Bicillin^®-1 (Powder) Instructions for Use

ATC Code

J01CE08 (Benzathine benzylpenicillin)

Active Substance

Benzathine benzylpenicillin (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Penicillin antibiotic, destroyed by penicillinase

Pharmacotherapeutic Group

Antibiotic, penicillin

Pharmacological Action

An antibiotic of the penicillin group with prolonged action, destroyed by penicillinase. It has a bactericidal effect. The mechanism of action is based on the disruption of peptidoglycan synthesis – the muropeptide of the cell membrane, which leads to the inhibition of the synthesis of the microorganism’s cell wall, suppressing the growth and reproduction of bacteria.

Active against gram-positive bacteria Streptococcus spp. (including Streptococcus pneumoniae, Streptococcus pyogenes group A), Staphylococcus spp. (non-penicillinase-producing), Corynebacterium diphtheriae; gram-negative bacteria Neisseria gonorrhoeae, Neisseria meningitidis; anaerobic bacteria Bacillus anthracis, Clostridium spp., Actinomyces israelii; also against Treponema spp.
The drug is resistant to Staphylococcus spp. that produce penicillinase.

Pharmacokinetics

Absorption

After intramuscular injection, Benzathine benzylpenicillin is hydrolyzed very slowly, releasing benzylpenicillin.
C_max in blood serum is reached 12-24 hours after injection.

Distribution and Metabolism

The long half-life provides a stable and prolonged concentration of the drug in the blood: on the 14th day after administration of 2.4 million IU of the drug, the concentration in serum is 0.12 µg/ml; on the 21st day after administration of 1.2 million IU – 0.06 µg/ml (1 IU=0.6 µg). Diffusion of the drug into fluids is complete, diffusion into tissues is very weak.

Plasma protein binding – 40-60%.

Benzathine benzylpenicillin penetrates the placental barrier in small amounts and is also excreted in breast milk.

Biotransformation of the drug is insignificant.

Excretion

It is excreted mainly by the kidneys unchanged. Up to 33% of the administered dose is excreted within 8 days.

Indications

For the treatment of infections caused by microorganisms sensitive to the drug

• Syphilis (as monotherapy);
• Yaws;
• Pinta;
• Acute tonsillitis;
• Scarlet fever.

For the prevention of infections caused by microorganisms sensitive to the drug

• Recurrent attacks after acute rheumatic fever;
• Erysipelas recurrences;
• Wound infection;
• Postoperative complications.

ICD codes

Dosage Regimen

Powder

The drug is administered only deep intramuscularly into the upper outer quadrant of the buttock. If blood appears in the syringe, indicating that the needle has entered a vessel, the syringe should be removed and the injection should be given in another place. If two injections are necessary, the drug should be administered into different buttocks.

The drug must not be administered intravenously!

For adults with preventive treatment of syphilis, a single dose of 2.4 million IU is prescribed; for primary syphilis – 1 injection (2.4 million IU) intramuscularly at 7-day intervals (course – 2 injections); for secondary and early latent syphilis – 1 injection (2.4 million IU) intramuscularly at 7-day intervals (course – 3 injections).

For preventive treatment of a child born to a mother with untreated syphilis, – 1 injection (50,000 IU/kg body weight) intramuscularly at 7-day intervals (course – 3 injections), the dose is divided in half and administered into different buttocks.

For preventive treatment of a child due to insufficient treatment of the mother or seroresistance of syphilis – 1 injection (50,000 IU/kg body weight) intramuscularly at 7-day intervals (course – 2 injections).

For treatment of yaws and pinta (endemic treponematoses)children – 1.2 million IU once; adults – 2.4 million IU once.

For acute tonsillitis, scarlet fever, erysipelas, wound infections in the acute phasechildren under 12 years – 0.6 million IU every 3 days or 1.2 million IU every 2-4 weeks depending on the severity of the infection; adults – 1.2-2.4 million IU once a week.

For prevention of recurrent attacks after acute rheumatic feverchildren with body weight <25 kg – 0.6 million IU every 3 weeks; children with body weight >25 kg – 1.2 million IU every 3 weeks; adolescents and adults – 2.4 million IU every 3 weeks. The duration of prophylaxis is determined individually.

For prevention of erysipelas recurrenceschildren – 0.6 million IU every 2 weeks or 1.2 million IU every 3-4 weeks; adults with seasonal recurrences – 2.4 million IU every 4 weeks for 3-4 months annually; with frequent recurrences – 2.4 million IU every 3-4 weeks for 2-3 years.

For prevention of postoperative infectionschildren – 0.6 million IU or 1.2 million IU; adults – 2.4 million IU every 7-14 days until complete recovery.

In renal impairment, doses are reduced according to CC: for CC from 10 to 50 ml/min, 75% of the daily dose of the drug is administered; for CC <10 ml/min, 25-50% of the daily dose of the drug is administered.

Rules for solution preparation
The suspension of the drug is prepared under aseptic conditions immediately before use: 3-5 ml of water for injections or 0.9% sodium chloride solution is introduced into the vial. The mixture is mixed until a uniform suspension is obtained by rapidly rotating the vial between the palms for at least 1 minute or by gently shaking the vial along its longitudinal axis for 30 seconds.

Adverse Reactions

Allergic reactions anaphylactic shock, urticaria, fever, joint pain, angioedema, exfoliative dermatitis, polymorphic erythema, difficulty breathing. In the treatment of syphilis, due to the release of endotoxins, a Jarisch-Herxheimer reaction may develop.

From the hematopoietic system: reversible anemia, leukopenia, thrombocytopenia.

From the digestive system: stomatitis, glossitis, nausea, vomiting, diarrhea, candidiasis, isolated cases of pseudomembranous colitis have been described with the use of the drug; rarely moderate transient increase in serum transaminase levels.

From the urinary system: rarely – acute interstitial nephritis.

With prolonged therapy, the development of superinfection with resistant microorganisms and fungi is possible.

The use of high doses of beta-lactam antibiotics, especially in renal failure, can cause the development of encephalopathy (including impaired consciousness, movement disorders, convulsions).

In children, local reactions to the administration of the drug may develop.

Contraindications

• Hypersensitivity to beta-lactam antibiotics (penicillins and cephalosporins).

With caution should be prescribed for a tendency to allergic reactions, pseudomembranous colitis, renal failure.

Use in Pregnancy and Lactation

Benzathine benzylpenicillin penetrates the placental barrier in small amounts and into breast milk. Use during pregnancy is possible only if the intended benefit to the mother outweighs the potential risk to the fetus.
It is recommended to stop breastfeeding if it is necessary to prescribe the drug.

Use in Renal Impairment

In renal impairment, doses are reduced according to CC: for CC from 10 to 50 ml/min, 75% of the daily dose of the drug is administered; for CC less than 10 ml/min, 25-50% of the daily dose of the drug is administered.

Special Precautions

If any allergic reactions occur, it is necessary to stop the administration of the drug and prescribe appropriate treatment. Severe and sometimes fatal allergic reactions up to the development of anaphylactic shock may be observed.

When collecting anamnesis, attention should be paid to the tolerance of previous treatment with penicillins. If there is a history of allergy to penicillin, the drug is strictly contraindicated. Allergic reactions to penicillin may be cross-reactive with allergic reactions to cephalosporins. In this regard, if there is a history of allergic reactions to cephalosporins, the appointment of penicillins is contraindicated.

The drug must not be administered subcutaneously, intravenously, endolumbally, or into body cavities. With accidental intravascular administration, transient anxiety and visual disturbances (Hoigne’s syndrome) may be noted. To avoid accidental intravascular administration of the drug, it is recommended to perform aspiration before intramuscular injection to detect possible entry of the needle into a vessel.

When treating venereal diseases, if syphilis is suspected, microscopic and serological tests should be performed before starting therapy and then for 4 months.

Due to the possibility of developing fungal lesions, it is advisable to prescribe B vitamins and vitamin C during treatment with the drug, and if necessary – nystatin and levorin.

It should be borne in mind that the use of the drug in insufficient doses or too early termination of treatment often leads to the emergence of resistant strains of pathogens.

Overdose

Currently, no cases of overdose of Bicillin^®-1 have been reported.

Drug Interactions

When prescribing Bicillin-1 concomitantly with NSAIDs (indomethacin, phenylbutazone, salicylates), allopurinol, probenecid, the possibility of competitive inhibition of the excretion of drugs from the body should be considered.

With simultaneous use of Bicillin-1 with bactericidal antibiotics (including cephalosporins, cycloserine, vancomycin, rifampicin, aminoglycosides), a synergistic effect is noted; with bacteriostatic antibiotics (including macrolides, chloramphenicol, lincosamides, tetracyclines) – antagonism of action.

Bicillin^®-1 increases the effectiveness of indirect anticoagulants (by suppressing intestinal microflora, reduces the prothrombin index).

Bicillin^®-1 reduces the effectiveness of oral contraceptives and medicinal products, in the process of metabolism of which para-aminobenzoic acid is formed.

With simultaneous use of Bicillin-1 with ethinylestradiol, the risk of breakthrough bleeding increases.

With simultaneous use of Bicillin-1 and allopurinol, the risk of developing allergic reactions (skin rash) increases.

Storage Conditions

The drug should be stored out of the reach of children, in a dry, cool place at a temperature not exceeding 15°C (59°F).

Shelf Life

Shelf life – 3 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.