Benzylpenicillin

Pharmacological properties

the drug is a water-soluble benzylpenicillin, which has a bactericidal effect on sensitive microorganisms by inhibiting the biosynthesis of the cell wall. 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-non-producing strains of staphylococci, as well as neisseriae, corynebacterium, bacillus anthomyocetiocariota for example leptospira, treponema, borrelia and other spirochetes, as well as numerous microorganisms (peptococci, peptostreptococci, fusobacteria, clostridia). in high concentrations, the drug is also active against other gram-negative microorganisms, for example escherichia coli, proteus mirabilis, salmonella, shigella, enterobacter aerogenes and alcaligenes faecalis. for infections caused by staphylococci, enterococci, E. coli or E. aerogenes, bacteriological studies, including sensitivity tests, are recommended. penicillinase production (e.g. staphylococci) leads to resistance.

Pharmacokinetics After using 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, 150-200 IU / ml are reached 15-30 minutes after the i / m administration of 10 million IU of the drug. After a short infusion (30 min), the 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 kidney and liver function in premature babies and infants is still undeveloped, 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). Excretion may also be delayed in elderly patients.

To increase the interval between doses, the drug can be combined with penicillin depot-forming drugs.

Indications

Infectious diseases caused by penicillin-sensitive microorganisms: sepsis, wound infections and skin infections, diphtheria (as an addition to antitoxin), pneumonia, empyema, erysipeloid, pericarditis, bacterial endocarditis, mediastenitis, 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 for complications caused by gonorrhea and syphilis; Lyme borreliosis after the first stage of the disease.

Application

Before the introduction, it is necessary to conduct a skin test for tolerability of the drug and procaine, provided that it is used for dilution, in the absence of contraindications to its conduct.

The drug is administered in / m, s / c, in / in (stream or drip), intrathecal, in the body cavity. The most common IM route of administration.

In / in: for moderate infections, a single dose of the drug for adults is usually 250,000–500,000 units, daily - 1,000,000–2,000,000 units; for severe infections, up to 10,000,000–20,000,000 units / day are administered; gas gangrene - up to 40,000,000-60,000,000 units. Typically, the daily dose for children under the age of 1 year is 50,000-100,000 units / kg body weight, older than 1 year - 50,000 units / kg, if necessary, the daily dose can be increased to 200,000-300,000 units / kg, according to life indications - up to 500,000 units / kg. The frequency of administration of the drug is 4-6 times a day. Benzylpenicillin is prepared immediately before use. For iv injection, a single dose (1,000,000–2,000,000 units) of the drug is dissolved in 5–10 ml of sterile water for injection or 0.9% sodium chloride solution and is administered slowly for 3-5 minutes. For iv drip administration, 2,000,000–5,000,000 IU of the antibiotic is 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.

In / in the drug is administered 1-2 times a day, combining with a / m introduction.

V / m: for moderate infections, a single dose of the drug for adults is usually 250,000–500,000 units, daily - 1,000,000–2,000,000 units; for severe infections, up to 10,000,000–20,000,000 units / day are administered; gas gangrene - up to 40,000,000-60,000,000 units. Typically, the daily dose for children under the age of 1 year is 50,000-100,000 units / kg body weight, older than 1 year - 50,000 units / kg, if necessary, the daily dose can be increased to 200,000-300,000 units / kg, according to life indications - up to 500,000 units / kg. The frequency of administration of the drug is 4-6 times a day. For i / m administration, 1-3 ml of sterile water for injection is added to the contents of the vial or 0.9% solution of sodium chloride, or 0.5% solution of procaine. The resulting solution is injected deep into the muscle into the upper outer quadrant of the buttock.

P / c: Benzylpenicillin is used for chipping infiltrates at a concentration of 100,000–200,000 units in 1 ml of 0.25–0.5% procaine solution. In the cavity (abdominal, pleural, etc.), the benzylpenicillin solution is administered to adults at a concentration of 10,000–20,000 units in 1 ml, for children - 2,000–5,000 units in 1 ml. Dissolve in sterile water for injection or 0.9% sodium chloride solution. The duration of treatment is 5-7 days, followed by a transition to the / m introduction.

Intrathecal: the drug is administered for purulent diseases of the brain, spinal cord, and meninges. Adults are prescribed at a dose of 5000-10 000 units, for children over the age of 1 year - 2000-5000 units, administered slowly - 1 ml / min once a day. The drug is diluted in sterile water for injection or in 0.9% sodium chloride solution at the rate of 1000 PIECES per 1 ml. Before injection, 5–10 ml of CSF 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 switch to the / m introduction.

Treatment of patients with syphilis and gonorrhea is carried out according to specially developed schemes.

Depending on the form and severity of the disease, benzylpenicillin is used from 7–10 days to ≥2 months (sepsis, septic endocarditis, etc.).

Contraindications

Hypersensitivity to benzylpenicillin and to other β-lactam antibiotics (penicillins, cephalosporins, carbapenems); newborns whose mothers are hypersensitive to penicillin antibiotics. epilepsy (with intralumbal administration). severe allergic reactions or ba or urticaria, history of hay fever.

Side effects

On the part of the blood system and lymphatic system: eosinophilia, leukopenia, neutropenia, granulocytopenia, thrombocytopenia, agranulocytosis, pancytopenia. and hemolytic anemia, bleeding disorders and a positive result during the Coombs test are also possible.

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 (AD, thrombocytopenic purpura, digestive tract 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 twitches; coma, symptoms of meningism, paresthesia.

Metabolic and nutritional disorders: electrolyte imbalance, which is possible with a quick dose of 10 million IU, an increase in plasma nitrogen level.

From the alimentary canal: stomatitis, glossitis, black tongue, nausea, vomiting, diarrhea.

From the hepatobiliary system: hepatitis, stagnation of bile.

On the part of the kidneys and urinary system: interstitial nephritis, nephropathy (with an iv dose of 10 million IU), albuminuria, cylindruria and hematuria. Oliguria or anuria, as a rule, disappear 48 hours after discontinuation of therapy. Diuresis can be restored after applying 10% mannitol solution.

Other: reactions at the injection site: with iv administration, the development of phlebitis or thrombophlebitis is possible; severe local reactions with i / m administration to infants; long-term 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 lysis of bacteria can cause the Yarish-Herksheimer reaction, which is characterized by the following symptoms: fever, chills, myalgia, headache, exacerbation of skin symptoms, tachycardia, vasodilation with a change HELL; hypersensitivity reactions (itching, laryngospasm, bronchospasm, arterial hypotension, vascular collapse), serum sickness (including manifestations such as fever, weakness, arthralgia, abdominal pain, rash (all types)), high doses can lead to heart failure.

special instructions

Before starting treatment, it is necessary to make 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) were noted in patients undergoing penicillin therapy. Such reactions occur more often in patients with a history of severe allergic reactions. Drug therapy should be discontinued and replaced with another appropriate treatment. Treatment for symptoms of an anaphylactic reaction may be needed, such as the immediate administration of epinephrine, steroids (iv) and emergency treatment of respiratory failure.

With extreme caution, the drug should be used 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, the absorption of the active substance from intramuscular depots can be reduced.

Patients taking the drug in high doses for more than 5 days should monitor the electrolyte balance, blood count and kidney function.

In severe renal impairment, the use of penicillin in high doses can cause cerebral disorders, convulsions, coma.

Caution should be exercised when using the drug in infants, patients with severe cardiopathy, hypovolemia, epilepsy, impaired renal or hepatic function.

With the on / in the introduction of the drug in high doses (10 million IU / day), the injection site should be changed every 2 days to prevent the development of superinfection and thrombophlebitis.

When the drug is administered to infants, serious local reactions may develop, therefore, intravenous administration should be preferred.

Long-term use of the drug can lead to the development of colonization of persistent microorganisms or yeast. Superinfection may occur, which requires careful monitoring of such patients.

In case of severe diarrhea characteristic of pseudomembranous colitis (in most cases caused by Clostridium difficile), it is recommended to stop using the drug and take appropriate measures. The use of drugs that inhibit peristalsis is contraindicated. In the treatment of sexually transmitted diseases with suspected syphilis before the start of therapy and within 4 months after its completion, serological studies are necessary.

To suppress or reduce the severity of the Yarish-Herxheimer reaction, at the first use of the drug, administer 50 mg of prednisolone or its equivalent.In patients with syphilis in the stage, which is manifested by damage to the cardiovascular system, blood vessels and meninges, the Yarish-Herxheimer reaction can be prevented by using prednisolone at 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, the aqueous solutions of benzylpenicillin sodium salt decompose to form decomposition products and metabolites.

Use during pregnancy and lactation. Benzylpenicillin crosses the placental barrier, and its concentration in the blood plasma of the fetus 1–2 hours after administration corresponds to the concentration in the blood plasma of the mother. 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 thorough assessment of the benefit / risk ratio.

Benzylpenicillin passes into breast milk in a small amount, so the risk of developing hypersensitivity in a baby cannot be ruled out. The use of the drug during breastfeeding is possible only when the expected benefit to the mother outweighs the potential risk to the baby.

Children. Used in children from birth. With extreme caution, the drug should be used in children under the age of 2 years.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. There was no negative impact on the ability to drive vehicles or work with other mechanisms.

Interactions

Penicillin preparations with 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 prescribed in full dose (the dose of the more toxic component can be reduced if a synergistic effect is indicated).

Bactericidal antibiotics used in combination with the drug include isoxazolylpenicillins, for example fluxloxacillin and other narrow-spectrum beta-lactam antibiotics, aminopenicillin, aminoglycosides. They should be administered by slow intravenous injection before the administration of benzylpenicillin. If possible, aminoglycosides should be entered in / m separately. It should be borne in mind the possibility of competitive inhibition of the process of elimination from the body with the simultaneous use of benzylpenicillin with anti-inflammatory, antirheumatic and antipyretic drugs (indomethacin, phenylbutazone, salicylates in high doses). Acetylsalicylic acid, probenecid, thiazide diuretics, furosemide, ethacrylic acid increase T_½ benzylpenicillin, increasing its concentration in blood plasma, resulting in an increased risk of developing its toxic effects by affecting the tubular secretion of the kidneys. Allopurinol increases the risk of allergic reactions (skin rashes). The use of benzylpenicillin can in some cases lead to a decrease in the effectiveness of oral contraceptives.

It is necessary to avoid simultaneous use with chloramphenicol, erythromycin, tetracycline, sulfonamides.

With simultaneous use with methotrexate, the excretion of the latter decreases and the risk of its toxicity increases.

Incompatibility. To prevent undesirable chemical reactions, two preparations for injection or infusion should not be mixed in one volume, and solutions containing glucose should also 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 slightly 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 injectable solutions containing cimetidine, cytarabine, chlorpromazine, dopamine, heparin, hydroxyzine, lactate, lincomycin, metaraminol, sodium bicarbonate, oxytetracycline, pentobarbital, tetracycline, sodium thiopental, vancomycin. Benzylpenicillin is incompatible with a complex of B vitamins and ascorbic acid.

Overdose

Overdose symptoms are largely consistent with the nature of the side effects. gastrointestinal upsets and disturbances in water-electrolyte balance are possible.

Treatment: there is no specific antidote. Treatment includes hemodialysis, gastric lavage, and symptomatic therapy; special attention should be paid to the water-electrolyte balance.

Storage conditions

In the original packaging at a temperature not exceeding 25 ° C.