Tobramycin-Gobbi - instructions for use, dose, side effects, contraindications

It blocks the 30S subunit of ribosomes and inhibits protein synthesis (bacteriostatic action). At higher concentrations, it disrupts the function of cytoplasmic membranes, causing cell death.

Highly active against gram-negative microorganisms; Pseudomonas aeruginosa, as well as for Acinetobacter spp., Escherichia coli, Klebsiella spp., Serratia spp., Providencia spp., Enterobacter spp., Proteus spp., Salmonella spp., Shigella spp .; for some gram-positive microorganisms: Staphylococcus spp. (including resistant to penicillins, cephalosporins), some strains of Streptococcus spp., Enterococcus spp.

Pharmacokinetics:

Tobramycin is a cationic polar molecule that does not immediately pass through epithelial membranes. The biological availability of tobramycin may vary due to individual differences in the performance of the nebulizer and the pathology of the airways. Absorption and distribution.

Concentrations in sputum: ten minutes after the first dose (300 mg) of the drug was inhaled, the average concentration of tobramycin is 1237 μg / g (range 35 to 7414 μg / g). Tobramycin does not accumulate in the phlegm.After 20 weeks of use, the mean concentration in sputum is 1024 μg / g 10 minutes after inhalation (in the range of 39 to 8085 μg / g). After 2 hours after inhalation, the concentration of tobramycin in sputum is 14% of its concentration in sputum 10 minutes after inhalation.

Concentrations in serum: the average concentration of tobramycin one hour after the inhalation of a single dose of 300 mg in patients with cystic fibrosis was 0.95 μg / g. After 20 weeks of therapy with tobramycin, the average serum concentration one hour after inhalation was 1.05 μg / g.

Excretion: elimination of tobramycin from the body during inhalation was not studied. The half-life of tobramycin from the blood plasma is approximately 2 hours after intravenous administration. With intravenous administration, the drug is excreted mainly by the kidneys by glomerular filtration. Binding of the drug to plasma proteins is less than 10%. With inhalation, the most likely excretion of tobramycin is mainly sputum.

Indications:Respiratory tract infections caused by Pseudomonas aeruginosa in patients with cystic fibrosis.

Contraindications:

Hypersensitivity (including to other aminoglycosides), children's age (up to 6 years), severe renal dysfunction (creatinine content more than 2 μg / ml).

Carefully:

In patients with impaired function of auditory or vestibular apparatus, with established or suspected renal diseases, with neuromuscular pathologies (Parkinsonism or other diseases accompanied by muscle weakness, including severe pseudo-paralytic myasthenia gravis, myasthenia gravis).

When the drug is inhaled with a nebulizer, activation of the cough reflex can be possible, so administration of the drug to patients with haemoptysis is possible in those cases when the expected benefit from therapy exceeds the potential risk of pulmonary hemorrhage.

Pregnancy and lactation:

Prescribe the drug in pregnancy should be only if there are "vital" indications and in those cases when the expected benefit for the mother exceeds the potential risk to the fetus. The use of the drug in pregnant women has not been studied. In experimental studies tobramycin had no teratogenic effect. However, when used during pregnancy aminoglycosides can have damaging effects on the fetus (congenital deafness).The decision to prescribe the drug during pregnancy should be taken by a doctor. It is necessary to inform patients receiving therapy with the drug during pregnancy or planning to become pregnant, about the potential risk to the fetus. It is not known whether tobramycin with breast milk after inhalation of the drug. Taking into account the possible ototoxic and nephrotoxic effect of tobramycin, it is recommended to stop breastfeeding if it is necessary to use the drug during lactation.

Dosing and Administration:

Inhalation for about 15 minutes, using a nebulizer, sitting or standing upright. Adults and children over 6 years of 300 mg twice a day for 28 days. The interval between administrations should be about 12 hours, but not less than 6 hours.

After the completion of the course, take a break for 28 days and follow the next course as described above.

This dosage form of the drug is not intended for intramuscular and intravenous administration.

Instructions for inhalation

The ampoule with the drug is opened and its contents are placed in the nebulizer chamber. Before the beginning of inhalation it is necessary to check the correctnessthe functioning of a nebulizer and an air compressor. Inhalation is continued until the entire drug is consumed. To ensure breathing through the mouth, it is recommended to use the nasal clip. The flow of the drug should be stable and even.

For proper inhalation, it is recommended that you read the instructions for using the nebulizer.

Side effects:

The most frequent adverse events associated with the use of the drug were voice changes and tinnitus. These phenomena were temporary and disappeared after discontinuation of therapy with the drug. Noise in the ears is not associated with auditory disorders and does not increase with repeated courses of therapy with the drug.

The incidence of adverse events with TOBRAMYCIN-GOBBI was evaluated as follows: sometimes> 0.1% to <1%, rarely from> 0.01% to <0.1%, very rarely <0.01%.

From the digestive system: rarely - nausea, loss of appetite, vomiting, ulcers of the oral mucosa; very rarely - diarrhea, abdominal pain and candidiasis of the oral mucosa.

From the hemopoietic system: rarely - lymphadenopathy.

From the nervous system: rarely - dizziness, very rarely - drowsiness.

From respiratory system: sometimes - voice changes (including hoarseness), aphonia, dyspnea, increased cough, sore throat; rarely - bronchospasm, tightness in the region of the sternum, increasing the amount of sputum, hemoptysis, worsening of respiratory function parameters, laryngitis, nasal bleeding, rhinitis, exacerbation of asthma; very rarely - hyperventilation, hypoxia, sinusitis.

From the senses: possible ototoxicity (often - ringing, buzzing in the ears, very rarely - pain in the ears of the individual cases of partial or total hearing loss) and vestibular and labyrinth disorders (very rarely - impaired coordination, rarely - dizziness, nausea, vomiting , instability), rarely - distortion of taste.

On the part of the body as a whole: rarely - chest pain, asthenia, fever, headache; very rarely - allergic reactions, including hives and itching, fungal infection, general malaise, back pain.

Dermatological reactions: rarely - a rash.

Signs such as discoloration, respiratory tract infections, myalgia, nasal polyps and otitis media,are symptoms of cystic fibrosis, but the relationship between drug use and the occurrence of these phenomena can not be excluded.

When the drug was used, no nephrotoxic effect was noted. In patients who underwent prolonged previous therapy with aminoglycosides, as well as in patients receiving concomitant intravenous therapy with aminoglycosides, several cases of hearing loss were recorded. Parenteral therapy with aminoglycosides is associated with side effects such as ototoxicity and nephrotoxicity.

Overdose:

Inhalational administration provides low absorption and bioavailability of the drug Tobramycin is poorly absorbed from the gastrointestinal tract, therefore, when the drug is taken orally, a toxic effect is unlikely.

One of the symptoms of a drug overdose is severe hoarseness.

Symptoms of an overdose with occasional intravenous administration included dizziness, tinnitus, hearing loss, respiratory failure and / or neuromuscular blockade, as well as impaired renal function.

To diagnose an overdose of the drug it is necessary to determine the concentration of tobramycin in the blood plasma.

In case of an overdose, the patient should be monitored and appropriate symptomatic treatment should be prescribed.

Interaction:

Strengthens the effect of nondepolarizing muscle relaxants. Reduces the effect of antimiasthenic drugs.

It is necessary to avoid the simultaneous and / or consistent use of tobramycin with drugs that have nephrotoxicity or ototoxicity.

Some diuretics can increase the toxicity of aminoglycosides by changing the concentrations of antibiotic in blood plasma and tissues. Tobramycin Do not use with furosemide, urea or mannitol.

Amphotericin B, cephalothin, ciclosporin, polymyxins enhance the nephrotoxic effect of the drug; Platinum compounds can also increase the potential toxicity of injected parenteral aminoglycosides (possibly enhancing nephrotoxic and ototoxic effects); cholinesterase inhibitors, botulinum neurotoxins enhance the effect on neuromuscular conductivity.

Special instructions:

The drug should be treated only under the supervision of a doctor who has experience in the treatment of cystic fibrosis. The drug should not be diluted or mixed with other drugs, including nebulizer vessels. If after a single inhalation application in the ampoule remained unused solution of the drug, it should be disposed of properly. Re-use unused solution is not allowed.

Treatment with the drug, alternating therapy courses with interruptions, is carried out as long as the clinical effect remains. With worsening of the course of the disease against the background of treatment with tobramycin, consideration should be given to the appointment of additional antimicrobial therapy active against Pseudomonas aeruginosa. With the use of the drug continue to follow the standard regime of physiotherapeutic procedures. If necessary, treatment with bronchodilators can be continued. Complex therapy is recommended in the following order: taking bronchodilators, physiotherapy procedures, inhalation of other medicines and in conclusion - inhalation with tobramycin.

Since after the inhalation of tobramycin in rare cases, the development of bronchospasm was noted, the first dose of the drug is inhaled under the supervision of a doctor. The prescribed bronchodilator therapy should be performed before the first inhalation of the drug. Before and after inhalation of tobramycin, it is necessary to determine the function of external respiration, the volume of a fixed exhalation (FEV1). With the development of bronchospasm in patients who do not receive bronchodilator therapy, the definition of FEV1 should be repeated, in some cases with the use of bronchodilators. If bronchospasm is not eliminated after using bronchodilators, then the cause of its development may be increased sensitivity to the drug. If suspected of an allergic reaction to inhalation, tobramycin should be discontinued and appropriate bronchodilator therapy initiated.

Before starting therapy with the drug, it is necessary to assess the function of the kidneys. After every 6 complete cycles of tobramycin therapy, the urea and creatinine levels in the blood plasma are repeatedly determined (1 cycle is a 28-day course of treatment followed by a 28-day break).

In the presence of signs of nephrotoxicity, drug treatment should be stopped until the content of tobramycin in the blood plasma is less than 2 μg / ml. After this, at the doctor's discretion, treatment can be resumed. In patients with impaired renal function, it is necessary to regularly determine the concentration of tobramycin in the blood plasma.

When the drug was used together with aminoglycosides administered intravenously, or in patients who previously received prolonged intravenous therapy with aminoglycosides, hearing impairment was observed. Given the potential ototoxicity of aminoglycosides, during the treatment with the drug, it is necessary to determine the severity of hearing in patients with any hearing impairment (tinnitus, reduced hearing acuity), and at the risk of such complications (especially with previous long-term systemic aminoglycoside therapy). In patients who received long-term systemic treatment with aminoglycosides, it is necessary to determine the severity of hearing before prescribing.

Given the risk of developing cumulative toxicity, it is necessary to ensure that patients are monitored,receiving concomitant parenteral therapy with other aminoglycoside antibiotics. Aminoglycosides can have a curare-like effect on neuromuscular transmission and enhance muscle weakness.

There is a theoretically possible risk that patients with inhaled tobramycin may develop Pseudomonas aeruginosa resistance to intravenous tobramycin.

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

The adverse effect of the drug on the ability to drive vehicles and engage in other activities that require concentration and speed of psychomotor reactions were not reported. However, given that the drug may cause dizziness or drowsiness, care should be taken when implementing these activities.

Form release / dosage:

Solution for inhalation 60 mg / ml.

Packaging:

5 ml (300 mg of active ingredient) of the drug into ampoules of low-density polyethylene with a capacity of 5 ml.

4 ampoules are placed in a bag of laminated foil.

For 28 ampoules (7 packets) or 56 ampoules (14 packs), together with the instructions for use, are placed in a cardboard box.

Storage conditions:

At a temperature of 2 to 8 ° C in a dark place.

Keep out of the reach of children.

Shelf life:

3 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LSR-006248/10

Date of registration:01.07.2010

The owner of the registration certificate:Laboratory Tutor SAASIFAALaboratory Tutor SAASIFAA Argentina

Manufacturer: & nbsp

Laboratorio TUTEUR S.A.C.I.F.I.A. Argentina

PROTERA, LTD. Russia

Representation: & nbspHEAD OF MEDICA SAHEAD OF MEDICA SASwitzerland

Information update date: & nbsp13.09.2015

Illustrated instructions

Instructions

Tobramycin-Gobbi (Tobramycin-Gobbi)