BENZATHINE BENZYLPENICILLIN TETRAHYDRATE 1.2MEGA FOR INJECTION (Each vial contains Benzathine Benzylpenicillin tetrahydrate 1.2mega)

Indications

• Mild to moderate susceptible infections
• Throat infections
• Otitis media
• Cellulitis
• Pneumonia
• Meningitis
• Meningococcal disease
• Endocarditis (in combination with other antibacterials)

Dosage

Children: For children weighing up to 40 kg: 80 mg/kg every 8 hours, increased if necessary to 80 mg/kg every 6 hours for more severe infections. For children weighing 40 kg and above: 3.2 g every 6-8 hours, increased if necessary. Neonates (up to 7 days): 25 mg/kg every 12 hours, increased if necessary to 25 mg/kg every 8 hours. Neonates (7 to 28 days): 25 mg/kg every 8 hours, increased if necessary to 50 mg/kg every 8 hours for severe infections.

Adults: For adults, the usual dose is 3.2 g every 6 hours for severe infections; for less severe infections, 1.2 g every 6 hours may be sufficient. Dosing frequency can be adjusted based on the severity of the infection.

Mechanism of action

Benzylpenicillin sodium inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins, leading to cell lysis and death in susceptible bacteria.

Pharmacodynamics

Benzylpenicillin sodium demonstrates bactericidal activity against Gram-positive bacteria and some Gram-negative bacteria. Its efficacy is influenced by the bacterial growth phase, with maximum activity observed during active cell division.

Pharmacokinetics

Benzylpenicillin sodium is administered via intramuscular or intravenous routes. It has a short half-life, requiring frequent dosing. The drug is primarily eliminated by renal excretion, necessitating dose adjustments in patients with renal impairment.

Adverse effects

• Eosinophilia
• Hypokalaemia
• Thrombophlebitis
• Cholestatic jaundice

Precautions

• High doses may lead to hypernatraemia due to sodium content.
• Caution in hepatic impairment.
• Caution in renal impairment; adjustment needed based on estimated glomerular filtration rate.

Pregnancy

Not known to be harmful.

Breast-feeding

Trace amounts in milk, but appropriate to use.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Intramuscular injection
• Slow intravenous injection
• Intravenous infusion

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 caused by susceptible organisms
• Pneumonia
• Meningitis
• Endocarditis
• Sepsis
• Skin and soft tissue infections
• Bone and joint infections

Dosage

Children: Refer to the BNF

Adults: Refer to the BNF for specific dosing guidelines based on the type and severity of infection.

Mechanism of action

Benzylpenicillin exerts its bactericidal effect by binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall. This binding inhibits the third and final stage of bacterial cell wall synthesis. The weakened cell wall ultimately leads to cell lysis, which is mediated by bacterial autolytic enzymes. The action of benzylpenicillin is dependent on its ability to reach and bind to these PBPs, which include transpeptidases, carboxypeptidases, and endopeptidases.

Pharmacodynamics

Benzylpenicillin is particularly effective against gram-positive bacteria and has activity against some gram-negative organisms as well. Its bactericidal nature is attributed to the inhibition of cell wall synthesis, which disrupts the structural integrity of the bacterial cell. Benzylpenicillin remains stable against hydrolysis by various beta-lactamases, including penicillinases and extended-spectrum beta-lactamases, enhancing its efficacy in treating infections caused by resistant strains.

Pharmacokinetics

Benzylpenicillin is administered via parenteral routes due to its poor oral bioavailability. It is widely distributed throughout the body, including the central nervous system, especially in the presence of inflammation. The drug is primarily eliminated by the kidneys through glomerular filtration and tubular secretion, with a half-life of approximately 30 minutes to 1 hour in healthy adults. Dosing may need adjustment in patients with renal impairment.

Contra-indications

• Hypersensitivity to benzylpenicillin or any other penicillins
• History of severe allergic reactions to beta-lactam antibiotics

Adverse effects

• Allergic reactions including rash, pruritus, and anaphylaxis
• Gastrointestinal disturbances such as nausea, vomiting, and diarrhea
• Hematologic effects including leukopenia, thrombocytopenia, and hemolytic anemia
• Renal toxicity in cases of high doses or prolonged use

Interactions

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

Precautions

• Use with caution in patients with renal impairment
• Monitor for signs of anaphylaxis during initial doses
• Consider alternative therapy in patients with a history of severe penicillin allergy

Pregnancy

Benzylpenicillin is generally considered safe to use during pregnancy, but it should be used only if clearly needed.

Breast-feeding

Benzylpenicillin is excreted in breast milk in small amounts and is considered safe for use during breastfeeding.

Storage

Store in a cool, dry place away from direct sunlight. Reconstituted solutions should be used promptly or stored in a refrigerator and used within 24 hours.

Formulations

• Benzylpenicillin sodium
• Benzylpenicillin potassium

Dosage

Children: Refer to relevant safety guidelines, as specific dosing information for clinical use is not provided in the BNF.

Adults: Refer to relevant safety guidelines, as specific dosing information for clinical use is not provided in the BNF.

Mechanism of action

Tetrachloride is a non-polar solvent that dissolves a wide range of organic compounds. It disrupts cellular membranes and can interfere with metabolic processes by forming reactive intermediates, leading to cellular damage. The mechanism may also involve the induction of oxidative stress and mitochondrial dysfunction.

Pharmacodynamics

The pharmacodynamic effects of tetrachloride are primarily linked to its role as a solvent and its cytotoxic properties. It can cause cellular damage, particularly in the liver, through lipid peroxidation and disruption of cellular integrity. Its effects may vary based on exposure duration, concentration, and route of administration, leading to acute or chronic toxicity.

Pharmacokinetics

Tetrachloride is absorbed through the respiratory tract, gastrointestinal tract, and skin. Once in the bloodstream, it distributes widely throughout body tissues, particularly in adipose tissue and the liver, where it undergoes biotransformation via cytochrome P450 enzymes. The elimination half-life can vary, but it is primarily excreted through the urine as metabolites. Accumulation may occur with prolonged exposure, leading to increased toxicity.

Pregnancy

There is insufficient data on the safety of tetrachloride in pregnancy. Caution is advised.

Breast-feeding

Caution is advised as the effects on nursing infants are not well-studied.

Storage

Store in a cool, dry place away from direct sunlight and heat sources. Keep in tightly closed containers.

Dosage

Children: Refer to specific drug information for paediatric dosing guidelines, as this will depend on the active compound and its therapeutic use.

Adults: Refer to specific drug information for adult dosing guidelines, as this will depend on the active compound and its therapeutic use.

Mechanism of action

The mechanism of action will depend on the specific active compound that is in the tetrahydrate form. Generally, tetrahydrates can improve the bioavailability of a drug by facilitating its dissolution in bodily fluids, which can enhance absorption in the gastrointestinal tract.

Pharmacodynamics

Pharmacodynamics will vary based on the specific drug in the tetrahydrate form. However, it generally involves the interaction of the drug with specific receptors or enzymes in the body, influencing physiological and biochemical processes. Tetrahydrate forms may affect the pharmacokinetics of the drug, altering its efficacy and safety profile.

Pharmacokinetics

Pharmacokinetics of a tetrahydrate form will depend on the parent compound. Typically, factors such as absorption, distribution, metabolism, and excretion can be influenced by the hydration state of the drug. Hydrates may have different solubility and stability profiles, which can impact the rate and extent of drug absorption.

Dosage

Children: Refer to specific guidelines or clinical recommendations for appropriate dosing.

Adults: Refer to specific guidelines or clinical recommendations for appropriate dosing.

Mechanism of action

Tetraphosphate acts as a phosphate donor in biochemical reactions, participating in the transfer of phosphate groups to other molecules. This mechanism is essential in the regulation of metabolic pathways and energy production within cells.

Pharmacodynamics

As a polyphosphate, tetraphosphate influences cellular processes by modulating the availability of phosphate. The compound is involved in energy metabolism, particularly in the synthesis and hydrolysis of ATP, and may also impact nucleic acid metabolism and signaling pathways that rely on phosphate.

Pharmacokinetics

The pharmacokinetics of tetraphosphate are not well-documented; however, it is generally assumed that, like other phosphate compounds, it may be absorbed and utilized in various tissues, with renal excretion being a likely route for elimination.

Indications

• pH stabilization in pharmaceutical formulations
• solubilization of poorly soluble drugs
• buffering agent in injectable preparations

Dosage

Children: Refer to specific product guidelines for paediatric dosing as it may vary based on formulation.

Adults: Refer to specific product guidelines for adult dosing as it may vary based on formulation.

Mechanism of action

Tetrasodium functions primarily as a buffering agent, helping to maintain the pH of pharmaceutical preparations. This stabilization is crucial in ensuring the solubility and bioavailability of active pharmaceutical ingredients, thereby enhancing their therapeutic effects.

Pharmacodynamics

The pharmacodynamic properties of tetrasodium relate to its ability to modulate pH levels in a solution. By maintaining optimal pH conditions, tetrasodium aids in preserving the stability and efficacy of various drugs, improving their overall therapeutic action.

Pharmacokinetics

Tetrasodium is generally not absorbed systemically when used in pharmaceutical formulations, as its primary role is localized within the preparation. Its pharmacokinetic profile is largely influenced by its solubility and stability in solution, which can affect the release and absorption of the active ingredients it is combined with.

Mechanism of action

By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, penicillin G inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that penicillin G interferes with an autolysin inhibitor. The penicillins and their metabolites are potent immunogens because of their ability to combine with proteins and act as haptens for acute antibody-mediated reactions. The most frequent (about 95 percent) or "major" determinant of penicillin allergy is the penicilloyl determinant produced by opening the beta-lactam ring of the penicillin. This allows linkage of the penicillin to protein at the amide group. "Minor" determinants (less frequent) are the other metabolites formed, including native penicillin and penicilloic acids. /Penicillins/ Bactericidal; inhibit bacterial cell wall synthesis. Action is dependent on the ability of penicillins to reach and bind penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. Penicillin-binding proteins (which include transpeptidases, carboxypeptidases, and endopeptidases) are enzymes that are involved in the terminal stages of assembling the bacterial cell wall and in reshaping the cell wall during growth and division. Penicillins bind to, and inactivate, penicillin-binding proteins, resulting in the weakening of the bacterial cell wall and lysis. /Penicillins/

Pharmacodynamics

Penicillin G is a penicillin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. The name "penicillin" can either refer to several variants of penicillin available, or to the group of antibiotics derived from the penicillins. Penicillin G has <i>in vitro</i> activity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of penicillin G results from the inhibition of cell wall synthesis and is mediated through penicillin G binding to penicillin binding proteins (PBPs). Penicillin G is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases.