The need to supplement the instructions for the use of medicinal products with the following information is revealed:
The section "Contraindications" should be presented in the following edition: "Hypersensitivity to any aminoglycosides; Pregnancy and lactation period; Children under 6 years of age (efficacy and safety have not been established to date).In patients with severe renal dysfunction (creatinine content in the blood plasma of more than 2 mg / dL or 176.8 mmol / l), there is no experience with tobramycin. "
The section "With caution" should be presented in the following edition: "In case of violations of auditory or vestibular apparatus, in patients with established or suspected renal diseases, with neuromuscular disorders such as parkinsonism or other diseases accompanied by muscle weakness, including severe pseudo-paralytic myasthenia gravismyasthenia gravis). Since inhalation of the drug with a nebulizer may activate the cough reflex, patients with hemoptysis tobramycin prescribe only in those cases when the expected benefit from therapy exceeds the potential risk of developing pulmonary hemorrhage. "
The section "Application during pregnancy and during breast-feeding" should be submitted in the following edition: "Pregnancy - Prescribe the drug during pregnancy should be only in cases where the expected benefit for the mother exceeds the potential risk to the fetus. The use of tobramycin 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). 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.
Breastfeeding period - It is not known whether the tobramycin with breast milk after inhalation of the drug. Considering the ototoxic and nephrotoxic effect of tobramycin, if it is necessary to use the drug during lactation it is recommended to stop feeding the baby with breast milk. "
The section "Method of administration and dose" should be supplemented with the following information: "Since the inhalation solution contains no preservatives, it should be used immediately after opening a sterile polyethylene ampoule! The contents of one polyethylene ampoule are used once.
If inhaled, the patient should sit or stand directly and calmly breathe through the mouthpiece of the nebulizer. The use of nasal clamps helps the patient to breathe properly through the mouth.
Use in patients of the older age group ≥65 years There is insufficient experience in the use of the drug in this category of patients; dosage regimen, in patients over 65 years of age must be selected individually. It is necessary to take into account the state of kidney function in the appointment of tobramycin to patients of the older age group.
Patients with hepatic insufficiency The efficacy and safety of tobramycin in patients with impaired liver function have not been studied. But, tobramycin is not metabolized by liver enzymes, therefore, changes in the systemic bioavailability of the drug in patients with hepatic insufficiency are unlikely.
Patients after transplantation The efficacy and safety of tobramycin in patients after transplantation has not been studied. "
The section "Side effect" is presented in the following edition: "When used in patients with cystic fibrosis, the following adverse events were reported most often: cough, pharyngitis, productive cough, asthenia, rhinitis, dyspnea, fever, lung function disorder, headache , chest pain, sputum change, hemoptysis, anorexia, decreased lung function, bronchial asthma,vomiting, abdominal pain, nausea and weight loss, pain in the oropharynx and larynx, taste disorders and dysphonia.
In children and adolescents, cough was noted more often than in adults, but adults more often than children interrupted treatment with the drug due to coughing.
In clinical studies, the most frequent AEs associated with taking the drug were voice changes and tinnitus.
Dysphonia was moderately pronounced and often occurred during the administration of the drug. All episodes of noise in the ears were temporary, disappeared after the termination of therapy with tobramycin and were not associated with deterioration of hearing. During the post-registration period, there were cases of hearing impairment (often together with noise in the ears) in patients receiving tobramycin therapy.
Some of the patients described simultaneously received systemic aminoglycosides.
AEs are grouped according to the classification of organs and systems of organs MedDRA, within each group are listed in order of decreasing frequency: very often (≥1 / 10), often (≥1 / 100, <1/10), infrequently (≥1 / 1000, <1/100), rarely (≥ 1/10000, <1/1000), very rarely (<1/10000), including individual messages.
Infectious and parasitic diseases
Often: pharyngitis, rhinitis;
often: infections of the upper respiratory tract.
Disturbances from the nervous system
Often: headache.
Hearing disorders and labyrinthine disorders
often: noise in ears.
Disturbances from the respiratory system, organs of the chest and mediastinum
Often: cough, productive cough, shortness of breath, pulmonary dysfunction, spitting color change, hemoptysis, bronchial asthma, pain in the oropharynx and larynx, dysphonia.
Disorders from the gastrointestinal tract
Often: anorexia, vomiting, abdominal pain, nausea, taste disorders.
Disturbances from musculoskeletal system and connective tissue
Often: pain in the chest; often: myalgia.
General disorders and disorders at the site of administration
Often: asthenia, fever, weight loss; often: general malaise.
Impact on the results of laboratory and instrumental studies
often: decreased lung function.
Below are the AEs detected in patients who used tobramycin in the course of clinical trials during the post-marketing period, as well as in clinical practice and laboratory studies.For AEs detected in clinical practice and laboratory studies, it is not possible to establish frequency of occurrence, therefore for these AEs it is indicated: "frequency is unknown".
Impaired nervous system: loss of voice, change in taste perception.
Hearing disorders and labyrinthine disturbances: loss of hearing.
Disturbances from the skin and subcutaneous tissues: reactions hypersensitivity, skin itching, hives, rash.
Disturbances from the respiratory system, chest and mediastinal organs: bronchospasm, pain in the oropharynx, increased sputum formation, pain in the chest.
General disorders and disorders at the site of administration: loss of appetite. "
The section "Interaction with other drugs" should be read as follows: "In clinical trials with the combined use of tobramycin with dornase alpha, β2-agonists, inhaled glucocorticosteroids, oral or parenteral antibiotics active against Pseudomonas aeruginosa, profile safety did not differ from that in the control group. It should be avoided 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 together with ethacrynic acid, furosemide, urea or mannitol for intravenous administration. The drugs listed below can also increase the potential toxicity of parenterally administered aminoglycosides: amphotericin B, cephalothin, ciclosporin, polymyxins (possibly enhancing nephrotoxic effect); platinum compounds (possibly enhancing nephrotoxic and ototoxic action); anticholinesterase drugs, botulinum toxin (effect on the neuromuscular system). "