FROMILID®
Active material: Clarithromycin
When ATH: J01FA09
CCF: Macrolide antibiotics
ICD-10 codes (testimony): A31.0, A48.1, B96.0, H66, J00, J01, J02, J03, J15, J15.7, J16.0, J20, J31, J32, J35.0, J42, K25, K26, L01, L02, L03, L08.0
When CSF: 06.07.01
Manufacturer: KRKA d.d. (Slovenia)
Pharmaceutical form, composition and packaging
Pills, Film-coated light yellow, Oval, lenticular; of presentations – mass of white shell with a layer of slightly yellowish.
| 1 tab. | |
| clarithromycin | 250 mg |
| -“- | 500 mg |
Excipients: corn starch, microcrystalline cellulose (Avicel PH 101, Avicel PH 102), colloidal silicon dioxide (anhydrous), pre-gelatinized starch, polacrilin potassium, talc, magnesium stearate.
The composition of the coating film: gipromelloza 6 cps, talc, quinoline yellow dye (E104), propylene glycol, Titanium dioxide (E171).
7 PC. – blisters (2) – packs cardboard.
Granules for oral suspension from white to light yellow in color, fine, with the smell of banana; preparing an aqueous slurry – yellowish-white, Homogeneous, with the smell of banana.
| 1 fl. | 5 ml susp hotovoy. | |
| clarithromycin | 1.5 g | 125 mg |
Excipients: carbomer 934P, povidone, gipromellozы phthalate (HP 55), talc, Castor oil, xanthan gum, banana flavor, lemon acid (Anhydrous), potassium sorbate, colloidal silicon dioxide (anhydrous), Titanium dioxide, sucrose.
25 g – vials of dark glass volume 100 ml (1) complete with a dosing syringe – packs cardboard.
Pharmacological action
Semisynthetic macrolide antibiotics. It inhibits the synthesis of proteins in microbial cell. Basically it has a bacteriostatic effect. In high concentrations it has a bactericidal effect on Streptococcus pyogenes, Streptococcus pneumoniae and Moraxella catarrhalis.
It is active against intracellular microorganisms: Legionella pneumophila, Chlamydia trachomatis, Chlamydia pneumoniae, Ureaplasma urealyticum, Mycoplasma pneumoniae; Gram-positive bacteria: Streptococcus pyogenes, Streptococcus pneumoniae, Streptococcus agalactiae, Streptococcus viridans, Staphylococcus aureus, Listeria monocytogenes, Corynebacterium spp., Bacillus spp.; Gram negative bacteria: Haemophilus influenzae, Haemophilus ducreyi, Moraxella catarrhalis, Bordetella pertussis, Neisseria gonorrhoeae, Neisseria meningitidis, Borrelia burgdorferi, Pasteurella multocida, Campylobacter spp. and Helicobacter pylori; Anaerobic bacteria: Eubacterium spp., Peptococcus spp., Propionibacterium spp., Clostridium perfringens, Bacteroides melaninogenicus. Preparation It is also active against Toxoplasma gondii, Mycobacterium spp. (except Mycobacterium tuberculosis).
Pharmacokinetics
Absorption
After oral clarithromycin is well absorbed from the gastrointestinal tract. Oral bioavailability – 55%. Food slows the absorption, but does not significantly influence the bioavailability of clarithromycin. Cmax achieved less, than 3 no.
Distribution
Plasma protein binding – more 90%.
When taken regularly for 250 mg / Css unchanged substance is 0.62-0.84 ug / ml, osnovnogo metabolite – 0.4-0.7 ug / ml, respectively; by increasing doses up to 500 mg / Css unchanged substance is 1.77-1.89 ug / ml, its metabolite in plasma – 0.67-0.8 ug / ml.
Clarithromycin easily penetrates tissue (lungs, tonsils, saliva, sputum and middle ear, skin and soft tissues of the body) and body fluid, where it reaches a concentration, almost 10 times the concentration in the serum.
Metabolism
About 20% clarithromycin immediately metabolized in the liver with the participation of every enzyme CYP3A4, CYP3A5 and CYP3A7 with the formation of the main metabolite – 14-hydroxy-clarithromycin, having pronounced activity against Haemophilus influenzae.
Deduction
T1/2 after administration at a dose 250 mg is from 3 to 4 no; postdose 500 mg – from 5 to 7 no. From 20 to 30% clarithromycin (40% when taking suspension) excreted unchanged in the urine, the remainder is excreted as metabolites.
Testimony
Treatment of infectious and inflammatory diseases, caused by sensitive pathogens, including:
- Infections of the upper respiratory tract and ENT (acute and chronic tonzillofaringit, acute and chronic recurrent sinusitis, acute otitis media);
- Infections of the lower respiratory tract (acute bacterial bronchitis, exacerbation of chronic bronchitis, community-acquired bacterial pneumonia, incl. pneumonia, caused by atypical pathogens);
- Infections of the skin and soft tissues;
- Infections, caused by mycobacteria (Mycobacterium avium complex, Mycobacterium kansasii, Mycobacterium Sea, Mycobacterium leprae);
- Preventing the spread of infections, caused by Mycobacterium avium complex (MAC ), HIV-infected patients with CD4 counts (T-helper lymphocytes) no more than 100 / mm3;
- Helicobacter pylori eradication in patients with duodenal ulcer or stomach (Only a combination therapy).
Dosage regimen
The drug is taken orally. The tablets should be swallowed whole, without breaking, drinking a small amount of liquid.
Adults and children over the age of 12 s and / or body weight > 33 kg usually prescribed for 250 mg every 12 no.
To treatment of acute sinusitis, severe infections and in the case, when the infection is caused by Haemophilus influenzae, appoint 500 mg clarithromycin every 12 no. A course of treatment 7-14 days.
With the aim of eradication of Helicobacter pylori Fromilid® administered at a dose of 250-500 mg 2 times / day, typically for 7 days, in combination with other drugs.
Children under the age of 12 s and / or body weight < 33 kg drug administered in form of suspension in a dose of 15 mg / kg body weight / day, razdelennoy of 2 admission. After oral suspension is recommended to give the child to drink some liquid. Suspension contains tiny granules, which should not chew, because their content has a bitter taste. With the included syringe for oral administration. One-filled syringe seats 5 ml suspension, contains 125 mg clarithromycin. The syringe should be washed after each use.
The dose for children is calculated taking into account the weight of the child, as shown in Table.
| The body weight of the child | Dose per ml (syringe) | Dose mg |
| from 8 kg to 10 kg | 2.5 -3 ml 2 times / day | 62.5 -75 mg |
| from 10 kg to 12 kg | 3-3.6 ml 2 times / day | 75-90 mg |
| from 12 kg to 14 kg | 3.6-4.2 ml 2 times / day | 90-105 mg |
| from 14 kg to 16 kg | 4.2-4.8 ml 2 times / day | 105-120 mg |
| from 16 kg to 18 kg | 4.8-5.4 ml 2 times / day | 120-135 mg |
| from 18 kg to 20 kg | 5.4-6.0 ml 2 times / day | 135-150 mg |
| from 20 kg to 22 kg | 6.0-6.6 ml 2 times / day | 150-165 mg |
| from 22 kg to 24 kg | 6.6-7.2 ml 2 times / day | 165-180mg |
| from 24 kg to 26 kg | 7.2-7.8 ml 2 times / day | 180-195 mg |
| from 26 kg to 28 kg | 7.8-8.4 ml 2 times / day | 195-210 mg |
| from 28 kg to 30 kg | 8.4-9.0 ml 2 times / day | 210-225 mg |
| from 30 kg to 33 kg | 9.0-10 ml 2 times / day | 250 mg |
The course of treatment usually lasts for 7-14 days.
To treatment and prevention of infection, caused by Mycobacterium avium complex, appoint 500 mg every 12 no. The dose can be increased. The maximum daily dose is 2 g.
Babies the drug is prescribed in a dose 15 mg / kg / day, razdelennoy of 2 admission. The dose should not exceed 500 mg every 12 no. The maximum daily dose, recommended children, is 1 g.
Treating infections, caused by Mycobacterium avium complex, long, duration is 6 months or more.
In patients with renal insufficiency with CC less 30 ml / min, or the content of serum creatinine 290 mmol / l (3.3 mg / dL), the dose should be reduced 2 times or double the interval between doses. The maximum duration of treatment in this patient group -14 days.
Rules suspension for oral administration
To prepare the suspension is necessary 42 ml of water. Pre-Shake, the pellets in it crumbled. Add 1/4 the volume of water in a bottle and shake to dissolve the granules. Add the remainder of water and shake well. The volume of the finished suspension should reach the line mark on the bottle.
Side effect
With the digestive system: nausea, vomiting, diarrhea, abdominal pain, stomatitis, glossitis, short-term discoloration of the teeth and tongue, pancreatitis, pseudomembranous enterocolitis, cholestatic jaundice, hepatitis, increase in liver transaminases and alkaline phosphatase, increase in serum bilirubin levels. Liver dysfunction may be severe, but it is usually reversible. Rarely – cases of liver failure and death largely on the background of severe concomitant diseases and / or concomitant medication.
From the central and peripheral nervous system: headache, vertigo, paresthesia, drowsiness, hallucinations, convulsions, psychosis, dizziness, confusion, a sense of fear, insomnia, nightmares, depersonalization, disorientation.
From the hematopoietic system: leukopenia, neutropenia.
From the senses: change in taste (disgevziya), olfactory, tinnitus, short-term hearing loss, passing after drug withdrawal.
Cardio-vascular system: QT prolongation on the ECG, type of ventricular tachycardia “pirouette”.
The respiratory system: breathlessness.
On the part of the musculoskeletal system: arthralgia, myalgia.
From the urinary system: interstitial nephritis, renal failure, increase in serum creatinine levels, Uric acid.
Metabolism: hypoglycemia in patients, taking hypoglycemic drugs.
Allergic reactions: skin rash, hives, itching, swelling of the face, anaphylactic shock, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), angioneurotic angioedema.
From the blood coagulation system: prolonged prothrombin time, thrombocytopenia (unusual bleeding, hemorrhage).
Other: long-term use may develop superinfection cases, candidiasis, microbial resistance (psevdomembranoznыy colitis, oral candidiasis).
Contraindications
- Severe hepatic impairment;
- Hepatitis (history);
- Porphyria;
- I trimester of pregnancy;
- Lactation;
- Odnovremennaya therapy terfenadinom, cizapridom, pimozide or astemizole;
- Children up to age 6 months (for the dosage form – granules for oral suspension) – there is no sufficient experience regarding the efficacy and safety of;
- Children up to age 12 s and / or children weighing less than 33 kg (for the dosage form – tablets, Film-coated);
- Congenital fructose intolerance, malabsorption syndrome glucose / galactose enzyme deficiency, or sucrase-isomaltase (only for the dosage form – granules for oral suspension);
- Hypersensitivity to the drug;
- Hypersensitivity to other macrolide antibiotics.
FROM caution should use the drug in patients with renal failure secondary to severe, hepatic failure, in the II and III trimesters of pregnancy.
Pregnancy and lactation
Application Fromilid® I trimester of pregnancy is contraindicated.
Application Fromilid® II and III trimester of pregnancy is possible only in cases, when the expected benefit of therapy for the mother outweighs the potential risk to the fetus.
If necessary, use during lactation should stop breastfeeding.
Cautions
In appointing the drug should be considered, Among macrolide antibiotics there is cross-resistance.
Patients with impaired hepatic function, and mild to moderate severity is not necessary to reduce the dose of the drug, If renal function is normal. Patients with severely impaired renal function dose should be reduced.
If you have chronic liver disease should be carried out regular monitoring of serum enzymes.
When concomitant administration of medicines, metabolized in the liver, recommended to control their concentration in the serum.
Treatment with antibiotics alters the normal flora of the intestine, so it is possible the development of superinfection, caused by resistant microorganisms.
Patients should be warned, that in severe persistent diarrhea, which may be caused by pseudomembranous colitis, he should see a doctor.
Periodically monitor the prothrombin time in patients, receiving clarithromycin concurrently with warfarin or other oral anticoagulants.
IN 125 mg granules for oral suspension 125 mg / 5 ml containing 1.6 g sucrose, and the drug is contraindicated in children with congenital fructose intolerance, with malabsorption syndrome glucose / galactose, or deficiency of the enzyme sucrase-isomaltase.
Use in Pediatrics
At present, there is insufficient data on the efficacy and safety of the drug in children aged 6 Months.
Effects on ability to drive vehicles and management mechanisms
The drug has no effect on the speed of psychomotor reactions while driving or operating machinery.
Overdose
Symptoms: vomiting, abdominal pain, headache, confusion.
Treatment: gastric lavage, further symptomatic therapy.
Drug Interactions
Clarithromycin is metabolized in the liver and can inhibit the activity of cytochrome P450 isozymes. With simultaneous use of clarithromycin and other drugs, metabolized with the participation of these isoenzymes, may increase the concentration of these agents in serum and the development of side effects. In an application Fromilid® with terfenadine, cizapridom, pimozide and astemizole may develop life-threatening arrhythmias (these combinations are contraindicated).
In an application Fromilid® increases the risk of side effects of theophylline, karʙamazepina, digoksina, Lovastatin, simvastatin, triazolama, midazolama, phenytoin, cyclosporine, dizopiramida, rifaʙutina, tacrolimus, itraconazole and ergot alkaloids; therefore, the combination therapy should monitor the concentrations of these drugs in the blood plasma.
Periodically monitor the prothrombin time in patients, receiving clarithromycin concurrently with warfarin or other oral anticoagulants.
In an application Fromilid® and zidovudine decreases absorption of zidovudine (between doses of these drugs should be an interval of at least 4 no).
The simultaneous use of ritonavir, clarithromycin, and leads to a significant increase in the concentration of clarithromycin and a significant reduction in the concentration of its metabolite 14-hydroxyclarithromycin serum.
Perhaps the development of cross-resistance between clarithromycin, Lincomycin and clindamycin.
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
Tablets should be stored in a dry, inaccessible to children at temperature not exceeding 25 ° C. Shelf life – 5 years.
Granules for suspension should be stored in a place inaccessible to children at temperature not above 30 ° C. Shelf life – 2 year. The obtained suspension can be used for 14 days, if it is stored in a dark place at a temperature not exceeding 25 ° C.
