Active substanceSodium colistimethateSodium colistimethate
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  • Colistin
    powder d / inhal. 
  • Dosage form: & nbsppowder for solution for inhalation
    Composition:

    1 bottle of the drug contains - active substance: sodium colistimethate 80.0 mg, which corresponds to 1,000,000 units.

    Description:

    White or almost white hygroscopic powder.

    Pharmacotherapeutic group:Antibiotic-polypeptide is cyclic
    ATX: & nbsp

    J.01.X.B.01   Colistin

    Pharmacodynamics:

    Sodium colitixtetate is a cyclic polypeptide antibiotic formed Bacillus polymyxa, subspecies colistinus. Sodium colistimethate is a derivative of methanesulfonic acid colistin. Sodium colistimethate has a bactericidal effect against gram-negative bacteria, which is based on a change in the structure and disruption of the function of the cytoplasmic and outer membranes due to disturbance of the processes of polarization of membrane structures. Caution is required when determining the sensitivity limits for the use of sodium colistimethate by inhalation according to the criteria of "sensitive or resistant".

    The drug is usually sensitive: Acinetobacter spp., Citrobacter spp., Escherichia coli, Haemophilus influenzae, Klebsiella spp., Pseudomonas aeruginosa, Salmonella spp., Shigella spp. A number of microorganisms can develop acquired resistance: Achromobacter xylosoxidans, Enterobacter spp., Stenotrophomonas maltophilia.

    Typically resistant to the drug following microorganisms: Burkholderia cepacia, gram-negative cocci, Proteus mirabilis, Serratia marcescens, Gram-positive bacteria (ex. Staphylococcus aureus), anaerobic bacteria.

    In case of severe infections or inefficiency of antimicrobial treatment, it is necessary to take into account local geographic features of resistance distribution, and microbiological detection of the pathogenic microorganism and its testing for susceptibility to Colistin should be necessary. Between the preparation of Colistin and polymyxin B there is complete cross-resistance. However, this is not observed between the preparation of Colistin and other antibiotics.
    Pharmacokinetics:Suction

    The absorption of sodium colistimethate after inhalation has strong individual differences. The recorded values ​​of the maximum concentration of sodium colistimetate in the blood serum after inhalation at a dose of 2 million units lie within the limits of the concentration below the detection limit to 0.53 mg / l. When comparing these parameters with the concentration of the drug in the blood serum after parenteral administration, it can be concluded that its absorption is insignificant, which is also confirmed by the fact that,that after inhalation of 2 million units of sodium colistimetate, the average value of total renal excretion is approximately 4%.

    After a period of 1 to 4 hours after inhalation 1 to 2 million units of sodium colistimethate, its concentration in sputum is 16 - 180 mg / l. In the lungs, about 15% of the administered dose is delayed.

    Distribution

    Penetration of the drug Colistin in the tissues and body fluids is limited, including in the cerebrospinal fluid through the inflamed meninges. Concentrations in the urine are 20 - 40 times higher than those in the serum. Binding to blood plasma proteins is small (less than 10%). The half-life of serum is 2-3 hours. Sodium colistimethate penetrates the placenta.

    Excretion

    After intravenous administration, about 60 % of the administered dose is excreted by the kidneys in unchanged form, where the maximum concentrations are reached 2 to 4 hours after administration. This, presumably, also applies to the part absorbed by the inhalation route of administration. Sodium colistimethate, not absorbed after inhalation, is presumably largely excreted with phlegm.

    Kinetics in individual subgroups of patients. Due to low systemic bioavailability with inhalations of the drug Colistin, the risk of cumulation of the drug in the body of patients with renal insufficiency is estimated as low.
    Indications:Inhalation use of Colistin is indicated for the treatment of respiratory tract infections caused by Gram-negative bacteria sensitive to colistimetate sodium, in particular Pseudomonas aeruginosa, for example in cystic fibrosis.
    Contraindications:- Hypersensitivity to colistimetate sodium or polymyxin B;

    - malignant myasthenia gravis (myasthenia gravis gravis);

    - Children under 6 years.
    Carefully:Hemoptysis, renal dysfunction, porphyria, bronchial hyperreactivity (see section "Special instructions"), simultaneous use with potentially nephrotoxic or neurotoxic drugs (see section "Interaction with other medicinal products").
    Pregnancy and lactation:

    Sodium colystimethate penetrates the placental barrier. During pregnancy sodium colistimethate in connection with the risk of developing nephro- and neurotoxic reactions in the fetus should be used only for "vital" indications and after consulting with the attending physician.

    Sodium colistimethate is excreted in the mother's milk.If it is necessary to use sodium colistimetate during lactation, breastfeeding should be discontinued. The ingestion of sodium colistimethate with mother's milk in the child's body can lead to an imbalance in the intestinal microflora with the development of diarrhea and colonization of the intestine Blastomyces spp. Consider the possibility of developing sensitization.
    Dosing and Administration:

    It is used by inhalation, for example through a nebulizer. The inhalation solution must be prepared immediately before the inhalation procedure.

    The daily dose of the drug for adults and children over 6 years is from 2 million units to 6 million units, depending on the severity of the disease. Usually 1 million units are used 2 times a day at intervals of 12 hours. With the development of pathogen resistance, the dose can be increased up to 3 times a day for 2 million units. The duration of the sanation therapy for primary colonization / infection caused by Pseudomonas aeruginosa, is from 3 weeks to 3 months. Temporary limitations of the duration of therapy for chronic infection caused by Pseudomonas aeruginosa does not exist.

    In patients with impaired renal function, the dose of the drug is not required to be reduced (also see the section "Special instructions").
    Side effects:

    To assess the incidence of adverse reactions, the following gradation is used: Very often: ≥1 / 10; Frequently: ≥1 / 100 - <1/10; Infrequently: ≥ 1/1000 - <1/100; Rarely: ≥ 1/10000 - <1/1000; Very rarely: ≤ 1/10000.

    Insufficient data: Based on the available data, it is impossible to estimate the frequency.

    Often

    From the respiratory system: bronchospasm, dyspnea, increased cough, increased sputum formation, mucositis of the respiratory tract, pharyngitis.

    Insufficient data

    Infections and invasions - Candidiasis of the oral cavity, with prolonged use, proliferation of resistant microorganisms is possible.

    From the immune system - hypersensitivity reactions such as rash, itching, angioedema.

    From the nervous system - dizziness, paresthesia.

    From the gastrointestinal tract - nausea, a burning sensation of the tongue, unpleasant taste sensations.

    From the genitourinary system - acute renal insufficiency.
    Overdose:

    With inhalational use of the preparation Colistin, the influx of sodium colistimetate into the systemic bloodstream and, consequently, the risk of intoxication is extremely insignificant. Until now, there have been no reports of the development of such reactions.

    If you randomly take the drug inside the development of toxic effects is unlikely, because sodium colistimethate very little absorbed from the gastrointestinal tract.
    Interaction:

    With the simultaneous use of potentially nephrotoxic drugs (aminoglycosides, cephalosporins, ciclosporin, loop diuretics, incl. furosemide, ethacrynic acid and others), treatment with Colistin should be done with caution because of the potential for increased nephrotoxicity.

    With the simultaneous use of Colistin with inhalation anesthetics, central and peripheral myorelaxants and aminoglycosides, the risk of blockade of neuromuscular transmission increases.
    Special instructions:

    As with other antibiotics, against the background of using the drug Colistin, strains of resistant microorganisms can appear. After the cancellation and / or replacement of therapy, it is possible to restore the effectiveness of the drug.

    Colistin as an inhaled monotherapy should not be used to treat exacerbations of chronic infection caused by Pseudomonas aeruginosa.

    Inhalational use of the drug Colistin can cause acute bronchospasm in patients with hypersensitivity.In this regard, the introduction of the first dose of Colistin for inhalations should be carried out under the supervision of experienced medical personnel who have experience in the treatment of cystic fibrosis, and inhalation should be preceded by the use of a bronchodilator if this is included in the treatment regimen of this patient. Before and after inhalation of the drug, Colistin should measure the volume of forced expiration in the first second (OOBi). If a patient who does not receive bronchodilator has signs of medically conditioned bronchial obstruction, the next application of the drug Colistin should be repeated a trial (FEVD, adding a bronchodilator.

    In case of hemoptysis use, the risk-benefit ratio should be taken into account, since inhalations of Colistin may increase cough.

    Patients with impaired renal function should carefully monitor the possibility of developing side effects from the nervous system and regularly monitor kidney function. Care should be taken when treating patients taking co-nephrotoxic drugs, it is necessary to monitor kidney function regularly.Joint use of neurotoxic drugs should be conducted with caution under the supervision of a physician.

    In porphyria, it must be taken into account that the use of Colistin can strengthen the clinical manifestations of this disease.

    When carrying out inhalation treatment with dornase alpha and Colistin, a break between inhalations should be made.

    Directions for proper use:

    To use antibiotics in the form of an aerosol, spray nebulizers (jet or ultrasonic) are recommended, which, when used with the appropriate compressor, should create most of the inhalation particles with a diameter of not more than 5 μm (for the most effective absorption by the lungs). When using and maintaining the nebulizer / nebulizer and compressor, follow the manufacturer's instructions. Standard nebulizers / nebulizers create a continuous aerosol flow, so the particles of the sprayed sodium colistimethate can evaporate into the environment. To avoid this, it is recommended to use standard nebulizers in well-ventilated rooms.The use of appropriate filters / valves will help minimize the evaporation of sodium colistimethate into the atmosphere.

    1. The bottle with powder is opened by removing the aluminum cap with the control of the first opening and opening the rubber stopper.

    2. An ampoule with 3 ml of physiological solution applied as a solvent is opened using a saw or an apparatus for opening ampoules.

    3. The contents of the ampoule are completely poured into a vial of powder. The powder is dissolved by gentle shaking.

    Strong shaking should be avoided due to excessive formation of foam.

    4. The solution is poured into a nebulizer and is administered by inhalation according to the instructions of the nebulizer manufacturer. The inhalation procedure is considered complete after the full use of 3 ml of the inhalation solution.

    5. The patient performs the inhalation procedure of the preparation Colistin in a sitting or standing position vertically, in a normal calm state, producing as deep as possible inhalations through the mouthpiece of the nebulizer. To facilitate inhaling through the mouth allows the use of a nasal clamp.

    6. After each use, the mouthpiece should be rinsed and disinfected, and the manufacturer's instructions should be followed.

    In patients receiving such types of inhalation therapy as bronchodilators, inhalation use of the drug Colistin should be carried out immediately after their use, as well as after physiotherapy procedures on the chest.

    The prepared solution of the drug Colistin should not be mixed with other drugs.

    The solution should be freshly prepared immediately before inhalation. The drug should be stored in its original packaging to protect the contents from exposure to light. The contents of the vial are intended for single use only, the unused remedy is to be disposed of.

    Effect on the ability to drive transp. cf. and fur:Colistin can change the reaction speed, for example, because of the possibility of developing dizziness, so during the treatment period it is necessary to refrain from driving vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions, you should not drink alcohol.
    Form release / dosage:Powder for solution for inhalation.
    Packaging:

    By 1000000 units of active substance in a vial of colorless glass sealed with a rubber stopper and aluminum-capped with the control of the first autopsy.

    By 3.0 ml of sodium chloride solution 0,9% in the ampoule of colorless glass type I. Application is allowed technological mark. places fault in the form of a point, and also double ring on the ampoule head.

    1 bottle and 1 ampoule with solvent is placed in a contour mesh packing, which is laid with instructure for use in a pack cardboard.

    For 60, 100 vials with the drug and 60, 100 ampoules with a solvent are placed with instructions for application in a box with partitions or lattices (for hospitals).

    Storage conditions:

    At a temperature of no higher than 25 ° C.

    Keep out of the reach of children place.

    Shelf life:

    3 years. Do not use after the expiration date. expiration date indicated on packaging.

    Terms of leave from pharmacies:On prescription
    Registration number:LS-002329
    Date of registration:31.08.2010 / 20.11.2017
    Expiration Date:Unlimited
    The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel
    Manufacturer: & nbsp
    Representation: & nbspTeva Teva Israel
    Information update date: & nbsp31.01.2018
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