Tobrisse - instructions for use, doses, side effects, contraindications

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

Description:Transparent solution from colorless to light yellow color.

Pharmacotherapeutic group:Antibiotic-aminoglycoside

ATX: & nbsp

J.01.G.B Other aminoglycosides

J.01.G.B.01 Tobramycin

Pharmacodynamics:

A broad-spectrum antibiotic from the aminoglycoside group. At low concentrations, it acts bacteriostatically (blocks 30S subunit of ribosomes and violates protein synthesis), and in higher bactericidal (disrupts protein synthesis and permeability of the cytoplasmic membrane of the microbial cell, causing its death).

Sensitive to tobramycin microorganisms: Aerobic Gram-positive microorganisms: Corynebacterium, Staphylococcus aureus (sensitive to methicillin); coagulase-negative types of staphylococci (sensitive to methicillin, including penicillin-resistant strains). Gram-negative bacteria: Species Acinetobacter; Escherichia coli; Haemophilus influenzae; kinds Klebsiella; kinds Moraxella; Morganella morganii; Pseudomonas aeruginosa.

Resistant to tobramycin microorganisms: Aerobic Gram-positive microorganisms: some species Staphylococcus, resistant to methicillin with a frequency of resistance to 50% of all types of staphylococci in some European countries; Streptococcus pneumoniae and most streptococcal strains of the group D.

Some gentamycin 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 against other classes of modified enzymes is also possible. The most common mechanism of acquired resistance to aminoglycosides is the inactivation of the antibiotic by modifying plasmids and transposon-encoded enzymes.

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

Microorganism	The minimum inhibitory concentration (mg / ml)
Staphylococcus aureus	0.2
Streptococcus pyogenes	12.5
Streptococcus pneumoniae	25
Pseudomonas aeruginosa	0.6
Escherichia coli	1.2
Klebsiella pneumoniae	0.8
Proteus mirabilis	1.2
Proteus vulgaris	1.2
Proteus morganii	1.2
Proteus rettgeris	2.5
Haemophilus	0.5
Neisseria	5.0

Pharmacokinetics:

With topical application, systemic absorption is low. Tobramycin poorly penetrates the cornea, and its concentration in aqueous humor after topical application of 0.3 % solution is not determined. Increasing the frequency of application can increase the concentration of tobramycin in aqueous humor.

Indications:Treatment of infectious diseases of anterior segment of the eyeball caused by microorganisms sensitive to tobramycin, in adults and children older than 2 months.

Contraindications:

Hypersensitivity to the components of the drug, the period of breastfeeding, children under 2 months.

Pregnancy and lactation:

Fertility

No clinical studies have been conducted to study the effect of tobramycin in the drug form of eye drops on fertility in humans.

Pregnancy

When oral administration of tobramycin at doses much higher than those for use as instillations, the phenomena of nephro- and ototoxicity are noted. Tobramycin when administered orally, it penetrates the placenta into amniotic fluid and fetal blood.In a study of the parenteral use of antibiotics-aminoglycosides, including tobramycin, there were no risks to the fetus. No high level of tobramycin in the plasma is expected after application as instillations.

Information about the use of the drug in the therapy of pregnant women is absent or limited. In animal studies, information has been obtained on reproductive toxicity. It is not recommended to use the drug during pregnancy.

Breastfeeding period

Tobramycin is excreted in breast milk in a significant amount when administered orally and parenterally. When applied as instillations, the system exposure of the drug is low, which makes it unlikely that excretion of tobramycin into breast milk. It is necessary to stop breastfeeding or interrupt / discontinue drug therapy, taking into account the benefits of therapy for the mother and the benefits of breastfeeding for the baby.

Dosing and Administration:

In the case of an easy flow of the infectious process, 1 drop into the conjunctival sac 2 times a day (morning and evening) for 7 ± 1 days. In the case of a severe course of the infectious process on the first day, 1 drop 4 times a day inperiod of wakefulness, in the subsequent - 1 drop to the affected eye twice a day during waking period, the total period of treatment is 7 ± 1 days.

To prevent contamination of the tip of the vial and solution, avoid contact with the eyelids, the peri-ocular area or other surfaces. After use, it is necessary to close the bottle tightly.

In the case of joint application with other medicines for topical application in ophthalmology, an interval of 5-10 minutes between instillations should be observed.

Application in the elderly

Do not require dose adjustment when used in the elderly.

Use in the pediatric population

The use of eye drops of tobramycin in 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 is not established.

Patients with renal and hepatic insufficiency

With topical application of tobramycin, its low system exposure is noted. In the case of combined use with systemic aminoglycoside antibiotics, it is necessary to monitor their level in the plasma to maintain the required systemic concentrations.

Side effects:

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

Information on adverse events was obtained during clinical trials and post-registration experience of the drug and classified according to the following gradation frequency: Often (≥1/10), often (from ≥1 / 100 to <1/10), infrequently (from ≥1 / 1,000 to <1/100), rarely (from ≥1 / 10,000 to <1 / 1,000), rarely (<1/10,000), with unknown frequency (frequency of occurrence can not be determined on the basis of available data). In each group of adverse events grouped according to the frequency of occurrence, adverse events are presented in descending order of severity.

Immune system disorders

Infrequent: hypersensitivity.

Disturbances from the nervous system

Infrequently: a headache.

Disturbances on the part of the organ of sight

Often: discomfort in the eye, conjunctival injection, allergic phenomena from the side of the eye, itchy eyelids; infrequently: keratitis, corneal erosion, visual impairment, blurred vision,erythema eyelids, discharge from the eyes, edema of the conjunctiva, eyelid edema, pain in the eye, dry eye syndrome, itching in the eye, lacrimation; with an unknown frequency: eye irritation.

Disturbances from the skin and subcutaneous fat

Infrequent: urticaria, dermatitis, madarose, leukoderma, itching, dry skin; from unknown frequency: rash, erythema.

Overdose:

No toxic effects are expected with local ophthalmic use of the drug or in the event of accidental ingestion of the contents of the vial. Clinical manifestations of an overdose with tobramycin in the form of instillations (including point keratitis, erythema eyelids, lacrimation, edema of the conjunctiva, itching of the eyelids) may be similar to the undesirable phenomena observed in a number of patients during treatment with the drug.

Interaction:

Studies of drug interaction with other drugs have not been conducted. With the combined use of ophthalmic forms of tobramycin and corticosteroids for topical application in ophthalmology, clinical symptoms of bacterial, fungal and viral diseases of the eye can be masked, and hypersensitivity reactions can be suppressed.

Special instructions:

Only for topical application in ophthalmology. The drug is not intended for use in the form of injections or oral administration.

Hypersensitivity to aminoglycosides for topical application in ophthalmology has been noted in a number of patients. When the symptoms of hypersensitivity develop, the drug should be discontinued. Cross-sensitivity to other aminoglycosides has been noted, therefore it must be taken into account that hypersensitivity to tobramycin may lead to hypersensitivity to other aminoglycosides for local or systemic use.

There have been serious adverse reactions, such as neurotoxicity, ototoxicity and nephrotoxicity, with oral administration of tobramycin. Care must be taken when combined with other aminoglycosides. As with long-term use of other antibiotics, excessive growth of microorganisms insensitive to tobramycin, including fungi, is possible. In case of development of superinfection, the use of the drug should be stopped.

It is not recommended to wear contact lenses during the treatment of infectious diseases of the organ of vision.

The composition of the drug is benzalkonium chloride, which can cause eye irritation and discoloration of soft contact lenses. Avoid contact with soft contact lenses. Patients should be instructed to remove contact lenses before using the drug and re-donning them no earlier than 15 minutes after instillation.

Effect on the ability to drive transp. cf. and fur:

Form release / dosage:

Eye drops 0,3%.

Packaging:

5 ml in a plastic bottle-dropper with a screw cap. Each vial-dropper along with the instruction for use is placed in a cardboard box.

Storage conditions:

At a temperature of no higher than 30 ° C in a dark place. Do not freeze.

Keep out of the reach of children.

Shelf life:

2 years.

30 days after opening the bottle.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-000202

Date of registration:11.02.2011 / 01.06.2016

Expiration Date:Unlimited

The owner of the registration certificate:Sentiss Pharma Pvt. Ltd.Sentiss Pharma Pvt. Ltd. India

Manufacturer: & nbsp

SENTISS PHARMA Pvt. Ltd India

Representation: & nbspSENTISS RUSS LLCSENTISS RUSS LLCRussia

Information update date: & nbsp24.10.2016

Illustrated instructions

Instructions

Tobrisse (Tobriss)