Heyirui Imipenem and Cilastatin Sodium for Injection and Sodium Chloride Injection

1. Indications and Usage
Severe Bacterial Infections:
Treatment of serious infections caused by susceptible bacteria, including intra-abdominal infections, gynecologic infections, lower respiratory tract infections, septicemia, skin and skin-structure infections, bone and joint infections, and endocarditis.
Mixed Aerobic/Anaerobic Infections:
Particularly effective against polymicrobial infections and those involving beta-lactamase-producing organisms that are resistant to other antibiotics .
2. Dosage and Administration
Route of Administration:
For Intravenous (IV) Infusion ONLY.
Recommended Dosage:
Adults: The total daily dose depends on the type and severity of infection and susceptibility of the organism.
Standard Dosing: Typically 15 to 25 mg/kg/day (based on imipenem/cilastatin ratio), divided into 3 to 4 doses.
Maximum Dose: Generally should not exceed 4 g/day or 50 mg/kg/day, whichever is lower .
Critical Administration Instructions:
Reconstitution: Dissolve the contents of the powder vial with the entirety of the accompanying 0.9% Sodium Chloride Injection ampoule/vial.
Concentration: The resulting solution is typically a 5 mg/mL solution.
Infusion Time:
Doses ≤ 500 mg: Infuse over approximately 20–30 minutes.
Doses > 500 mg: Infuse over approximately 40–60 minutes .
3. Mechanism of Action
Imipenem (Antibiotic):
A broad-spectrum carbapenem antibiotic that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs).
Cilastatin (Enzyme Inhibitor):
A specific inhibitor of dehydropeptidase I (DHP-I), an enzyme found in the renal brush border.
Purpose: Cilastatin prevents the degradation of imipenem in the kidney, thereby maintaining effective antibacterial concentrations in the urine and blood. It also reduces the potential for nephrotoxicity associated with imipenem .
4. Safety and Warnings
Seizures:
Imipenem/cilastatin has been associated with seizures and other CNS adverse experiences.
Risk Factors: Patients with CNS disorders (e.g., brain lesions, history of seizures), renal dysfunction, or those receiving excessive doses.
Hypersensitivity:
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported.
Contraindication: Contraindicated in patients with a known hypersensitivity to any component of this product or to drugs in the same class (e.g., penicillins, cephalosporins) .
Renal Impairment:
Dosage adjustment is required for patients with renal dysfunction (Creatinine Clearance < 70 mL/min) .
5.Adverse Reactions and Clinical Research
Most Common Adverse Reactions:
Nausea, vomiting, diarrhea, injection site reactions (pain, inflammation), and skin rash.
Clinical Research Highlights:
Studies demonstrate that the pre-mixed formulation with sodium chloride maintains chemical stability and antibacterial efficacy comparable to manually prepared solutions, while reducing preparation errors .
6.Drug Interactions
Probenecid:
Concomitant administration of probenecid with imipenem/cilastatin results in higher and more prolonged serum concentrations of both imipenem and cilastatin.
Valproic Acid:
Co-administration of imipenem/cilastatin with valproic acid or divalproex sodium can reduce the serum concentrations of the anticonvulsant, potentially leading to loss of seizure control .
7.Pharmaceutical Information
Chemical Composition:
Powder Vial: Imipenem (as monohydrate) and Cilastatin Sodium.
Solvent Ampoule: 0.9% Sodium Chloride Injection.
Appearance: White to off-white powder; Colorless to slightly yellow liquid.
Storage: Store at controlled room temperature.