Zimilast is a sterile formulation of imipenem (a thienamycin antibiotic) and cilastatin sodium (the inhibitor of the renal dipeptidase, dehydropeptidase I), with sodium bicarbonate added as a buffer. Zimilast is a potent broad-spectrum antibacterial agent for IV administration.
Pharmacology: Adults: Intravenous infusion of Zimilast over 20 min results in peak plasma levels of imipenem antimicrobial activity that range from 14-24 mcg/mL for the 250-mg dose, from 21-58 mcg/mL for the 500-mg dose and from 41-83 mcg/mL for the 1000-mg dose. At these doses, plasma levels of imipenem antimicrobial activity decline to ≤1 mcg/mL in 4-6 hrs. Peak plasma levels of cilastatin following a 20-min IV infusion of Zimilast. Range from 15-25 mcg/mL for the 250-mg dose, from 31-49 mcg/mL for the 500-mg dose and from 56-88 mcg/mL for the 1000-mg dose.
The plasma half-life of each component is approximately 1 hr. The binding of imipenem to human serum proteins is approximately 20% and that of cilastatin is approximately 40%. Approximately 70% of the administered imipenem is recovered in the urine within 10 hrs after which no further urinary excretion is detectable. Urine concentrations of imipenem in excess of 10 mcg/mL can be maintained for up to 8 hrs with Zimilast at the 500-mg dose. Approximately 70% of the cilastatin sodium dose is recovered in the urine within 10 hrs of administration of Zimilast.
Treatment of serious infections caused by susceptible strains of the designated microorganisms in the following conditions: Lower Respiratory Tract Infections: Staphylococcus aureus (penicillinase-producing strains), Acinetobacter species, Enterobacter species, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae*, Klebsiella species, Serratia marcescens.
Complicated and Uncomplicated Urinary Tract Infections: Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing strains)*, Enterobacter species, Escherichia coli, Klebsiella species, Morganella morganii*, Proteus vulgaris*, Providencia rettgeri*, Pseudomonas aeruginosa.
Intra-abdominal Infections: Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing strains)*, Staphylococcus epidermidis, Citrobacter species, Enterobacter species, Escherichia coli, Klebsiella species, Morganella morganii*, Proteus species, Pseudomonas aeruginosa, Bifidobacterium species, Clostridium species, Eubacterium species, Peptococcus species, Peptostreptococcus species, Propionibacterium species*, Bacteroides species including B. fragilis, Fusobacterium species.
Gynecologic Infections: Enterococcus faecalis, Staphylococcus aureus (penicillase-producing strains)*, Staphylococcus epidermidis, Streptococcus agalactiae (group B streptococci), Enterobacter species*, Escherichia coli, Gardnerella vaginalis, Klebsiella species*, Proteus species, Bifidobacterium species*, Peptococcus species*, Peptostreptococcus species, Propionibacterium species*, Bacteroides species including B. fragilis*.
Bacterial Septicemia: Enterococcus faecalis, Staphylococcus aureus (penicillase-producing strains), Enterobacter species, Escherichia coli, Klebsiella species, Pseudomonas aeruginosa, Serratia species*, Bacteroides species including B. fragilis*.
Bone and Joint Infections: Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing strains), Staphylococcus epidermidis, Enterobacter species, Pseudomonas aeruginosa.
Skin and Skin Structure Infections: Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing strains), Staphylococcus epidermidis, Acinetobacter species, Citrobacter species, Enterobacter species, Escherichia coli, Klebsiella species, Morganella morganii, Proteus vulgaris, Providencia rettgeri*.
Pseudomonas aeruginosa, Serratia species, Peptococcus species, Peptostreptococcus species, Bacteroides species including B. fragilis, Fusobacterium species*.
Endocarditis: Staphylococcus aureus (penicillinase-producing strains).
Polymicrobic Infections: Polymicrobic infections including those in which S. pneumoniae (pneumonia, septicemia), S. pyogenes (skin and skin structure) or nonpenicillinase-producing S. aureus is one of the causative organisms. However, monobacterial infections due to these organisms are usually treated with narrower spectrum antibiotics eg, penicillin G.
*Efficacy for this organism in this organ system was studied in fewer than 10 infections.
Adults: The dosage recommendations for Zimilast represent the quantity of imipenem to be administered. An equivalent amount of cilastatin is also present in the solution.
The total daily dosage for Zimilast should be based on the type or severity of infection, and given in equally divided doses based on consideration of degree of susceptibility of the pathogen(s), renal function and body weight. Adult patients with impaired renal function, as judged by creatinine clearance=70 mL/min/1.73 m2, require adjustment of dosage.
Fully Susceptible Organisms Including Gram-Positive and Gram-Negative Aerobes and Anaerobes: Mild: 250 mg every 6 hrs. Total Daily Dose: 1 g. Moderate: 500 mg every 8 hrs; 500 mg every 6 hrs. Total Daily Dose: 1.5 g; 2 g. Severe Life-Threatening Only: 500 mg every 6 hrs. Total Daily Dose: 2 g. Uncomplicated Urinary Tract Infection: 250 mg every 6 hrs. Total Daily Dose: 1 g. Complicated Urinary Tract Infection: 500 mg every 6 hrs. Total Daily Dose: 2 g.
Moderately Susceptible Organisms, Primarily Some Strains of P. Aeruginosa: Mild: 500 mg every 6 hrs. Total Daily Dose: 2 g. Moderate: 500 mg every 6 hrs; 1 g every 8 hrs. Total Daily Dose: 2 g; 3 g. Severe Life-Threatening Only: 1 g every 8 hrs; 1 g every 6 hrs. Total Daily Dose: 3 g; 4 g. Uncomplicated Urinary Tract Infection: 250 mg every 6 hrs. Total Daily Dose: 1 g. Complicated Urinary Tract Infection: 500 mg every 6 hrs. Total Daily Dose: 2 g.
Due to the high antimicrobial activity of Zimilast, it is recommended that the maximum total daily dosage not exceed 59 mg/kg/day or 4 g daily, whichever is lower.
Children: Children 3 months: The recommended dose for non-central nervous system (CNS) infections is 15-25 mg/kg/dose administered every 6 hrs.
Based on studies in adults, the maximum daily dose for treatment of infections with fully susceptible organisms is 2 g daily and of infections with moderately susceptible organisms (primarily some strains of P. aeruginosa) is 4 g daily. Higher doses (up to 90 mg/kg/day in older children) have been used in patients with cystic fibrosis.
Children ≤3 months (Weighing 1500 g): The following dosage schedule is recommended for non-CNS infections: 4 weeks to 3 months: 25 mg/kg every 6 hrs; 1-4 weeks: 25 mg/kg every 8 hrs; <1 week: 25 mg/kg every 12 hrs.
Doses ≤500 mg should be given by IV infusion over 15-30 min.
Doses >500 mg should be given by IV infusion over 40-60 min.
Zimilast is not recommended in pediatric patients with CNS infections because of risk of seizures. Zimilast is not recommended in pediatric patients <30 kg with impaired renal function.
Administration: Each 125-, 250- or 500-mg dose should be given by IV administration over 20-30 min. Each 750- or 1000-mg dose should be infused over 40-60 min. In patients who develop nausea during the infusion, the rate of infusion may be slowed.
Hypersensitivity to any of the components of Zimilast.
Patients with meningitis because safety and efficacy have not been established.
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving therapy with β-lactams. These reactions are more apt to occur in persons with a history of sensitivity to multiple allergens.
Serious anaphylactic reactions require immediate emergency treatment with epinephrine, oxygen, steroids IV and airway management, including intubation, may also be administered as indicated.
Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Zimilast and may range in severity from mild diarrhea to fatal colitis.
General: Central Nervous System (CNS) adverse experiences eg, confusional states, myoclonic activity and seizures have been reported during treatment with Zimilast especially when recommended dosages were exceeded.
Patients with creatinine clearances of 5 mL/min/1.73 m2 should not receive Zimilast unless hemodialysis is instituted within 48 hrs.
For patients on hemodialysis, Zimilast is recommended only when the benefit outweighs the potential risk of seizures.
Skipping doses or not completing the full course of therapy may decrease the effectiveness of the immediate treatment, and increase the likelihood that bacteria will develop resistance and will not be treatable by Zimilast or other antibacterial drugs in the future. Diarrhea is common problem caused by antibiotics.
Zimilast is not for direct infusion.
Use in pregnancy & lactation: Pregnancy Category: C.
Zimilast should be used during pregnancy only if the potential benefit justifies the potential risk to the mother and fetus.
Caution should be exercised when Zimilast is administered to nursing women.
Pregnancy Category: C. Zimilast should be used during pregnancy only if the potential benefit justifies the potential risk to the mother and fetus.
Caution should be exercised when Zimilast is administered to nursing women.
Generalized seizures have been reported in patients who received ganciclovir and Zimilast. It is not recommended that probenecid be given with Zimilast. It should be not be mixed with or physically added to other antibiotics. However, Zimilast may be administered concomitantly with other antibiotics eg, aminoglycosides.
J01DH51 - imipenem and cilastatin ; Belongs to the class of carbapenems. Used in the systemic treatment of infections.
Sign Out
