Bicillin®-5

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT BICILLIN®-5 (BICILLIN®-5)

Composition:

Active substance:

1 vial contains: bicillin-5, powder 1,500,000 IU (a mixture of sterile benzathine benzylpenicillin (bicillin-1) – 1,200,000 IU, sterile benzylpenicillin procaine salt – 300,000 IU).

Pharmaceutical form. Powder for suspension for injection.

Main physicochemical properties: white powder or white with a slightly yellowish tint.

Pharmacotherapeutic group.

Antibacterial medicinal products for systemic use. Combinations of β-lactamase-sensitive penicillins. ATC code J01CE30.

Pharmacological Properties.

Pharmacodynamics.

The drug exhibits bactericidal action by inhibiting the synthesis of muropeptides in the microbial cell wall. It is active against Gram-positive microorganisms: Staphylococcus spp. (except those producing penicillinase), Streptococcus spp. (including Streptococcus pneumoniae), Corynebacterium diphtheriae, Bacillus anthracis; Gram-negative microorganisms: Neisseria gonorrhoeae, Neisseria meningitidis, Actinomyces israelii; as well as Treponema spp., and spore-forming anaerobes. Resistant to the drug's action are most Gram-negative bacteria, mycobacteria, fungi, viruses, and protozoa.

Pharmacokinetics.

The drug exhibits prolonged action. After intramuscular administration, a depot of the drug is formed in muscle tissue. A high concentration of the drug is achieved within the first hours after injection. Therapeutic concentrations of benzylpenicillin are maintained in the blood for 28 days or longer in the majority of patients (both children and adults). The drug is primarily eliminated via the kidneys; a small amount is excreted in sputum, sweat, saliva, tears, and it penetrates into breast milk.

Clinical characteristics.

Indications.

Treatment of infections caused by microorganisms sensitive to the drug, in cases where prolonged maintenance of a constant drug concentration in the blood is required.

The use of Bicillin®-5 is especially indicated for year-round prophylaxis of rheumatic fever recurrences in adults and children.

Contraindications.

Hypersensitivity to β-lactam antibiotics (penicillins, cephalosporins, carbapenems), procaine;

Bronchial asthma, urticaria, hay fever, and severe allergic reactions.

Interaction with other medicinal products and other types of interactions.

When used concomitantly with bactericidal antibiotics (including cephalosporins, cycloserine, vancomycin, rifampicin, aminoglycosides), a synergistic effect is observed; with bacteriostatic antibiotics (including macrolides, chloramphenicol, lincomycin, tetracyclines) – antagonism.

Bicillin®-5 reduces the efficacy of oral contraceptives and ethinylestradiol (risk of breakthrough bleeding). Combination with nonsteroidal anti-inflammatory drugs is not recommended. Benzylpenicillin reduces the clearance and increases the toxicity of methotrexate.

Concomitant use with allopurinol increases the risk of developing allergic reactions.

Pharmacokinetic interactions. When used concomitantly, diuretics, allopurinol, phenylbutazone, and NSAIDs reduce tubular secretion and increase penicillin concentration.

Possible competitive inhibition of elimination processes should be considered when benzylpenicillin is used concomitantly with anti-inflammatory and antipyretic agents (indomethacin, phenylbutazone, high-dose salicylates). Aspirin, probenecid, thiazide diuretics, furosemide, and ethacrynic acid increase the half-life of benzylpenicillin, elevating its plasma concentration, thereby increasing the risk of its toxic effects due to impact on renal tubular secretion. Allopurinol increases the risk of allergic reactions (skin rash).

Avoid concomitant use with chloramphenicol, erythromycin, tetracycline, and sulfonamides.

Concomitant use with methotrexate reduces the latter's excretion and increases the risk of its toxicity.

Penicillins may interfere with diagnostic tests, for example, glucose determination in urine using copper sulfate, direct antiglobulin test (Coombs test), and certain tests for serum proteins or urinary protein. Penicillins may also interfere with tests using bacteria, such as the Guthrie test for phenylketonuria, which employs the microorganism Bacillus subtilis.

Special precautions.

It is necessary to determine whether there have been any reactions to drugs of the (β-lactam and/or procaine) group during previous use. The drug should be administered with caution to patients prone to allergic reactions. If signs of allergic reactions occur, Bicillin®-5 should be discontinued and appropriate therapy initiated.

To prevent adverse reactions, the drug should be administered by intramuscular injection only.

In patients with known hypersensitivity to cephalosporins, cross-allergy should be considered as a possibility.

Severe and sometimes fatal hypersensitivity reactions (anaphylactic reactions) have been reported in patients receiving penicillin therapy. Such reactions are more likely to occur in patients with a history of severe allergic reactions.

Treatment of anaphylactic reactions may require immediate administration of epinephrine, corticosteroids (intravenously), and emergency management of respiratory insufficiency.

The drug should be used with particular caution in patients with hay fever, urticaria, and other allergic disorders.

Neutropenia has been commonly observed in patients receiving high doses of β-lactams, and the incidence has been noted in patients treated for 10 days or longer. Monitoring of white blood cells is recommended during prolonged high-dose therapy.

The drug is not recommended for the treatment of patients with acute lymphocytic leukemia or infectious mononucleosis due to an increased risk of erythematous skin rashes. It should be noted that in patients with diabetes mellitus, absorption of the active ingredient from the intramuscular depot may be reduced.

In patients with severe renal impairment, high doses of penicillin may cause neurotoxic effects, leading to cerebral disturbances, seizures, and coma.

Caution should be exercised when administering the drug to patients with severe cardiopathy, hypovolemia, epilepsy, or impaired renal or hepatic function. Hepatic, renal, and hematological status should be monitored during prolonged high-dose therapy.

Prolonged use of the drug may lead to colonization by resistant microorganisms or fungi. Superinfection may occur, requiring careful monitoring of such patients.

In case of severe diarrhea characteristic of pseudomembranous colitis (mostly caused by Clostridium difficile), discontinuation of the drug is recommended and appropriate measures should be taken. The use of agents that inhibit peristalsis is contraindicated. In the treatment of sexually transmitted diseases with suspected syphilis, serological testing should be performed before starting therapy and repeated 4 months after its completion.

To suppress or alleviate the Jarisch-Herxheimer reaction upon first administration of the drug, it is recommended to administer 50 mg of prednisolone or its equivalent.

In patients with syphilis in stages involving the cardiovascular system, blood vessels, or meninges, the Jarisch-Herxheimer reaction can be prevented by administering prednisolone 50 mg daily or an equivalent corticosteroid for 1–2 weeks.

Freshly prepared injectable or infusion solutions must be used immediately. Even when stored in the refrigerator, aqueous solutions of sodium benzylpenicillin decompose, forming degradation products and metabolites.

Contact of the skin with penicillins should be avoided, as sensitization may occur.

Use during pregnancy or breastfeeding.

There are no data available on the use of Bicillin®-5 during pregnancy or breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

Currently, there are no reports; however, the possibility of adverse reactions affecting the central nervous and cardiovascular systems should be considered.

Administration and Dosage

Before administration, obtain a patient history of tolerance to the drug and local anesthetics!

Bicillin®-5 must be administered only intramuscularly! Intravenous administration is contraindicated!

For children aged 3 to 8 years: administer Bicillin®-5 once at a dose of 600,000 IU once every 3 weeks.

For children aged 8 years and older: administer at a dose of 1,200,000 IU once every 4 weeks.

For adults: administer a single dose of 1,500,000 IU once every 4 weeks.

More frequent administration of Bicillin®-5 is contraindicated. Typically, treatment duration depends on disease severity and ranges from 3 to 12 months.

Instructions for Preparation and Administration of the Suspension.
Prepare the Bicillin®-5 suspension aseptically immediately before use. Under pressure, inject 9 mL of sterile water for injection, 0.9% sodium chloride solution, or 0.25–0.5% procaine solution into the vial containing the drug. Mix the contents thoroughly until a homogeneous suspension is formed. Administer the suspension by deep intramuscular injection into the upper outer quadrant of the gluteal muscle (administer 2 injections into alternating buttocks).

Before injecting the Bicillin®-5 suspension, ensure the needle has not entered a blood vessel. If blood appears, withdraw the needle and administer the injection at another site.

Children.

The drug is indicated for children aged 3 years and older. When administering Bicillin®-5 to children, preparing the Bicillin®-5 suspension with procaine solution is contraindicated.

Overdose.

Symptoms include toxic effects on the central nervous system: reflex excitation, headache, nausea, vomiting, seizures, myalgia, arthralgia, signs of meningism, coma. In such cases, discontinue administration of the drug.

Treatment is symptomatic and includes hemodialysis, peritoneal dialysis; special attention should be given to restoring fluid and electrolyte balance.

Adverse reactions.

Immune system disorders: skin rash, pruritus, swelling, exfoliative dermatitis, fever, arthralgia, urticaria, contact dermatitis, anaphylactic or anaphylactoid reactions including bronchial asthma; thrombocytopenic purpura, gastrointestinal symptoms, angioneurotic edema (Quincke's edema), anaphylactic shock, which may be fatal if medical assistance is not provided promptly and appropriately; serum sickness, possible reactions at the injection site.

Respiratory system disorders: bronchospasm, laryngospasm.

Central and peripheral nervous system disorders: dizziness, tinnitus, headache.

Gastrointestinal disorders: nausea, vomiting, stomatitis, glossitis, black discoloration of the tongue, diarrhea, pseudomembranous colitis, hepatitis, cholestasis.

Urinary and reproductive system disorders: interstitial nephritis.

Cardiovascular disorders: impaired myocardial pump function, fluctuations in arterial pressure, tachycardia.

Blood and lymphatic system disorders: positive Coombs test results, hemolytic anemia, leukopenia, neutropenia, thrombocytopenia, agranulocytosis, eosinophilia.

Local reactions: pain at the injection site possible.

Other: superinfection caused by drug-resistant microflora (yeast-like fungi, gram-negative microorganisms) may occur in debilitated patients, newborns, and elderly individuals during prolonged treatment. In patients undergoing treatment for syphilis, Jarisch-Herxheimer reaction may also occur secondary to bacteriolysis, characterized by the following symptoms: fever, chills, myalgia, headache, exacerbation of skin symptoms, tachycardia, vasodilation with changes in arterial pressure.

This reaction may be dangerous in cardiovascular syphilis or conditions where there is a serious risk of increased local damage, e.g., optic nerve atrophy.

Shelf life. 4 years.

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

Incompatibility. Do not mix Biсillin®-5 solution with other injectable solutions.

Packaging. 1,500,000 IU in vials.

Prescription status. Prescription only.

Manufacturer. JSC "Kyivmedpreparat".

Manufacturer's address.

139 Saksaganskoho Street, Kyiv, 01032, Ukraine.