Polymyxin B
Latin name: Polymyxin B
ATX code: J01XB02
Active ingredient: polymyxin B (polymyxin B)
Manufacturer: LLC "ABOLmed" (Russia), Jodas Expoim Pvt. (India)
Description and photo updated: 2018-16-07
Polymyxin B is a polycyclic antibiotic that has a bactericidal effect.
Release form and composition
Polymyxin B is available in the form of a lyophilisate for the preparation of a solution for injection: a porous mass in the form of a powder or a tablet, almost white or white [25 mg or 50 mg in glass vials with a volume of 5 ml, in a cardboard box 1 bottle complete with a solvent (in ampoules of 5 ml or 10 ml - 1 or 2 pcs.) or without; in a cardboard box 5 bottles complete with solvent (5 ml or 10 ml - 5 pcs.) or without it].
1 bottle with a lyophilisate contains the active ingredient: polymyxin B sulfate (in terms of the amount of polymyxin B1, B1-I, B2, B3) - 25 mg or 50 mg.
Solvent: water for injection.
Pharmacological properties
Pharmacodynamics
Polymyxin B is an antibacterial drug with a bactericidal effect. The active substance is produced by the spore-forming bacteria Bacillus polymyxa, 1 mg of purified polymyxin B base corresponds to the content of 10,000 U (unit of action) polymyxin B. The mechanism of action of the drug is due to its ability to adsorb on phospholipids of the membrane of the microbial cell, which leads to an increase in permeability and disruption of the membrane integrity. causing lysis of bacteria.
Most gram-negative bacteria are susceptible to Polymyxin B, including Escherichia coli, Pseudomonas aeruginosa, Shigella speciales (spp.), Enterobacter spp., Salmonella spp., Haemophilus influenzae, Klebsiella spp., Bordetella pertussis.
Shows moderate activity against Fusobacterium spp., Bacteroides fragilis and other Bacteroides spp.
Polymyxin B is not active against anaerobic microorganisms, fungi, coccal aerobic microorganisms (Streptococcus spp., Including Streptococcus pneumoniae, Staphylococcus spp., Neisseria meningitidis, Neisseria gonorrhoeae), gram-positive bacteria Corynebacterium spp. and Mycobacterium tuberculosis.
Desensitization to the drug is slow. Full cross-resistance occurs with polymyxin E and colistin.
Pharmacokinetics
After intramuscular (i / m) administration, the maximum concentration (C max) of polymyxin B sulfate in the blood plasma is reached after 1–2 hours and is 2–7 mg / ml. Against the background of intravenous (iv) administration at a dose of 2–4 mg per 1 kg of patient weight, C max in blood plasma is 2–8 mg / ml.
Plasma protein binding - 50% of the administered dose.
It penetrates poorly through tissue barriers, including the placenta, does not cross the blood-brain barrier, and enters breast milk in small quantities.
The active substance is not metabolized, it tends to accumulate upon repeated administration.
The half-life (T 1/2) is 3-4 hours.
It is excreted unchanged: through the kidneys within 72–96 hours - 60%, the rest through the intestines.
In severe renal failure, T 1/2 can be from 48 to 72 hours.
Indications for use
According to the instructions, Polymyxin B is used to treat the following severe infectious diseases and conditions caused by sensitive gram-negative microorganisms with multiple resistance to the effects of other antibiotics: pneumonia, meningitis, sepsis, bacteremia, generalized wound infection.
Contraindications
- myasthenia gravis;
- period of pregnancy;
- breast-feeding;
- hypersensitivity to polymyxins.
Polymyxin B should be used with caution in patients with chronic renal failure.
Instructions for the use of Polymyxin B: method and dosage
The ready-made solution of lyophilisate is used by intramuscular, intravenous and intrathecal administration.
For intravenous drip injection, Polymyxin B is dissolved in the following proportions: for adults - at the rate of 50 mg of lyophilisate per 300-500 ml of 5% dextrose solution, for children - an individual dose is dissolved in 30-100 ml of 5-10% dextrose solution. The infusion rate is 60–80 drops per minute.
For intramuscular administration, the lyophilisate is dissolved at the rate of 50 mg of the active substance in 2 ml of water for injection, 1% procaine solution or 0.9% sodium chloride solution.
For intrathecal administration, 10 ml of 0.9% sodium chloride solution is added to 50 mg of the drug, the concentration of the resulting solution is 5 mg / ml.
Recommended dosage for patients with normal renal function:
- IV injection: adults, children over the age of 1 year - at the rate of 1.5-2.5 mg per 1 kg of patient weight, the maximum daily dose is not more than 2.5 mg per 1 kg. For children under 1 year old, an increase in the daily dose is allowed, taking into account clinical indications, up to 4 mg per 1 kg of body weight. The dose received is divided into 2 administrations with an interval of 12 hours;
- intramuscular injection (only in cases of impossibility of intravenous injection): adults, children over the age of 1 year - at the rate of 2.5-3 mg per 1 kg of body weight per day. The received dose should be divided into 3-4 injections with an interval of 6-8 hours. For children under 1 year old, an increase in the daily dose is allowed, taking into account clinical indications, up to 4 mg per 1 kg of body weight. Frequency rate of introduction - 4 times a day with an interval of 6 hours;
- intrathecal administration, for therapy of choice in meningitis caused by Pseudomonas aeruginosa: adults, children over the age of 2 years - at a dose of 5 mg once a day. After 3-4 injections, the procedure is performed once every 2 days. Treatment should be continued for 14 days after receiving a negative culture response and reaching a normal level of glucose concentration in the cerebrospinal fluid. For children under 2 years of age, Polymyxin B is prescribed in a dose of 2 mg once a day for 3-4 days or 2.5 mg once every 2 days. Upon receiving a negative result of bacteriological culture and restoration of the normal glucose level in the cerebrospinal fluid, the patient is prescribed a dose of 2.5 mg 1 time in 2 days for 14 days.
When treating patients with impaired renal function, a dosage regimen must be adjusted. It is produced by lowering the usual dose of Polymyxin B for patients with normal renal function, taking into account creatinine clearance (CC) in the following manner:
- CC 20-50 ml / min: 75-100%;
- CC 5–20 ml / min: 50%;
- CC less than 5 ml / min: 15%.
The daily dose must be divided into 2 administrations with an interval of 12 hours.
Side effects
- from the nervous system: drowsiness, dizziness, paresthesia, ataxia, meningeal symptoms (headache, facial flushing, stiff neck muscles, fever, an increase in the amount of protein and cells in the cerebrospinal fluid), impaired consciousness, neuromuscular blockade;
- from the digestive system: decreased appetite, nausea, pain in the epigastric region, pseudomembranous colitis;
- from the respiratory system: apnea, paralysis of the respiratory muscles;
- from the urinary system: cylindruria, azotemia, proteinuria, albuminuria, renal tubular necrosis;
- from the senses: visual impairment;
- allergic reactions: itching, rash, eosinophilia;
- local reactions: a feeling of pain at the site of the i / m injection, phlebitis, thrombophlebitis, periphlebitis;
- others: candidiasis, superinfection.
Overdose
Symptoms: nephrotoxicity, ototoxicity, respiratory muscle paralysis.
Treatment: the appointment of supportive and symptomatic therapy.
special instructions
Parenteral use of the drug is indicated only in a hospital setting.
For Enterobacter spp., Pseudomonas aeruginosa and other infections caused by gram-negative microorganisms, Polymyxin B should be prescribed in cases where the pathogen is resistant to antimicrobial drugs with lower toxicity.
Long-term treatment must be accompanied by regular monitoring of renal function, which is carried out 1 time in 2 days.
To reduce the sensation of pain during i / m administration, it is recommended to use a 1% solution of procaine to dissolve the lyophilisate.
There is a risk of developing pseudomembranous colitis caused by Clostridium difficile. It can occur both against the background of long-term use of the drug, and 14-21 days after discontinuation of therapy. Symptoms of its manifestations include: diarrhea, leukocytosis, fever, abdominal pain, blood and mucus production with feces. When these phenomena appear, the administration of Polymyxin B should be stopped. If the diagnosis is confirmed, the patient is prescribed ion-exchange resins (colestipol, colestyramine), measures are taken to restore the water-electrolyte balance. The use of vancomycin or metronidazole is indicated.
The use of drugs that inhibit intestinal peristalsis is contraindicated.
To reduce the risk of developing undesirable effects on the part of the kidney or nervous system, it is recommended to avoid the simultaneous use of Polymyxin B with other drugs with neurotoxic and / or nephrotoxic properties.
Influence on the ability to drive vehicles and complex mechanisms
The use of Polymyxin B can cause drowsiness, dizziness and other undesirable phenomena on the part of the nervous system, therefore, during the period of treatment, patients are advised to be careful with potentially hazardous activities, including driving and working with complex mechanisms.
Application during pregnancy and lactation
The use of Polymyxin B during gestation and lactation is contraindicated.
If it is necessary to prescribe the drug during lactation, breastfeeding should be discontinued.
Pediatric use
Recommended daily dosage of Polymyxin B for children with normal kidney function:
- intravenous administration: at the age of over 1 year - at the rate of 1.5–2.5 mg per 1 kg of the child's weight, up to 1 year - up to 4 mg per 1 kg of weight, depending on clinical indications. The dose received is divided into 2 administrations with an interval of 12 hours;
- i / m introduction: at the age of over 1 year - 2.5-3 mg per 1 kg of body weight, dividing into 3-4 injections with an interval of 6-8 hours; under 1 year old - up to 4 mg per 1 kg of body weight, divided into 4 injections with an interval of 6 hours;
- intrathecal administration, for therapy of choice in meningitis caused by Pseudomonas aeruginosa: over the age of 2 years - at a dose of 5 mg once for 3-4 days. Then the procedure is performed once every 2 days, treatment should be continued for 14 days after receiving a negative bacteriological culture response and reaching a normal level of glucose concentration in the cerebrospinal fluid. Under the age of 2 years - 2 mg 1 time per day for 3-4 days or 2.5 mg 1 time per 2 days. Upon receiving a negative result of bacteriological culture and restoration of the normal glucose level in the cerebrospinal fluid, the patient is prescribed a dose of 2.5 mg 1 time in 2 days for 14 days.
With impaired renal function
Polymyxin B should be used with caution to treat patients with impaired renal function.
The appointment of the daily dose of the drug is made taking into account the CC: with CC 20-50 ml / min it should be 75-100% of the dose for patients with normal renal function, with CC 5-20 ml / min - 50%, with CC less than 5 ml / min - 15%. The daily dose is divided into 2 administrations with an interval of 12 hours.
Drug interactions
With the simultaneous use of Polymyxin B:
- non-depolarizing muscle relaxants and other neurotoxic agents: increase the risk of developing respiratory muscle paralysis, therefore, a combination with them should be avoided;
- ampicillin: causes a synergistic action against most gram-negative bacteria;
- tetracycline, chloramphenicol, carbenicillin, sulfonamides, trimethoprim: there is a synergism of action against Proteus spp., Pseudomonas aeruginosa, Serratia spp.;
- aminoglycosides (streptomycin, kanamycin, neomycin, gentamicin): increase the risk of neuromuscular blockade, nephro- and ototoxicity;
- amphotericin B: enhances its nephrotoxic effect.
Polymyxin B sulfate solution is pharmaceutically incompatible with the following agents: ampicillin sodium salt, chloramphenicol, cephalosporin antibiotics, tetracycline, heparin, amino acid solutions. For parenteral use of the drug, mixing them is contraindicated.
Analogs
Analogs of Polymyxin B are: Vilimixin, Polymyxin M sulfate, Vellobactin-B, Subviksin.
Terms and conditions of storage
Keep out of the reach of children.
Store at temperatures up to 25 ° C in a dark place.
The shelf life is 3 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Polymyxin B
There are few reviews of Polymyxin B from practicing doctors, who indicate the high effectiveness of the drug in the treatment of infectious diseases caused by enterobacteria, brucella, E. coli and Pseudomonas aeruginosa. However, at present, Polymyxin B is not produced in the country and is not available in the pharmacy chain. This is mainly due to its toxicity and a high degree of likelihood of developing severe adverse events from the blood and kidneys.
Price for Polymyxin B in pharmacies
The price of Polymyxin B is unknown due to the fact that the drug is currently not available in the pharmacy network.
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
