Parenteral Bone and joint infections, Gynaecological infections, Intra-abdominal infections, Meningitis, Respiratory tract infections, Septicaemia, Skin and soft tissue infections, Urinary tract infections
Adult: Available preparations:
Cefoperazone 0.5 g and sulbactam 0.5 g powder for solution for inj or infusion
Cefoperazone 1 g and sulbactam 1 g powder for solution for inj or infusion
Recommended dose: 1 g/1 g to 2 g/2 g (1:1 ratio). In severe or refractory infections, doses may be increased up to 4 g/4 g (1:1 ratio). All doses are given 12 hourly in equally divided doses via IV inj over 3 minutes, IV infusion over 15-60 minutes or IM. Additional administration of cefoperazone (without sulbactam) may be required in patients receiving 1:1 dose ratio. Max dose of sulbactam: 4 g daily. Doses are individualised based on the expected susceptible pathogens, severity and site of infection. Refer to local guidelines on appropriate dosing frequencies and recommendations. Child: Available preparations:
Cefoperazone 0.5 g and sulbactam 0.5 g powder for solution for inj or infusion
Cefoperazone 1 g and sulbactam 1 g powder for solution for inj or infusion
Recommended dose: 0.02 g/0.02 g/kg to 0.04 g/0.04 g/kg daily (1:1 ratio). In serious or refractory infections, doses may be increased to 0.08 g/0.08 g/kg daily (1:1 ratio). All doses are given 6-12 hourly in equally divided doses via IV inj over 3 minutes, IV infusion over 15-60 minutes, or IM. In neonates, doses are given 12 hourly. Max dose of sulbactam: 0.08 g/kg/day. Refer to local guidelines on appropriate dosing frequencies and recommendations.
Renal Impairment
In patients undergoing haemodialysis, dosing must be scheduled to follow a dialysis period.
CrCl (mL/min)
Dosage
<15
Max: 0.5 g sulbactam 12 hourly (max: 1 g sulbactam daily).
15-30
Max: 1 g sulbactam 12 hourly (max: 2 g sulbactam daily).
Hepatic Impairment
Severe: Dosing adjustment may be required.
Reconstitution
IV: Reconstitute vials labelled as 1 g and 2 g with 3.4 mL and 6.7 mL of compatible diluent, respectively. Appropriate diluents include sterile water for injection, 5% dextrose in water, or 0.9% NaCl. Further dilute the reconstituted solution to 20 mL using the same diluent of the initial solution or with Lactated ringer’s solution.
Incompatibility
Incompatible with aminoglycosides; initial reconstitutions with Lactated ringer’s solution (IV) and 2% lidocaine HCl solution (IM).
Contraindications
Hypersensitivity to cefoperazone, sulbactam, or other β-lactam antibacterials (e.g. cephalosporin, penicillin).
Special Precautions
Patient with severe biliary obstruction, poor diet, malabsorption states (e.g. cystic fibrosis). Patient on prolonged IV alimentation regimens or receiving anticoagulant therapy. Renal and severe hepatic impairment. Pregnancy and Lactation.
Adverse Reactions
Significant: Vitamin K deficiency resulting to coagulopathy, overgrowth of nonsusceptible organisms (prolonged use). Blood and lymphatic system disorders: Neutropenia, leucopenia, eosinophilia, thrombocytopenia, hypoprothrombinaemia. Gastrointestinal disorders: Nausea, vomiting, diarrhoea. General disorders and administration site conditions: Pyrexia, chills, infusion site phlebitis, injection site pain. Hepatobiliary disorders: Jaundice. Investigations: Decreased haemoglobin, haematocrit; increased AST, ALT, blood alkaline phosphatase, blood bilirubin. Nervous system disorders: Headache. Renal and urinary disorders: Haematuria. Skin and subcutaneous tissue disorders: Pruritus, urticaria, maculopapular rash. Vascular disorders: Hypotension, vasculitis. Potentially Fatal:Clostridium-difficile-associated diarrhoea, hypersensitivity reactions including anaphylactoid and severe cutaneous adverse reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, dermatitis exfoliative); serious haemorrhage.
Monitoring Parameters
Monitor haematologic status (e.g. prothrombin time), renal, and hepatic function as clinically indicated. Perform culture and susceptibility tests; consult local institutional recommendations before treatment initiation due to antibiotic resistance risks.
Drug Interactions
May increase INR with anticoagulants (e.g. warfarin) thereby potentiating the risk for bleeding.
Food Interaction
May cause flushing, sweating, headache, and tachycardia when given concomitantly with alcohol.
Lab Interference
May result to false-positive reaction for glucose in urine using Benedict’s or Fehling’s solution and false-positive direct Coomb’s test.
Action
Description: Mechanism of Action: Cefoperazone is a 3rd generation cephalosphorin that inhibits the final stage of bacterial cell wall synthesis of actively dividing cells by binding to specific penicillin-binding proteins (PBPs). It is susceptible to degradation by β-lactamases which are produced by certain resistant bacteria.
Sulbactam, a penicillanic acid sulfone, inhibits β-lactamase activity, thereby preventing cefoperazone inactivation and enhances the cefoperazone spectrum of activity. It does not exert clinically significant antibacterial effect alone, except against Neisseriaceae and Actinobacter. Pharmacokinetics: Absorption: Cefoperazone: Time to peak plasma concentration: 1-2 hours (IM). Distribution: Well distributed in the body tissues and fluids (e.g. gall bladder, appendix, skin, fallopian tubes, ovary, uterus). Crosses placenta, enters the breast milk (small amounts).
Cefoperazone: Plasma protein binding: 82-93%. Excretion: Cefoperazone: Mainly in the bile; via urine (30% as unchanged drug). Elimination half-life: Approx 2 hours.
Sulbactam: Via urine: Approx 84%. Elimination half-life: Approx 1 hour.
Chemical Structure
Cefoperazone Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 44187, Cefoperazone. https://pubchem.ncbi.nlm.nih.gov/compound/Cefoperazone. Accessed July 29, 2020.
Sulbactam Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 130313, Sulbactam. https://pubchem.ncbi.nlm.nih.gov/compound/Sulbactam. Accessed July 29, 2020.
Storage
Store below 30°C. Protect from light. Reconstituted solution may be stored at 25°C for 24 hours or between 2-8°C for 7 days.
J01DD62 - cefoperazone and beta-lactamase inhibitor ; Belongs to the class of third-generation cephalosporins. Used in the systemic treatment of infections.
References
Anon. Cefoperazone and Sulbactam. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 09/06/2020.Buckingham R (ed). Cefoperazone Sodium. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 09/06/2020.Buckingham R (ed). Sulbactam. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 09/06/2020.Cefoperazone. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 23/07/2020.Sulperazon (Haupt Pharma Latina S.r.l.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my/. Accessed 23/07/2020.Sulperazone (Haupt Pharma Latina S.r.l.). MIMS Malaysia. http://www.mims.com/malaysia. Accessed 09/06/2020.
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