Bicillin^®-5 (Powder) Instructions for Use

Marketing Authorization Holder

Sintez PJSC (Russia)

ATC Code

J01CE30 (Beta-lactamase-sensitive penicillins in combination)

Active Substances

Benzathine benzylpenicillin (Rec.INN registered by WHO)

Procaine benzylpenicillin (BAN adopted for use in the UK)

Dosage Form

Bicillin®-5

Powder for suspension for intramuscular injection 1.2 million IU + 300 thousand IU: fl. 1 or 10 pcs.

Dosage Form, Packaging, and Composition

Powder for the preparation of a suspension for intramuscular injection white or white with a slightly yellowish tint, prone to clumping, forming a stable suspension upon the addition of water.

1200000 IU+300000 IU – vials with a capacity of 10 ml (1) – cardboard packs.
1200000 IU+300000 IU – vials with a capacity of 10 ml (10) – cardboard packs.

Clinical-Pharmacological Group

Penicillin antibiotic, destroyed by penicillinase

Pharmacotherapeutic Group

Systemic antibacterial agents; beta-lactam antibacterial agents, penicillins; beta-lactamase sensitive penicillins

Pharmacological Action

A combined bactericidal antibiotic, consisting of two long-acting salts of benzylpenicillin.

It suppresses the synthesis of the microorganism’s cell wall. Active against gram-positive microorganisms Staphylococcus spp. (non-penicillinase producing), Streptococcus spp. (including Streptococcus pneumoniae), Corynebacterium diphtheriae, anaerobic spore-forming rods, Bacillus anthracis, Clostridium spp., Actinomyces israelii; gram-negative microorganisms Neisseria gonorrhoeae, Neisseria meningitidis, Treponema spp.

Strains of Staphylococcus spp. that produce penicillinase are resistant to the drug’s action.

Pharmacokinetics

Bicillin^®-5 is a long-acting drug; a high concentration of the antibiotic in the blood persists for up to 4 weeks.

Benzathine benzylpenicillin

After intramuscular injection, Benzathine benzylpenicillin is hydrolyzed very slowly, releasing benzylpenicillin. The maximum concentration of the drug in the blood serum is reached 12-24 hours after the injection. The long half-life provides a stable and prolonged concentration of the drug in the blood: on the 14th day after the administration of 2,400,000 IU of the drug, the concentration in the serum is 0.12 µg/ml; on the 21st day after the administration of 1,200,000 IU of the drug – 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 is 40-60%. Benzathine benzylpenicillin passes in small amounts through the placental barrier and also penetrates into the mother’s breast milk. The biotransformation of the drug is insignificant. It is excreted mainly by the kidneys unchanged. Up to 33% of the administered dose is excreted within 8 days.

Benzylpenicillin

The maximum concentration in blood plasma after intramuscular administration is reached in 20-30 minutes. The half-life of the drug is 30-60 minutes, in renal failure 4-10 hours or more. Plasma protein binding is 60%. It penetrates into organs, tissues and biological fluids, except for cerebrospinal fluid, eye tissues and the prostate gland. When the meningeal membranes are inflamed, it penetrates the blood-brain barrier. It passes through the placenta and penetrates into breast milk. It is excreted by the kidneys unchanged.

Indications

Infectious and inflammatory diseases caused by susceptible pathogens

• Long-term (year-round) prevention of relapses of rheumatism;
• Syphilis, yaws;
• Streptococcal infections (excluding infections caused by group B streptococci) – acute tonsillitis, scarlet fever, wound infections, erysipelas.

ICD codes

Dosage Regimen

Intramuscularly.

Adults 1.2 million IU + 300 thousand IU once every 4 weeks.

Preschool children – 480 thousand IU + 120 thousand IU once every 3 weeks, children over 8 years old – 960 thousand IU + 240 thousand IU once every 4 weeks.

Sterile water for injection, isotonic sodium chloride solution or 0.25-0.5% procaine (novocaine) solution are used to prepare the suspension.

The Bicillin^®-5 suspension is prepared aseptically, immediately before use (ex tempore): 5-6 ml of solvent is introduced slowly (at a rate of 5 ml per 20-25 seconds) under pressure into the vial with the drug. The contents of the vial are mixed and shaken along the longitudinal axis of the vial until a homogeneous suspension is formed. The presence of bubbles on the surface of the suspension near the walls of the vial is allowed. The Bicillin^®-5 suspension is administered deep intramuscularly into the upper outer quadrant of the gluteal muscle immediately after preparation. Rubbing the gluteal muscle after injection is not recommended. If the administration is delayed immediately after preparation, the physical and colloidal properties of the suspension change, which may impede its movement through the syringe needle.

Adverse Reactions

Allergic reactions anaphylactic shock, anaphylactoid reactions, urticaria, fever, arthralgia, angioneurotic edema, multiform exudative erythema, exfoliative dermatitis.

Laboratory parameters anemia, thrombocytopenia, leukopenia, hypocoagulation.

Other stomatitis, glossitis.

Contraindications

• Hypersensitivity to the drug, benzylpenicillin and other beta-lactam antibiotics;
• Lactation period.

With caution: pregnancy, renal failure, burdened allergy history, bronchial asthma, pseudomembranous colitis.

Use in Pregnancy and Lactation

Bicillin^®-5 penetrates the placental barrier and into mother’s milk in small amounts. Use during pregnancy is possible only if the intended benefit to the mother outweighs the potential risk to the fetus.

It is recommended to discontinue breastfeeding if it is necessary to prescribe the drug.

Use in Renal Impairment

Use with caution in renal failure.

Pediatric Use

Used according to indications

Special Precautions

Do not administer subcutaneously, intravenously, endolumbally, or into body cavities.

With accidental intravascular administration, transient feelings of depression, 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 performing an intramuscular injection to detect possible entry of the needle into a vessel.

When treating syphilis, before starting therapy and then for 4 months, it is necessary to conduct microscopic and serological studies. Due to the development of fungal infections, it is advisable to simultaneously prescribe B vitamins and vitamin C, and if necessary, systemic antifungal drugs. It must be taken into account that the use of insufficient doses or too early termination of treatment often leads to the emergence of resistant strains of pathogens.

Drug Interactions

Bactericidal antibiotics (including cephalosporins, vancomycin, rifampicin, aminoglycosides) have a synergistic effect; bacteriostatic antibiotics (including macrolides, chloramphenicol, lincosamides, tetracyclines) have an antagonistic effect.

It increases the effectiveness of indirect anticoagulants (by suppressing the intestinal microflora, reduces the prothrombin index); reduces the effectiveness of oral contraceptives, drugs in the process of metabolism of which para-aminobenzoic acid is formed, ethinyl estradiol – the risk of developing breakthrough bleeding.

Diuretics, allopurinol, tubular secretion blockers, phenylbutazone, NSAIDs, by reducing tubular secretion, increase the concentration of benzylpenicillin in the blood and tissues.

Allopurinol increases the risk of developing allergic reactions (skin rash).

Storage Conditions

List B. In a dry place at a temperature not exceeding 20°C (68°F). Keep out of the reach of children.

Shelf Life

Shelf life – 3 years.

Dispensing Status

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.