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

In 1 tablet 125 mg, 250 mg, 500 mg, 1000 mg contains: active substance azithromycin dihydrate (in terms of azithromycin) 131.027 mg (125.0 mg) / 262.055 mg (250.0 mg) / 524.109 mg (500.0 mg) / 1048.218 mg (1000.0 mg); Excipients: sodium saccharinate dihydrate 9,750 mg / 19,500 mg / 39,000 mg / 78,000 mg, microcrystalline cellulose (type 101) 4.973 mg / 9.945 mg / 19.891 mg / 39.782 mg, microcrystalline cellulose (type 102) 82,200 mg / 164,400 mg / 328,800 mg / 657,600 mg Crospovidone type A 20,650 mg / 41,300 mg / 82,600 mg / 165,200 mg, povidone K-30 5,500 mg / 11,000 mg / 22,000 mg / 44,000 mg, sodium lauryl sulfate 0,800 mg / 1,600 mg / 3,200 mg / 6,400 mg, silicon dioxide colloid 1,100 mg / 2,200 mg / 4,400 mg / 8,800 mg, magnesium stearate 2,750 mg / 5,500 mg / 11,000 mg / 22,000 mg, a banana flavor of 6,500 mg / - / - / -, an orange flavoring / 13,000 mg / 26,000 mg / 52,000 mg, aspartame 9,750 mg / 19,500 mg / 39,000 mg / 78,000 mg.

Description:

Dosage of 125 mg. Round flat tablets white or almost white with beveled edges and with the inscription "TEVA 125" on one side.

Dosage of 250 mg. Round flat tablets white or almost white with beveled edges, with a risk on one side and with an embossed inscription "TEVA 250" on the other side.

Dosage of 500 mg. Round flat tablets of white or almost white color with bevelled edges, with a risk on one side and with an embossed inscription "TEVA 500" on the other side.

Dosage of 1000 mg. Round flat tablets white or almost white with bevelled edges, with two perpendicular risks on one side and with an embossed "TEVA 1000" on the other side.

Pharmacotherapeutic group:Antibiotic - azalide

ATX: & nbsp

J.01.F.A.10 Azithromycin

Pharmacodynamics:

Azithromycin is a bacteriostatic broad-spectrum antibiotic from the group of macrolides-azalides. It has a wide spectrum of antimicrobial action. The mechanism of action of azithromycin is associated with the suppression of protein synthesis of a microbial cell. Linking to the ribosome 50S-subunits, inhibits peptidranslokase at the translation stage and suppresses protein synthesis, slowing the growth and multiplication of bacteria. In high concentrations has a bactericidal effect.

It has activity against a number of gram-positive, gram-negative, anaerobes, intracellular and other microorganisms.

Microorganisms may initially be resistant to the action of the antibiotic or may acquire resistance to it.

The sensitivity scale of microorganisms to azithromycin

(Minimum inhibitory concentration (MIC), mg / l):

Microorganisms	MIC, mg / l
Microorganisms	Sensitive	Sustainable
Staphylococcus	≤ 1	> 2
Streptococcus A, B, C, G	≤ 0,25	> 0,5
Streptococcus pneumonia	≤ 0,25	> 0,5
Haemophilus influenzae	≤ 0,12	> 4
Moraxella catarrhalis	≤ 0,5	> 0,5
Neisseria gonorrhoeae	≤ 0,25	> 0,5

In most cases, sensitive 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 perfringens

Fusobacterium spp.

Prevotella spp.

Porphyriomonas spp.

4. Other microorganisms

Chlamydia trachomatis

Chlamydia pneumoniae

Chlamydia psittaci

Mycoplasma pneumoniae

Mycoplasma hominis

Mycoplasma genitalium

Borrelia burgdorferi

Microorganisms capable of developing resistance to azithromycin

Gram-positive aerobes

Streptococcus pneumoniae penicillin-resistant

Initially, resistant microorganisms

Gram-positive aerobes

Enterococcus faecalis

Staphylococci (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 well absorbed and quickly distributed in the body. After a single dose of 500 mg bioavailability - 37% (the effect of "first pass"), 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 the histohematological 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% more than in healthy tissues.

In azithromycin, a very long half-life is 35-50 hours. The half-life of tissues is much longer. The therapeutic concentration of azithromycin is maintained up to 5-7 days after the last dose. Azithromycin is output, basically, in the unchanged form - 50% of the intestine, 6% of the kidneys. In the liver, demethylated, losing activity.

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);

· infections of the lower respiratory tract: 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) - migrating erythema (erythema migrans);

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

Contraindications:

Hypersensitivity to azithromycin, erythromycin, other macrolides or ketolides,or other components of the drug; impaired hepatic function; phenylketonuria; children under 3 years; simultaneous reception with ergotamine and dihydroergotamine.

Carefully:

Myasthenia gravis; impaired hepatic and mild liver function gravity; terminal renal failure with GFR (glomerular filtration rate) less than 10 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), fluoroquinolones (moxifloxacin and levofloxacin), with disturbances of the water-electrolyte balance, especially in the case hypokalemia or hypomagnesemia, c clinically significant bradycardia, cardiac arrhythmia or severe heart failure; simultaneous use of digoxin, warfarin, cyclosporine.

Pregnancy and lactation:

In pregnancy and during breastfeeding apply only if the intended benefit to the mother exceeds the potential risk to the fetus and the baby.If it is necessary to use the drug during breastfeeding, it is recommended to suspend breastfeeding.

WHO recommends azithromycin as a drug of choice in the treatment of chlamydial infection in pregnant women.

Dosing and Administration:

Inside, 1 hour before or 2 hours after eating.

Dispersible tablet can be swallowed whole and washed with water, it is also possible to dissolve the dispersible tablet in at least 50 ml of water. Before receiving, the resulting suspension should be thoroughly mixed.

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

With infections of the upper and lower respiratory tract, ENT organs, skin and soft tissues:

500 mg once a day for 3 days (exchange dose of 1.5 g).

With Lyme disease (the initial stage of borreliosis) - migratory erythema (erythema migrans): 1 time per day for 5 days: 1st day - 1000 mg, then from the 2nd to the 5th day - 500 mg (course dose 3.0 g).

In cases of urinary tract infections caused by Chlamydia trachomatis (urethritis, cervicitis): uncomplicated urethritis / cervicitis - 1000 mg once.

Children aged 3 to 12 years with body weight less than 45 kg

With 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). For the convenience of dosing, it is recommended to use the table number 1.

Table №1. Dose calculation Sumamed^® for children weighing less than 45 kg

Body mass	The dose of azithromycin in mg
18-30 kg	250 mg of azithromycin
31-44 kg	375 mg of azithromycin
not less than 45 kg	apply doses recommended for adults

Children younger than 3 years of age are recommended to use the drug Sumamed^®, a powder for the preparation of a suspension for ingestion of 100 mg / 5 ml or Sumamed^®forte, powder for the preparation of a suspension for oral administration of 200 mg / 5 ml.

With pharyngitis / tonsillitis caused by Streptococcus pyogenes, drug Sumamed^® apply at a dose of 20 mg / kg / day for 3 days (exchange dose of 60 mg / kg). The maximum daily dose is 500 mg / day.

With Lyme disease (the initial stage of borreliosis) - migratory erythema (erythema migrans): 20 mg / kg once a day on the 1st day, then at the rate of 10 mg / kg 1 time per day from 2 to 5 days.

For the convenience of use in children, the dose rate of 60 mg / kg it is recommended to take the drug Sumamed^®, a powder for the preparation of a suspension for ingestion of 100 mg / 5 ml or Sumamed^®forte, powder for the preparation of a suspension for oral administration of 200 mg / 5 ml.

When violation of kidney function: in patients with GFR 10-80 ml / min dose adjustment is not required.

When a violation of liver function: in patients with impaired liver function of mild and moderate severity, dose adjustment is not required.

Elderly patients: correction of the dose is not required. Caution should be exercised in elderly patients with persistent pro-arrhythmic factors due to a high risk of arrhythmias, including pirouette-type arrhythmias.

Side effects:

The incidence of adverse events is classified according to WHO recommendations: very often - not less than 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%; The unknown frequency can not 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; an unknown frequency is pseudomembranous colitis.

On the part of the blood and lymphatic system: infrequently - leukopenia, neutropenia, eosinophilia; very rarely - thrombocytopenia, hemolytic anemia.

From the side of metabolism and nutrition: infrequently - anorexia.

Allergic reactions: infrequently - angioedema, hypersensitivity reaction; an unknown frequency is an anaphylactic reaction.

From the nervous system: often - headache; infrequently - dizziness, dyspnoea, paresthesia, drowsiness, insomnia, nervousness; rarely - agitation; unknown frequency - hypoesthesia, anxiety, aggression, fainting, convulsions, psychomotor hyperactivity, loss of smell, perversion of smell, loss of taste sensations, myasthenia gravis, delirium, hallucinations.

From the side of the organ of vision: infrequently - impaired vision.

From the side of the hearing organ and labyrinthine 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, "tides" of blood to the face; unknown frequency - lowering blood pressure, increasing the interval QT on the electrocardiogram, arrhythmia of the type "pirouette", ventricular tachycardia.

From the respiratory system: infrequently - shortness of breath, nosebleed.

From the gastrointestinal tract: very often - diarrhea; often - nausea, vomiting, abdominal pain; infrequent - meteorism, dyspepsia, constipation, gastritis, dysphagia, bloating, dryness of the oral mucosa, belching, ulcers of the oral mucosa, increased secretion of the salivary glands; very rarely - a discoloration of the tongue, pancreatitis.

From the liver and biliary tract: infrequently - hepatitis; rarely - a violation of the liver, cholestatic jaundice; unknown frequency - hepatic insufficiency (in rare cases - with a fatal outcome, mainly on the background of a severe liver function disorder); liver necrosis, fulminant hepatitis.

From the skin and subcutaneous tissues: infrequently - dermal rash, itching, hives, dermatitis, dry skin, sweating; rarely - the reaction of photosensitization; unknown frequency - Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, drug rash with eosinophilia and systemic manifestations (DRESS-syndrome).

From the side of the musculoskeletal system: infrequently - osteoarthritis, myalgia, back pain, pain in the neck; unknown frequency - arthralgia.

From the side of the kidneys and urinary tract: infrequently - dysuria, pain in the kidney; unknown frequency - interstitial nephritis, acute renal failure.

From the genitals and the breast: infrequently - metrorrhagia, dysfunction of testicles.

Other: infrequently - edema, asthenia, malaise, fatigue, face swelling, 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, increased activity of aspartate aminotransferase, alanine aminotransferase, increased bilirubin concentration in the blood plasma, increased urea concentration in the blood plasma, increased plasma creatinine concentration, a change in the potassium content in the blood plasma, increased activity of alkaline phosphatase in the blood plasma, an increase in the chloride content in the blood plasma , increased blood glucose, increased platelet count, decreased hematocrit, increased bicarbonate concentration in blood plasma,change in the content of sodium in the blood plasma.

Overdose:

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

Treatment: symptomatic.

Interaction:

Antacid preparations

Antacid preparations do not affect the bioavailability of azithromycin, but reduce the maximum concentration in the blood by 30%, so the drug should be take at least one hour before or two hours after taking these drugs and meals.

Cetirizine

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.

Didanosine (dideoxyinosine)

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

Digoxin (substrates of P-glycoprotein)

Simultaneous use of macrolide antibiotics, including azithromycin, with P-glycoprotein substrates, such as digoxin, leads to an increase in the concentration of substrate P-glycoprotein in the blood serum.Thus, with 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 the pharmacokinetics, including the excretion of zidovudine or its glucuronide metabolite by the kidneys. However, the use of azithromycin caused an increase in the concentration phosphorylated zidovudine, a clinically active metabolite in peripheral blood mononuclear cells. The clinical significance of this fact is unclear.

Azithromycin weakly interacts with isoenzymes of the cytochrome P450 system. It was not revealed that azithromycin participates in pharmacokinetic interactions similar to erythromycin and other macrolides. Azithromycin not is an inhibitor and inducer of cytochrome P450 isoenzymes.

Alcoloids ergot

Given the theoretical possibility of the emergence of ergotism, simultaneous the use of azithromycin with derivatives of ergot alkaloids is not recommended.

The pharmacokinetic studies of the simultaneous use of azithromycin anddrugs, the metabolism of which occurs with the participation of isoenzymes of the cytochrome P450 system.

Atorvastatin

Simultaneous use of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not cause a change in the concentrations of atorvastatin in blood plasma (based on the inhibition of GMA-CoA reductase). However, in the post-marketing period, separate reports were received on cases of rhabdomyolysis in patients receiving concomitantly azithromycin and statins.

Carbamazepine

In pharmacokinetic studies involving healthy volunteers, there was no significant effect on the concentration of carbamazepine and its active metabolite in blood plasma in patients receiving concomitantly 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 have been observed, provided cimetidine is administered 2 hours before azithromycin.

Anticoagulants of indirect action (coumarin derivatives)

In pharmacokinetic studies azithromycin did not affect the anticoagulant effect of a single dose of 15 mg of warfarin taken by healthy volunteers.It was reported about the potentiation of anticoagulant effect after simultaneous use of azithromycin and anticoagulants indirect action (coumarin derivatives). Although a causal relationship has not been established, consideration should be given to the need for frequent monitoring of prothrombin time with the use of azithromycin in patients who receive oral anticoagulants indirect action (coumarin derivatives).

Cyclosporin

In a pharmacokinetic study involving healthy volunteers who within 3 days were ingested azithromycin (500 mg / day once), and then cyclosporine (10 mg / kg / day once), there was a significant increase in the maximum plasma concentration (C_max) and the area under the curve "concentration-time" (AUC0-5) cyclosporine. Care should be taken when using these drugs at the same time. If it is necessary to simultaneously use these drugs, it is necessary to monitor the concentration of cyclosporine in the blood plasma and adjust the dose accordingly.

Efavirenz

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

Fluconazole

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, but there was a decrease C_max azithromycin (by 18%), which had no clinical significance.

Indinavir

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).

Methylprednisolone

Azithromycin does not significantly affect the pharmacokinetics of methylprednisolone.

Nelfinavir

Simultaneous use of azithromycin (1200 mg) and nelfinavir (750 mg 3 times a day) causes an increase in the equilibrium concentrations of azithromycin in blood serum. Clinically significant side effects were not observed and dosage adjustment of azithromycin in its simultaneous application from nelfinavir is not it takes.

Rifabutin
Simultaneous use of azithromycin and rifabutin is not affects concentration of each drugs in blood serum. With the simultaneous use of azithromycin and rifabutin was sometimes observed neutropenia. Despite the fact that neutropenia was associated with use of rifabutin, a causal relationship between the use of a combination of azithromycin and rifabutin and neutropenia is not installed. Sildenafil

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

Terfenadine

In pharmacokinetic studies, nointeraction between azithromycin and terfenadine. It was reported about isolated cases, when the possibility of such interaction could not be completely ruled out, but there was not a single concrete evidence that such interaction took place.

It was found that the simultaneous use of terfenadine and macrolides may cause arrhythmia and lengthening of the interval QT.

Theophylline

There was no interaction between azithromycin and theophylline.

Triazolam / midazolam

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

Trimethoprim / sulfamethoxazole

Simultaneous use of trimethoprim / sulfamethoxazole with azithromycin does not revealed a significant impact on C_max, total exposure or renal excretion of trimethoprim or sulfamethoxazole. The concentrations of azithromycin in serum corresponded to those detected in other studies.

Special instructions:

In case of missing one dose of the drug Sumamed^®, the missed dose should be taken as soon as possible, and the following - with interruptions at 24h.

Sumamed Drug^® should be take at least one hour before or two hours after taking antacid preparations.

Sumamed Drug^® should be used with caution in patients with impaired liver function of mild to moderate severity due to the possibility of developing fulminant hepatitis and severe hepatic insufficiency.

In the presence of symptoms of impaired liver function, such as rapidly growing asthenia, jaundice, darkening of the urine, a tendency to bleeding, hepatic encephalopathy,- therapy with Sumamed^® it is necessary to stop and conduct a study of the functional state of the liver.

For violations of kidney function: in patients with GFR 10-80 ml / min dose adjustment is not required.

As with the use of other antibacterial drugs, with the drug Sumamed^® should regularly monitor patients for the presence of unresponsive microorganisms and signs of development of superinfections, including fungal ones.

Sumamed Drug^® Do not use longer courses than indicated in the instructions, since the pharmacokinetic properties of azithromycin allow us to recommend a short and simple dosing regimen.

There is no data on the possible interaction between azithromycin and derivatives of ergotamine and dihydroergotamine, but because of the development of ergotism with the simultaneous use of macrolides with derivatives of ergotamine and dihydroergotamine, this combination is not recommended.

With prolonged use of the drug Sumamed^® possibly the development of pseudomembranous colitis caused by Clostridium difficile, both in the form of mild diarrhea, and severe colitis. With the development of antibiotic-associated diarrhea against the background of taking the drug Sumamed^®, and also 2 months after the end of therapy, clostridial pseudomembranous colitis should be excluded. Drugs that inhibit the intestinal peristalsis are contraindicated.

When treating macrolides, including azithromycin, prolonged cardiac repolarization and interval QT, increasing the risk of developing cardiac arrhythmias, including arrhythmias such as "pirouette".

Care should be taken when using Sumamed^®: in patients with the presence of pro-arrhythmic factors (especially in elderly patients), including, with congenital or acquired lengthening of the interval QT;

in patients taking antiarrhythmic drugs classes IA (quinidine, procainamide), III (dofetilide, amiodarone and sotalol), cisapride, terfenadine, antipsychotics (pimozide), antidepressants (citalopram), fluoroquinolones (moxifloxacin and levofloxacin); in patients with violations of water-electrolyte balance, especially in the case of hypokalemia or hypomagnesemia; in patients with clinically significant bradycardia, cardiac arrhythmia, or severe heart failure. Application of the drug Sumamed^® can provoke the development of myasthenic syndrome or cause an exacerbation of myasthenia gravis.

Effect on the ability to drive transp. cf. and fur:

With the development of undesirable effects from the nervous system and the organ of vision, care should be taken when performing actions requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets are dispersible 125 mg, 250 mg, 500 mg, 1000 mg.

Packaging:

125 mg, 250 mg: 6 tablets in PVC / PE / PVDC / PE / PVC / aluminum blister. 1 blister with instructions for use in a cardboard box.

500 mg: 3 tablets in PVC / PE / PVDC / PE / PVC / aluminum blister. For 1 or 2 blisters together with instructions for use in a cardboard box.

1000 mg: 1 tablet in PVC / PE / PVDC / PE / PVC / aluminum blister. For 1 or 3 blisters together with instructions for use in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003260

Date of registration:20.10.2015 / 29.06.2017

Expiration Date:20.10.2020

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Manufacturer: & nbsp

PLIVA HRVATSKA, d.o.o. Croatia

Representation: & nbspTeva Teva Israel

Information update date: & nbsp08.11.2017

Illustrated instructions

Instructions

Sumamed® (Sumamed®)