Bicillin-3, 1200000 units 10 ml

Pharmacotherapeutic group: biosynthetic penicillin antibiotic

ATX code: [J01SE30]

Pharmacokinetics

After intramuscular administration, it is slowly absorbed with release from the benzylpenicillin depot. When administered once, it persists at an average therapeutic concentration for 6-7 days. Time required to reach maximum concentration (TCmax) in plasma is 12-24 hours after injection. On the 14th day after 2.4 million units have been injected, serum concentrations are 0.12 µg/ml; on the 21st day after 1.2 million units have reached 0.06 µg/ml (1 unit = 0.6 µg). Fluid penetration is high, tissue penetration is low. Binding with plasma proteins is 40-60%. It penetrates through the placental barrier and is detected in the mother’s milk. It is metabolized insignificantly, it is excreted mainly by kidneys unchanged.

Pharmacodynamics

A combined bactericidal drug of 3 ‑salts of benzylpenicillin: dibenzyl-ethylenediamine, procaine, sodium, having a long action. It suppresses the synthesis of the cell wall of microorganisms.

It is active against Gram-positive microorganisms:

Staphylococcus spp. (non-penicillinase forming), Streptococcus spp, including Streptococcus pneumoniae, Corynebacterium diphtheriae;

Anaerobic spore-forming bacilli:

Bacillus anthracis, Clostridium spp, Actinomyces israelii;

Gram-negative microorganisms:

Neisseria gonorrhoeae, Neisseria meningitidis, Treponema spp.

Penicillinase-producing strains of Staphylococcus spp. are resistant to the drug.

Indications

Active ingredient

Composition

How to take, the dosage

The duration of use of the drug is chosen by the attending physician depending on the severity of the disease, the sensitivity of the pathogen and the overall effectiveness of the therapy.

Prevention of rheumatic fever recurrence should be carried out at least 5 years after the last attack.

Adults

Syphilis

In the treatment of primary syphilis, a single dose of the drug is 1.8 million IU. The injections are given twice a week. The course of treatment is at least 5 injections.

In the treatment of secondary, secondary relapsed and latent early syphilis a single dose of the drug is 1.8 million units. Injections are carried out twice a week. The course of treatment is at least 10 injections.

Streptococcal infections

In rust inflammation, streptococcal upper respiratory tract infections caused by group A streptococci, the drug is administered once in a dose of 1.2 million IU or 2.4 million IU depending on the severity of infection.

Frambiesia

In the treatment of frambiesia, the drug is administered once in a dose of 1.2 million IU.

Prevention of rheumatism

In prevention of rheumatism, the drug is administered in a dose of 600,000 IU every 2 weeks or in a dose of 1.2 million IU every 3 to 4 weeks.

Patient special groups

There is no need to adjust the dose of the drug in elderly patients, patients with hepatic or renal dysfunction. However, caution should be exercised in these groups of patients (see section “Special Precautions”).

Preparation of suspension

For preparation of the suspension it is used sterile water for injection, isotonic sodium chloride solution or 0.25-0.5% novocaine solution (5-6 ml), prepared ex tempore. The solvent is injected into the vial slowly, at a rate of 5 ml in 20-25 s. The vial with the mixture is shaken gently in the direction of its longitudinal axis until a homogeneous suspension (or slurry) is formed. Bubbles are allowed on the surface of the suspension at the walls of the vial. The suspension is injected immediately deep into the upper outer quadrant of the buttock.

If necessary, 2 injections are made in different buttocks. Rubbing of the buttock after injection is not recommended. In prolonged contact with water or the other solutions mentioned above, the physical and colloidal properties of the drug change, resulting in an uneven suspension and difficulty in passing through the syringe needle.

Interaction

Co-administration is not recommended

Since penicillin derivatives act only on dividing microbial cells, the drug should not be combined with bacteriostatic antibacterial drugs (e.g., macrolides, chloramphenicol, lincosamides, tetracyclines). Combinations with other antibacterial drugs are possible only if a synergistic, or at least additive, effect of the drug combination can be expected.

In order to avoid undesirable pharmaceutical interactions, the drug should not be administered in the same syringe with other drugs.

Combinations to be used with caution

In concomitant use with nonsteroidal anti-inflammatory drugs (indomethacin, phenylbutazone, salicylates), probenecid, allopurinol the possibility of competitive inhibition of drug excretion must be kept in mind.

The use of probenecid leads to inhibition of tubular secretion of benzylpenicillin, resulting in increased serum concentrations of the drug and its half-life.

In addition, probenecid inhibits the transport of penicillin from the cerebrospinal fluid, so the simultaneous administration of probenecid further reduces the penetration of benzylpenicillin into brain tissue.

The concomitant use with oral anticoagulants may enhance their properties (as vitamin K antagonists) and increase the risk of bleeding. Frequent monitoring of the international normalized ratio (INR) is recommended, with dose adjustments of the vitamin K antagonist both during and after treatment with the drug.

The risk of bradycardia increases significantly when co-administered with digoxin.

Decreases excretion of methotrexate, which may increase its toxicity.

Special Instructions

The drug should not be injected into tissues with reduced blood supply. Before starting therapy a thorough history of possible sensitization to penicillins and/or other beta-lactam antibiotics should be taken. Severe (up to anaphylactic shock) and sometimes fatal allergic reactions may occur during treatment with the drug. The patient should be informed about possible allergy symptoms and the need to inform the doctor immediately about their occurrence. In case of allergic reactions, treatment with the drug should be stopped immediately and symptomatic therapy should be prescribed, if necessary.

In 5-10% of cases, allergic reactions to penicillin may be cross-reacted with allergic reactions to cephalosporins. In this regard, penicillins are contraindicated if there is a history of allergic reactions to cephalosporins.

Particular caution should be exercised in the following groups of patients:

– Patients with bronchial asthma, skin allergic rashes have an increased risk of hypersensitivity reactions. Such patients should remain under medical supervision for at least 30 minutes after the injection of the drug. In case of allergic reactions the drug should be discontinued, if necessary symptomatic and/or antishock therapy is indicated;

– Patients with renal and/or hepatic impairment (see also section “Dosage and administration”);

– Patients with concomitant dermatomycosis (possible development of paraallergic reactions).

In general principle, patients who are prone to hypersensitivity reactions should, if possible, be monitored for at least 30 minutes after administration of the antibiotic, because severe immediate hypersensitivity reactions may occur even after the first administration of the drug.

In syphilis therapy, a Jarisch-Herxheimer reaction (fever, chills, other general and local symptoms) may develop due to massive lysis of the bacteria and release of endotoxins.

Two to 12 hours after drug administration, headache, sweating, chills, myalgia, arthralgia, nausea, tachycardia, and increased and then decreased blood pressure may occur.

These symptoms go away after 10-12 hours.

The patient should be informed that these reactions are common transient complications of antibiotic treatment. If a Jarisch-Herxheimer reaction occurs, appropriate symptomatic therapy should be given to eliminate or reduce the severity of the symptoms.

In patients with diabetes mellitus, due to impaired peripheral circulation, the absorption of the drug into the systemic bloodstream may be delayed. The drug should not be administered into tissues with impaired perfusion.

The drug should not be administered subcutaneously, intravenously, endolumbaneously or into body cavities.

Periodic monitoring of renal function and peripheral blood counts should be performed with prolonged use of the drug (more than 5 days).

In case of accidental subcutaneous injection, there may be a painful thickening at the site of injection. The soreness may decrease if ice is placed over the injection site.

Inadvertent intravascular injection may cause transient anxiety and visual disturbances (Hoyne syndrome).

The symptoms usually subside within one hour. If symptoms are severe, sedation may be necessary.

The development of Nikolau syndrome, an acute drug-induced embolism of the vessels of the skin, is possible against the background of the use of the drug. Nicolaou syndrome is a rare complication occurring with intramuscular drug administration, the manifestations of which include necrosis of the skin and/or underlying tissues of varying severity. Serious complications such as arterial thrombosis and tissue necrosis (gangrene) can occur with accidental intra-arterial drug administration. The initial manifestations of these complications may be pale “spots” on the skin of the gluteal area. As a result of the high pressure at the injection site, retrograde throw of the drug into the common iliac artery, aorta or spinal arteries may be observed.

In order to avoid accidental intravascular injection, aspiration is recommended prior to intramuscular injection to identify possible needle entry.

Stretching of the buttock after injection is not recommended.

Repeated injections into the same area of muscle tissue during long-term depo-penicillin treatment (e.g., syphilis treatment) may result in damage to that area of tissue and a local increase in vascularization. Subsequent injections increase the likelihood of the administered substance entering the bloodstream directly by direct injection into a blood vessel due to increased pressure during administration or due to “rubbing” of the site where the drug depot was created.

In prolonged treatment, it is recommended to choose the site for the next injection at a considerable distance from the site of the previous injection.

In the treatment of venereal diseases, if syphilis is suspected, dark-field microscopy should be performed before starting therapy and then serological tests should be performed within 4 months. In cases of congenital syphilis, cerebrospinal fluid (CSF) should also be tested.

If CNS involvement (neurosyphilis) cannot be ruled out, other penicillin drugs that penetrate the CSF better should be used.

In severe pyo-inflammatory diseases (severe pneumonia, empyema, sepsis, meningitis, peritonitis) drugs creating a higher concentration of benzylpenicillin in the blood plasma are required. Water-soluble salts of the drug should be used.

In case of severe, persistent diarrhea, pseudomembranous colitis should be suspected (possible symptoms are watery stools with blood/mucus, tenesmus, diffuse spastic abdominal pain, fever). This condition may be life-threatening, therapy with the drug should be immediately withdrawn, and appropriate therapy based on the sensitivity of the pathogen identified (e.g., oral vancomycin 250 mg 4 times a day) should be prescribed. Drugs that inhibit intestinal peristalsis are contraindicated.

Because of the possibility of fungal lesions, it is advisable to use B vitamins and vitamin C during treatment with benzylpenicillin. If fungal infection is suspected, the use of antifungal drugs is indicated.

It should be taken into account that the use of the drug in insufficient doses or too early discontinuation of treatment often leads to the emergence of resistant strains of pathogens. The possibility of the emergence of resistant strains of pathogens should be considered in long-term treatment. If secondary infections (superinfections) occur, appropriate measures should be taken.

The effect on the results of diagnostic laboratory tests

– Positive direct Coombs reaction is observed in patients receiving benzylpenicillin. After withdrawal of penicillin, the direct antiglobulin test may remain positive for 6-8 weeks.

– Determination of urine proteins using precipitate methods (sulfosalicylic acid, trichloroacetic acid), the Folin-Cchocalteu method or the biuret method can lead to false-positive results. Thus, the protein in the urine must be determined by other methods.

– Determination of amino acids in urine using the ninhydrin method may also lead to false-positive results.

Penicillins bind to albumin. In electrophoresis, erroneous bisalbuminemia may occur when determining albumin content.

– In benzylpenicillin therapy, non-enzymatic determination of glucose and urobilinogen in urine can lead to false positives.

– Elevated urinary 17-ketosteroids (using the Zimmerman reaction) may be observed with benzylpenicillin treatment.

– The drug is used with caution in patients with impaired renal excretory function because of the risk of hyponatremia. It is recommended to monitor renal function when using the drug.

The sodium content of a single dose of the drug is 7.73 mg or 0.336 mmol for 600000 IU dosing and 15.46 mg or 0.672 mmol for 1200000 IU dosing.

Impact on driving and operating machinery

At the time of treatment, caution should be exercised while driving vehicles and engaging in other potentially dangerous activities requiring increased concentration and quick psychomotor reactions.

Contraindications

Hypersensitivity to drugs of the group of penicillin and other beta-lactam antibiotics, to procaine, children under 18 years of age.

With caution

Pregnancy, breast-feeding, renal failure, allergic diseases, including bronchial asthma, pollinosis (including anamnesis), pseudomembranous colitis.

Side effects

Infections and invasions

In long-term therapy – superinfection with resistant microorganisms and fungi.

Disorders of the blood and lymphatic system: hemolytic anemia, anemia, thrombocytopenia, leukopenia, hypocoagulation.

Intune system disorders: anaphylactic shock, Jarisch-Herxheimer reaction, anaphylactoid reactions (asthma attack, purpura, gastrointestinal symptoms).

Mental disorders: Hoyne syndrome (acute penicillin psychotic syndrome).

Nervous system disorders: neuropathy.

Gastrointestinal disorders: stomatitis, glossitis, diarrhea, vomiting, pseudomembranous colitis.

Liver and biliary tract disorders: hepatitis, cholestasis.

Dermatological and subcutaneous tissue disorders: urticaria, angioedema, erythema multiforme, exfoliative dermatitis, parallergic reactions may develop in patients with concomitant dermatomycoses (due to similarity of antigens of penicillin and dermatophyte metabolites), Stevens-Johnson syndrome, Lyell syndrome.

Muscular, skeletal and connective tissue disorders: arthralgia, joint pain.

River and urinary tract disorders: nephropathy, interstitial nephritis.

General disorders and reactions at the injection site: fever, pain at the injection site, infiltrates at the injection site, Nicolaou syndrome (acute drug-induced embolism of the skin vessels).

Laboratory and instrumental data: positive direct Coombs reaction, moderate transient increase in serum transaminase activity.

Overdose

Pregnancy use

Pregnant use is possible only when the estimated benefit to the mother exceeds the potential risk to the fetus.

If it is necessary to use the drug during lactation, discontinuation of breastfeeding should be considered.

Similarities