Tobriss, eye drops 0.3% 5 ml

an aminoglycoside antibiotic

ATX code: S01AA12

Pharmacological action

.Pharmacodynamics

A broad-spectrum antibiotic of the aminoglycoside group. At low concentrations it is bacteriostatic (blocks 30S ribosome subunit and disrupts protein synthesis), but at higher concentrations it is bactericidal (disrupts protein synthesis and permeability of cytoplasmic membrane of microbial cell, causing its death).

Tobramycin-sensitive microorganisms: Aerobic Gram-positive microorganisms: Corynebacterium, Staphylococcus aureus (methicillin-sensitive); coagulase-negative Staphylococcus species (methicillin-sensitive, including penicillin-resistant strains). Gram-negative bacteria: Acinetobacter species; Escherichia coli; Haemophilus influenzae; Klebsiella species; Moraxella species; Morganella morganii; Pseudomonas aeruginosa.

Tobramycin-resistant microorganisms: Aerobic gram-positive microorganisms: some Staphylococcus species resistant to methicillin with resistance rates of up to 50% of all Staphylococcus species in some European countries; Streptococcus pneumoniae and most strains of group D Streptococci.

Some gentamicin-resistant strains retain high sensitivity to tobramycin.

The emergence of resistance to tobramycin is the result of modification and inactivation of antibiotics by enzymes present in the periplasmic space of bacteria. There are three different mechanisms by which aminoglycosides are inactivated: acetylation of amino groups, phosphorylation of hydroxyl groups and adenylation of hydroxyl groups.

Variable sensitivity between aminoglycoside antibiotics relative to other classes of modified enzymes is also possible. The most common mechanism of acquired resistance to aminoglycosides is inactivation of the antibiotic by plasmid and transposon-encoded enzyme modification.

The following are critical minimum inhibitory concentration (MIC) values that separate sensitive S microorganisms (MIC ≤4mg/ml) from conditionally sensitive microorganisms and conditionally sensitive microorganisms from resistant, R (resistant) ≥8 mg/ml. Resistance can vary geographically for the relevant microbial species, so local information regarding resistant microorganisms is desirable, especially when treating severe infections.

Pharmacokinetics

When used topically, systemic absorption is low. Tobramycin poorly penetrates through the cornea and its concentration in aqueous humor after topical administration of 0.3% solution is undetectable. Increasing the frequency of administration may increase the concentration of tobramycin in aqueous humor.

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Indications

Treatment of infectious diseases of the anterior segment of the eyeball caused by tobramycin-sensitive microorganisms in adults and children over 2 months.

Active ingredient

Tobramycin

Composition

Each ml of the drug contains:

Active ingredient:tobramycin-3 mg.

Associates:

Benzalkonium chloride 0.1 mg, hypromellose 2.5 mg, edetate disodium 1.0 mg, sodium chloride 9.0 mg, sodium hydroxide or hydrochloric acid to pH 7.5, water for injection to 1 ml.

How to take, the dosage

In case of a mild course of the infectious process, 1 drop in the conjunctival sac twice a day (morning and evening) for 7 ± 1 days. In case of a severe course of the infectious process on the first day – 1 drop 4 times a day during the waking period, later – 1 drop in the affected eye twice a day during the waking period, the total treatment period of 7 ± 1 days.

To prevent contamination of the tip of the dropper bottle and the solution it is necessary to avoid its contact with the eyelids, periorbital area or other surfaces. The bottle should be closed tightly after use.

If used together with other topical ophthalmic drugs, an interval of 5-10 minutes between instillations should be observed.

Application in the elderly

Dose adjustment is not required when used in the elderly.

Application in the pediatric population

The use of tobramycin eye drops by patients older than 2 months in the same dosages as in adults is possible. The efficacy and safety of the drug in patients younger than 2 months has not been established.

Application in patients with renal and hepatic impairment

Low systemic exposure is noted when tobramycin is used topically. When co-administered with systemic aminoglycoside antibiotics, their plasma levels should be monitored to maintain the required systemic concentrations.

Interaction

No studies of drug interaction with other drugs have been conducted. When combined use of ophthalmic forms of tobramycin and corticosteroids for topical use in ophthalmology, clinical symptoms of bacterial, fungal and viral diseases of the visual organ, as well as hypersensitivity reactions may be masked.

Special Instructions

For topical use in ophthalmology only. The drug is not intended to be administered by injection or oral administration. Hypersensitivity to aminoglycosides for topical use in ophthalmology has been reported in a number of patients. If symptoms of hypersensitivity develop, the drug should be discontinued. Cross-sensitivity to other aminoglycosides has been noted; therefore, it should be taken into account that in case of development of hypersensitivity to tobramycin, hypersensitivity to other aminoglycosides for local or systemic use is possible. Serious adverse reactions such as neurotoxicity, ototoxicity and nephrotoxicity have been reported with oral administration of tobramycin. Caution is required when combined with other aminoglycosides. As with long-term use of other antibiotics, overgrowth of microorganisms insensitive to tobramycin, including fungi, is possible. In case of superinfection the drug should be discontinued. It is not recommended to wear contact lenses during treatment of infectious diseases of the vision. The drug contains benzalkonium chloride, which may cause eye irritation and discoloration of soft contact lenses. Contact of the drug with soft contact lenses should be avoided. Patients should be instructed to remove their contact lenses before using the product and put them back on no earlier than 15 minutes after instillation.

Synopsis

Transparent solution from colorless to light yellow color.

Contraindications

Hypersensitivity to the components of the drug, breast-feeding period, children under 2 months of age.

Side effects

The most common adverse events with the use of the drug were toxicity and local hypersensitivity, including itching of the eyelids, eyelid edema, lacrimation, and conjunctival injection.

The reports of adverse events were obtained from clinical studies and post-registration experience with the drug and were classified according to the following frequency of occurrence gradation: Very common (>1/10), common (>1/100 to <1/10), infrequent (>1/1,000 to <1/100), rare (>1/10,000 to <1/1,000), very rare (<1/10,000), with unknown frequency (incidence cannot be determined based on available data). In each group of adverse events, grouped according to frequency of occurrence, adverse events are presented in descending order of severity.

Immune system disorders

Infrequent: hypersensitivity.

Nervous system disorders

Infrequent: headache.

Visual organ disorders

Often: discomfort in the eye, conjunctival injection, allergic phenomena from the visual organ, itching of the eyelids; infrequent: keratitis, corneal erosion, visual impairment, blurred vision, erythema of the eyelids, ocular discharge, conjunctival edema, eyelid swelling, pain in the eye, dry eye syndrome, itching in the eye, lacrimation; with unknown frequency: eye irritation.

Skin and subcutaneous fatty tissue disorders

Infrequent: urticaria, dermatitis, madarosis, leucoderma, itching, dry skin; with unknown frequency: rash, erythema.

Overdose

No toxic effects are expected from topical ophthalmic use of the drug or in case of accidental swallowing of the vial contents. Clinical manifestations of overdose when using tobramycin by instillation (including pitting keratitis, eyelid erythema, lacrimation, conjunctival edema, itching of eyelids) may be similar to the adverse events reported in some patients during treatment with the drug.

Pregnancy use

Fertility

There have been no clinical studies on the effect of tobramycin in the dosage form of eye drops on fertility in humans.

Pregnancy

In oral administration of tobramycin in doses significantly higher than those for instillation use, nephrotoxicity and ototoxicity have been reported. Oral administration of tobramycin penetrates through the placenta into the amniotic fluid and fetal blood. No fetal risks have been observed in studies of parenteral use of aminoglycoside antibiotics, including tobramycin. High plasma levels of tobramycin are not expected after instillation administration.

There is no or limited information on the use of the drug in the therapy of pregnant women. Reproductive toxicity has been reported in animal studies. The use of the drug during pregnancy is not recommended.

Breastfeeding

Tobramycin is excreted into breast milk in significant amounts when administered orally and parenterally. When administered by instillation, systemic exposure of the drug is low, which makes excretion of tobramycin into breast milk unlikely. Breastfeeding should be discontinued or therapy with the drug should be interrupted/terminated, taking into account the benefit of therapy for the mother and the benefit of breastfeeding for the child.

Similarities

Tobrex, Tobropt