Pliva Hrvatska d.o.o. #Antibacterial_preparations #Preparations_for_the_treatment_of_infections #HEALTH_CARE
Indications for use
Infectious and inflammatory diseases caused by microorganisms sensitive to the preparation: infections of the upper respiratory tract and ENT organs (pharyngitis / tonsillitis, sinusitis, otitis media); lower respiratory tract infections: acute bronchitis, exacerbation of chronic bronchitis, pneumonia, incl. caused by atypical pathogens; infections of the skin and soft tissues (erysipelas, impetigo, secondarily infected dermatoses); the initial stage of Lyme disease (borreliosis) - erythema migrans (erithema migrans); urinary tract infections caused by Chlamydia trachomatis (urethritis, cervicitis).
Compound
Active ingredient: Azithromycin dihydrate (in terms of azithromycin) - 1048.218 mg (1000.0 mg). Excipients: sodium saccharinate dihydrate - 78,000 mg, microcrystalline cellulose (type 101) - 39,782 mg, microcrystalline cellulose (type 102) - 657,600 mg, crospovidone type A -1 65,200 mg, povidone K-30 - 44,000 mg, sodium lauryl sulfate - 6,400 mg, colloidal silicon dioxide 8,800 mg, magnesium stearate 22,000 mg, banana flavor 6,500 mg, orange flavor 52,000 mg, aspartame 78,000 mg.
Method of administration and dosage
Inside, 1 hour before or 2 hours after a meal. The dispersible tablet can be swallowed whole and washed down with water, or the dispersible tablet can be dissolved in at least 50 ml of water. Stir the resulting suspension thoroughly before taking. Adults and children over 12 years old with a body weight of more than 45 kg: For infections of the upper and lower respiratory tract, ENT organs, skin and soft tissues, 500 mg once a day for 3 days (course dose 1.5 g) ... In Lyme disease (the initial stage of borreliosis) - erythema migrans (erithema migrans) 1 time per day for 5 days: 1st day - 1000 mg, then from the 2nd to the 5th day - 500 mg each (course dose 3 , 0 d). In case of urinary tract infections caused by Clamydia trachomatis (urethritis, cervicitis): uncomplicated urethritis / cervicitis - 1000 mg once. Children aged 3 to 12 years with a body weight of less than 45 kg. For infections of the upper and lower respiratory tract, ENT organs, skin and soft tissues: at the rate of 10 mg / kg body weight 1 time per day for 3 days (course dose 30 mg / kg). In children under 3 years of age, it is recommended to use the preparation Sumamed, powder for preparation of a suspension for oral administration of 100 mg / 5 ml or Sumamed forte, powder for preparation of a suspension for oral administration of 200 mg / 5 ml. For pharyngitis / tonsillitis caused by Streptococcus pyogenes, Sumamed is used at a dose of 20 mg / kg / day for 3 days (course dose of 60 mg / kg). The maximum daily dose is 500 mg / day. In Lyme disease (the initial stage of borreliosis) - erythema migrans (erithema migrans), 20 mg / kg once a day on the 1st day, then at the rate of 10 mg / kg once a day from the 2nd to the 5th day ... For ease of use in children of a course dose of 60 mg / kg, it is recommended to take the preparation Sumamed, powder for preparation of a suspension for oral administration of 100 mg / 5 ml or Sumamed forte, powder for preparation of a suspension for oral administration of 200 mg / 5 ml. In case of impaired renal function: in patients with a GFR of 10-80 ml / min, dose adjustment is not required. In case of impaired liver function: in patients with impaired liver function of mild and moderate severity, dose adjustment is not required. Elderly patients: No dose adjustment required. Caution should be exercised in elderly patients with persistent proarrhythmogenic factors due to the high risk of arrhythmias, including pirouette-type arrhythmias.
Contraindications
Hypersensitivity to azithromycin, erythromycin, other macrolides or ketolides, or other components of the preparation; severe liver dysfunction; phenylketonuria; children under 3 years old; simultaneous reception with ergotamine and dihydroergotamine. With care: myasthenia gravis; dysfunction of the liver of mild to moderate severity; end-stage renal failure with GFR (glomerular filtration rate) less than 10 ml / min; in patients with the presence of proarrhythmogenic factors (especially in elderly patients): with congenital or acquired prolongation of the QT interval, in patients receiving therapy with antiarrhythmic preparations of classes IA (quinidine, procainamide), III (dofetilide, amiodarone and sotalol), cisapride, terfenadine. antipsychotic preparations (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin and levofloxacin), with disturbances in the water and electrolyte balance, especially in the case of hypokalemia or hypomagnesemia, with clinically significant bradycardia, arrhythmia of the heart or severe heart failure; simultaneous use of digoxin, warfarin, cyclosporin. Application during pregnancy and during breastfeeding: during pregnancy and during breastfeeding, use only if the intended benefit to the mother outweighs the potential risk to the fetus and child. If it is necessary to use the preparation during breastfeeding, it is recommended to suspend breastfeeding.
Pharmachologic effect
Pharmacodynamics. Azithromycin is a broad-spectrum bacteriostatic antibiotic from the group of macrolides-azalides. Possesses a wide spectrum of antimicrobial action. The mechanism of action of azithromycin is associated with the suppression of microbial cell protein synthesis. By binding to the 50S-subunit of the ribosome, it inhibits peptide translocase at the stage of translation and suppresses protein synthesis, slowing down the growth and reproduction of bacteria. In high concentrations, it has a bactericidal effect. Has activity against a number of gram-positive, gram-negative, anaerobes, intracellular and other microorganisms. Microorganisms may initially be resistant to antibiotic action or may acquire resistance to it. In most cases, sensitive microorganisms. Gram-positive aerobes: Staphylococcus aureus metecillin-sensitive, Streptococcus pneumoniae penicillin-sensitive, Streptococcus pyogenes. Gram-negative aerobes: Haemophilus influenzae, Haemophilus parainfluenzae, Legionella pneumophila, Moraxella catarrhalis, Pasteurella multocida, Neisseria gonorrhoeae. Anaerobes: Clostridum perfringens, Fusobacterium spp., Prevotella spp., Porphyriomonas spp. Other microorganisms: Chlamydia trachomatis, Chlamydia pneumoniae, Chlamydia psittaci, Mycoplasma pneumoniae, Mycoplasma hominis, Mycoplasma genitalium, Borella burgdorferi. Microorganisms capable of developing resistance to azithromycin. Gram-positive aerobes: Streptococcus pneumoniae is penicillin-sensitive. Initially resistant microorganisms. Gram-positive aerobes: Enterococcus faecalis, Staphilococci (methicillin-resistant staphylococci exhibit a very high degree of resistance to macrolides). Gram-positive bacteria resistant to erythromycin. Anaerobes: Bacteroides fragilis. Pharmacokinetics: After oral administration, azithromycin is well absorbed and rapidly distributed in the body. After a single dose of 500 mg, bioavailability is 37% ("first pass" effect), the maximum concentration (0.4 mg / l) in the blood is created after 2-3 hours, the apparent volume of distribution is 31.1 l / kg, protein binding inversely proportional to the concentration in the blood and is 7-50%. Penetrates through cell membranes (effective for infections caused by intracellular pathogens). It is transported by phagocytes to the site of infection, where it is released in the presence of bacteria. Easily passes histohematogenous barriers and enters the tissues. Concentration in tissues and cells is 10-50 times higher than in plasma, and in the focus of infection - 24-34% higher than in healthy tissues. Azithromycin has a very long half-life of 35-50 hours. The half-life from tissues is much longer. The therapeutic concentration of azithromycin lasts up to 5-7 days after taking the last dose. Azithromycin is excreted mainly unchanged - 50% by the intestines, 6% by the kidneys. In the liver, it is demethylated, losing activity.
Side effect
The frequency of side effects is classified in accordance with the WHO recommendations: very often - at least 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0.1%, but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rarely - less than 0.01%; unknown frequency - cannot be estimated from the available data. Infectious diseases: infrequently - 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: infrequently - leukopenia, neutropenia, eosinophilia; very rarely - thrombocytopenia, hemolytic anemia. From the side of metabolism and nutrition: infrequently - anorexia. Allergic reactions: infrequently - angioedema, hypersensitivity reaction; unknown frequency - anaphylactic reaction. From the side of the nervous system: often - headache; infrequently - dizziness, impaired taste, paresthesia, drowsiness, insomnia, nervousness; rarely - agitation; unknown frequency - hypesthesia, anxiety, aggression, fainting, convulsions, psychomotor hyperactivity, loss of smell, perversion of smell, loss of taste, myasthenia gravis, delirium, hallucinations. From the side of the organ of vision: infrequently - visual impairment. From the side of the organ of hearing and labyrinth disorders: infrequently - hearing disorder, vertigo; unknown frequency - hearing impairment, including deafness and / or tinnitus. From the side of the cardiovascular system: infrequently - a feeling of palpitations, "hot flushes" of blood to the face; unknown frequency - a decrease in blood pressure, an increase in the QT interval on the electrocardiogram, arrhythmia of the "pirouette" type, ventricular tachycardia. From the respiratory system: infrequently - shortness of breath, epistaxis. From the gastrointestinal tract: very often - diarrhea; often - nausea, vomiting, abdominal pain; infrequently - flatulence, dyspepsia, constipation, gastritis, dysphagia, bloating, dryness of the oral mucosa, belching, ulcers of the oral mucosa, increased secretion of the salivary glands; very rarely - discoloration of the tongue, pancreatitis. From the liver and biliary tract: infrequently - hepatitis; rarely - liver dysfunction, cholestatic jaundice; unknown frequency - liver failure (in rare cases - fatal, mainly against the background of severe liver dysfunction); liver necrosis, fulminant hepatitis. Skin and subcutaneous tissue disorders: infrequently - skin rash, itching, urticaria, dermatitis, dry skin, sweating; rarely - photosensitivity reaction; acute generalized exanthematous pustulosis (OGEP); unknown frequency - Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, preparation rash with eosinophilia and systemic manifestations (DRESS syndrome). From the side of the musculoskeletal system: infrequently - osteoarthritis, myalgia, back pain, neck pain; unknown frequency - arthralgia. From the side of the kidneys and urinary tract: infrequently - dysuria, pain in the kidney area; unknown frequency - interstitial nephritis, acute renal failure. On the part of the genitals and mammary gland: infrequently - metrorrhagia, dysfunction of the testicles. Others: infrequently - edema, asthenia, malaise, fatigue, facial edema, chest pain, fever, peripheral edema. Laboratory data: often - a decrease in the number of lymphocytes, an increase in the number of eosinophils, an increase in the number of basophils, an increase in the number of monocytes, an increase in the number of neutrophils, a decrease in the concentration of bicarbonates in the blood plasma; infrequently - an increase in the activity of aspartate aminotransferase, alanine aminotransferase, an increase in the concentration of bilirubin in the blood plasma, an increase in the concentration of urea in the blood plasma, an increase in the concentration of creatinine in the blood plasma, a change in the content of potassium in the blood plasma, an increase in the activity of alkaline phosphatase in the blood plasma, an increase in the content of chlorides in the blood plasma , an increase in the concentration of glucose in the blood, an increase in the number of platelets, a decrease in hematocrit, an increase in the concentration of bicarbonates in the blood plasma, a change in the sodium content in the blood plasma.
Overdose
Symptoms: nausea, temporary hearing loss, vomiting, diarrhea. Treatment: symptomatic.
Interaction
Antacids do not affect the bioavailability of azithromycin, but reduce the maximum blood concentration by 30%, so the preparation should be taken at least one hour before or two hours after taking these preparations and food. Cetirizine. Simultaneous use of azithromycin with cetirizine (20 mg) for 5 days in healthy volunteers did not lead to pharmacokinetic interaction and a significant change in the QT interval. Didanosine (dideoxyinosine). The simultaneous use of azithromycin (1200 mg / day) and didanosine (400 mg / day) in 6 HIV-infected patients did not reveal changes in the pharmacokinetic indications of didanosine compared with the placebo group. The simultaneous use of macrolide antibiotics, including azithromycin, with P-glycoprotein substrates, such as digoxin and colchicine, leads to an increase in the concentration of P-glycoprotein substrate in the blood serum. Thus, with the simultaneous use of azithromycin and digoxin, it is necessary to take into account the possibility of increasing the concentration of digoxin in the blood serum. Zidovudine. The simultaneous use of azithromycin (a single dose of 1000 mg and repeated administration of 1200 mg or 600 mg) has little effect on pharmacokinetics, including the excretion of zidovudine or its glucuronide metabolite by the kidneys. However, the use of azithromycin caused an increase in the concentration of phosphorylated zidovudine, a clinically active metabolite, in peripheral blood mononuclear cells. The clinical significance of this finding is unclear. Azithromycin weakly interacts with isoenzymes of the cytochrome P450 system. It was not revealed that azithromycin is involved in pharmacokinetic interactions similar to erythromycin and other macrolides. Azithromycin is not an inhibitor and inducer of cytochrome P450 isoenzymes. Ergot alkaloids. Given the theoretical possibility of ergotism, the simultaneous use of azithromycin with derivatives of ergot alkaloids is not recommended. Pharmacokinetic studies were carried out for the simultaneous use of azithromycin and preparations, the metabolism of which occurs with the participation of isoenzymes of the cytochrome P450 system. Atorvastatin. The simultaneous use of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not cause changes in plasma concentrations of atorvastatin (based on the analysis of inhibition of MMC-CoA reductase). However, in the post-registration period, there were separate reports of cases of rhabdomyolysis in patients receiving both azithromycin and statins. Carbamazepine. In pharmacokinetic studies with the participation of healthy volunteers, no significant effect on the concentration of carbamazepine and its active metabolite in the blood plasma was found in patients receiving simultaneously azithromycin. 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 detected, provided that cimetidine was used 2 hours before azithromycin. Indirect anticoagulants (coumarin derivatives). In pharmacokinetic studies, azithromycin did not affect the anticoagulant effect of a single 15 mg dose of warfarin taken by healthy volunteers. It was reported about the potentiation of the anticoagulant effect after the simultaneous use of azithromycin and indirect anticoagulants (coumarin derivatives). Despite the fact that a causal relationship has not been established, one should take into account the need for frequent monitoring of prothrombin time when using azithromycin in patients who receive indirect oral anticoagulants (coumarin derivatives). Cyclosporine.In a pharmacokinetic study involving healthy volunteers who took azithromycin (500 mg / day once) and then cyclosporine (10 mg / kg / day once) for 3 days, a significant increase in the maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC) of cyclosporin. Caution should be exercised with the simultaneous use of these preparations. If the simultaneous use of these preparations is necessary, it is necessary to monitor the concentration of cyclosporine in the blood plasma and adjust the dose accordingly. Efavirenz. The 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. Fluconazole. The 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, a decrease in Cmax of azithromycin (by 18%) was observed, which had no clinical significance. Indinavir. The simultaneous use of azithromycin (1200 mg once) did not cause a statistically significant effect on the pharmacokinetics of indinavir (800 mg three times a day for 5 days). Methylprednisolone. Azithromycin has no significant effect on the pharmacokinetics of methylprednisolone. Nelfinavir. The 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 serum. No clinically significant side effects were observed, and no dose adjustment of azithromycin is required when used simultaneously with nelfinavir. Rifabutin. The simultaneous use of azithromycin and rifabutin does not affect the concentration of each preparation in the blood serum. 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. Sildenafil When used in healthy volunteers, there was no evidence of the effect of azithromycin (500 mg / day daily for 3 days) on AUC and Cmax of sildenafil or its main circulating metabolite. Terfenadine. In pharmacokinetic studies, there was no evidence of an interaction between azithromycin and terfenadine. Isolated cases were reported where the possibility of such an interaction could not be completely ruled out, however, there was no concrete evidence that such an interaction took place. It was found that the simultaneous use of terfenadine and macrolides can cause arrhythmias and prolongation of the QT interval. Theophylline. There was no interaction between azithromycin and theophylline. Triazolam / midazolam. There were no significant changes in pharmacokinetic parameters with the simultaneous use of azithromycin with triazolam or midazolam in therapeutic doses. Trimethoprim / sulfamethoxazole. The simultaneous use of trimethoprim / sulfamethoxazole with azithromycin did not reveal a significant effect on Cmax, total exposure or renal excretion of trimethoprim or sulfamethoxazole. Serum azithromycin concentrations were consistent with those found in other studies.
special instructions
In case of missing one dose of Sumamed, the missed dose should be taken as early as possible, and the subsequent ones should be taken at intervals of 24 hours. Sumamed should be taken at least one hour before or two hours after taking antacids. The preparation Sumamed should be used with caution in patients with mild and moderate hepatic dysfunction due to the possibility of developing fulminant hepatitis and severe liver failure. In the presence of symptoms of liver dysfunction, such as: rapidly increasing asthenia, jaundice, dark urine, a tendency to bleeding, hepatic encephalopathy, therapy with Sumamed should be discontinued and a study of the functional state of the liver should be carried out. In case of impaired renal function: in patients with a GFR of 10-80 ml / min, dose adjustment is not required. As with the use of other antibacterial preparations, during therapy with Sumamed, patients should be regularly examined for the presence of refractory microorganisms and signs of the development of superinfections, including fungal infections. The preparation Sumamed should not be used for longer courses than indicated in the instructions, since the pharmacokinetic properties of azithromycin make it possible to recommend a short and simple dosing regimen. There is no data on a possible interaction between azithromycin and ergotamine and dihydroergotamine derivatives, but due to the development of ergotism with the simultaneous use of macrolides with ergotamine and dihydroergotamine derivatives, this combination is not recommended. With prolonged use of Sumamed, the development of pseudomembranous colitis caused by Clostridium difficile is possible, both in the form of mild diarrhea and severe colitis. With the development of antibiotic-associated diarrhea while taking the preparation Sumamed, as well as 2 months after the end of therapy, clostridial pseudomembranous colitis should be excluded. Preparations that inhibit intestinal motility are contraindicated. In the treatment with macrolides, including azithromycin, lengthening of cardiac repolarization and QT interval was observed, increasing the risk of developing cardiac arrhythmias, including arrhythmias of the "pirouette" type. Caution should be exercised when using Sumamed: in patients with the presence of proarrhythmogenic factors (especially in elderly patients), including those with congenital or acquired lengthening of the QT interval; in patients taking antiarrhythmic preparations of classes IA (quinidine, procainamide), III (dofetilide, amiodarone and sotalol), cisapride, terfenadine, antipsychotics (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin and levofloxacin); in patients with impaired water and electrolyte balance, especially in the case of hypokalemia or hypomagnesemia; in patients with clinically significant bradycardia, cardiac arrhythmias, or severe heart failure. The use of the preparation Sumamed can provoke the development of myasthenic syndrome or exacerbate myasthenia gravis. As in the case of the use of erythromycin and other macrolides, there have been isolated cases of serious allergic reactions, including angioedema and anaphylaxis (rarely fatal), dermatological reactions, including acute generalized exanthematous pustulosis (OGEP), Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, preparation rash with eosinophilia and systemic manifestations (DRESS syndrome). Some of the reactions were recurrent and required longer observation and treatment. If an allergic reaction develops, the preparation should be discontinued and appropriate treatment initiated. It should be borne in mind that after the withdrawal of symptomatic therapy, the symptoms of an allergic reaction may recur. Influence on the ability to drive vehicles, mechanisms: with the development of undesirable effects on the part of the nervous system and the organ of vision, care should be taken when performing actions that require increased concentration of attention and speed of psychomotor reactions.
Storage conditions
Keep out of the reach of children, at a temperature not exceeding 25 ° C.
$37.99 BUY ONLINE
MORE
No comments:
Post a Comment