Pliva Hrvatska d.o.o. #Antibacterial_preparations #Preparations_for_the_treatment_of_infections #HEALTH_CARE
Pharmacotherapeutic group
Antibiotic azalide.
Pharmacokinetics
When taken orally, azithromycin is well absorbed and rapidly redistributed from plasma to tissues and organs. After a single oral intake of 500 mg of azithromycin, 37% of the preparation is absorbed and after 2-3 hours the plasma Cmax of the preparation is 0.41 μg / ml. It is known that food intake can reduce the absorption of azithromycin, however, due to the lack of the manufacturer's own data on the effect of food on the pharmacokinetics of azithromycin when taking Sumamed® in the form of a suspension, it should be taken at least 1 hour before or after 2 h after eating.
The preparation is rapidly distributed throughout the body, high concentrations, 50 times higher than the concentration of azithromycin in plasma, are observed in tissues. Depending on the organ / tissue, the concentration of the preparation ranges from 1-9 μg / ml. The volume of distribution averages 31 l / kg.
The therapeutic concentration of azithromycin in the tissues is observed within 5-7 days after taking the last dose. Penetrates into cells, including phagocytes, which migrate to the inflammation focus, contributing to the creation of therapeutic concentrations of the preparation that exceed the MIC for infectious agents. The concentration of azithromycin in infected tissues is higher than in uninfected tissues. It has a long T1 / 2 and is slowly excreted from tissues (on average - 2-4 days).
Excretion of azithromycin with bile is the main route of excretion. On average, up to 50% is excreted in the bile in an unchanged form. The remaining 50% are excreted in the form of 10 metabolites formed in the process of N- and O-demethylation, hydroxylation of desosamine and the aglycone ring and as a result of cleavage of the conjugate cladinose. Metabolites have no antibacterial activity. On average, 6% of the administered dose of the preparation is excreted in the urine.
In elderly patients (over 65 years old), the volume of distribution is slightly higher (30%) compared with patients who are less than 45 years old, which is not clinically significant and does not require a dosage change.
The pharmacokinetics of azithromycin in healthy volunteers after a single intravenous infusion lasting more than 2 hours at a dose of 1000-4000 mg (solution concentration - 1 mg / ml) has a linear relationship and is proportional to the administered dose. T1 / 2 of the preparation is 65-72 hours. The high level of the observed volume of distribution (33.3 l / kg) and plasma clearance (10.2 ml / min / kg) suggests that the prolonged T1 / 2 of the preparation is a consequence of antibiotic accumulation in tissues followed by its slow release.
In healthy volunteers with intravenous infusion of azithromycin at a dose of 500 mg (solution concentration - 1 mg / ml) for 3 hours, the Cmax of the preparation in the blood serum was 1.14 μg / ml. The minimum serum level (0.18 μg / ml) was observed over 24 hours and the area under the concentration-time curve was 8.03 μg / ml / h.
Similar pharmacokinetic values were obtained in patients with community-acquired pneumonia who were administered intravenous (3-hour) infusions for 2 to 5 days. After daily administration of azithromycin at a dose of 500 mg (duration of infusion - 1 hour) for 5 days, an average of 14% of the dose is excreted in the urine during the 24-hour dosing interval.
Pharmacodynamics
Possesses a wide spectrum of antimicrobial action. By binding to the 50S-subunit of the ribosome, it inhibits the biosynthesis of microorganism proteins. In high concentrations, it has a bactericidal effect. Has activity against gram-positive, gram-negative anaerobes, intracellular and other microorganisms.
Has no effect on gram-positive bacteria resistant to erythromycin.
Composition, release form and packaging
Tablets - 1 tab .:
active substance azithromycin dihydrate 131.027 mg, respectively, in terms of azithromycin 125.00 mg;
excipients: calcium hydrogen phosphate anhydrous 29.873 mg, hypromellose 1.50 mg, corn starch 12.00 mg, pregelatinized starch 12.00 mg, microcrystalline cellulose 10.00 mg, sodium lauryl sulfate 0.60 mg, magnesium stearate 3.00 mg;
shell: hypromellose 3.40 mg, indigo carmine dye (E132) 0.10 mg, titanium dioxide (E171) 0.56 mg, polysorbate 80 0.14 mg, talc 2.80 mg.
6 tablets in a PVC / aluminum foil blister.
1 blister with instructions for use in a cardboard box.
Description of the dosage form
Blue round, biconvex tablets with "PLIVA" engraving on one side and "125" on the other side.
Broken view - from white to almost white.
Indications for use
- infections of the upper respiratory tract and ENT organs;
- lower respiratory tract infections: acute bronchitis, exacerbation of chronic bronchitis, pneumonia, incl. caused by atypical pathogens ;;
- infections of the skin and soft tissues;
- urinary tract infections (urethritis, cervicitis).
Contraindications for use
- severe impairment of liver and kidney function;
- lactation period;
- simultaneous reception with ergotamine and dihydroergotamine;
- hypersensitivity to azithromycin and other components of the preparation;
- hypersensitivity to antibiotics of the macrolide group;
- children under 12 years of age and body weight less than 45 kg (for capsules and tablets 500 mg);
- children under 3 years of age (for tablets 125 mg).
With caution, sumamed should be prescribed in case of moderate impairment of liver and kidney function, in patients with impairments or a predisposition to arrhythmias and prolongation of the QT interval.
Pregnancy and lactation
During pregnancy, the use of sumamed is possible only if the potential benefit of therapy to the mother outweighs the possible risk to the fetus.
If it is necessary to use sumamed during lactation, breastfeeding should be discontinued
Side effects
From the hematopoietic system: rarely - thrombocytopenia, neutropenia, eosinophilia.
From the side of the central nervous system and peripheral nervous system: sometimes - dizziness / vertigo, headache, drowsiness, convulsions; rarely - paresthesia, asthenia, insomnia, hyperactivity, aggressiveness, anxiety, nervousness.
From the digestive system: often - nausea, vomiting, diarrhea, abdominal pain and cramps; sometimes - diarrhea, flatulence, indigestion, anorexia; rarely - constipation, discoloration of the tongue, pseudomembranous colitis, cholestatic jaundice, hepatitis, changes in the values of laboratory parameters of liver function; very rarely - liver dysfunction and liver necrosis (possibly fatal).
Allergic reactions: sometimes - itching, skin rashes; rarely - angioedema, urticaria, photosensitivity, anaphylactic reaction, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.
Preparation interactions
Sumamed® (capsules, coated tablets, powder for oral suspension)
Antacids (containing aluminum, magnesium, ethanol) and food intake significantly reduce the absorption of azithromycin (capsules and suspension), so the preparation should be taken at least 1 hour before or 2 hours after taking these preparations and food. It does not bind to the enzymes of the cytochrome P-450 complex and, unlike macrolide antibiotics, to date, no interaction with theophylline, terfenadine, carbamazepine, methylprednisolone, cimetidine, triazolam, digoxin has been observed. Macrolides, when taken simultaneously with cycloserine, indirect anticoagulants, methylprednisolone, felodipine and preparations that undergo microsomal oxidation (cyclosporine, hexobarbital, ergot alkaloids, valproic acid, disopyramide, bromocriptinic preparations, phenytoin, slow down the perceptible preparations, and inhibit the concentration of these preparations) while with the use of azalides, such an interaction has not been observed to date.
If it is necessary to take it together with warfarin, it is recommended to carefully monitor PT (an increase in PT and the incidence of hemorrhages is possible). With the simultaneous administration of macrolides with ergotamine and dihydroergotamine, their toxic effect (vasospasm, dysesthesia) is possible. Lincosamides weaken, and tetracycline and chloramphenicol increase the effectiveness of azithromycin. Pharmaceutically incompatible with heparin.
Sumamed® (lyophilisate for preparation of solution for infusion)
Although there are no data on the interaction of azithromycin and ergot alkaloids, care must be taken because simultaneous administration can lead to an increase in the concentration of alkaloids in the blood and to the development of symptoms of overdose (ergotism), which is noted when alkaloids are taken together with macrolides; Macrolide antibiotics increase the blood concentration of theophylline, terfenadine, warfarin, carbamazepine, phenytoin, digoxin, cyclosporin, ergotamine, triazolam and midazolam, thereby enhancing their effect. Unlike macrolides, azithromycin does not inhibit cytochrome P450, therefore, when it is prescribed with the above preparations, no similar interactions are observed.
Method of administration and dosage
Inside, without chewing, at least 1 hour before or 2 hours after meals, 1 time per day.
Adults and children over 12 years old weighing more than 45 kg
For infections of the upper and lower respiratory tract, ENT organs. Skin and soft tissues: 1 tablet (500 mg) 1 time per day for 3 days (course dose 1.5 g).
With acne vulgar of moderate severity: 1 tablet (500 mg) 1 time per day for 3 days, then 1 tablet (500 mg) 1 time per week for 9 weeks (course dose 6.0 g).
The first weekly tablet should be taken 7 days after taking the first daily tablet (8th day from the start of treatment), the next 8 weekly tablets should be taken at intervals of 7 days.
In Lyme disease (the initial stage of borreliosis) - erythema migrans (erythema migrans): once a day for 5 days: 1st day - 1.0 g (2 tablets of 500 mg), then from the 2nd to the 5th day - 1 tablet (500 mg) (course dose 3.0 g).
For urinary tract infections caused by Chlamydia trachomatis (urethritis, cervicitis): uncomplicated urethritis / cervicitis - 1 g (2 tablets of 500 mg) once.
Fly between the ages of 3 and 12 and weigh 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).
Calculation of the dose of Sumamed® for children weighing less than 45 kg
Body weight 18-30 kg - 2 tablets (250 mg azithromycin).
Body weight 31-44 kg - 3 tablets (375 mg azithromycin).
Body weight not less than 45 kg - apply the doses recommended for adults.
In children under 3 years of age, it is recommended to use Sumamed® preparations, powder for preparation of oral suspension 100 mg / 5 ml and Sumamed® forte, powder for preparation of oral suspension 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.
In Lyme disease (the initial stage of borreliosis) - erythema migrans (erythema migrans): 20 mg / kg once a day on the 1st day, then at the rate of 10 mg / kg I 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 Sumamed® preparations, powder for preparation of a suspension for oral administration of 100 mg / 5 ml and Sumamed® forte, powder for preparation of a suspension for oral administration of 200 mg / 5 ml.
In case of impaired renal function: when used in patients with impaired night function of mild and moderate severity (CC more than 40 ml / min), dose adjustment is not required.
In case of impaired liver function: when used in patients with impaired liver function of mild and moderate severity, dose adjustment is not required.
Elderly patients: No dose adjustment required. Since the elderly may already have current proarrhythmic conditions, caution should be exercised when using Sumamed® due to the high risk of developing cardiac arrhythmias, including pirouette-type arrhythmias.
Overdose
Symptoms: nausea, temporary hearing loss, vomiting, diarrhea.
Treatment: gastric lavage, symptomatic therapy.
Precautions and special instructions
When using Sumamed® in patients with diabetes mellitus, as well as with a low-calorie diet, it is necessary to take into account that the suspension contains sucrose (0.32 XE / 5 ml).
In case of missing one dose of Sumamed®, the missed dose should be taken as early as possible, and subsequent doses should be taken at intervals of 24 hours. Sumamed® should be taken at least one hour before or two hours after taking antacids.
Sumamed® should be taken with caution in patients with mild to moderate hepatic impairment 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 of mild and moderate severity (CC more than 40 ml / min), therapy with Sumamed® should be carried out with caution under the control of the state of renal function.
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 Sumamed®, as well as 2 months after the end of therapy, clostridial pseudomembranous colitis should be excluded.
When treated with macrolides, including azithromycin, lengthening of cardiac repolarization and the QT interval was observed, increasing the risk of developing cardiac arrhythmias, including arrhythmias of the tina "pirouette", which can lead to cardiac arrest.
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 class IA antiarrhythmics (quinidine, procainamide), III (dofetilide, amiodarone and sotalol), cisapride, terfenadine, antipsychotics (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin, electrolysis vodofloxacin) balance, especially in the case of hypokalemia or hypomagnesemia, clinically significant bradycardia, cardiac arrhythmias or severe heart failure.
The use of Sumamed® can provoke the development of myasthenic syndrome or exacerbate myasthenia gravis.
Influence on the ability to drive vehicles and use 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
At room temperature
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