Toby Podhaler - instructions for use, doses, side effects, contraindications

mass and composition of the capsule shell: 61.0 mg (hypromellose -, 93.8%, water purified 5.0%, carrageenan (E 407) 0.8%, potassium chloride 0.4%, printing ink blue, (shellac, aluminum lacquer based on indigo carmine (E132), titanium dioxide, macrogol) - a sufficient amount, carnauba wax - a sufficient amount). . .

Description:solid transparent capsule № 2, with radially printed blue ink characters "NVR AVCI" on a lid and "" "" on the housing or "" "" on the lid and "NVR AVCI" on the case. The contents of the capsules are white or almost white powder.

Pharmacotherapeutic group:Antibiotic of aminoglycoside group

ATX: & nbsp

J.01.G.B Other aminoglycosides

J.01.G.B.01 Tobramycin

Pharmacodynamics:Tobramitsin is an antibiotic aminoglycoside synthesized by fungi of the genus

Streptomyces tenebrarius. Tobramycin inhibits protein synthesis, which leads to a change in the cell membrane, destruction of the cell wall and subsequent death of the bacterial cell permeability. In concentrations equal to or slightly higher than the minimum inhibitory concentration (MIC), tobramycin bactericidal action against Pseudomonas aeruginosa. Use of the drug within 3 cycles of therapy did not affect the sensitivity of the majority andof the studied strains R. aeruginosa to tobramycin.

In clinical trials tobramycin for inhalation It was shown that decreased sensitivity to tobramycin in vitro Not necessarily reflected in the clinical effectiveness of the drug.The highest concentration of tobramycin in sputum is provided by administration with the aid of an inhaler, which leads to a significant decrease in the concentration R. aeruginosa in sputum and a significant improvement in lung function. In clinical studies, in some patients receiving therapy with TOBI Podhaler, an increase in the minimal inhibitoryconcentrations of aminoglycosides in Pseudomonas aeruginosa.

Pharmacokinetics:ATsating

Serum concentrations: After inhalation of a single dose of tobramycin in 112 mg (4 capsules of 28 mg) in patients with cystic fibrosis, the maximum serum concentration (C_max) of tobramycin was 1.02 ± 0.53 μg / ml, and the mean time to reach mthe maximum concentration (Tma_x) - 1 hour. At the end of the 4-week treatment cycle (112 mg twice daily), the maximum serum concentration of tobramycin 1 hour after inhalation was 1.99 ± 0.59 μg / ml.

Concentrations in sputum: After inhalation of a single dose of 112 mg (4 capsules of 28 mg) of the drug in patients with cystic fibrosis. Tobacco in sputum was 1047 ± 1080 μg / g.

Distribution

Apparent volume of distribution tobramycin in the central circulation in patients with cystic fibrosis is 85.1 l. Despite the fact that the volume distribution changes in depending on body mass index

(BMI) and lung function (FEV1), studies have shown that with a change in BMI or FEV1 Cmax and the minimum concentration (C_min) do not change significantly.

Metabolism

Tobramycin is not metabolized, and in mostly excreted unchanged by the kidneys.

Excretion

Tobramycin is excreted from the systemic blood flow, preferably by rlubochkovoy filtration in unmodified form. In patients with cystic fibrosis, the apparent final half-life of tobramycin from serum after the inhalation of a single dose of 112 mg is about 3 hours.

Apparent serum clearance Tobramycin is 14.5 l / h.

Pharmacokinetics in special cases

Dysfunction of the liver

Pharmacokinetic features The use of the drug in patients with impaired liver function has not been studied. Because the tobramycin is not metabolized by the liver, then its function is not expected to worsen when the drug is used.

Renal impairment

In patients with concentration serum creatinine> 2 mg / dl and urea nitrogen concentration in blood> 40 mg / dL the pharmacodynamics of the drug has not been studied.

The influence of age, gender and race

ACCESSORIES

The pharmacokinetics of tobramycin are not depends on the age of the patients (data on patients from 6 to 66 years old), gender and of race.

Indications:

: Prolonged treatment of chronic pulmonary infection caused by Pseudomonas aeruginosa; 'in patients with cystic fibrosis aged 6 years and older.

Contraindications:

-Improved sensitivity to tobramycin, to any aminoglycosides and other components of the drug;

-Pregnancy and the period of breastfeeding;

-Children under 6 years of age (efficacy and safety of use in children under 6 years old have not been established to date).

Carefully:

If you have one of the listed

DISEASES BEFORE RECEPTION OF THE PREPARATION

ALWAYS CONSULT YOURSELF WITH

BREAKTHROUGH.

Care should be taken when application of Tobi®

Podhaler® patients with the following

diseases (current or

history): violations by

auditory or vestibular

apparatus, impaired renal function,

neuromuscular disorders, such as

Parkinsonism or other diseases,

accompanied by muscle

weakness, including severe

pseudo-paralytic myasthenia gravis

{that as tenia gravis). It should be observed

caution in prescribing

patients of advanced age.

There is no data on the application

in patients with hemoptysis

(> 60 ml per day). Since

inhalation of the drug is possible

activation of the cough reflex, the decision to use Toby® Podhaler® in patients with

hemoptysis is possible only if

The benefits of therapy exceed possible

risks, including the risk of developingthe

Pregnancy and lactation:

Pregnancy

Data on the use of inhaled forms of tobramycin in pregnant women is not enough. Toby use * Podhaler * during pregnancy

it is contraindicated.

In studies of tobramycin in animals, there is no teratogenic effect. However, high concentrations of aminoglycosides in the blood of pregnant women can have an adverse effect on the fetus (eg, the development of congenital deafness), as well as nephrotoxic effects on the mother's body.

Women of childbearing age before use of the drug should be are informed of the potential risk adverse effect of the drug on the fetus in period of pregnancy.

Breastfeeding period

It is not known whether tobramycin at breast milk after inhalation introduction. The use of the drug in the period breastfeeding it is contraindicated.

Dosing and Administration:

Toby® Podhaler® is only for inhalation with using the supplied inhaler (cm. "Instructions for use").

Toby® Podhaler can not enter in any other way

except for inhalation.

Capsules of the drug can not be swallow. !! For inhalation of the drug it is impossible use any other device other than the inhaler.

The drug should be treated with Only under the supervision of a doctor who has experience in the treatment of cystic fibrosis. The drug Tobi® Podhaler® is prescribed adults and children over 6 years old by 112 mg (contents of 4 capsules) 2 times a day (morning and evening) for 28 days regardless of the patient's body weight.

The interval between inhalations of the drug should be about 12 hours, but not less than 6 hours.After a 28-day course of therapy, a break in the use of the drug should be 28 days. It should be strictly abide by the above regimealternating 28-day courses of therapy with 28-day intervals.

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 bronchodilator, physiotherapeutic procedures, inhalation of other drugs and in conclusion - inhalation of Toby® Podhaler®.

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 Tobi® Podhaler®, consideration should be given to the appointment of an additional antimicrobial therapy, active in

respect R. aeruginosa.

Patients aged> 65 years

Experience in the use of the drug in

patients aged> 65 years

is insufficient to develop any

recommendations for the use of the drug

in this category of patients.

Patients with impaired renal function

Experience with Toby® Podhaler® in patients with concentration

creatinine> 2 mg / dL and nitrogen content

urea of blood> 40 mg / dl is absent.

Patients with impaired function

liver

Experience with Toby® Podhaler® in patients with impaired

the liver function is absent. Because the

tobramycin is not metabolized to

the deterioration of its function on the

background therapy with the drug is unlikely.

Side effects:

When used in patients with cystic fibrosis, infected R. aeruginosa, the most frequently reported the following undesirable phenomena (AE): cough, impaired function lung, productive cough, fever, shortness of breath, pain in the oropharynx and larynx, taste disorders and dysphonia. Children and adolescents were coughing more often than adults, but adults are more likely than children, the drug was stopped due to a cough.

Most AEs described in the background the use of Toby® Podhaler®, had an easy or moderate character.

The degree of expression of the NNS was different between cycles of therapy. AEs are grouped according to classification of organs and systems of organs MedDRA, within each group are listed in decreasing order frequency of occurrence: Often (> 1/10); often (> 1/100, <1/10); infrequently (> 1/1 000, <1/100); rarely (> 1/10 000, <1/1 000); very rarely (<1/10 000), including individual message.

Infectious and parasitic diseases: often - infections of the upper respiratory tract.

Impaired nervous system: very often - a headache.

Violations from the side of the hearing and labyrinthine violations: often - hearing loss (frequency - 1%), ringing and noise in the ears (1.9%).

Vascular disorders: often - nosebleeds.

Disturbances from respiratory

SYSTEMS. BRAIN CORD AND MEDIASTRY ORGANS: very often - shortness of breath,

pulmonary dysfunction, dysphonia, cough, hemoptysis, aphonia (1% frequency): often - wheezing, bronchospasm (frequency - 1.6%), wheezing, chest discomfort, nasal congestion.

Disturbances from the gastrointestinal tract: very often - pain in the oropharynx; often - nausea, vomiting, diarrhea, irritation of the mucous membrane of the pharynx, taste disorders.

Hskin and subcutaneous tissue disorders: often - a rash. Disturbances from the musculoskeletal and connecting FABRICS: often - musculoskeletal pain in the chest. General disorders and disorders at the site of administration: very often - an increase in body temperature.

Tool and data sets: often - reduction of FEV, reduction of other indicators of lung function, hyperglycemia.

11a background of therapy with Toby Podhaler^to the frequency of cough was higher in the group of patients 6-13 lay down. When the drug is inhaled, the incidence of severe cough (2.6%) was higher in comparison with the group of patients receiving tobramycin in the form of a solution for inhalation administered by a nebulizer (1.9%). Below are the AEs detected in patients who used Toby Podhalsr^to in clinical trials in post-marketing period, as well as in routine clinical practice and laboratory studies. For this category of AH, it is not possible to determine the frequency of occurrence, so for these AEs it is indicated: "frequency is unknown". General disorders and disorders at the site of administration: malaise.

Disturbance from respiratory system, chest organs and mediastinum: change in color of sputum.

IF ANY OF THE SIDE EFFECTS INDICATED IN THE INSTRUCTION, SUFFERED. OR YOU HAVE NOTEED ANY OTHER SIDE EFFECTS NOT INDICATED IN THE INSTRUCTIONS, REPORT THIS TO THE DOCTOR.

Overdose:

There are no data on the overdose of Tobi® Podhaler.

Maximum daily allowance the dose of the drug is not established. To detect an overdose, a determination of tobramycin concentration in serum is used.

If you accidentally ingest the capsule toxic effect of tobramycin is unlikely, because tobramycin characterized by low absorption.

Treatment: When signs appear acute toxic lesion, it is necessary to immediately cancel the drug and examine the function of the kidneys.

To excrete tobramycin from the body can use hemodialysis.

Interaction:

Drug Interactions of Toby®Podhaler® was not performed.

It is not recommended simultaneous and / or sequential use of the drug with other drugs, with nephrotoxic and ototoxic effect.

Not recommended simultaneous use of the drug with diuretic means (ethacrynic acid, furosemide, urea, mannitol for intravenous administration) due to possible strengthening of toxic action of aminoglycosides due to changes in the concentration of antibiotic in serum and tissues.

No signs of drug interaction in a joint use of Toby® Podhaler® with dornase alpha, bronchodilators, glucocorticosteroids for inhalation and macrolides.

Special instructions:ABOUTTOTOXICITY AND NEFROTOPHICITY

Given the potential ototoxicity of aminoglycosides, prior to initiation of treatment with Toby® Podhaler®, and periodically during therapy, hearing sensitivity should be determined in patients with any hearing impairment (tinnitus, hearing loss), and at the risk of such complications (especially if there is a previous long-term systemic therapy with aminoglycosides).

Before treatment with Tobi® Podhaler, and then as often as this it is necessary, The renal function, including measurement of blood urea nitrogen concentration or serum creatinine levels.

In patients with or an alleged violation of the function of the hearing or kidneys should monitor the concentration of tobramycin in the blood serum.

In the development of violations by organ of hearing, vestibular apparatus or kidney therapy drug should be discontinued, from possibility of further renewal with a decrease concentrations of tobramycin in blood serum up to values <2 mcg / ml. It is necessary to monitor the concentration of tobramycin in the blood serum only with the help of approved methods. Have patients who received previous long-term systemic therapy with aminoglycosides (or other drugs capable of causing renal dysfunction), it is necessary to determine the concentration of tobramycin in serum as often as necessary.

Bronchospasm

Against the background of therapy with Tobi® Podhaler®, bronchospasm may develop, so the first dose of the drug should be administered under the supervision of a doctor. Before and after inhalation of the drug, lung function measurements (OOBi). If the patient is suspected of developing bronchospasm as an allergic reaction, the drug should be discontinued.

Cough

Have children younger than 13 years with the use of Toby® Podhaler®, the occurrence of cough is more likely than in adult patients. The occurrence of cough may require the use of tobramycin as an alternative solution for inhalation 300 mg / 5 ml as an alternative therapy.If you save cough is recommended the possibility of appointing others antibiotics.

Neuromuscular disorders

Aminoglycosides can provide curare-like effect on neuromuscular transmission and enhance muscle weakness.

Decreased sensitivity

Pseudomonas aeruginosa Against the background of therapy with Toby Podhaler® is possibly a reversible increase in tobramycin MIC in specific strains Pseudomonas aeruginosa.

Methods for determination of antimicrobial sensitivity in vitro to tobramycin can be used for sensitivity monitoring strains Pseudomonas aeruginosa, isolated from patients with cystic fibrosis.

Efficiency and safety application of the drug in patients with

FEV <25% and> 75% of the due or patients with infection caused by

Burkholderia cepacia, not installed.

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

The effect of the drug on the ability to drive vehicles and / or work with mechanisms has not been studied. The influence of Toby® Podhaler® on the ability to drive and work with machinery is unlikely

Form release / dosage:

Capsules with powder for inhalation, 28 mg. .

Packaging:

8 capsules per blister Al / Al with perforation (morning / evening).

1 inhaler in a plastic case.

For 7 blisters and 1 pencil case with an inhaler along with the instruction in a pack (weekly packing).

For 4 week packages and 1 pencil case with inhaler in a cardboard box (monthly pack).

Storage conditions:

In a dry place at a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years.