Fromilid

General characteristics. Structure:

KERNEL:
Active agent:
кларитромицин 250 mg or 500 mg

Excipients: starch corn, cellulose microcrystallic (Avicei of PH 101), cellulose microcrystallic (Avicei of PH 102), silicon dioxide colloid, anhydrous, starch prezhelatinizirovanny, полакрилин potassium, talc, magnesium stearate.

COVER:
gipromelloza of 6 cps, talc, dye quinolinic yellow (E104), propylene glycol, titanium dioxide (E171)

1 bottle contains 25 g of granules:
Active agent:
кларитромицин 1,5 g

Excipients: carbomer 934P, povidone, gipromelloza phthalate (HP 55), talc, castor oil, gum xanthane, fragrance banana, citric acid, anhydrous, potassium sorbate, silicon dioxide colloid, anhydrous, titanium dioxide, sucrose.

Description
Tablets of 250 mg: oval, biconvex tablets, film coated light yellow color. A look on a break: the mass of white color with a layer of a cover of slightly yellowish color.

Tablets of 500 mg: oval, biconvex tablets, film coated light yellow color. A look on a break: the mass of white color with a layer of a cover of slightly yellowish color.

Granules for preparation of suspension for intake: small granules, from white till light yellow color with a banana smell.
Description of suspension: homogeneous water suspension of yellow-white color with a banana smell.

Pharmacological properties:

Pharmacodynamics. Klaritromitsin is a semi-synthetic antibiotic from group of macroleads.

It inhibits synthesis of protein in a microbic cell, generally has bacteriostatic action; in big concentration has bactericidal effect on Streptococcus pyogenes, Streptococcus pneumoniae and Moraxella catarrhalis. Microorganisms sensitive to a klaritromitsin: Mycoplasma pneumoniae, Legionella pneumophila, Chlamydia trachomatis and Chlamydia pneumoniae, Ureaplasma urealyticum; gram-positive microorganisms (Streptococcus pyogenes, Streptococcus pneumoniae, Streptococcus agalactiae, Streptococcus viridans, Staphylococcus aureus, Listeria monocytogenes, Corynebacterium spp., Bacillus spp.); gram-negative microorganisms (Haemophilus influenzae and Haemophilus ducreyi, Moraxella catarrhalis, Bordetella pertussis, Neisseria gonorrhoeae and Neisseria meningitidis, Borrelia burgdorferi, Pasteurella multocida, Campylobacter spp. and Helicobacter pylori); some anaerobe bacterias (Eubacterium spp., Peptococcus spp., Propionibacterium spp., Clostridium perfringens and Bacteroides melaninogenicus); Toxoplasma gondii and all mycobacteria, except for Mycobacterium tuberculosis.

Pharmacokinetics. Klaritromitsin is well soaked up from digestive tract. Bioavailability - 55% at intake. Food slows down absorption, but does not influence significantly bioavailability of a klaritromitsin. Communication with proteins - more than 90%. About 20% of a klaritromitsin are immediately metabolized in a liver by enzymes of CYP3A4, CYP3A5 and CYP3A7 cytochrome in the main metabolite - 14-hydroxy-klaritromitsin having the expressed activity concerning Haemophilus influenzae. The maximum plasma concentration is reached (TCmax) less, than in 3 hours. At regular reception on 250 mg/days equilibrium concentration (Css) of not changed drug - 0,62 - 0.84 mkg/ml and its main metabolite — 0,4 - 0,7 mkg/ml respectively; at increase in a dose up to 500 mg/days of Css of invariable drug 1,77 - 1.89 mkg/ml and its metabolite in plasma - 0,67 - 0,8 mkg/ml. Klaritromitsin easily gets into fabrics (easy, palatine tonsils, saliva, a phlegm and a middle ear, skin and soft tissues of an organism) and organism liquid where reaches concentration, almost by 10 times exceeding concentration in serum. The elimination half-life after reception of a dose of 250 mg makes from 3 to 4 hours; after reception of a dose of 500 mg - from 5 to 7 hours. From 20 to 30% of a klaritromitsin (40% at suspension reception) are removed in not changed look by kidneys, other part is removed in the form of metabolites.

Indications to use:

The infectious and inflammatory diseases caused by microorganisms, sensitive to drug:
• infections of upper parts of respiratory tracts (acute and chronic tonzillofaringit, acute and chronic recurrent sinusitis, acute average otitis),
• infections of lower parts of respiratory tracts (acute bacterial bronchitis, an exacerbation of chronic bronchitis, community-acquired bacterial pneumonia, including the pneumonia caused by atypical activators);
• infections of skin and soft tissues;
• the infections caused by mycobacteria (Mycobacterium avium complex, Mycobacterium kansasii, Mycobacterium marinum, Mycobacterium leprae);
• prevention of spread of infections, caused by the Mycobacterium avium (MAC), HIV complex - the infected patient with the maintenance of lymphocytes of CD4 (T - helper lymphocytes) no more than 100 in 1 mm3;
• Helicobacter pylori eradikation at patients with a peptic ulcer of a duodenum or stomach (always in a combination with other drugs).

Route of administration and doses:

Inside to swallow tablets entirely, washing down with a small amount of liquid. Tablets should not be broken.

To adults and children 12 years are aged more senior and/or body weight> 33 kg usually appoint 250 mg each 12 hours. For treatment of acute sinusitis, heavy infections and in case the infection is caused by Haemophilus influenzae, appoint 500 mg of a klaritromitsin each 12 hours. Course of treatment of 7-14 days.

For the purpose of N.'s eradikation of pylori кларитромицин it is appointed in a dose of 250 mg - 500 mg two times a day, usually within 7 days, in a combination with other medicines.

To children 12 years are aged younger and/or with a body weight less than 33 kg usually appoint the suspension at the rate of 15 mg/kg of body weight a day divided into two receptions. It is recommended to give a little liquid after suspension reception. Suspension contains tiny granules which should not be chewed as their contents have bitter taste. The syringe is provided for peroral administration of drug. One filled syringe contains 5 ml of the suspension containing 125 mg of a klaritromitsin. Wash out the syringe after each use. The drug dose in pediatrics is calculated on the body weight of the child.

The scheme of dosing at children:

The body weight            of the child Doz in ml (syringe)                of Doz in mg
From 8 kg to 10         kg 2,5 ml - 3 ml 2 times in days      of 62,5 mg - 75 mg
From 10 kg to 12       kg 3 ml - 3,6 ml 2 times in days      of 75 mg - 90 mg
From 12 kg to 14       kg 3,6 ml - 4,2 ml 2 times in days   of 90 mg-105 mg
From 14 kg to 16       kg 4,2 ml - 4,8 ml 2 times in days   of 105 mg-120 mg
From 16 kg to 18       kg 4,8 ml - 5,4 ml 2 times in days   of 120 mg - 135 mg
From 18 kg to 20       kg 5,4 ml - 6,0 ml 2 times in days   of 135 mg-150 mg
From 20 kg to 22       kg 6,0 ml - 6,6 ml 2 times in days   of 150 mg - 165 mg
From 22 kg to 24       kg 6,6 ml - 7.2 ml 2 times in days   of 165 mg-180 mg
From 24 kg to 26       kg 7,2 ml - 7,8 ml 2 times in days   of 180 mg - 195 mg
From 26 kg to 28       kg 7,8 ml - 8,4 ml 2 times in days   of 195 mg - 210 mg
From 28 kg to 30       kg 8,4 ml - 9,0 ml 2 times in days   of 210 mg - 225 mg
From 30 kg to 33       kg 9,0 ml - 10 ml 2 times in days    of 250 mg

The course of treatment usually proceeds within 7-14 days.

For treatment and prevention of spread of the infection caused by a bacterium of Mycobacterium avium complex it is necessary to appoint 500 mg of drug each 12 hours. The dose can be increased. The maximum daily dose makes 2 g. To children appoint a dose of a klaritromitsin from calculation - 15 mg/kg of body weight a day, divided into two receptions. The dose of drug should not exceed 500 mg each 12 hours. The maximum daily dose recommended to children makes 1 g.

Treatment of the infection caused by Mycobacterium avium complex, long, 6 months and more.

In case of a renal failure if the clearance of creatinine makes less than 30 ml/min., or creatinine of serum makes more than 290 mmol/l (3,3 mg / 100 ml), the dose should be reduced twice or to double an interval between receptions. The maximum duration of treatment at patients of this group - 14 days.

Suspension preparation:
Preparation of suspension requires 42 ml of water.
Previously stir up a bottle that granules in it were scattered. Add 1/4 volumes of water to a bottle and shake up before dissolution of granules. Add the rest of water and well stir up. The volume of ready suspension has to reach the line of a mark in a bottle.

Features of use:

Among makrolidny antibiotics there is a cross resistance.
Correction of a dose of drug is not necessary for patients with disturbance of hepatic function of average degree if renal function meets standard.
However, the dose of drug should be reduced for patients with disturbances of renal function of heavy degree. In the presence of chronic diseases of a liver it is necessary to carry out regular control of enzymes of blood serum.
At co-administration of the medicines which are metabolized a liver it is recommended to measure their concentration in blood serum.
In case of joint appointment with warfarin or other indirect anticoagulants it is necessary to control a prothrombin time.
Now there is no enough experience concerning efficiency and at treatment of children 6 months are younger than safety of use of a klaritromitsin.
Treatment by antibiotics changes normal flora of intestines therefore the superinfection caused by resistant microorganisms can be observed. In case of heavy, persistent diarrhea which can indicate pseudomembranous colitis, it is necessary to interrupt administration of drug and to consult at the attending physician.
In 125 mg of granules for preparation of suspension for intake, 125 mg / 5 the ml contains 1,6 g of sucrose therefore drug is not recommended to children with inborn intolerance of fructose, with sprues of a glucose/galactose or deficit of enzyme of invertase-isomaltase.

Influence on ability to driving and other mechanical means: drug has no effect on the speed of psychomotor reactions of the patient during the driving or work with mechanisms.

Side effects:

From the alimentary system: nausea, vomiting, diarrhea, abdominal pain, stomatitis, glossitis, short-term decolouration of teeth and language, pancreatitis, pseudomembranous coloenteritis, cholestatic jaundice, hepatitis. Abnormal liver functions can be heavy, but usually reversible. Cases of a liver failure and death generally against the background of serious associated diseases and/or the accompanying medicinal therapy were very seldom observed.

From the central and peripheral nervous system: headache, вертиго, paresthesias, drowsiness, hallucinations, spasms, psychosis, dizziness, confusion of consciousness, sensation of fear, sleeplessness, "dreadful" dreams, depersonalization, disorientation.

From bodies of a hemopoiesis and lymphatic system: leukopenia, thrombocytopenia.

From sense bodys: taste change (dysgeusia), sense of smell, a ring in ears, the short-term hearing loss passing after drug withdrawal.

From cardiovascular system: lengthening of an interval of QT on an ECG, ventricular tachycardia like "pirouette" ("torsades de pointes").

From respiratory system: asthma.

From a musculoskeletal system: arthralgia, mialgiya.

From urinogenital system: intersticial nephrite, renal failure.

Allergic reactions: skin сьпь, urticaria, a skin itch, puffiness of the person, an acute anaphylaxis, Stephens's syndrome - Johnson, a toxic epidermal necrolysis (Lyell's disease), a Quincke's disease of Quincke.

Laboratory indicators: increase in activity of "hepatic" transaminases and an alkaline phosphatase, increase in serumal levels of bilirubin, creatinine, uric acid, lengthening of a prothrombin time, thrombocytopenia (unusual bleedings, hemorrhages), a leukopenia, a neutropenia, a hypoglycemia at the patients accepting hypoglycemic medicines.

Others: at prolonged use development of cases of superinfection, candidiasis, stability of microorganisms (pseudomembranous colitis, oral cavity candidiasis) is possible.

Interaction with other medicines:

Klaritromitsin is metabolized in a liver where he can inhibit effect of enzymes of a complex of R-450 cytochrome. At simultaneous treatment klaritromitsiny and other drugs which are metabolized by means of this system, concentration of the last can raise and cause by-effects. Therefore терфенадин, цизаприд, or астемизол it is not necessary to appoint Pimozidum during treatment klaritromitsiny because of threat of development of life-threatening arrhythmias. It is recommended to measure concentration of theophylline, carbamazepine, digoxin, a lovastatin, a simvastatin, a triazrlam, midazolam, Phenytoinum, cyclosporine, Disopyramidum, a rifabutin, a takrolimus, an itrakonazol and alkaloids of an ergot in serum when they are appointed along with klaritromitsiny as the risk of probability of side effects of the last increases. It is necessary to control periodically a prothrombin time at the patients receiving кларитромицин along with warfarin or other peroral anticoagulants.

Co-administration of a klaritromitsin and zidovudine reduces absorption of a zidovudine (between use of medicines the interval is necessary not less than 4 hours). Co-administration of a ritonavir and klaritromitsin leads to substantial increase of level of maintenance of a klaritromitsin in serum and to considerable decrease in level of maintenance of its metabolite of a 14-gidroksiklaritromitsin in serum. Development of cross resistance between klaritromitsiny, lincomycin and clindamycin is possible.

Contraindications:

• hypersensitivity to a klaritromitsin or other antibacterial drugs from group of macroleads or to other components of drug;
• liver failure of heavy degree;
• hepatitis (in the anamnesis);
• porphyria;
• I trimester of pregnancy;
• lactation period;
• simultaneous therapy with terfenadiny, tsizapridy, Pimozidum or astemizoly;
• the children's age up to 6 months (for a dosage form - granulate for preparation of suspension for intake) - is not available sufficient experience concerning efficiency and safety of use;
• children up to 12 years and/or with a body weight less than 33 kg (for a dosage form - a tablet, film coated);
• inborn intolerance of fructose, a sprue of a glucose/galactose or deficit of enzyme of invertase-isomaltase (only for a dosage form - a granule for preparation of suspension for intake).

With care: The II-III trimesters of pregnancy, the moderated and expressed renal failure, a liver failure.

Pregnancy and period of a lactation

Klaritromitsin it is possible to apply in II and III trimesters of pregnancy only when the expected advantage for mother exceeds potential risk for a fruit. In need of use of drug in the period of a lactation it is necessary to interrupt breastfeeding.

Overdose:

Symptoms: vomiting, abdominal pain, headache and confusion of consciousness. Treatment: gastric lavage, symptomatic therapy.

Storage conditions:

Tablets, film coated.
To store in the dry place, at a temperature not higher than 25 Pages.

Granules for preparation of suspension for intake.
To store at a temperature not higher than 30 Pages. Ready suspension is suitable within 14 days at a temperature not above 25 °C, in the place protected from light. To store in the place, unavailable to children.

Period of validity
Tablets, film coated: 5 years.
Granules for preparation of suspension for intake: 2 years.

Not to use after expiry date.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, on 250 mg and 500 mg. On 7 tablets in the blister. On 2 blisters in a pack cardboard together with the application instruction.

Granules for preparation of suspension for intake, 125 mg / 5 ml. 25 g of granules in a bottle of dark glass with a capacity of 100 ml, from circular ready suspension, risky on 60 ml, corked by a plastic stopper with a rassekatel of liquid and a plastic cover with control of the first opening. 1 bottle complete with the dosing syringe and the application instruction in a pack cardboard.