Fromilid uno
Fromilid uno: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Fromilid Uno
ATX code: J01FA09
Active ingredient: clarithromycin (clarithromycin)
Manufacturer: KRKA, d.d. (KRKA, dd) (Slovenia)
Description and photo updated: 22.11.2018
Prices in pharmacies: from 150 rubles.
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Fromilid uno is a semi-synthetic antimicrobial drug from the macrolide group; an inhibitor of protein synthesis in microbial cells, which has a predominantly bacteriostatic and, to some extent, bactericidal effect.
Release form and composition
Fromilid uno is produced in the form of tablets of prolonged action, film-coated: biconvex, oval, on one side marked U; on the break, a brown-yellow film shell and a white or almost white rough mass stand out (in blisters of 5 pcs., in a cardboard box 1 blister; in blisters of 7 pcs., in a cardboard box of 1 or 2 blisters).
1 tablet contains:
- active ingredient: clarithromycin - 500 mg (equivalent to the content of the active substance - 980-1020 μg / mg);
- auxiliary ingredients: sodium calcium alginate, sodium alginate, lactose monohydrate, polysorbate-80, povidone, colloidal silicon dioxide, magnesium stearate, talc;
- film shell: hypromellose, dye iron oxide yellow (E 172), titanium dioxide (E 171), propylene glycol, talc.
Pharmacological properties
Pharmacodynamics
The active component of Fromilid uno is clarithromycin, a semisynthetic antibiotic of the macrolide group that binds to the 50S-ribosomal subunit and suppresses protein synthesis of bacteria sensitive to it.
In in vitro studies, clarithromycin is highly active against standard laboratory bacterial strains and isolated during clinical practice in patients with both aerobic and anaerobic gram-positive and gram-negative patients. The MIC (minimum inhibitory concentration) of clarithromycin for most pathogens is, on average, one log2 dilution lower than the MIC of erythromycin.
In vitro, clarithromycin is highly active against Mycoplasma pneumoniae and Legionella pneumophila. In relation to Helicobacter pylori, it exhibits bactericidal activity, which increases with a decrease in the acidity of the medium and is higher for neutral pH than for acidic.
Data from in vitro and in vivo studies confirm that clarithromycin is active against clinically significant mycobacterial species. Enterobacteriaceae and Pseudomonas spp., Like other gram-negative bacteria that do not ferment lactose, are not sensitive to clarithromycin.
Microorganisms, the activity of clarithromycin against most of which has been proven both in vitro and in clinical practice:
- gram-positive aerobes: Staphylococcus aureus, Listeria monocytogenes, Streptococcus pyogenes, Streptococcus pneumoniae;
- gram-negative aerobes: Legionella pneumophila, Haemophilus influenzae / parainfluenzae, Neisseria gonorrhoeae, Moraxella catarrhalis;
- other infections: Chlamydia pneumoniae (including Taiwan acute respiratory agent - TWAR), Mycoplasma pneumoniae;
- mycobacteria: Mycobacterium chelonae, Mycobacterium kansasii, Mycobacterium leprae, Mycobacterium fortuitum; Mycobacterium avium complex (MAC), including Mycobacterium avium.
The production of β-lactamase has no effect on the activity of clarithromycin.
Most staphylococcal strains that show resistance to methicillin and oxacillin are also resistant to clarithromycin.
During the study of the sensitivity of Helicobacter pylori to clarithromycin on isolates isolated from 104 patients before the start of the drug administration, strains resistant to clarithromycin were isolated in 4 cases; in 2 - strains with moderate resistance; in the remaining 98 cases, clarithromycin was active against Helicobacter pylori isolates.
Microbial strains, for most of which clarithromycin is active in vitro (the safety and efficacy of its use in clinical practice has not been confirmed by studies, therefore, its practical significance remains unclear):
- gram-positive aerobes: Streptococci (groups C, F, G), Streptococcus agalactiae, Viridans group streptococci;
- gram-negative aerobes: Bordetella pertussis and Pasteurella multocida;
- gram-positive anaerobes: Clostridium perfringens, Propionibacterium acnes, Peptococcus niger;
- gram-negative anaerobes: Bacteroides melaninogenicus;
- campylobacter: Campylobacter jejuni;
- spirochetes: Borrelia burgdorferi and Treponema pallidum.
The main metabolite of clarithromycin is 14-hydroxyclarithromycin (14-OH-clarithromycin), its microbiological activity is the same as that of the parent substance, or (in relation to most microorganisms) is two times weaker. Only in relation to Haemophilus influenzae, the metabolite is twice as effective. Under conditions both in vitro and in vivo in relation to Haemophilus influenzae, the parent compound with the main metabolite exhibits an additive effect or synergism of action (depending on the bacterial strain).
Pharmacokinetics
Clarithromycin is rapidly absorbed from the gastrointestinal tract (GIT). Its absolute bioavailability is about 50%. Due to the reception of repeated doses of Fromilid, uno cumulation practically does not occur, and the nature of metabolism remains almost unchanged.
The binding of clarithromycin to blood plasma proteins in vitro occurs by 70% in the range of doses taken of the drug of 0.45–4.5 μg / ml. At 45 μg / ml, the binding rate decreases to 41%, possibly due to saturation of the binding sites. This effect is observed only under conditions of concentrations that are many times higher than therapeutic ones.
Taking 1 tablet of Fromilid uno (500 mg of clarithromycin) once a day after meals provides the maximum concentration in blood plasma (Cmax): clarithromycin - 1.3 μg / ml, its hydroxylated metabolite 14-OH-clarithromycin - 0.48 μg / ml … The half-life (T1 / 2) is, respectively, 5.3 and 7.7 hours.
When taking a single dose of 1000 mg of clarithromycin (2 tablets of 500 mg), Cmax of clarithromycin is 2.4, its metabolite is 0.67 μg / ml. T1 / 2, respectively, 5.8 and 8.9 hours. The time to reach the maximum concentration (TCmax) with oral administration of clarithromycin at a dose of both 500 and 1000 mg is about 6 hours. In comparison, it can be seen that T1 / 2 of clarithromycin and its metabolite with increasing dose tends to lengthen, but Cmax 14-OH- clarithromycin did not increase in proportion to the oral dose of clarithromycin. Such indicators, combined with a decrease in the formation of 14-hydroxylated and N-demethylated products of clarithromycin at high dosages, indicate the nonlinear nature of its metabolism, which becomes more pronounced at high dosages.
The kidneys excrete ~ 40% of the oral dose of clarithromycin; intestines ~ 30%.
Clarithromycin and its hydroxylated metabolite quickly penetrate into tissues and fluids. According to limited data, the level of clarithromycin in the cerebrospinal fluid when taken orally is insignificant and reaches only 1–2% of the serum concentration with normal BBB (blood-brain barrier) permeability. Concentration in tissues, as a rule, is several times higher than serum concentration.
In case of moderate and severe liver dysfunction, but with preserved renal function, the dosage regimen does not need to be adjusted. The steady-state concentration of clarithromycin in the blood (Css) and its systemic clearance do not differ from those in healthy patients. At the same time, the Css of the clarithromycin metabolite in liver dysfunction is lower than in normal hepatic function.
With impaired renal function, an increase in the concentration of clarithromycin (Cmax and Cmin) in the blood plasma is observed. As well as an increase in T1 / 2 and AUC of both clarithromycin and its metabolite (14-OH-clarithromycin). The elimination constant decreases, the excretion of the substance by the kidneys decreases. The variability of these indicators depends on the degree of impairment of renal function.
In the elderly, the plasma concentration of clarithromycin and its active metabolite 14-OH-clarithromycin in the blood was higher, and the excretion rate was lower than in the control group of young patients. But after adjusting the dosage regimen taking into account creatinine clearance (CC), the difference leveled off. Therefore, the pharmacokinetic parameters of the drug mainly change under the influence of renal function and do not depend on the patient's age.
Indications for use
According to the instructions, Fromilid uno is recommended for the treatment of the following infectious and inflammatory diseases caused by microorganisms sensitive to clarithromycin:
- pharyngitis, tonsillitis, acute otitis media, sinusitis and other infections of the ENT organs and upper respiratory tract;
- bronchitis, community-acquired pneumonia and other lower respiratory tract infections;
- folliculitis, erysipelas and other infections of the skin and soft tissues.
Contraindications
Absolute:
- CRF (chronic renal failure) in severe degree with CC less than 30 ml / min;
- severe liver failure, aggravated by renal failure;
- intrahepatic cholestasis and / or history of cholestatic jaundice (hepatitis) due to the use of clarithromycin;
- porphyria;
- simultaneous therapy with astemizole, cisapride, pimozide, terfenadine, ergotamine (and other ergot alkaloids), oral midazolam, HMG-CoA reductase inhibitors (statins that are largely metabolized by the CYP3A4 isoenzyme, such as lovastatin - simvastatin increased risk of myopathy, including rhabdomyolysis), colchicine, ticagrelor, or ranolazine;
- history of congenital or documented lengthening of the QT interval on the electrocardiogram (ECG), ventricular arrhythmias or ventricular tachycardia such as pirouette;
- hypokalemia (due to the risk of lengthening the QT interval on the ECG);
- lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
- pregnancy in the first trimester;
- lactation (breastfeeding);
- age: in the treatment of tonsillitis and acute otitis media - under 18 years old; for other indications - under 12 years old;
- hypersensitivity to macrolides, clarithromycin and other components of the drug.
Fromilid uno is taken with caution in the II-III trimesters of pregnancy, with mild and moderate renal failure (CC more than 30 ml / min), moderate and severe hepatic failure, myasthenia gravis, coronary artery disease (ischemic heart disease), severe heart failure, hypomagnesemia, severe bradycardia (less than 50 beats / min).
Caution should be exercised when concomitant use of clarithromycin with the following substances / preparations:
- benzodiazepines (triazolam, alprazolam, intravenous midazolam);
- inducers of the CYP3A isoenzyme (carbamazepine, omeprazole, cyclosporine, cilostazol, disopyramide, methylprednisolone), indirect anticoagulants (warfarin), quinidine, rifabutin, tacrolimus, sildenafil, vinblastine;
- inducers of the CYP3A4 isoenzyme (carbamazepine, rifampicin, phenytoin, St. John's wort, phenobarbital);
- calcium channel blockers (CCBs), metabolized by the CYP3A4 isoenzyme (amlodipine, verapamil, diltiazem);
- other ototoxic drugs, especially aminoglycosides;
- statins that do not depend on the metabolism of the isoenzyme CYP3A4 (fluvastatin);
- antiarrhythmic drugs IA (procainamide, quinidine) and class III (amiodarone, dofetilide, sotalol).
Instructions for the use of Fromilid uno: method and dosage
The tablets are taken orally, during meals, without chewing or breaking, swallowing whole.
Recommended daily dosage: children over 12 years of age and adult patients - Fromilid uno 500 mg (1 tablet) once a day.
For the treatment of tonsillitis and otitis media, the drug is prescribed only to adult patients over 18 years of age - Fromilid uno 500 mg (1 tablet) once a day.
In the case of severe disease, the dose is increased to 1000 mg (2 tablets) once a day.
The standard duration of treatment is 5-14 days, except for the treatment of community-acquired pneumonia and sinusitis, which require treatment for at least 6 to 14 days.
Side effects
Classification of the World Health Organization (WHO) to determine the incidence of side effects: very often - not less than 0.1%; often - from 0.01 to 0.1%; infrequently - from 0.001 to 0.01%; rarely - from 0.0001 to 0.001%; extremely rare - less than 0.0001%, including isolated cases; with uncertain frequency - it is impossible to estimate the frequency based on the available data.
The frequency of side effects due to the intake of Fromilid uno on the part of systems and organs:
- digestive system: often - nausea, dyspepsia, abdominal pain, increased activity of liver enzymes; infrequently - diarrhea, vomiting, stomatitis, glossitis, oral mucosa candidiasis, acute pancreatitis, discoloration of tooth enamel and tongue, hepatocellular / cholestatic hepatitis, pseudomembranous colitis, cholestatic jaundice, anorexia, dryness of the oral mucosa, constipation, constipation, gastritis; extremely rarely - liver failure with a fatal outcome, mainly against the background of concomitant serious diseases and / or the simultaneous administration of other drugs;
- skin and subcutaneous tissue: often - hyperhidrosis; with an indeterminate frequency - acne, drug rash (including with eosinophilia and systemic symptoms), erysipelas, erythrasma;
- nervous system: often - headache; infrequently - drowsiness, paresthesia, anxiety, convulsions, hallucinations, psychosis, confusion, dizziness, fear, nightmares, insomnia, depersonalization, tremors, disorientation, depression; with an indefinite frequency - mania;
- sense organs: often - dysgeusia (distortion / loss of taste); infrequently - noise (ringing) in the ears, up to hearing loss (restored after the cancellation of Fromilid uno), vertigo; extremely rarely - cases of violation of the sense of smell;
- cardiovascular system: infrequently - ventricular tachycardia, including pirouette-type arrhythmias, ventricular flutter / fibrillation, prolongation of the QT interval on the ECG;
- hematopoietic system: rarely - thrombocytopenia (unusual hemorrhage, bleeding), leukopenia; with an indefinite frequency - agranulocytosis;
- musculoskeletal system: infrequently - arthralgia, myalgia; with an undefined frequency - myopathy;
- urinary system: infrequently - interstitial nephritis; with an indeterminate frequency - renal failure;
- allergic reactions: infrequently - itchy skin / rash, skin flushing, urticaria, Stevens-Johnson syndrome (malignant exudative erythema), Lyell's syndrome (toxic epidermal necrolysis), anaphylaxis; with an indefinite frequency - Shenlein's purpura - Henoch;
- laboratory data: infrequently - an increase in the concentration of creatinine, hypoglycemia (including when used simultaneously with hypoglycemic drugs), an increase in the activity of alkaline phosphatase (ALP), an increase in the level of bilirubin; with an indefinite frequency - an increase in the international normalized ratio (INR), an increase in prothrombin time;
- other reactions: secondary infections (development of resistance to microorganisms); infrequently - asthenia.
Overdose
Symptoms of an overdose of clarithromycin when taken orally in large doses are gastrointestinal disturbances. Changes in mental status, paranoid behavior, hypoxemia, and hypokalemia have been reported in a patient with a history of bipolar disorder after taking 8,000 mg of clarithromycin.
It is recommended to carry out measures for the evacuation of the unabsorbed drug from the gastrointestinal tract (induction of vomiting, gastric lavage, intake of activated carbon, etc.) and symptomatic treatment. For drugs from the macrolide group, including clarithromycin, the ineffectiveness of hemo- and peritoneal dialysis in order to reduce their concentration in blood serum has been proven.
special instructions
Long-term use of antibiotics can result in the formation of colonies with an increased number of resistant bacteria and fungi, the so-called superinfection, which requires appropriate therapy.
There have been reports of cases of development of hepatic dysfunction against the background of the use of clarithromycin with an increase in the activity of liver enzymes in the blood plasma and with hepatocellular / cholestatic hepatitis with or without jaundice. Hepatic dysfunction can be severe, but it is usually reversible. Fatal liver failure has been reported, mainly due to the presence of serious concomitant diseases and / or the simultaneous use of other drugs. The appearance of signs / symptoms of hepatitis (skin itching, jaundice, anorexia, dark urine, abdominal pain on palpation) requires immediate discontinuation of therapy. In patients with chronic liver disease, it is necessary to regularly monitor the activity of liver enzymes in the blood serum.
Treatment with virtually any antibacterial agent, including clarithromycin, can cause mild to life-threatening pseudomembranous colitis. Since antibacterial drugs can change the normal intestinal microflora, as a result of which the growth of the main causative agent of pseudomembranous colitis, Clostridium difficile, increases. Disease should be suspected in all patients who develop diarrhea following antibiotic use. At the end of the course of antibiotic therapy, the patient requires close medical supervision. There were reports of the development of pseudomembranous colitis two months after the end of antibiotic treatment.
The use of macrolides, including clarithromycin, lengthens the period of myocardial repolarization and the QT interval, increasing the risk of cardiac arrhythmias (including pirouette-type arrhythmias).
The development of cross-resistance in relation to clarithromycin and other macrolide antibiotics, as well as clindamycin and lincomycin, is not excluded.
Due to the increasing resistance to macrolides of Streptococcus pneumoniae, it is important to conduct sensitivity testing when prescribing clarithromycin for the treatment of patients with community-acquired pneumonia. In patients with hospital-acquired pneumonia, clarithromycin is used in combination with appropriate antibiotics.
The most common infections of the skin and soft tissues of mild to moderate severity are caused by Staphylococcus aureus and Streptococcus pyogenes. At the same time, both pathogens can show resistance to macrolides. Therefore, it is important to conduct a test to determine the spectrum of their sensitivity to antibiotics.
Antibiotics of the macrolide group can be used to treat infections caused by Corynebacterium minutissimum (corynebacterium minutissimum, the causative agent of erythrasma, chronic pseudomycosis), acne vulgaris and erysipelas, as well as when penicillin cannot be used.
In acute hypersensitivity reactions [anaphylaxis, Stevens-Johnson syndrome, Lyell's syndrome, drug rash with eosinophilia and systemic symptoms (DRESS-syndrome)], it is necessary to immediately stop taking clarithromycin and conduct symptomatic therapy.
With the simultaneous use of clarithromycin with warfarin or other indirect anticoagulants, INR and prothrombin time (PT) should be monitored.
Influence on the ability to drive vehicles and complex mechanisms
Consideration should be given to the possibility of such side effects of clarithromycin as dizziness, vertigo, confusion and disorientation when performing potentially hazardous activities, including driving and other complex machinery.
Application during pregnancy and lactation
The safety of clarithromycin use in pregnant and lactating women has not been reliably established.
During pregnancy (especially in the first trimester), Fromilid uno can be taken only in the absence of alternative therapy and a clinically significant excess of the potential benefit to the mother over the likely risk to the fetus.
Clarithromycin in small quantities passes into breast milk, and therefore breastfeeding should be discontinued during therapy.
Pediatric use
In pediatric practice, Fromilid uno is not prescribed for the treatment of children (adolescents): under the age of 12 - for all indications; under the age of 18 - in the treatment of tonsillitis and acute otitis media.
With impaired renal function
- severe renal failure (CC less than 30 ml / min): the use of Fromilid uno is contraindicated;
- moderate renal dysfunction (CC 30-60 ml / min): the dose of the drug is halved (no more than 1 tablet - 500 mg per day).
For violations of liver function
With moderate and severe hepatic failure Fromilid uno is prescribed with caution.
Use in the elderly
In elderly patients, it may be necessary to adjust the dosage regimen of Fromilid uno, taking into account creatinine clearance (CC), associated with age-related renal dysfunction.
Drug interactions
Due to the high pharmacological activity of clarithromycin, its drug interaction with a large number of drugs / agents is possible.
In the section "Contraindications" there is a list of drugs, joint administration with which Fromilida uno is contraindicated, and a list of drugs, joint therapy with which is carried out with caution and requires medical supervision.
Analogs
Fromilid uno analogs are Zimbaktar, Klabaks, Kispar, Klarbakt, Clarithromycin Ecositrin, Clarithromycin retard-OBL, Clarithromycin-OBL, Clarithromycin-TEVA, Claricin, Claritrosin, Klacid, Klacid SR, Klasine, Klerimed, Seyarcoater, Romoclarecler, Fromilid, etc.
Terms and conditions of storage
Store in original packaging at temperatures up to 25 ° C. Keep out of the reach of children.
The shelf life is 3 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews of Fromilida Uno
According to reviews, Fromilid uno is a very effective drug for the rapid treatment of severe and advanced infections. Practically no cases of adverse reactions are described, except for isolated mentions of stomach problems, which may have arisen due to non-compliance with the recommendations for taking pills.
As the disadvantages of Fromilid uno, they point to the large size of the tablets, extensive instructions with a large number of contraindications and side effects, the cost, according to some patients, is quite high.
Price for Fromilid Uno in pharmacies
Approximate price of Fromilida uno, prolonged-release film-coated tablets, for 5 pcs. in the package - 279 rubles; 7 pcs. - 359 rubles; 14 pcs. - 610 rubles.
Fromilid uno: prices in online pharmacies
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Drug name Price Pharmacy |
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Fromilid Uno 500 mg film-coated tablets of prolonged action 5 pcs. RUB 150 Buy |
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Fromilid Uno 500 mg film-coated tablets of prolonged action 7 pcs. RUB 200 Buy |
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Fromilid UNO tablets p.p. prolonged action 500mg 5 pcs. 248 r Buy |
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Fromilid UNO tablets p.p. prolonged action 500mg 7 pcs. RUB 290 Buy |
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Fromilid Uno 500 mg film-coated tablets of prolonged action 14 pcs. 557 r Buy |
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
