Kolistin-Belpharm 2 000 000 IU
The International Nonproprietory Name: KOLISTIN
Medical uses:
The drug is intended to treat infections caused by susceptible microorganisms.
Parenteral use:
Treatment of some severe infections caused by gram-negative bacteria, including lower respiratory tract and urinary tract infections, when more commonly used systemic antibacterials are contraindicated or ineffective due to the development of bacterial resistance.
Inhalation treatment:
Treatment of pulmonary infection caused by Pseudomonas aeruginosa in patients with cystic fibrosis.
The drug is intended to treat infections caused by susceptible microorganisms.
Parenteral use:
Treatment of some severe infections caused by gram-negative bacteria, including lower respiratory tract and urinary tract infections, when more commonly used systemic antibacterials are contraindicated or ineffective due to the development of bacterial resistance.
Inhalation treatment:
Treatment of pulmonary infection caused by Pseudomonas aeruginosa in patients with cystic fibrosis.
Dosage and packaging2 000 000 IU
№1, №5, №36
Scope of applicationPulmonology, urology
Form of vacationOn prescription
Pharmacotherapeutic groupPolymyxins
INSTRUCTIONS FOR MEDICAL USE OF
COLISTIN-BELPHARM
Medicine trade name: Colistin - Belpharm
Active ingredient (INN): Colistimethate sodium
Medicine form: powder for preparation of injection solution for intravenous administration and inhalation 1000000 ME or 2000000 ME
Composition for 1 bottle:
Active substance:
Colistimethate sodium – 1000000 ME or 2000000 ME
Description: white or almost white powder. Hygroscopic
Pharmacotherapeutic group: antibiotic of cyclonic polypeptides group
ATX Code : J01XB01
Pharmacological properties
Pharmacodynamics
Colistin – cyclonic polypeptidic antibiotic, produced by Bacillus Polymyxa var. colistinus, belonging to the group of polymyxins. The active ingredient of Colistin-Belpharm is colismethate sodium, which is a derivative of colistin methanesulfonic acid.
The drug has a bactericidal effect against gram-negative bacteria, which is based on changes in the structure and dysfunction of the cytoplasmic and outer membranes of bacteria due to the processes of polarization of membrane structures.
Antibacterial activity of colistimethate sodium applies only to aerobic gram-negative bacteria with a hydrophobic outer membrane.
Bactericidal effect of polymyxins against sensitive microorganisms depends on the concentration. The fAUC/MIC index (minimum inhibitory concentration) correlates with clinical effectiveness.
Active ingredient (INN): Colistimethate sodium
Medicine form: powder for preparation of injection solution for intravenous administration and inhalation 1000000 ME or 2000000 ME
Composition for 1 bottle:
Active substance:
Colistimethate sodium – 1000000 ME or 2000000 ME
Description: white or almost white powder. Hygroscopic
Pharmacotherapeutic group: antibiotic of cyclonic polypeptides group
ATX Code : J01XB01
Pharmacological properties
Pharmacodynamics
Colistin – cyclonic polypeptidic antibiotic, produced by Bacillus Polymyxa var. colistinus, belonging to the group of polymyxins. The active ingredient of Colistin-Belpharm is colismethate sodium, which is a derivative of colistin methanesulfonic acid.
The drug has a bactericidal effect against gram-negative bacteria, which is based on changes in the structure and dysfunction of the cytoplasmic and outer membranes of bacteria due to the processes of polarization of membrane structures.
Antibacterial activity of colistimethate sodium applies only to aerobic gram-negative bacteria with a hydrophobic outer membrane.
Bactericidal effect of polymyxins against sensitive microorganisms depends on the concentration. The fAUC/MIC index (minimum inhibitory concentration) correlates with clinical effectiveness.
*EUCAST - European Committee on testing sensitivity to antimicrobial medicinal drugs.
**Checkpoints are used for dosage: 2 000 000 – 3 000 000 ME 3 times a day. Loading dose can be taken up to 9 000 000 ME.
The most sensitive to sodium colistimethate are Acinetobacter baumannii, Citrobacter spp., Escherichia coli, Haemophilus influenzae, Pseudomonas aeruginosa.
Acquired resistance may vary depending on geographic location and time relative to selected bacterial species.
Acquired resistance is possible for Stenotrophomonas maltophilia, Achromobacter xylosoxidans (formerly Alcaligenes xylosoxidans). Resistant gram-negative bacteria include Proteus spp., Providencia spp., Serratia spp., Burkholderia cepacia and related species.
Cross-resistance between colistimethate sodium and polymyxin B is possible. Because the mechanism of action of polymyxins is different from that of other antibiotics, resistance to colistimethate sodium and polymyxin B by the above mechanism does not imply resistance to other groups of drugs.
Pharmacokinetics
Absorption
Absorption from the gastrointestinal tract in healthy people occurs in small quantities.
When administered by inhalation, the absorption of colistimethate sodium varies greatly between individuals and depends on the particle size of the aerosol, the nebulizer system and the patient's lung condition. When inhaled, serum concentrations of colistimethate sodium may vary from 0 to potentially therapeutic concentrations of 4 mg/L or higher. About 15% of the administered dose of sodium colistimethate is retained in the lungs. Due to the low systemic bioavailability during inhalation administration, the risk of retention of colistimethate sodium in the body of patients with renal failure is low. However, the possibility of systemic absorption during inhalation must be taken into account.
Distribution
Protein binding is negligible. Colistimethate sodium accumulates in the liver, kidneys, brain, heart and muscles. The drug can penetrate the placenta.
Penetration of colistin into the cerebrospinal fluid is minimal, but increases with meningeal inflammation.
Metabolism and excretion
In vivo, colistimethate sodium is converted to a base (colistin). Colistimethate sodium is excreted primarily through the kidneys by glomerular filtration. In healthy people, 60-70% of sodium colistimethate is excreted unchanged in the urine within 24 hours. The drug is not excreted with bile.
After intravenous administration, the half-life of colistimethate sodium in healthy people is approximately 3 hours. When used by patients with cystic fibrosis, the half-life of colistimethate sodium is 3.4 ± 1.4 hours. In critically ill patients, the half-life increases to 9-18 hours.
Methods for removing colistimethate sodium by inhalation have not been studied.
The absorbed portion of colistimethate sodium is presumably excreted unchanged by the kidneys. The unabsorbed portion after inhalation is presumably excreted in sputum. In patients with cystic fibrosis who received colistimethate sodium in the form of inhalation at a dose of 1,000,000 IU 2 times a day for 3 months, the drug was not detected in the urine.
Pharmacokinetics in special clinical cases
In case of renal failure, the reduction in the dose of colistimethate sodium is required for preventing the accumulation of the medicinal drug in organism.
Kinetics of the colistimethate sodium in children and adults, including patients of older age, subject to normal renal function.
Data regarding to the use medicinal drug in the infants are limited. In such group of patients, it is necessary to possibility of higher maximum concentrations in blood plasma and longer half-life period must be considered, as well as controlling the level of active substance in the blood serum.
Indications for use
The drug is intended for the treatment of infections caused by sensitive microorganisms.
Parenteral use
Treatment of certain severe infections caused by gram-negative bacteria, including lower respiratory tract and urinary tract infections, when more commonly used systemic antibacterial agents are contraindicated or ineffective due to the development of bacterial resistance.
Inhalation use
Treatment of pulmonary infection caused by Pseudomonas aeruginosa in patients with cystic fibrosis.
Directions for use and dosage
Colistin-Belpharm is used parenterally and in the form of inhalations.
Parenteral use
The dosage regimen and duration of therapy are determined depending on the type and severity of the infection, the sensitivity of the pathogenic microorganism, the patient's condition, as well as the patient's age, body weight and renal function.
The optimal dosage regimen for Colistin-Belpharm is based on the calculation of loading and maintenance doses. The maximum loading and maintenance doses for patients in critical condition are 9,000,000 IU, in exceptional cases they can reach 12,000,000 IU. The first maintenance dose should be administered after 24 hours.
The calculation of the loading dose is the same for all categories of patients, regardless of renal failure.
For adults and teenagers, the maintenance dose can be 9,000,000 IU, divided into 2-3 doses.
In patients with impaired renal function (creatinine clearance <50 ml/min), a dose reduction is indicated. The recommended frequency of administration of the drug is 2 times a day.
**Checkpoints are used for dosage: 2 000 000 – 3 000 000 ME 3 times a day. Loading dose can be taken up to 9 000 000 ME.
The most sensitive to sodium colistimethate are Acinetobacter baumannii, Citrobacter spp., Escherichia coli, Haemophilus influenzae, Pseudomonas aeruginosa.
Acquired resistance may vary depending on geographic location and time relative to selected bacterial species.
Acquired resistance is possible for Stenotrophomonas maltophilia, Achromobacter xylosoxidans (formerly Alcaligenes xylosoxidans). Resistant gram-negative bacteria include Proteus spp., Providencia spp., Serratia spp., Burkholderia cepacia and related species.
Cross-resistance between colistimethate sodium and polymyxin B is possible. Because the mechanism of action of polymyxins is different from that of other antibiotics, resistance to colistimethate sodium and polymyxin B by the above mechanism does not imply resistance to other groups of drugs.
Pharmacokinetics
Absorption
Absorption from the gastrointestinal tract in healthy people occurs in small quantities.
When administered by inhalation, the absorption of colistimethate sodium varies greatly between individuals and depends on the particle size of the aerosol, the nebulizer system and the patient's lung condition. When inhaled, serum concentrations of colistimethate sodium may vary from 0 to potentially therapeutic concentrations of 4 mg/L or higher. About 15% of the administered dose of sodium colistimethate is retained in the lungs. Due to the low systemic bioavailability during inhalation administration, the risk of retention of colistimethate sodium in the body of patients with renal failure is low. However, the possibility of systemic absorption during inhalation must be taken into account.
Distribution
Protein binding is negligible. Colistimethate sodium accumulates in the liver, kidneys, brain, heart and muscles. The drug can penetrate the placenta.
Penetration of colistin into the cerebrospinal fluid is minimal, but increases with meningeal inflammation.
Metabolism and excretion
In vivo, colistimethate sodium is converted to a base (colistin). Colistimethate sodium is excreted primarily through the kidneys by glomerular filtration. In healthy people, 60-70% of sodium colistimethate is excreted unchanged in the urine within 24 hours. The drug is not excreted with bile.
After intravenous administration, the half-life of colistimethate sodium in healthy people is approximately 3 hours. When used by patients with cystic fibrosis, the half-life of colistimethate sodium is 3.4 ± 1.4 hours. In critically ill patients, the half-life increases to 9-18 hours.
Methods for removing colistimethate sodium by inhalation have not been studied.
The absorbed portion of colistimethate sodium is presumably excreted unchanged by the kidneys. The unabsorbed portion after inhalation is presumably excreted in sputum. In patients with cystic fibrosis who received colistimethate sodium in the form of inhalation at a dose of 1,000,000 IU 2 times a day for 3 months, the drug was not detected in the urine.
Pharmacokinetics in special clinical cases
In case of renal failure, the reduction in the dose of colistimethate sodium is required for preventing the accumulation of the medicinal drug in organism.
Kinetics of the colistimethate sodium in children and adults, including patients of older age, subject to normal renal function.
Data regarding to the use medicinal drug in the infants are limited. In such group of patients, it is necessary to possibility of higher maximum concentrations in blood plasma and longer half-life period must be considered, as well as controlling the level of active substance in the blood serum.
Indications for use
The drug is intended for the treatment of infections caused by sensitive microorganisms.
Parenteral use
Treatment of certain severe infections caused by gram-negative bacteria, including lower respiratory tract and urinary tract infections, when more commonly used systemic antibacterial agents are contraindicated or ineffective due to the development of bacterial resistance.
Inhalation use
Treatment of pulmonary infection caused by Pseudomonas aeruginosa in patients with cystic fibrosis.
Directions for use and dosage
Colistin-Belpharm is used parenterally and in the form of inhalations.
Parenteral use
The dosage regimen and duration of therapy are determined depending on the type and severity of the infection, the sensitivity of the pathogenic microorganism, the patient's condition, as well as the patient's age, body weight and renal function.
The optimal dosage regimen for Colistin-Belpharm is based on the calculation of loading and maintenance doses. The maximum loading and maintenance doses for patients in critical condition are 9,000,000 IU, in exceptional cases they can reach 12,000,000 IU. The first maintenance dose should be administered after 24 hours.
The calculation of the loading dose is the same for all categories of patients, regardless of renal failure.
For adults and teenagers, the maintenance dose can be 9,000,000 IU, divided into 2-3 doses.
In patients with impaired renal function (creatinine clearance <50 ml/min), a dose reduction is indicated. The recommended frequency of administration of the drug is 2 times a day.
Colistin is able to penetrate the semipermeable membrane during conventional hemodialysis and continuous veno-venous hemofiltration or hemodiafiltration (CVVHF or NVVHDF).
For patients on hemodialysis, the following dosage is recommended:
- days without hemodialysis: 2,250,000 IU per day (2,200,000 - 2,300,000 IU/day);
- days of hemodialysis: 3,000,000 IU per day. The drug should be administered after hemodialysis. The daily dose must be divided into 2 doses.
For NVVGF or NVVGDF, the dosing regimen corresponds to the dosing regimen in patients with normal renal function. The daily dose must be divided into 3 doses.
Colistimethate sodium should be administered with caution to patients with impaired liver function.
No dose adjustment is required in elderly patients with normal renal function.
When choosing a dosage regimen in children, renal maturity must be taken into account. The dose should be based on ideal body weight.
Children weighing ≤ 40 kg are prescribed 75,000 - 150,000 IU/kg per day, divided into 3 doses.
The dosage regimen for children weighing ≥ 40 kg corresponds to the dosage regimen for adults.
In exceptional cases, in children with cystic fibrosis, doses exceeding 150,000 IU/kg per day may be used.
High doses of colistimethate sodium should be used with extreme caution in children in serious condition, in children with impaired renal function, and in children under 1 year of age under close medical supervision.
Colistin-Belpharm should be administered intravenously by slow infusion over 30-60 minutes.
In patients with a fully implanted venous access device (TIVAD), a bolus injection of Colistin-Belpharm (up to 2,000,000 IU dissolved in 10 ml of diluent) can be used, administered over at least 5 minutes.
Inhalation use
For local treatment of lower respiratory tract infections, the drug is used in the form of inhalation. The course of treatment is determined individually and depends on the clinical condition of the patient. Inhaled use of colistimethate sodium must be carried out under medical supervision.
For adults and children over 2 years of age, Colistin-Belpharm is prescribed at a dose of 1,000,000 IU - 2,000,000 IU 2-3 times a day (up to 6,000,000 IU per day).
For children under 2 years of age, Colistin-Belpharm is prescribed at a dose of 500,000 IU - 1,000,000 IU 2 times a day (up to 2,000,000 IU per day).
No dosage adjustment is required for elderly patients, patients with impaired liver function, or patients with impaired renal function; however, caution should be exercised when prescribing Colistin-Belpharm to patients with impaired renal function.
Rules for preparing and administering the solution
The drug does not contain preservatives, so when preparing solutions it is necessary to follow standard aseptic rules.
Parenteral administration
Colistin-Belpharm should be administered as an IV bolus injection over 5 minutes or as an IV infusion over 30-60 minutes.
To prepare a solution for intravenous bolus injection, the contents of the Colistin-Belpharm vial are dissolved in 10 ml of water for injection or 0.9% sodium chloride solution. The solvent should be introduced into the vial slowly, gently shaking the vial until a clear solution is formed, avoiding the appearance of foam.
For intravenous infusion, the resulting solution for intravenous bolus injection is quantitatively transferred into a bottle or container with water for injection or 0.9% sodium chloride solution, diluted to 50-200 ml and mixed carefully.
The solution for intravenous infusion should be used immediately after preparation!
The unused remainder of the drug solution must be disposed.
To avoid administering a dose less than required, the drug must be completely dissolved. The prepared solution must be carefully removed from the bottle.
Inhalation use
To prepare a solution for inhalation, the contents of the bottle are first dissolved in
3 ml of 0.9% sodium chloride solution or water for injection. The required amount of the prepared solution is poured into a sprayer, which is connected to the air/oxygen supply device, and used according to the instructions for using the device.
For the use of aerosolized antibiotics, spray nebulizers (jet type or ultrasonic) are recommended, which, when used with an appropriate compressor, create inhalable particles with a diameter of no more than 5 microns (for most effective absorption by the lungs). When using the sprayer and compressor, you must follow the device manufacturer's instructions.
The patient performs the drug inhalation procedure in a sitting or standing position strictly vertically in a normal, calm state, taking as deep breaths as possible through the mouthpiece of the nebulizer. You can use a nose clip to make breathing through your mouth easier.
After each use, the mouthpiece should be rinsed and disinfected following the manufacturer's instructions.
Patients receiving bronchodilators should inhale Colistin-Belpharm immediately after their use, as well as after physiotherapeutic procedures on the chest.
Freshly prepared solutions for intravenous bolus injection and inhalation in manufacturer's vials retain their physical and chemical stability for 24 hours in a place protected from light at a temperature of 2-8°C (refrigerator). From a microbiological point of view, the drug should be used immediately, otherwise responsibility for the time and storage conditions during use rests with the consumer.
The unused remainder of the drug solution must be disposed.
Side effect
Parenteral use
The likelihood of developing adverse reactions may be related to age, renal function and the general condition of the patient.
From the immune system: skin rash, anaphylactic reactions, drug fever. If such reactions are detected, the use of colistimethate sodium should be discontinued.
From the nervous system: neurotoxicity (may be associated with overdose, poorly selected dose in patients with renal failure and concomitant use of neuromuscular blockers or other drugs with similar neurological effects; dose reduction may help reduce these symptoms); respiratory arrest, transient sensory disturbances (facial paresthesia, dizziness); vasomotor instability, slurred speech, visual disturbances, confusion, or psychosis.
Patients with cystic fibrosis may experience moderate neurological reactions that resolve on their own during treatment or after its cessation.
From the gastrointestinal tract: gastrointestinal disorders.
From the skin and subcutaneous tissues: generalized itching, urticaria.
From the kidneys and urinary tract: impaired renal function, renal failure.
Impaired renal function usually occurs after the use of doses higher than recommended in patients with normal renal function, or due to an insufficiently reduced dose of the drug in patients with renal failure, or due to concomitant use of other nephrotoxic drugs. These adverse reactions are usually reversible and disappear after discontinuation of therapy. In patients with cystic fibrosis taking recommended doses of the drug, nephrotoxicity reactions rarely occur. Signs of nephrotoxicity may occur in critically ill hospitalized patients without diagnosed cystic fibrosis.
Local reactions: irritation at the injection site.
Inhalation use
From the respiratory system: reflex cough, bronchospasm, respiratory arrest, increased sputum production, respiratory tract mucositis, pharyngitis.
Infections: oral candidiasis.
From the immune system: skin rash, itching, angioedema. If such reactions are detected, the use of colistimethate sodium should be stopped.
From the gastrointestinal tract: nausea, burning sensation of the tongue, unpleasant taste.
Contraindications
Hypersensitivity to colistimethate sodium and polymyxin B.
Interaction with other drugs
Do not use simultaneously with drugs with neurotoxic and/or nephrotoxic effects, for example, aminoglycosides (gentamicin, amikacin, netilmicin and tobramycin). When used concomitantly with cephalosporins, the risk of nephrotoxicity may increase.
Caution should be exercised when colistimethate sodium is administered in different dosage forms as information on possible resulting toxicity is limited.
Possible drug interactions should be considered when colistimethate sodium is used concomitantly with drugs that inhibit or induce enzymes that metabolize the drug, or with drugs that are substrates for renal metabolism.
Because colistin affects acetylcholine release, non-depolarizing muscle relaxants should be used with caution in patients receiving colistimethate sodium as it may prolong the effect of the muscle relaxants.
Simultaneous use of colistimethate sodium and macrolides such as azithromycin and clarithromycin, or fluoroquinolones such as norfloxacin or ciprofloxacin should be used with caution in patients with myasthenia gravis.
Neuromuscular blockers should be used with extreme caution in patients receiving colistimethate sodium.
With the simultaneous use of colistimethate sodium in the form of inhalation with inhaled anesthetics, central and peripheral muscle relaxants and aminoglycosides, the risk of blocking neuromuscular transmission increases.
Data regarding the interaction of colistimethate sodium with other drugs in vivo, as well as regarding the mechanism of its elimination from the body, are limited. In in vitro studies of human hepatocytes, colistimethate sodium or colistin did not induce the activity of any of the P450 (CYP) enzymes tested (CYP1A2, 2B6, 2C8, 2C9, 2C19 and 3A4/5).
Special instructions
Usage in period of pregnancy and breast feeding
Clinical safety of colistimethate sodium during pregnancy is not established. Colistimethate sodium is able to permeate through placental barrier and may result in embryonal toxicity. Medicinal drug is not supposed to use during pregnancy, expect the cases, when potential benefit of its use justifies the risk of the fetus. In each case, medicinal drug should be taken under the direct supervision of the doctor!
Colistimethate sodium can pass into breast milk, therefore, if it is necessary to use colistimethate sodium during lactation, you should consider stopping breastfeeding.
Use in pediatrics
Colistimethate sodium should be prescribed with caution to children under 1 year of age, since this group of patients is characterized by insufficient functional maturity of the kidneys.
Effect on the ability to drive a car or operate machinery
Neurotoxicity with possible dizziness, confusion and blurred vision may occur during use of colistimethate sodium. If such reactions occur, patients are advised to refrain from driving vehicles and operating complex machinery during the period of use of the drug.
Special instructions
Colistimethate sodium should be used with caution in patients with porphyria.
If the recommended dose of colistimethate sodium is exceeded when administered parenterally, nephrotoxicity may occur.
Colistimethate sodium should be prescribed with caution to patients with impaired renal function. It is recommended to assess the renal function of such patients at the beginning of treatment, monitor it during therapy and monitor for the occurrence of side effects from the nervous system (facial paresthesia, muscle weakness, dizziness, slurred speech, vasomotor instability, visual disturbances, confusion, psychosis and breathing arrest). Perioral paresthesia and paresthesia of the extremities should be monitored as they are signs of overdose.
It is also necessary to monitor the concentration of colistimethate sodium in the blood serum.
In the event of an allergic reaction, treatment with colistimethate sodium should be discontinued and appropriate measures taken.
When administered intravenously, colistimethate sodium does not cross the blood-brain barrier to a clinically significant extent.
Antibiotic-associated and pseudomembranous colitis, which can occur with all antibacterial agents, can also occur when taking colistimethate sodium. Their severity can range from mild to life-threatening. If diarrhea occurs while taking colistimethate sodium, therapy should be discontinued and a Clostridium difficile treatment should be prescribed. Drugs that inhibit peristalsis should not be prescribed.
Colistin-Belpharm should not be used as inhaled monotherapy in the treatment of acute chronic infections caused by Pseudomonas aeruginosa. Inhaled colistimethate sodium may cause bronchospasm, which can be prevented or treated with appropriate β2-agonists. Therefore, the administration of the first dose of Colistin-Belpharm should be carried out under the supervision of experienced medical personnel, and the use of bronchodilators, if included in the patient’s treatment regimen, should precede the inhalation use of Colistin-Belpharm. If β2-agonists are not effective, treatment should be discontinued.
It is recommended to monitor forced expiratory volume in the first second before and after inhalation of the drug. If the patient shows signs of drug-induced bronchial obstruction, the next time Colistin-Belpharm is used, the test should be repeated, adding a bronchodilator.
Inhaled colistimethate sodium may worsen cough, so the risk-benefit ratio should be carefully assessed when used for hemoptysis.
It is necessary to take a break between dornase alfa inhalations and Colistin-Belpharm inhalations.
When treated with colistimethate sodium, strains of resistant microorganisms may appear. Restoring the effectiveness of the drug is possible after discontinuation and/or modification of therapy.
Overdose
An overdose of colistimethate sodium may cause neuromuscular blockade, which in turn can lead to muscle weakness, shortness of breath and respiratory arrest. An overdose can cause acute renal failure, which is characterized by a decrease in urination, as well as an increase in the concentration of nitrogen in urea and creatinine in the blood plasma.
There is no specific antidote for an overdose of colistimethate sodium. Maintenance therapy is recommended. To increase the rate of drug elimination, forced diuresis with mannitol, prolonged hemodialysis, or peritoneal dialysis can be used, but their effectiveness has not been proven.
When using the drug by inhalation, the entry of sodium colistimethate into the systemic circulation and, therefore, the risk of developing intoxication is extremely insignificant. There is no data on the development of such reactions.
If the drug is accidentally taken orally, the development of toxic effects is unlikely, since colistimethate sodium is very little absorbed from the gastrointestinal tract.
Release form
1 000 000 ME or 2 000 000 ME vial for injection volume of 10 ml or 20 ml.
By 1 or 5 vials together with instructions of use in a cardboard box.
Packaging for hospitals: 36 vials with corresponding amount of instructions of use in group boxes.
Storage conditions
Store in dry place, protected from light at the temperature not higher than 25C.
Store in a place out of reach of children.
Expiration date
Expiration date is 2 years.
Do not use after expiration date, shown at the packaging.
Conditions for release from pharmacies
On prescription
Manufacturer/ name and address od organization, accepting claims (offers) regarding the quality of medicinal product in the territory of Republic of Uzbekistan
FE LLC “BELPHARM”, Republic of Uzbekistan, Tashkent city, Kichik Khalka yuli and Badamzar str., 37
www.belpharm.uz
For patients on hemodialysis, the following dosage is recommended:
- days without hemodialysis: 2,250,000 IU per day (2,200,000 - 2,300,000 IU/day);
- days of hemodialysis: 3,000,000 IU per day. The drug should be administered after hemodialysis. The daily dose must be divided into 2 doses.
For NVVGF or NVVGDF, the dosing regimen corresponds to the dosing regimen in patients with normal renal function. The daily dose must be divided into 3 doses.
Colistimethate sodium should be administered with caution to patients with impaired liver function.
No dose adjustment is required in elderly patients with normal renal function.
When choosing a dosage regimen in children, renal maturity must be taken into account. The dose should be based on ideal body weight.
Children weighing ≤ 40 kg are prescribed 75,000 - 150,000 IU/kg per day, divided into 3 doses.
The dosage regimen for children weighing ≥ 40 kg corresponds to the dosage regimen for adults.
In exceptional cases, in children with cystic fibrosis, doses exceeding 150,000 IU/kg per day may be used.
High doses of colistimethate sodium should be used with extreme caution in children in serious condition, in children with impaired renal function, and in children under 1 year of age under close medical supervision.
Colistin-Belpharm should be administered intravenously by slow infusion over 30-60 minutes.
In patients with a fully implanted venous access device (TIVAD), a bolus injection of Colistin-Belpharm (up to 2,000,000 IU dissolved in 10 ml of diluent) can be used, administered over at least 5 minutes.
Inhalation use
For local treatment of lower respiratory tract infections, the drug is used in the form of inhalation. The course of treatment is determined individually and depends on the clinical condition of the patient. Inhaled use of colistimethate sodium must be carried out under medical supervision.
For adults and children over 2 years of age, Colistin-Belpharm is prescribed at a dose of 1,000,000 IU - 2,000,000 IU 2-3 times a day (up to 6,000,000 IU per day).
For children under 2 years of age, Colistin-Belpharm is prescribed at a dose of 500,000 IU - 1,000,000 IU 2 times a day (up to 2,000,000 IU per day).
No dosage adjustment is required for elderly patients, patients with impaired liver function, or patients with impaired renal function; however, caution should be exercised when prescribing Colistin-Belpharm to patients with impaired renal function.
Rules for preparing and administering the solution
The drug does not contain preservatives, so when preparing solutions it is necessary to follow standard aseptic rules.
Parenteral administration
Colistin-Belpharm should be administered as an IV bolus injection over 5 minutes or as an IV infusion over 30-60 minutes.
To prepare a solution for intravenous bolus injection, the contents of the Colistin-Belpharm vial are dissolved in 10 ml of water for injection or 0.9% sodium chloride solution. The solvent should be introduced into the vial slowly, gently shaking the vial until a clear solution is formed, avoiding the appearance of foam.
For intravenous infusion, the resulting solution for intravenous bolus injection is quantitatively transferred into a bottle or container with water for injection or 0.9% sodium chloride solution, diluted to 50-200 ml and mixed carefully.
The solution for intravenous infusion should be used immediately after preparation!
The unused remainder of the drug solution must be disposed.
To avoid administering a dose less than required, the drug must be completely dissolved. The prepared solution must be carefully removed from the bottle.
Inhalation use
To prepare a solution for inhalation, the contents of the bottle are first dissolved in
3 ml of 0.9% sodium chloride solution or water for injection. The required amount of the prepared solution is poured into a sprayer, which is connected to the air/oxygen supply device, and used according to the instructions for using the device.
For the use of aerosolized antibiotics, spray nebulizers (jet type or ultrasonic) are recommended, which, when used with an appropriate compressor, create inhalable particles with a diameter of no more than 5 microns (for most effective absorption by the lungs). When using the sprayer and compressor, you must follow the device manufacturer's instructions.
The patient performs the drug inhalation procedure in a sitting or standing position strictly vertically in a normal, calm state, taking as deep breaths as possible through the mouthpiece of the nebulizer. You can use a nose clip to make breathing through your mouth easier.
After each use, the mouthpiece should be rinsed and disinfected following the manufacturer's instructions.
Patients receiving bronchodilators should inhale Colistin-Belpharm immediately after their use, as well as after physiotherapeutic procedures on the chest.
Freshly prepared solutions for intravenous bolus injection and inhalation in manufacturer's vials retain their physical and chemical stability for 24 hours in a place protected from light at a temperature of 2-8°C (refrigerator). From a microbiological point of view, the drug should be used immediately, otherwise responsibility for the time and storage conditions during use rests with the consumer.
The unused remainder of the drug solution must be disposed.
Side effect
Parenteral use
The likelihood of developing adverse reactions may be related to age, renal function and the general condition of the patient.
From the immune system: skin rash, anaphylactic reactions, drug fever. If such reactions are detected, the use of colistimethate sodium should be discontinued.
From the nervous system: neurotoxicity (may be associated with overdose, poorly selected dose in patients with renal failure and concomitant use of neuromuscular blockers or other drugs with similar neurological effects; dose reduction may help reduce these symptoms); respiratory arrest, transient sensory disturbances (facial paresthesia, dizziness); vasomotor instability, slurred speech, visual disturbances, confusion, or psychosis.
Patients with cystic fibrosis may experience moderate neurological reactions that resolve on their own during treatment or after its cessation.
From the gastrointestinal tract: gastrointestinal disorders.
From the skin and subcutaneous tissues: generalized itching, urticaria.
From the kidneys and urinary tract: impaired renal function, renal failure.
Impaired renal function usually occurs after the use of doses higher than recommended in patients with normal renal function, or due to an insufficiently reduced dose of the drug in patients with renal failure, or due to concomitant use of other nephrotoxic drugs. These adverse reactions are usually reversible and disappear after discontinuation of therapy. In patients with cystic fibrosis taking recommended doses of the drug, nephrotoxicity reactions rarely occur. Signs of nephrotoxicity may occur in critically ill hospitalized patients without diagnosed cystic fibrosis.
Local reactions: irritation at the injection site.
Inhalation use
From the respiratory system: reflex cough, bronchospasm, respiratory arrest, increased sputum production, respiratory tract mucositis, pharyngitis.
Infections: oral candidiasis.
From the immune system: skin rash, itching, angioedema. If such reactions are detected, the use of colistimethate sodium should be stopped.
From the gastrointestinal tract: nausea, burning sensation of the tongue, unpleasant taste.
Contraindications
Hypersensitivity to colistimethate sodium and polymyxin B.
Interaction with other drugs
Do not use simultaneously with drugs with neurotoxic and/or nephrotoxic effects, for example, aminoglycosides (gentamicin, amikacin, netilmicin and tobramycin). When used concomitantly with cephalosporins, the risk of nephrotoxicity may increase.
Caution should be exercised when colistimethate sodium is administered in different dosage forms as information on possible resulting toxicity is limited.
Possible drug interactions should be considered when colistimethate sodium is used concomitantly with drugs that inhibit or induce enzymes that metabolize the drug, or with drugs that are substrates for renal metabolism.
Because colistin affects acetylcholine release, non-depolarizing muscle relaxants should be used with caution in patients receiving colistimethate sodium as it may prolong the effect of the muscle relaxants.
Simultaneous use of colistimethate sodium and macrolides such as azithromycin and clarithromycin, or fluoroquinolones such as norfloxacin or ciprofloxacin should be used with caution in patients with myasthenia gravis.
Neuromuscular blockers should be used with extreme caution in patients receiving colistimethate sodium.
With the simultaneous use of colistimethate sodium in the form of inhalation with inhaled anesthetics, central and peripheral muscle relaxants and aminoglycosides, the risk of blocking neuromuscular transmission increases.
Data regarding the interaction of colistimethate sodium with other drugs in vivo, as well as regarding the mechanism of its elimination from the body, are limited. In in vitro studies of human hepatocytes, colistimethate sodium or colistin did not induce the activity of any of the P450 (CYP) enzymes tested (CYP1A2, 2B6, 2C8, 2C9, 2C19 and 3A4/5).
Special instructions
Usage in period of pregnancy and breast feeding
Clinical safety of colistimethate sodium during pregnancy is not established. Colistimethate sodium is able to permeate through placental barrier and may result in embryonal toxicity. Medicinal drug is not supposed to use during pregnancy, expect the cases, when potential benefit of its use justifies the risk of the fetus. In each case, medicinal drug should be taken under the direct supervision of the doctor!
Colistimethate sodium can pass into breast milk, therefore, if it is necessary to use colistimethate sodium during lactation, you should consider stopping breastfeeding.
Use in pediatrics
Colistimethate sodium should be prescribed with caution to children under 1 year of age, since this group of patients is characterized by insufficient functional maturity of the kidneys.
Effect on the ability to drive a car or operate machinery
Neurotoxicity with possible dizziness, confusion and blurred vision may occur during use of colistimethate sodium. If such reactions occur, patients are advised to refrain from driving vehicles and operating complex machinery during the period of use of the drug.
Special instructions
Colistimethate sodium should be used with caution in patients with porphyria.
If the recommended dose of colistimethate sodium is exceeded when administered parenterally, nephrotoxicity may occur.
Colistimethate sodium should be prescribed with caution to patients with impaired renal function. It is recommended to assess the renal function of such patients at the beginning of treatment, monitor it during therapy and monitor for the occurrence of side effects from the nervous system (facial paresthesia, muscle weakness, dizziness, slurred speech, vasomotor instability, visual disturbances, confusion, psychosis and breathing arrest). Perioral paresthesia and paresthesia of the extremities should be monitored as they are signs of overdose.
It is also necessary to monitor the concentration of colistimethate sodium in the blood serum.
In the event of an allergic reaction, treatment with colistimethate sodium should be discontinued and appropriate measures taken.
When administered intravenously, colistimethate sodium does not cross the blood-brain barrier to a clinically significant extent.
Antibiotic-associated and pseudomembranous colitis, which can occur with all antibacterial agents, can also occur when taking colistimethate sodium. Their severity can range from mild to life-threatening. If diarrhea occurs while taking colistimethate sodium, therapy should be discontinued and a Clostridium difficile treatment should be prescribed. Drugs that inhibit peristalsis should not be prescribed.
Colistin-Belpharm should not be used as inhaled monotherapy in the treatment of acute chronic infections caused by Pseudomonas aeruginosa. Inhaled colistimethate sodium may cause bronchospasm, which can be prevented or treated with appropriate β2-agonists. Therefore, the administration of the first dose of Colistin-Belpharm should be carried out under the supervision of experienced medical personnel, and the use of bronchodilators, if included in the patient’s treatment regimen, should precede the inhalation use of Colistin-Belpharm. If β2-agonists are not effective, treatment should be discontinued.
It is recommended to monitor forced expiratory volume in the first second before and after inhalation of the drug. If the patient shows signs of drug-induced bronchial obstruction, the next time Colistin-Belpharm is used, the test should be repeated, adding a bronchodilator.
Inhaled colistimethate sodium may worsen cough, so the risk-benefit ratio should be carefully assessed when used for hemoptysis.
It is necessary to take a break between dornase alfa inhalations and Colistin-Belpharm inhalations.
When treated with colistimethate sodium, strains of resistant microorganisms may appear. Restoring the effectiveness of the drug is possible after discontinuation and/or modification of therapy.
Overdose
An overdose of colistimethate sodium may cause neuromuscular blockade, which in turn can lead to muscle weakness, shortness of breath and respiratory arrest. An overdose can cause acute renal failure, which is characterized by a decrease in urination, as well as an increase in the concentration of nitrogen in urea and creatinine in the blood plasma.
There is no specific antidote for an overdose of colistimethate sodium. Maintenance therapy is recommended. To increase the rate of drug elimination, forced diuresis with mannitol, prolonged hemodialysis, or peritoneal dialysis can be used, but their effectiveness has not been proven.
When using the drug by inhalation, the entry of sodium colistimethate into the systemic circulation and, therefore, the risk of developing intoxication is extremely insignificant. There is no data on the development of such reactions.
If the drug is accidentally taken orally, the development of toxic effects is unlikely, since colistimethate sodium is very little absorbed from the gastrointestinal tract.
Release form
1 000 000 ME or 2 000 000 ME vial for injection volume of 10 ml or 20 ml.
By 1 or 5 vials together with instructions of use in a cardboard box.
Packaging for hospitals: 36 vials with corresponding amount of instructions of use in group boxes.
Storage conditions
Store in dry place, protected from light at the temperature not higher than 25C.
Store in a place out of reach of children.
Expiration date
Expiration date is 2 years.
Do not use after expiration date, shown at the packaging.
Conditions for release from pharmacies
On prescription
Manufacturer/ name and address od organization, accepting claims (offers) regarding the quality of medicinal product in the territory of Republic of Uzbekistan
FE LLC “BELPHARM”, Republic of Uzbekistan, Tashkent city, Kichik Khalka yuli and Badamzar str., 37
www.belpharm.uz
© Belpharm. All Rights Reserved.
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Developed in manufact.pro