Tobrex eye drops 3mg/ml 5ml №1

Name:
Tobrex drops Ch. 0.3% in vial.-cap. 5 ml in pack No. 1
Description:
Transparent solution from colorless to light yellow or brown. The main active ingredient is tobramycin. Release form Drops. Pharmacological action Pharmacodynamics Mechanism of action: Tobramycin is an active, fast-acting, broad-spectrum bactericidal aminoglycoside antibiotic. The main effect on bacterial cells is manifested through inhibition of the assembly and synthesis of the polypeptide on the ribosome. Mechanism of resistance: Tobramycin resistance develops through various mechanisms, including: 1) a change in the subunit of the ribosome within the bacterial cell; 2) violation of the transport of tobramycin into the cell; 3) inactivation of tobramycin by adenylation, phosphorylation and acetylation by enzymes. Genetic information about the formation of inactivating enzymes can be carried by bacterial chromosomes or plasmids. Cross-resistance with other aminoglycosides is possible. Breakpoints: Below are the breakpoints and in-vitro spectrum for systemic use. These breakpoints may not be applicable for topical ophthalmic use, as higher concentrations are observed and the physical/chemical conditions at the injection site may affect drug activity. In accordance with EUCAST, the following breakpoints have been established for tobramycin: Enterobacteriaceae S?2 mg/l, R>4 mg/l; Pseudomonas spp. S?4 mg/l, R>4 mg/l; Acinetobacter spp. S?4 mg/l, R>4 mg/l; Staphylococcus spp. S?1 mg/l, R>1 mg/l; regardless of the type S?2 mg/l, R>4 mg/l. Clinical Efficacy Against Specific Pathogens: The information below is a rough guide to possible susceptibility of microorganisms to the tobramycin contained in TOBREX. The following are strains of microorganisms that are found in external eye infections, such as conjunctivitis. The incidence of acquired resistance in some strains may vary by location and time, so it is desirable to have local information on microbial resistance. In particular, expert advice is needed in the treatment of severe infections in settings where microbial resistance is such that the efficacy of tobramycin, at least in some types of infections, is questionable. Susceptible strains: – aerobic gram-positive microorganisms: Bacillus megaterium. Bacillus pumilus, Corynebacterium accolens, Corynebacterium bovis, Corynebacterium macginleyi, Corynebacterium pseudodiphtheriticum, Kocuria kristinae, Staphylococcus aureus (methicillin sensitive – MSSA), Staphylococcus epidermidis (coagulase positive and negative) Staphylococcus haemolyticus (methicillin sensitive), Streptococ – MSSH from group A beta-hemolytic, some types of non-hemolytic and some Streptococcus pneumoniae). – aerobic Gram-negative microorganisms: Acinetobacter calcoaceticus, Enterobacter aerogenes, Escherichia coli, Acinetobacter junii, Acinetobacter ursingii, Citrobacter koseri, H. aegyptius, Haemophilus influenzae, Klebsiella oxytoca, Klebsiellae, Morganella morganii, Moraxella catarrhosensista, Moraxella pneumoniae, some species Neisseria, Proteus mirabilis, most strains of Proteus vulgaris. Pseudomonas aeruginosa, Serratia liquifaciens. Strains that can become resistant: Acinetobacter baumanii, Bacillus cereus, Bacillus thuringiensis, Kocuria rhizophila, Staphylococcus haemolyticus (methicillin-resistant – MRSH), Staphylococcus (other coagulase-negative species), Serratia marcescens. Microorganisms with their own resistance: – aerobic gram-positive microorganisms: Enterococci faecalis, Staphylococcus aureus (methicillin-resistant – MRSA), Streptococcus mitis, Streptococcus pneumonia, Streptococcus pyogenes, Streptococcus sanguis; – aerobic gram-negative microorganisms: Haemophilus influenzae, Stenotrophomonas maltophilia, Chryseobacterium indologenes, Burkholderia cepacia; – anaerobic microorganisms: Propionibacterium acnes. Bacterial susceptibility studies show that, in some cases, gentamicin-resistant organisms remain susceptible to tobramycin. Pharmacokinetic/Pharmacodynamic relationship: No specific pharmacokinetic/pharmacodynamic pattern has been established for TOBREX. Published in vitro and in vivo studies show that tobramycin has a prolonged post-antibiotic effect, effectively inhibiting bacterial growth despite low serum concentrations. In studies on systemic use, higher maximum concentrations were reported with a single daily application compared with a multiple daily dosing regimen. Meanwhile, the totality of available data suggests that a single daily systemic application is equivalent in effectiveness to a multiple daily dosing regimen. Tobramycin has a concentration-dependent bactericidal effect at levels above the minimum inhibitory (MIC) and minimum bactericidal (MBC) concentrations. Clinical Study Data: Aggregate safety data from clinical trials can be found in the Adverse Reactions section. Elderly patients: There were no clinical differences in safety or efficacy between the elderly and other adult patients. Pediatric patients: More than 600 pediatric patients participated in 10 clinical studies in which tobramycin eye drops or eye ointment were used to treat bacterial conjunctivitis, blepharitis, or blepharoconjunctivitis. The age of the patients ranged from 1 to 18 years. In general, the safety profile for pediatric patients did not differ from that for adult patients. For children under 1 year of age, there are no dosage recommendations due to the lack of relevant data. Pharmacokinetics Absorption: Tobramycin poorly penetrates the cornea and conjunctiva in rabbits and is minimally absorbed by the tissues of the eye after topical application. In addition, systemic absorption of tobramycin with topical ophthalmic preparations containing tobramycin at a concentration close to TOBREX (0.3%) is clinically insignificant. Due to the high concentration of tobramycin in TOBREX, a much higher concentration at the site of infection (eye surface) is achieved than the MICs of most resistant strains (MICs > 64 µg/ml; the concentration of tobramycin in the human eye one minute after a single dose of TOBREX is 848 ± 674 µg/ml). The concentration of tobramycin in the tear of a healthy person exceeds the MIC90 (16 μg / ml, as described for ophthalmic strains) for at least 44 minutes after the use of TOBREX. Distribution: The volume of distribution in humans is 0.26 l/kg. The binding of tobramycin to human plasma proteins remains low at less than 10%. Biotransformation: Tobramycin is excreted predominantly unchanged in the urine. Excretion: Tobramycin is rapidly and actively excreted by glomerular filtration in the urine in a predominantly unchanged form. The plasma half-life is approximately two hours. Systemic clearance in adult patients with normal renal function ranges from 0.05 to 0.1 l / h / kg and decreases with a decrease in renal function. Linearity/non-linearity: Ophthalmic or systemic absorption with increasing dose concentrations with topical ophthalmic use has not been studied. Therefore, a linear relationship between exposure and dose cannot be established. Patients with hepatic and renal impairment: There are no studies evaluating the use of TOBREX in this type of patient. However, due to the low systemic absorption of tobramycin when applied topically, dose adjustment is not required. Pediatric patients: TOBREX can be used in children 1 year of age and older at the same dosage as in adults. There are limited data on the use of TOBREX in children under 1 year of age. Indications for use TOBREX is indicated for the treatment of external infections of the eyes and their appendages in adults and children aged 1 year and older, caused by bacteria sensitive to tobramycin, including bacteria that are not susceptible to most other antibiotics, especially Pseudomonas aeruginosa. As with other antibiotics, antimicrobial therapy should be monitored. Dosage and administration Dosage; – for diseases of mild severity: 1 or 2 drops in the eye(s) every 4 hours; – for more severe infections: 2 drops in the eye(s) every hour until improvement is achieved, after which the dosage should be reduced before stopping treatment. The duration of treatment depends on the origin of the infection and may vary from a few days to several weeks. Use in pediatric patients: TOBREX eye drops can be used in children from 1 year of age at the same dosage as in adults. Currently available application data are listed in the Pharmacodynamics section. The safety and efficacy of this drug in children under the age of 1 year has not been established, data are not available. Use in elderly patients: There are no differences in clinical data on the efficacy and safety of use in adults and elderly patients. Use in patients with concomitant liver and kidney disease: The efficacy and safety of TOBREX in patients with concomitant liver and kidney disease have not been established. Method of application: For local use in ophthalmology. After opening the vial, before using the drug, remove the tear-off ring, which provides control of the first opening. Keep bottle tightly closed after use. After instillation of eye drops, it is recommended to press the inner corner of the eyes or close the eyelids, which will help reduce systemic absorption and reduce the likelihood of systemic adverse reactions. If several ophthalmic drugs are used simultaneously for treatment, an interval of at least 5 minutes between their use should be observed. If an eye ointment is used for treatment, it should be applied last. To prevent contamination of the suspension and dropper tip, care should be taken not to touch the eyelids, surrounding areas, or any other surface with the dropper tip. Compliance with the following recommendations will help when instilling the drug: WASH HANDS THOROUGHLY BEFORE INSERTING. TIP YOUR HEAD BACK. PULL LOWER EYELID DOWN AND LOOK UP. DROP 1-2 DROPS INTO THE SPACE BETWEEN THE EYELID AND THE EYEBALL. DO NOT TOUCH THE TIP OF THE BOTTLE TO YOUR EYELIDS, EYELASHES AND DO NOT TOUCH IT WITH YOUR HANDS. CLOSE YOUR EYE AND BLET IT WITH A DRY COTTON SWAB. WITHOUT OPENING YOUR EYES, LIGHTLY PRESS ITS INNER CORNER FOR 2 MINUTES. THIS WILL IMPROVE THE EFFICIENCY OF THE DROPS AND REDUCE THE RISK OF DEVELOPING SYSTEMIC ADVERSE REACTIONS. Use during pregnancy and lactation Pregnancy: There are limited data on the use of TOBREX in pregnant women. Tobramycin crosses the placental barrier after intravenous administration to pregnant women. In utero ototoxicity caused by tobramycin is not expected. Animal studies have shown reproductive toxicity at doses in excess of the maximum human dose of TOBREX. Tobramycin did not cause teratogenicity in studies in rats and rabbits. The use of TOBREX during pregnancy is possible only in cases of obvious need. Breast-feeding: Tobramycin is excreted into breast milk after systemic administration. It is not known whether tobramycin is excreted in breast milk after topical ophthalmic use. It is unlikely that significant amounts of tobramycin will be found in breast milk and cause clinical effects in the newborn after topical application of this drug. Since a risk to the nursing infant cannot be ruled out, a decision should be made to discontinue breastfeeding or discontinue/abstain from treatment, taking into account the benefit of breastfeeding for the baby and the benefit of treatment for the woman. Reproductive function: Studies evaluating the effect of topical ophthalmic use of the drug TOBREX on human reproductive function have not been conducted. Influence on the ability to drive a vehicle and work with mechanisms Like any eye drops, the drug can lead to a temporary decrease in visual acuity and affect the ability to drive a vehicle and work with mechanisms. If the patient’s visual clarity is temporarily reduced after using the drug, it is not recommended to drive a vehicle and engage in activities that require increased attention and reaction until it is restored. PrecautionsFor topical use in ophthalmology only. Do not take orally or inject. Some patients may develop hypersensitivity to topical aminoglycosides. The severity of hypersensitivity reactions can vary from local to general reactions such as erythema, pruritus, urticaria, skin rash, anaphylaxis, anaphylactoid or bullous reactions. If signs of hypersensitivity reactions appear during the use of this medicinal product, treatment should be discontinued. Cross-sensitivity is possible with other aminoglycosides. If the topical application of the drug TOBREX is combined with the intake of other aminoglycosides orally, their total concentration in the blood serum should be especially carefully checked (see section “Adverse reactions”). Caution should be exercised as serious adverse reactions such as neurotoxicity, ototoxicity and nephrotoxicity have been reported in patients receiving systemic therapy with tobramycin. As with other antibiotics, prolonged use of TOBREX may lead to the growth of non-susceptible organisms, including fungi. With the development of superinfection, it is necessary to prescribe appropriate therapy. It is not recommended to wear contact lenses during the treatment of ophthalmic infections. Therefore, patients should be advised not to wear contact lenses during treatment with this drug. In addition, TOBREX eye drops contain benzalkonium chloride, which can cause irritation and discolor soft contact lenses. Avoid contact of the drug with soft contact lenses. Patients should be aware that contact lenses should be removed before using TOBREX. After instillation of the drug, it is recommended to wait 15 minutes before putting on contact lenses. To reduce the systemic absorption of TOBREX after instillation, the following is recommended: close the eyelids for 2 minutes; press the inner corner of the eye for 2 minutes with a finger. Interactions with other drugs Clinically significant interactions with topical ophthalmic use are not described. Simultaneous and / or sequential use of aminoglycosides (tobramycin) and other systemic, oral or topical drugs with neurotoxic, ototoxic or nephrotoxic effects may increase the toxicity of the drug, therefore, such use should be avoided if possible. With the simultaneous use of topical corticosteroids in combination with tobramycin, they can mask the clinical manifestations of a bacterial, fungal or viral infection, as well as suppress hypersensitivity reactions. Contraindications Hypersensitivity to the active substance or to any excipient listed in the “Composition” section. Hypersensitivity to aminoglycosides. Composition Each ml of the preparation contains: active substance: tobramycin – 3.0 mg; excipients: boric acid, anhydrous sodium sulfate, sodium chloride, tyloxapol, benzalkonium chloride, sodium hydroxide and / or sulfuric acid (for pH adjustment), purified water. Excipients, the presence of which must be taken into account in the composition of the medicinal product: benzalkonium chloride – 0.1 mg. Overdose Based on the characteristics of this drug, overdose, both in its topical application in ophthalmology, and in case of accidental ingestion of the contents of one vial, is unlikely. Clinically documented signs and symptoms of TOBREX overdose (pitting keratitis, erythema, increased lacrimation, eyelid pruritus and swelling) are similar to adverse reactions observed in some patients. In the event of a local overdose of TOBREX, it is recommended to flush the eye(s) with warm water. Side effects The most common adverse reactions to TOBREX are symptoms of local toxicity and hypersensitivity, including itching and swelling in the eyelids, redness of the eyes, itching of the eyes and increased lacrimation. The following adverse reactions are classified by frequency of occurrence: very often (?1/10), often (from?1/100 to <1/10), infrequently (from?1/1000 to <1/100), rarely (from?1 /10,000 to <1/1000), very rare (<1/10,000), or not known (cannot be estimated from available data). Adverse reactions in each group are presented by frequency in descending order of severity / danger. The list of adverse reactions has been established based on the results of clinical trials and post-registration spontaneous reports. The following adverse reactions have been reported with TOBREX: System Organ Classification - MedDRA Preferred Term (B.15.1) Immune System Disorders - Uncommon: Hypersensitivity Not Known: Anaphylactic Reaction Nervous System Disorders - Uncommon: Headache Ophthalmic Disorders - Common: ocular discomfort, ocular hyperemia Uncommon: keratitis, corneal erosion, decreased visual acuity, blurred vision, eyelid erythema, eyelid oedema, eye discharge, eyelid disorders, conjunctival edema, eye irritation, eye pain, dry eye , itchy eyes, increased tearing Not known: ocular allergy, itching of the eyelids Skin and subcutaneous tissue disorders - Uncommon: urticaria, dermatitis, madarosis (loss of eyelashes), leukoderma, pruritus, dry skin. Not known: rash, erythema, Steven's syndrome - Johnson, erythema multiforme