fluoroquinolone and (moxifloxacin and levofloxacin), in patients with fluid and electrolytic imbalance, particularly in case of hypokalemia or hypomagnesemia with clinically significant bradycardia, cardiac arrhythmia or severe heart failure; simultaneous administration of digoxin, warfarin, cyclosporine.
Administration during pregnancy and lactation period
The drug can be administered during pregnancy only when potential benefit to the mother out-weighs any potential risk to the fetus. Breastfeeding shall be discontinued for the period of treatment (data on penetration into the breast milk is not available).

Cautions

In case of missed dose, the missed dose should be administered as soon as possible, and the sub-sequent dose should be administered at intervals of 24 hours. An interval 2 hours shall be held for simultaneous administration of antacids. Azithromycin should be administered with care in patients with mild or moderate liver dysfunc-tion because of the potential for fulminant hepatitis and hepatic failure; in patients with mild and moderate renal dysfunction (with monitoring of the kidney function).
In case of symptoms of liver dysfunction (rapidly increasing asthenia, jaundice, darkening of the urine, a tendency to bleeding, hepatic encephalopathy) therapy with azithromycin should be dis-continued and the functional state of the liver shall be examined. Simultaneous administration of azithromycin with derivatives of ergotamine and dihydroergota-mine is contradicted because of possible development of ergotism. Similar to administration of other antibacterial drugs, the patients receiving azithromycin should be examined regularly for susceptible microorganisms and signs of superinfections, including fungal ones.
Administration of the drug of azithromycin can cause pseudomembranous colitis caused by-Clostridium difficile, both in the form of mild diarrhea and severe colitis. In case of antibiotic-associated diarrhea after administration of the drug azithromycin, and also 2 months after the end of the therapy, clostridial pseudomembranous colitis should be ruled out. During the treatment with azithromycin, administration of the drugs inhibiting the intestinal peristalsis is contraindicated.
Effects on ability to drive and use machines
Avoid activities related to required high concentration of attention and rapid psychomotor reac-tions (including driving) during the drug treatment.

Dosing and Administration

Oral administration without chewing 1 hour prior to or 2 hours after a meal once per day. Urinary tract infections caused by Chlamydia trachomatis (urethritis, cervicitis): uncomplicated urethritis/cervicitis - 1 g (1 tablet 1000 mg) once.
Administration in patients with mild and moderate renal dysfunction does not require dose cor-rection.
Administration in patients with mild and moderate liver dysfunction and in elderly patients does not require dose correction.

Side effect

 • Adverse digestive system effects: anorexia, nausea, vomiting, discoloration of the tongue, dryness of the oral mucosa, belching, ulcers of the oral mucosa, increased secretion of the salivary glands, abdominal pain, flatulence, constipation, dyspepsia, dysphagia, bloating, diarrhea, pseudomembranous colitis, melena, pancreatitis, increased activity of liver transaminases, biliru-bin level, hepatitis, cholestatic jaundice, fulminant hepatitis, hepatic failure(possibly fatal), liver necrosis; in addition, a decrease in appetite, gastritis.
• Adverse cardiovascular effects: palpitations, pain in the chest, blood pressure drop, the QT interval elongation on an electrocardiogram, pirouette arrhythmia, ventricular tachycardia, face flushes.
• Adverse hematopoietic organ effects: leukopenia, neutropenia, eosinophilia, thrombocytopenia, hemolytic anemia.
• Adverse nervous system effects: dizziness, headache, vertigo, somnolency, paresthesia, agitation, fatigue, tinnitus, hyperkinesia, anxiety, neurosis, sleep disorders, sweating, insomnia, hypo-esthesia, aggression, fainting, seizures, psychomotor hyperactivity, nervousness, agitation, delir-ium, hallucinations.
• Adverse sense organ effects: visual impairment, conjunctivitis, reversible hearing disorders up to deafness, hearing disorder, taste disorders, loss of taste, perversion of smell, loss of smell.
• Adverse urinary and genital system effects: vaginal candidiasis, dysuria, pain in the kidney, interstitial nephritis, acute renal failure, metrorrhagia, dysfunction of the testicles.
• Allergic reactions: rash, hives, skin itching, angioedema, anaphylactic reaction, Steve-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme.
• Adverse skin effects: dermatitis, dry skin, photosensitization.
• Adverse locomotor system effects: myasthenia gravis, myalgia, back pain, neck pain, ar-thralgia, osteoarthritis.
• Adverse respiratory system effects: dyspnea, epistaxis.
• Infectious diseases: rhinitis, pharyngitis, respiratory diseases, pneumonia, gastroenteritis, candidamycosis of the oral mucosa.
• Other: asthenia, face swelling, fever, peripheral edema.
• Investigations: in the blood plasma: increased count of basophils, monocytes, neutrophils, decreased or increased concentration of bicarbonates, increased activity of alkaline phosphatase, increased chlorine content, increased concentration of glucose, increased platelet count, increased hematocrit, change in the sodium content, increased concentration of urea, creatinine, change in potassium content.
Overdose
Symptoms: severe nausea, temporary loss of hearing, vomiting, diarrhea.
Treatment: stomach lavage, expectant therapy.

Interaction with other medicines

Antacids (Al3 + and Mg2 + -containing), ethanol and food slow down and reduce absorption of azithromycin (for oral dosage forms), so the interval between their doses should be 1 hour before or 2 hours after oral administration these medications and food intake.
Combined administration of warfarin and azithromycin (at usual doses) does not change pro-thrombin time have been detected, however, considering that the interaction of macrolides and warfarin can enhance the anticoagulation effect, careful monitoring of prothrombin time in pa-tients is required.
Azithromycin interacts slightly with cytochrome P450 isoenzymes, it has not been found that azithromycin is involved in pharmacokinetic interactions similar to erythromycin and other mac-rolides, azithromycin is not an inducer and inhibitor of cytochrome P450 isoenzymes.
In comparison with macrolides, no interaction with theophylline, terfenadine, carbamazepine, triazolam, digoxin was reported.
Terfenadine and azithromycin shall be administered concurrently with care, since it has been es-tablished that simultaneous administration of terfenadine and various types of antibiotics causes arrhythmia and elongation of the ventricular complex duration reflecting duration of the ventric-ular systole.
According to this the aforementioned complications shall not be excluded after combined admin-istration of terfenadine and azithromycin. Ergotamine and dihydroergotamine: increased toxic effect (vasospasm, dysesthesia).
Macrolides slow down excretion, increase plasma concentrations and toxicity of cycloserine, in-direct anticoagulating agents, methylprednisolone, felodipine, and drugs that undergo microso-mal oxidation (carbamazepine, terfenadine, cyclosporine, hexobarbital, ergot alkaloids, valproic acid, disopyramide, bromocriptine, phenytoin, oral hypoglycemic drugs), however, no such in-teraction was observed after administration of azalides (including azithromycin).
Lincosamides reduce and tetracycline and chloramphenicol increase the efficacy of azithromycin.
With cetirizine: simultaneous administration of azithromycin with cetirizine (20 mg) during 5 days in healthy volunteers did not cause pharmacokinetic interaction and significant change in the QT interval.
With didanosine: simultaneous administration of azithromycin (1200 mg/day) and didanosine (400 mg/day) in 6 patients with HIV did not change the pharmacokinetic indications of didano-sine compared with the placebo group.
With zidovudine: simultaneous administration of azithromycin (at single dose 1000 mg and re-peated administration of 1200 mg or 600 mg) has little effect on the pharmacokinetics, including kidney excretion, zidovudine or its glucuronide metabolite.
However administration of azithro-mycin increase the concentration of phosphorylated zidovudine, a clinically active metabolite in the peripheral blood mononuclear cells. The clinical significance of this fact is unclear.
With atorvastatin: simultaneous administration of atorvastatin (10 mg per day on a daily basis) and azithromycin (500 mg daily) did not cause changes in the plasma concentrations of atorvas-tatin (based on analysis of inhibition of GMA-CoA reductase). However, individual reports have been received about rhabdomyolysis cases in patients receiving both azithromycin and statins simultaneously.
With cimetidine: according to the results of the study aimed at determining the effect of a single dose of cimetidine, administered 2 hours before administration of azithromycin, on its pharma-cokinetics, no changes were detected.
With efavirenz: simultaneous administration of azithromycin (600 mg/day once) and efavirenz (400 mg/day) daily during 7 days did not cause any significant pharmacokinetic interaction.
With fluconazole: simultaneous administration of azithromycin (1200 mg once) did not change the pharmacokinetics of fluconazole (800 mg once). The total exposure and the half-life of azithromycin did not change after simultaneous administration of fluconazole, but decreased maximum concentration of azithromycin by 18% was observed which was not significant.
With indinavir: simultaneous administration of azithromycin (1200 mg once) did not cause sig-nificant effect on the pharmacokinetics of indinavir (800 mg three times per day during 5 days).
With nelfinavir: simultaneous administration of azithromycin (1200 mg) and nelfinavir (750 mg 3 times per day) increases the equilibrium plasma concentration of azithromycin, significant adverse effects have not been observed and azithromycin dose correction for administration with nelfinavir is not required.
With rifabutin: simultaneous administration of azithromycin and rifabutin simetimes caused neu-tropenia, despite the fact that neutropenia was associated with administration of rifabutin, the relation to the combined administration of azithromycin and rifabutin and neutropenia has not been determined.
With sildenafil: administration in healthy volunteers did not show the effect of azithromycin (500 mg/day during 3 days) in combination on the area under the pharmacokinetic concentration-time (AUC) curve, maximum concentration (Cmax), time to the maximum concentration (Tmax), rate of elimination and half-life of sildenafil or its main circulating metabolite.
With trimethoprim / sulfamethoxazole: simultaneous administration of trimethoprim / sulfa-methoxazole with azithromycin did not significantly affect the maximum concentration, total exposure or renal excretion of trimethoprim or sulfamethoxazole. The concentrations of azithromycin in the serum corresponded to those detected during other studies.
Simultaneous administration of azithromycin and cyclosporine requires dose correction of cyclo-sporine.

Form release

Storage conditions

In a dry, dark place at temperature maximum 25 °С.

Expiration date

2 years