BENZATHINE BENZYL PENICILLIN

Indications

• Rheumatic fever prevention
• Syphilis treatment
• Streptococcal infections
• Bacterial endocarditis prophylaxis

Dosage

Children: For children, the recommended dose for rheumatic fever prophylaxis is 600,000 units for those weighing less than 27 kg, and 1.2 million units for those weighing 27 kg or more, administered every 3 to 4 weeks.

Adults: The usual adult dose for the treatment of syphilis is a single intramuscular injection of 2.4 million units. For rheumatic fever prophylaxis, the recommended dose is 1.2 million units every 3 to 4 weeks.

Mechanism of action

Benzathine exerts its antibacterial effect by inhibiting bacterial cell wall synthesis. It binds to penicillin-binding proteins (PBPs) within the bacterial cell wall, leading to cell lysis and death. This mechanism is effective against a wide range of gram-positive bacteria, particularly Streptococcus species.

Pharmacodynamics

The pharmacodynamics of benzathine penicillin involves the drug's ability to maintain therapeutic concentrations in the body for an extended period. The prolonged release from the injection site allows for sustained antibacterial activity, making it effective in treating infections such as rheumatic fever and syphilis. The drug is particularly effective against organisms that are sensitive to penicillin.

Pharmacokinetics

Benzathine is administered intramuscularly, where it is slowly absorbed into the bloodstream. The peak plasma concentrations occur within 12 to 24 hours after administration, with a half-life that can extend up to several days, depending on the dosage and individual patient factors. It is primarily excreted by the kidneys. Due to its long-acting nature, benzathine is suitable for single-dose treatment regimens in certain infections.

Contra-indications

• Hypersensitivity to benzathine or any component of the formulation
• Severe allergies to other penicillins or beta-lactam antibiotics

Adverse effects

• Allergic reactions, including anaphylaxis
• Rash
• Fever
• Angioedema
• Nausea
• Vomiting
• Diarrhea
• Superinfection with prolonged use

Interactions

• May have reduced efficacy when administered concurrently with bacteriostatic antibiotics such as tetracyclines
• Probenecid may increase the serum concentrations of benzathine

Precautions

• Use with caution in patients with a history of allergies or asthma
• Monitor for signs of anaphylaxis during and after administration
• Evaluate renal function in patients receiving high doses or prolonged therapy

Pregnancy

Benzathine is classified as category B. Animal studies have shown no harm; however, adequate and well-controlled studies in pregnant women are lacking.

Breast-feeding

Benzathine is excreted in breast milk. Caution is recommended when administering to breastfeeding mothers.

Storage

Store in a cool, dry place, away from light. Do not freeze.

Formulations

• Benzathine benzylpenicillin injection
• Benzathine penicillin G suspension

Indications

• Bacterial infections
• Pneumonia
• Meningitis
• Syphilis
• Endocarditis
• Skin and soft tissue infections

Dosage

Children: Paediatric dosing for benzylpenicillin is determined by the child's weight and the severity of the infection. Refer to the BNF for Children for specific dosing guidelines.

Adults: The usual adult dose for benzylpenicillin varies based on the type and severity of the infection. It is generally administered via intramuscular or intravenous routes. For severe infections, doses may range from 1 to 4 million units every 4 to 6 hours.

Mechanism of action

Benzylpenicillin exerts its antibacterial effects by inhibiting the synthesis of bacterial cell walls. It binds to penicillin-binding proteins (PBPs) located inside the bacterial cell wall, disrupting the transpeptidation process, which is crucial for cross-linking peptidoglycan layers. This inhibition leads to cell lysis and death of the bacteria.

Pharmacodynamics

Benzylpenicillin demonstrates time-dependent bactericidal activity, meaning its effectiveness is related to the duration of time the drug concentration remains above the minimum inhibitory concentration (MIC) for the target bacteria. It has a narrow spectrum of activity, primarily targeting Gram-positive cocci and some Gram-negative rods.

Pharmacokinetics

Benzylpenicillin is typically administered parenterally due to poor oral absorption. It is rapidly distributed throughout the body and can penetrate various tissues, including the central nervous system during inflammation. The drug is primarily eliminated by renal excretion, with a half-life of approximately 30 minutes to 1 hour in healthy individuals. Dosage adjustments may be necessary in patients with renal impairment.

Interactions

• leflunomide+benzylpenicillin: Unknown (increases exposure)
• nitisinone+benzylpenicillin: Unknown (increases exposure)
• teriflunomide+benzylpenicillin: Unknown (increases exposure)

Pregnancy

Benzylpenicillin is generally considered safe to use during pregnancy, as it is a penicillin antibiotic and has a long history of use.

Breast-feeding

Benzylpenicillin is excreted in breast milk in small amounts, but it is not expected to have adverse effects on a nursing infant.

Storage

Store in a cool, dry place, protected from light. Reconstituted solutions should be used promptly or stored in a refrigerator and used within a limited time frame.

Formulations

• Benzylpenicillin injection

Indications

• Bacterial infections
• Pneumonia
• Streptococcal infections
• Syphilis
• Meningitis
• Endocarditis
• Skin infections

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations based on the type of penicillin and indication.

Adults: Refer to the BNF for specific dosing recommendations based on the type of penicillin and indication.

Mechanism of action

Penicillin targets penicillin-binding proteins (PBPs) located inside the bacterial cell wall. By binding to these proteins, penicillin disrupts the transpeptidation process, which is essential for cell wall structural integrity. This results in weakened cell walls, causing osmotic instability and ultimately leading to cell lysis and death.

Pharmacodynamics

Penicillin exhibits bactericidal activity, meaning that it kills bacteria rather than merely inhibiting their growth. Its effectiveness is generally dependent on the growth phase of the bacteria, as it is most active against actively dividing cells. The spectrum of activity varies among different penicillins, with some being more effective against specific bacterial strains.

Pharmacokinetics

Penicillin is primarily absorbed in the gastrointestinal tract, with its bioavailability varying depending on the specific type of penicillin. It is primarily excreted by the kidneys, with a half-life that typically ranges from 30 minutes to 2 hours, depending on the formulation. Dosage adjustments may be necessary in patients with renal impairment to prevent accumulation and toxicity.

Contra-indications

• History of hypersensitivity to penicillins
• Severe allergic reactions to beta-lactam antibiotics

Adverse effects

• Allergic reactions such as rash, urticaria, and anaphylaxis
• Gastrointestinal disturbances including nausea, vomiting, and diarrhea
• Superinfection due to alteration of normal flora
• Hematologic reactions such as leukopenia, thrombocytopenia

Interactions

• valproate+penicillins: Severe (increases risk of adverse effects)
• allopurinol+penicillins: Unknown (increases risk of skin rash)
• leflunomide+penicillins: Unknown (increases exposure)
• nitisinone+penicillins: Unknown (increases exposure)
• penicillins+phenindione: Unknown (increases risk of bleeding events)
• teriflunomide+penicillins: Unknown (increases exposure)

Precautions

• Use with caution in patients with renal impairment
• Monitor for signs of allergic reactions
• Consider alternative therapy in patients with a history of severe allergies

Pregnancy

Penicillins are generally considered safe to use during pregnancy; however, consult local guidelines and assess benefits versus risks.

Breast-feeding

Penicillins are excreted in breast milk in small amounts; generally considered safe, but monitor infant for possible effects.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Oral tablets
• Oral suspension
• Intravenous injection
• Intramuscular injection