SANTRIAX S 1000 POWDER FOR INJECTION (Ceftriaoxone 1000mg and Sulbactam 500mg

Indications

• Bacterial meningitis
• Community-acquired pneumonia
• Skin and soft tissue infections
• Urinary tract infections
• Sepsis
• Intra-abdominal infections
• Pelvic inflammatory disease

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations based on the child's age, weight, and clinical condition.

Adults: Refer to the BNF for specific dosing guidelines based on the infection being treated and patient factors.

Mechanism of action

Ceftriaxone exerts its antibacterial effect by inhibiting bacterial cell wall synthesis. It binds to penicillin-binding proteins (PBPs) within the bacterial cell wall, disrupting the transpeptidation process necessary for cell wall integrity. This leads to cell lysis and death in susceptible bacteria, making it effective against a wide range of pathogens.

Pharmacodynamics

The pharmacodynamic properties of ceftriaxone include a time-dependent killing effect, where the duration of time that plasma concentrations remain above the minimum inhibitory concentration (MIC) is crucial for its efficacy. Ceftriaxone demonstrates a prolonged half-life, allowing for once-daily dosing in many cases, which can improve patient compliance and ease of administration.

Pharmacokinetics

Ceftriaxone is well absorbed when administered intravenously or intramuscularly, achieving high plasma concentrations. It has a volume of distribution of approximately 7-12 L/kg and is approximately 85% bound to plasma proteins. Ceftriaxone is eliminated primarily via the kidneys, with around 50-60% excreted unchanged in the urine. The elimination half-life is approximately 6-8 hours, which can be extended in patients with renal impairment.

Contra-indications

• Hypersensitivity to ceftriaxone or other cephalosporins
• Severe allergic reactions to penicillin
• Neonates with hyperbilirubinemia
• Concurrent use with calcium-containing solutions in neonates

Adverse effects

• Diarrhea
• Nausea
• Vomiting
• Rash
• Allergic reactions
• Elevated liver enzymes
• Thrombocytopenia
• Nephrotoxicity
• Superinfection with prolonged use

Interactions

• Increased risk of nephrotoxicity when combined with other nephrotoxic agents
• Probenecid may increase ceftriaxone levels
• Calcium-containing solutions should not be mixed or simultaneously infused

Precautions

• Use with caution in patients with a history of gastrointestinal disease, particularly colitis
• Monitor renal function in patients with renal impairment
• Caution in patients with a history of hypersensitivity reactions

Pregnancy

Ceftriaxone is categorized as pregnancy category B. It is generally considered safe for use during pregnancy, but should be used only if clearly needed.

Breast-feeding

Ceftriaxone is excreted in breast milk in small amounts. Caution is advised when administering to nursing mothers, as it may affect the infant.

Storage

Store at room temperature away from light, in a dry place. Reconstituted solutions should be stored in the refrigerator and used within a short period.

Formulations

• Injection: 1 g, 2 g vials (lyophilized powder for reconstitution)

Indications

• Infections caused by beta-lactamase producing organisms
• Complicated skin and soft tissue infections
• Intra-abdominal infections
• Respiratory tract infections
• Urinary tract infections

Dosage

Children: Refer to BNF for Children for specific dosing recommendations based on the child's age, weight, and the type of infection.

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

Mechanism of action

Sulbactam is a competitive, irreversible inhibitor of bacterial beta-lactamases, particularly potent against class C beta-lactamases. It binds to the active site of the enzyme, preventing it from hydrolyzing beta-lactam antibiotics, which enhances the effectiveness of these antibiotics against resistant bacterial strains.

Pharmacodynamics

When administered with beta-lactam antibiotics, sulbactam broadens their antibacterial spectrum by inhibiting the enzymes responsible for their hydrolysis. Although sulbactam has weak intrinsic antibacterial activity on its own, it can effectively bind to penicillin-binding proteins in certain bacteria, contributing to its therapeutic effect. It helps restore the activity of beta-lactam antibiotics against a wide range of beta-lactamase-producing gram-positive and gram-negative bacteria.

Pharmacokinetics

Sulbactam is administered parenterally and is typically well absorbed. It has a short half-life, necessitating frequent dosing when used alone. The drug is primarily excreted unchanged in the urine. Its pharmacokinetic profile may vary based on the formulation used and the presence of co-administered antibiotics.

Pregnancy

There is limited data on the use of sulbactam in pregnancy. It should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known if sulbactam is excreted in human milk. Caution is advised when administering to breastfeeding women.

Storage

Store in a cool, dry place, away from direct light. Protect from moisture.

Formulations

• Injectable solution

Mechanism of action

Sulbactam is a competitive, irreversible bacterial beta (β)-lactamase inhibitor. It is reported to be more potent against class C beta-lactamases.

Pharmacodynamics

When given together with beta-lactam antibiotics, sulbactam broadens their antibacterial spectrum by blocking the enzyme involved in their hydrolysis. Sulbactam alone possesses weak intrinsic antibacterial activity except against the _Neisseriaceae_, _Acinetobacter spp._, and _Bacteroides fragilis_ as it can bind to the penicillin-binding proteins. Sulbactam restores the activity of beta-lactam antibiotics against a range of beta-lactamase-producing gram-positive and gram-negative bacteria.