SANOXONE 2g INJECTION (Each vial contains Ceftriaxone sodium USP 2g)

Indications

• Community-acquired pneumonia
• Meningitis
• Skin and soft tissue infections
• Bone and joint infections
• Intra-abdominal infections
• Urinary tract infections

Mechanism of action

Ceftriaxone works by inhibiting mucopeptide synthesis in the bacterial cell wall. The beta-lactam moiety of ceftriaxone binds to carboxypeptidases, endopeptidases, and transpeptidases in the bacterial cytoplasmic membrane, which are crucial for cell-wall synthesis and cell division. This binding leads to loss of enzyme activity, resulting in the production of defective cell walls and ultimately causing bacterial cell death.

Pharmacodynamics

Ceftriaxone exhibits bactericidal activity, primarily through the inhibition of cell wall synthesis mediated by its binding to penicillin-binding proteins (PBPs). It is effective against a variety of bacteria, including gram-positive and gram-negative organisms, and shows stability against hydrolysis by several beta-lactamases. However, resistance can develop through beta-lactamase production, alterations in PBPs, or reduced permeability of the bacterial cell wall. It is important to note that ceftriaxone should not be mixed or administered in the same IV line with calcium-containing products due to the risk of precipitation.

Pharmacokinetics

Ceftriaxone has a high volume of distribution and is widely distributed throughout the body, including in the central nervous system. It is primarily eliminated via the urine, with approximately 50-60% of the dose excreted unchanged. The drug has a long half-life, which supports once-daily dosing. Ceftriaxone's pharmacokinetics can be influenced by factors such as age, renal function, and severity of infection.

Contra-indications

• Hypersensitivity to ceftriaxone or other cephalosporins
• Newborns who require calcium treatment due to the risk of precipitation

Adverse effects

• Diarrhea
• Nausea
• Vomiting
• Rash
• Anaphylaxis
• Biliary sludge or gallbladder pseudolithiasis
• Elevated liver enzymes
• Thrombocytopenia

Interactions

• Calcium-containing solutions or medications (risk of precipitation)
• Probenecid (may increase ceftriaxone levels)
• Aminoglycosides (may increase nephrotoxicity)

Precautions

• Use with caution in patients with renal impairment
• Monitor for signs of an allergic reaction
• Evaluate liver function periodically during prolonged therapy
• Be aware of potential for superinfection with prolonged use

Pregnancy

Ceftriaxone is classified as category B. Animal studies have not demonstrated risk to the fetus, but there are no adequate and well-controlled studies in pregnant women.

Breast-feeding

Ceftriaxone is excreted in breast milk in small amounts. Caution is advised when administering to nursing mothers.

Storage

Store at 20 to 25 degrees Celsius (68 to 77 degrees Fahrenheit). Protect from light and moisture.

Formulations

• Intravenous injection
• Intramuscular injection
• Powder for solution for injection

Mechanism of action

Ceftriaxone works by inhibiting the mucopeptide synthesis in the bacterial cell wall. The beta-lactam moiety of ceftriaxone binds to carboxypeptidases, endopeptidases, and transpeptidases in the bacterial cytoplasmic membrane. These enzymes are involved in cell-wall synthesis and cell division. Binding of ceftriaxone to these enzymes causes the enzyme to lose activity; therefore, the bacteria produce defective cell walls, causing cell death.

Pharmacodynamics

Ceftriaxone is a cephalosporin/cephamycin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. Ceftriaxone has <i>in vitro</i> activity against gram-positive aerobic, gram-negative aerobic, and anaerobic bacteria. The bactericidal activity of ceftriaxone results from the inhibition of cell wall synthesis and is mediated through ceftriaxone binding to penicillin-binding proteins (PBPs). Ceftriaxone is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended-spectrum beta-lactamases. However, resistance to ceftriaxone usually occurs through beta-lactamase hydrolysis, altered PBPs, or reduced bacterial cell permeability. Ceftriaxone should not be mixed with or giving in the same IV line as diluents/products containing calcium as they may cause ceftriaxone to precipitate. Ceftriaxone use may also cause biliary sludge or gallbladder pseudolithiasis.