Pharmacological properties
Pharmacodynamics. The drug is a water-soluble benzylpenicillin, which has a bactericidal effect on sensitive microorganisms by inhibiting cell wall biosynthesis. The spectrum of action of benzylpenicillin extends to streptococci of groups A, B, C, G, H, L and M, streptococcus pneumoniae, streptococcus viridans, enterococci, penicillinase-producing strains of staphylococci, as well as neisseriae, corynebacteria, bacillus anthracis, actinomycetes, pasteurella multocida, varieties of spirochetes, such as leptospira, treponema, borrelia and other spirochetes, as well as numerous microorganisms (peptococci, peptostreptococcus, fusobacteria, clostridia). In high concentrations, the drug is also active against other gram-negative microorganisms, such as escherichia coli, proteus mirabilis, salmonella, shigella, enterobacter aerogenes and alcaligenes faecalis. In infections caused by staphylococci, enterococci, E. coli or E. aerogenes, bacteriological investigations, including susceptibility testing, are recommended. Penicillinase production (e.g. by staphylococci) leads to resistance.
Pharmacokinetics. After the use of penicillin in high doses, therapeutic concentrations are also achieved in hard-to-reach tissues such as heart valves, bones and cerebrospinal fluid. C max in blood plasma of 150-200 IU / ml is achieved 15-30 min after i / m administration of 10 million IU of the drug. After short-term infusions (30 min) levels can reach a maximum of 500 IU / ml. Binding to plasma proteins is ≈55% of the total dose. Most of the administered dose (50-80%) is excreted by the kidneys unchanged (85-95%). Excretion of the active substance with bile is limited to a small part of the dose (≈5%).
Since the functions of the kidneys and liver in premature children and infants are not yet developed, T ½ from blood plasma is from ≈3 hours. Therefore, the interval between doses should be at least 8-12 hours (depending on the degree of maturity of the organ). Elimination may also be delayed in elderly patients.
To increase the interval between doses, the drug can be combined with depot penicillin preparations.
Indication
Infectious diseases caused by penicillin-sensitive microorganisms: sepsis, wound infections and skin infections, diphtheria (as an adjunct to antitoxin), pneumonia, empyema, erysipelas, pericarditis, bacterial endocarditis, mediastinitis, peritonitis, meningitis, brain abscess, arthritis, osteomyelitis; genital tract infections caused by fusobacteria; as well as for specific infections: anthrax; infections caused by clostridia, including tetanus, listeriosis, pasteurellosis; fever caused by rat bites; fusospirochetosis, actinomycosis; treatment of complications caused by gonorrhea and syphilis; Lyme borreliosis after the first stage of the disease.
Application
Before administration, it is necessary to conduct a skin test for tolerance to the drug and procaine, provided that it is used for dilution, in the absence of contraindications to its conduct.
The drug is administered intramuscularly, subcutaneously, intravenously (by jet or drip), intrathecally, into the body cavity. The most common route of administration is intramuscular.
In / in: for moderate infections, a single dose of the drug for adults is usually 250,000-500,000 U, daily - 1,000,000-2,000,000 U, for severe infections, up to 10,000,000-20,000,000 U / day is administered, for gas gangrene - up to 40,000,000-60,000,000 U. Usually, the daily dose for children under 1 year old is 50,000-100,000 U / kg of body weight, over 1 year old - 50,000 U / kg, if necessary, the daily dose can be increased to 200,000-300,000 U / kg, for vital indications - up to 500,000 U / kg. The frequency of administration of the drug is 4-6 times a day. Benzylpenicillin solution is prepared immediately before its use. For intravenous injection, a single dose (1,000,000-2,000,000 IU) of the drug is dissolved in 5-10 ml of sterile water for injection or 0.9% sodium chloride solution and administered slowly over 3-5 minutes. For intravenous drip administration, 2,000,000-5,000,000 IU of the antibiotic are dissolved in 100-200 ml of 0.9% sodium chloride solution or 5% glucose solution and administered at a rate of 60-80 drops per minute.
The drug is administered intravenously 1-2 times a day, combining with intramuscular administration.
In / m: for moderate infections, a single dose of the drug for adults is usually 250,000-500,000 U, daily - 1,000,000-2,000,000 U, for severe infections, up to 10,000,000-20,000,000 U / day is administered, for gas gangrene - up to 40,000,000-60,000,000 U. Usually, the daily dose for children under 1 year old is 50,000-100,000 U / kg of body weight, over 1 year old - 50,000 U / kg, if necessary, the daily dose can be increased to 200,000-300,000 U / kg, for vital indications - up to 500,000 U / kg. The frequency of administration of the drug is 4-6 times a day. For intramuscular administration, 1-3 ml of sterile water for injection or 0.9% sodium chloride solution or 0.5% novocaine solution is added to the contents of the vial. The resulting solution is injected deep into the muscle in the upper outer quadrant of the buttock.
Intrathecally: the drug is administered for purulent diseases of the brain, spinal cord, meninges. Adults are prescribed a dose of 5000-10,000 IU, children over 1 year old - 2000-5000 IU, administered slowly - 1 ml/min 1 time per day. The drug is diluted in sterile water for injection or in 0.9% sodium chloride solution at the rate of 1000 IU per 1 ml. Before injection, 5-10 ml of cerebrospinal fluid is removed from the spinal canal and added to the antibiotic solution in equal proportions. Injections are repeated for 2-3 days, after which they are switched to i / m administration.
Treatment of patients with syphilis and gonorrhea is carried out according to specially developed regimens.
Depending on the form and severity of the disease, Benzylpenicillin is used from 7-10 days to ≥2 months (sepsis, septic endocarditis, etc.).
Contraindication
Hypersensitivity to benzylpenicillin and other β-lactam antibiotics (penicillins, cephalosporins, carbapenems); newborns whose mothers have hypersensitivity to penicillin antibiotics. epilepsy (with intralumbar injection). severe allergic reactions or urticaria, hay fever in history.
Side effects
From the side of the blood and lymphatic system: eosinophilia, leukopenia, neutropenia, granulocytopenia, thrombocytopenia, agranulocytosis, pancytopenia. as well as possible hemolytic anemia, blood clotting disorders and a positive result when conducting a Coombs test.
On the part of the immune system: allergic reactions, including urticaria, erythema multiforme, exfoliative dermatitis, contact dermatitis, angioedema, fever, joint pain, anaphylactic or anaphylactoid reactions (BA, thrombocytopenic purpura, gastrointestinal symptoms).
From the nervous system: with high-dose infusion (adults 20 million IU), there is a particularly high risk of seizures in patients with severe renal impairment, epilepsy, meningitis, cerebral edema, or when using an extracorporeal circulation apparatus; neurotoxic reactions, including hyperreflexia, myoclonic twitching; coma, symptoms of meningism, paresthesia.
Metabolic and nutritional disorders: electrolyte imbalance, which is possible with rapid administration of a dose of 10 million IU, increased nitrogen levels in blood plasma.
Gastrointestinal tract: stomatitis, glossitis, black tongue, nausea, vomiting, diarrhea.
From the hepatobiliary system: hepatitis, bile stasis.
From the kidneys and urinary system: interstitial nephritis, nephropathy (with intravenous administration of a dose of 10 million IU), albuminuria, cylindruria and hematuria. Oliguria or anuria, as a rule, pass 48 hours after discontinuation of therapy. Diuresis can be restored after the use of 10% mannitol solution.
Other: reactions at the injection site: with intravenous administration, the development of phlebitis or thrombophlebitis is possible; severe local reactions with intramuscular administration in infants; prolonged use of antibiotics can lead to the development of secondary superinfection caused by resistant microorganisms; candidiasis in the treatment of syphilis or other infectious diseases caused by spirochetes, the process of bacterial lysis can cause the Jarisch-Herxheimer reaction, which is characterized by the following symptoms: increased body temperature, chills, muscle pain, headache, exacerbation of skin symptoms, tachycardia, vasodilation with changes in blood pressure; hypersensitivity reactions (itching, laryngospasm, bronchospasm, hypotension, vascular collapse), serum sickness (including such manifestations as fever, weakness, joint pain, abdominal pain, rash (all types)), high doses can lead to the development of heart failure.
Special instructions
Before starting treatment, it is necessary to perform a preliminary test for the possibility of a hypersensitivity reaction to penicillins and cephalosporins. In patients with hypersensitivity to cephalosporins, the possibility of cross-allergy should be considered.
Severe and sometimes fatal cases of hypersensitivity (anaphylactic reactions) have been reported in patients receiving penicillin therapy. Such reactions occur more frequently in patients with a known history of severe allergic reactions. Therapy with the drug should be discontinued and other appropriate treatment should be instituted. Treatment of symptoms of anaphylactic reactions may be necessary, such as immediate administration of adrenaline, steroids (IV) and emergency treatment for respiratory failure.
The drug should be used with extreme caution in patients with hay fever, urticaria, and other allergic diseases.
Penicillin is not recommended for the treatment of patients with acute lymphocytic leukemia or infectious mononucleosis due to the increased risk of erythematous skin rashes. It should be borne in mind that in patients with diabetes mellitus, absorption of the active substance from intramuscular depots may be reduced.
Patients taking the drug in high doses for more than 5 days should have their electrolyte balance, blood count, and kidney function monitored.
In severe renal impairment, the use of penicillin in high doses can cause cerebral disorders, seizures, and coma.
Caution should be exercised when using the drug in infants, patients with severe cardiopathy, hypovolemia, epilepsy, and impaired renal or hepatic function.
When administering the drug to infants, serious local reactions may develop, so preference should be given to intravenous administration.
Prolonged use of the drug may lead to the development of colonization with resistant microorganisms or yeasts. Superinfection is possible, which requires careful monitoring of such patients.
In the event of severe diarrhea typical of pseudomembranous colitis (most often caused by Clostridium difficile), it is recommended to discontinue use of the drug and take appropriate measures. The use of agents that inhibit peristalsis is contraindicated. In the treatment of venereal diseases with suspected syphilis, serological tests should be performed before starting therapy and within 4 months after its completion.
To suppress or reduce the severity of the Jarisch-Herxheimer reaction, 50 mg of prednisolone or its equivalent should be administered at the first use of the drug. In patients with syphilis in the stage manifested by damage to the cardiovascular system, blood vessels and meninges, the Jarisch-Herxheimer reaction can be prevented by using prednisolone 50 mg/day or an equivalent steroid for 1-2 weeks.
Freshly prepared solutions for injection or infusion should be used immediately. Even when stored in a refrigerator, aqueous solutions of benzylpenicillin sodium salt decompose to form degradation products and metabolites.
Use during pregnancy and breastfeeding. Benzylpenicillin penetrates the placental barrier, and its concentration in the fetal blood plasma 1-2 hours after administration corresponds to the concentration in the maternal blood plasma. Available data on the use of the drug during pregnancy indicate the absence of a negative effect on the fetus / newborn. The use of the drug during pregnancy is possible only after a careful assessment of the benefit / risk ratio.
Benzylpenicillin passes into breast milk in small amounts, so the risk of hypersensitivity in the child cannot be excluded. The use of the drug during breastfeeding is possible only if the expected benefit to the mother outweighs the potential risk to the child.
Children. Used in children from birth. The drug should be used with extreme caution in children under 2 years of age.
Ability to influence the reaction rate when driving vehicles or working with other mechanisms. No negative impact on the ability to drive vehicles or work with other mechanisms has been identified.
Interactions
Penicillin preparations that have a bactericidal effect should not be used in combination with bacteriostatic antibiotics. Combination with other antibiotics is advisable only when a synergistic effect or any additional effect can be expected. The individual components of the therapeutic combination should be administered in full dose (the dose of the more toxic component can be reduced if a synergistic effect is shown).
Bactericidal antibiotics used in combination with the drug include isoxazolylpenicillins, such as flucloxacillin and other narrow-spectrum beta-lactam antibiotics, aminopenicillin, aminoglycosides. They should be administered by slow IV injection before the administration of benzylpenicillin. If possible, aminoglycosides should be administered IM separately. The possibility of competitive inhibition of the process of excretion from the body should be borne in mind when penicillin is used simultaneously with anti-inflammatory, antirheumatic and antipyretic agents (indomethacin, phenylbutazone, salicylates in high doses). Acetylsalicylic acid, probenecid, thiazide diuretics, furosemide, ethacrynic acid increase T ½ of benzylpenicillin, increasing its concentration in blood plasma, as a result of which the risk of its toxic effect increases by affecting the tubular secretion of the kidneys. Allopurinol increases the risk of allergic reactions (skin rashes). The use of penicillin may in some cases lead to a decrease in the effectiveness of oral contraceptives.
Concomitant use with chloramphenicol, erythromycin, tetracycline, sulfonamides should be avoided.
When used simultaneously with methotrexate, the excretion of the latter is reduced and the risk of its toxicity increases.
Incompatibility. To prevent undesirable chemical reactions, two drugs for injection or infusion should not be mixed in the same volume, and solutions containing glucose should not be used.
The drug is incompatible with metal ions, especially copper, mercury, zinc and zinc compounds, which may be part of the rubber stoppers of infusion bottles. Substances with oxidizing and reducing properties, alcohol, glycerin, macrogol and other hydroxyl compounds can also inactivate it. In weakly alkaline solutions, the drug is rapidly inactivated by cysteine and other aminothiol compounds. Sympathomimetic amines are also incompatible with benzylpenicillin.
The drug should not be used in glucose solution.
Do not mix with other injection solutions containing cimetidine, cytarabine, chlorpromazine, dopamine, heparin, hydroxyzine, lactate, lincomycin, metaraminol, sodium bicarbonate, oxytetracycline, pentobarbital, tetracycline, sodium thiopental, vancomycin. Benzylpenicillin is incompatible in solution with vitamin B complex and ascorbic acid.
Symptoms of overdose largely correspond to the nature of the side effects. Gastrointestinal disorders and disturbances of water and electrolyte balance are possible.
Treatment: There is no specific antidote. Treatment includes hemodialysis, gastric lavage, and symptomatic treatment; special attention should be paid to water and electrolyte balance.
Storage conditions
In the original packaging at a temperature not exceeding 25 °C.
