Dosage guidance:
Safety: Not the preferred carbapenem for neonates due to limited pharmacokinetic data and risk of seizures, particularly in the setting of drug accumulation; not recommended for CNS infections (Ref).
Dosing: Dosage recommendations are based on imipenem component.
General dosing:
Preterm and term neonates (Ref): IV:
Imipenem Component Dosing in Preterm and Term Neonates | |
---|---|
Postnatal age (days) |
Dose |
≤7 days |
25 mg/kg/dose every 12 hours |
>7 days |
25 mg/kg/dose every 8 hours |
Dosage guidance:
Dosing: Dosage recommendations are based on imipenem component.
General dosing: Infants, Children, and Adolescents: IV: 15 to 25 mg/kg/dose every 6 hours; maximum dose: 1,000 mg/dose (Ref). Note: Doses on the higher end of the range are recommended for infections caused by susceptible Pseudomonas aeruginosa (Ref).
Intra-abdominal infection, complicated: Infants, Children, and Adolescents: IV: 15 to 25 mg/kg/dose every 6 hours; maximum dose: 500 mg/dose. Duration dependent upon age, source of infection, and surgical status. Typical duration is 4 to 7 days unless source control inadequate; in some circumstances (ie, acute or gangrenous appendicitis without perforation managed with surgery), therapy should be limited to ≤24 hours (Ref).
Melioidosis ( Burkholderia pseudomallei infection): Infants, Children, and Adolescents: IV: Initial: 25 mg/kg/dose every 6 hours; maximum dose: 1,000 mg/dose (Ref). Duration of parenteral therapy for initial intensive therapy is typically ≥14 days, though a longer duration may be necessary depending on disease severity and site of infection; after initial intensive therapy, transition to oral eradication therapy (Ref).
Mycobacterial (nontuberculous) infection, pulmonary infection in patients with cystic fibrosis:
Infants, Children, and Adolescents: IV: 15 to 20 mg/kg/dose every 12 hours as part of an appropriate combination regimen; maximum dose: 1,000 mg/dose. The duration of parenteral therapy is generally 3 to 12 weeks depending on clinical response, followed by transition to oral and/or inhaled therapy; total treatment duration is ≥12 months after culture conversion (Ref).
Neutropenic fever, empiric treatment: Limited data available: Children and Adolescents: IV: 15 to 25 mg/kg/dose every 6 hours; maximum dose: 1,000 mg/dose (Ref). Duration of empiric therapy is typically until blood cultures are negative at 48 hours and patient has been clinically well and afebrile ≥24 hours with evidence of marrow recovery (Ref).
Peritonitis (peritoneal dialysis): Infants, Children, and Adolescents: Intraperitoneal: Continuous: Loading dose: 250 mg per liter of dialysate; maintenance dose: 50 mg per liter (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: Renally adjusted dose recommendations are based on doses of 15 to 25 mg/kg/dose every 6 hours (Ref). The manufacturer does not recommend use in pediatric patients weighing <30 kg with impaired renal function (not defined) due to lack of data.
Altered kidney function:
Infants, Children, and Adolescents:
GFR 30 to 50 mL/minute/1.73 m2: IV: Administer 7 to 13 mg/kg/dose every 8 hours (Ref).
GFR 10 to 29 mL/minute/1.73 m2: IV: Administer 7.5 to 12.5 mg/kg/dose every 12 hours (Ref).
GFR <10 mL/minute/1.73 m2: IV: Administer 7.5 to 12.5 mg/kg/dose every 24 hours (Ref).
Hemodialysis, intermittent: Moderately dialyzable (20% to 50%).
Infants, Children, and Adolescents: IV: 7.5 to 12.5 mg/kg/dose every 24 hours (administer after hemodialysis on dialysis days) (Ref).
Peritoneal dialysis (PD): Infants, Children, and Adolescents: IV: 7.5 to 12.5 mg/kg/dose every 24 hours (Ref).
CRRT: Infants, Children, and Adolescents: IV: 7 to 13 mg/kg/dose every 8 hours (Ref).
There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Imipenem and cilastatin: Drug information")
Dosage guidance:
Dosing: Doses presented are based on imipenem component. Infusion method: Dosing is presented based on the traditional infusion method over 30 minutes, unless otherwise specified.
Clinical considerations: An extended infusion strategy has a greater likelihood of attaining pharmacokinetic/pharmacodynamic targets and may offer clinical benefit in patients with severe infections or less susceptible pathogens (Ref). Some experts recommend extended infusion (ie, 500 mg every 6 hours over 3 hours) for treatment of infections caused by certain resistant organisms (eg, carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Enterobacterales) (Ref).
Usual dosage range:
Traditional intermittent infusion method: IV: 500 mg every 6 hours infused over 30 minutes or 1 g every 6 to 8 hours infused over 40 to 60 minutes.
Extended infusion method (off label): IV: 500 mg to 1 g every 6 hours infused over 3 hours (Ref). May give a loading dose of 500 mg to 1 g over 30 minutes, especially when rapid attainment of therapeutic drug concentrations is desired (eg, sepsis) (Ref).
Bloodstream infection (gram-negative bacteremia):
Note: For empiric therapy of known or suspected gram-negative organisms (including Pseudomonas aeruginosa) or pathogen-directed therapy for organisms resistant to other agents (Ref).
IV: 500 mg every 6 hours (IDSA [Mermel 2009]); for empiric therapy in patients with neutropenia, severe burns, sepsis, or septic shock, give as part of an appropriate combination regimen. Note: For critical illness or infection with an organism with an elevated minimum inhibitory concentration, some experts prefer the extended infusion method (Ref).
Duration of therapy: Usual duration is 7 to 14 days depending on the source, pathogen, extent of infection, and clinical response; a 7-day duration is recommended for patients with uncomplicated Enterobacteriaceae infection who respond appropriately to antibiotic therapy (Ref). Longer durations may be warranted in immunocompromised patients (Ref).
Cystic fibrosis, acute pulmonary exacerbation (off-label use):
Note: For empiric or targeted treatment of P. aeruginosa or other gram-negative bacilli (Ref).
IV: 500 mg to 1 g every 6 hours, most often given as part of an appropriate combination regimen (Ref). Note: Some experts use the extended infusion method to optimize exposure (Ref). Duration is usually 10 to 14 days, depending on clinical response (Ref).
Diabetic foot infection, moderate to severe (off-label use):
Note: As a component of empiric therapy in patients at risk for P. aeruginosa (eg, significant water exposure, macerated wound) or other gram-negative bacteria resistant to other agents (Ref).
IV: 500 mg every 6 hours. Duration (which may include oral step-down therapy) is usually 2 to 4 weeks in the absence of osteomyelitis (Ref).
Intra-abdominal infection, health care–associated or high-risk community-acquired infection:
Note: For community-acquired infection, reserve for patients who cannot tolerate a beta-lactam or are at risk for infection with an extended-spectrum beta-lactamase (ESBL)–producing organism (eg, known colonization or prior infection with an ESBL-producing organism) (Ref).
Cholecystitis, acute uncomplicated: IV: 500 mg every 6 hours or 1 g every 8 hours; continue for 1 day after gallbladder removal or until clinical resolution in patients managed nonoperatively (Ref).
Other intra-abdominal infection (eg, cholangitis, complicated cholecystitis, appendicitis, diverticulitis, intra-abdominal abscess): IV: 500 mg every 6 hours or 1 g every 8 hours. Total duration (which may include transition to oral antibiotics) is 4 to 5 days following adequate source control (Ref). For diverticulitis or uncomplicated appendicitis managed without intervention, duration is 10 to 14 days (Ref); for perforated appendicitis managed with laparoscopic appendectomy, 2 to 4 days may be sufficient (Ref). Note: For patients who are critically ill or at high risk for infection with drug-resistant pathogens, some experts favor the extended infusion method (Ref).
Melioidosis (Burkholderia pseudomallei infection) or glanders (B. mallei infection) (alternative agent) (off-label use):
Initial intensive therapy: IV: 25 mg/kg up to 1 g every 6 to 8 hours for 14 days (Ref); a longer duration may be necessary depending on disease severity and site of infection (Ref). Some experts prefer meropenem over imipenem (Ref) and recommend adding sulfamethoxazole/trimethoprim for patients with focal disease of the CNS, prostate, bone, joint, skin, or soft tissue (Ref). Note: Following the course of parenteral therapy, eradication therapy with oral antibiotics for ≥12 weeks is recommended (Ref).
Mycobacterial (nontuberculous, rapidly growing) infection (off-label use):
IV: 500 mg to 1 g twice daily (Ref); some experts also suggest these doses up to 3 times daily (Ref). Give as part of an appropriate combination regimen. The optimal duration of therapy is unknown but generally the duration of parenteral therapy is 2 to 12 weeks depending on pathogen, severity of infection, and other patient-specific factors, followed by long-term oral maintenance therapy; consult an infectious diseases specialist for specific recommendations (Ref).
Neutropenic enterocolitis (typhlitis) (alternative agent) (off-label use):
Note: Reserve for patients colonized or infected with a resistant gram-negative bacillus, such as an ESBL-producing organism (Ref).
IV: 500 mg every 6 hours; continue until neutropenia is resolved and clinically improved, then switch to oral antibiotics. The total duration of antibiotics is generally 14 days following recovery from neutropenia (Ref).
Neutropenic fever, high-risk cancer patients (empiric therapy) (off-label use):
Note: High-risk patients are those expected to have an ANC ≤100 cells/mm3 for >7 days or an ANC ≤100 cells/mm3 for any expected duration if there are ongoing comorbidities (eg, sepsis, mucositis, significant hepatic or renal dysfunction) (Ref); some experts use an ANC cutoff of <500 cells/mm3 to define high-risk patients (Ref).
IV: 500 mg every 6 hours (Ref) until afebrile for ≥48 hours and neutropenia has resolved (ANC ≥500 cells/mm3 and increasing); if specific infection is identified, give for standard duration if longer than the duration of neutropenia. Additional agent(s) may be needed depending on clinical status (Ref). Some experts prefer the extended infusion method, particularly in patients who are critically ill (Ref).
Nocardiosis, severe (off-label use):
Note: Due to concerns for resistance, susceptibility testing should be performed on isolates (Ref).
IV: 500 mg every 6 hours as part of an appropriate combination regimen (Ref). Consult an infectious diseases specialist for specific treatment recommendations.
Duration of therapy: Prolonged treatment is required (range: 6 months to ≥1 year [at least several weeks of parenteral therapy followed by oral therapy]) (Ref).
Peritonitis, treatment (peritoneal dialysis) (off-label route):
Note: Intraperitoneal administration is preferred to IV administration unless the patient has sepsis (Ref).
Intermittent (every other exchange): Intraperitoneal: 500 mg added to the dialysate solution with every other exchange; allow to dwell ≥6 hours (Ref).
Continuous (with every CAPD exchange): Intraperitoneal: Loading dose: 250 mg/L with first dialysate exchange; maintenance dose: 50 mg/L with each subsequent dialysate exchange (Ref).
Duration: For patients with adequate clinical response, duration of therapy is ≥3 weeks. For patients with no improvement after 5 days, remove catheter and treat with appropriate systemic antibiotics for 14 days after catheter removal (Ref).
Pneumonia:
Community-acquired pneumonia:For empiric therapy of inpatients at risk of infection with a multidrug-resistant (MDR) gram-negative pathogen(s), including P. aeruginosa:
IV: 500 mg every 6 hours as part of an appropriate combination regimen. Total duration (which may include oral step-down therapy) is a minimum of 5 days; a longer course may be required for patients with an immunocompromising condition, severe or complicated infection, or for P. aeruginosa infection. Patients should be clinically stable with normal vital signs prior to discontinuation (Ref).
Hospital-acquired or ventilator-associated pneumonia: For empiric therapy (often as part of an appropriate combination regimen) or pathogen-specific therapy; reserve for patients with or at risk for MDR gram-negative pathogen(s) (eg, ESBL-producing Enterobacterales, P. aeruginosa, Acinetobacter spp.) (Ref):
IV: 500 mg every 6 hours. Duration of therapy varies based on disease severity and response to therapy; treatment is typically given for 7 days (Ref). Note: Some experts prefer extended infusion for critical illness or when treating a susceptible organism with an elevated minimum inhibitory concentration (Ref).
Sepsis and septic shock (broad-spectrum empiric therapy, including P. aeruginosa) (off-label use):
IV: 500 mg every 6 hours or 1 g every 8 hours in combination with other appropriate agent(s) when applicable (Ref). Initiate therapy as soon as possible once there is recognition of sepsis or septic shock. Duration is dependent on underlying source and patient response; short courses are preferred, when appropriate. Discontinue if a noninfectious etiology is identified (Ref). Note: Some experts prefer the extended infusion method (Ref).
Skin and soft tissue infection, moderate to severe:
Note: For patients with necrotizing infections, select surgical site infections (intestinal, GU tract), or patients with or at risk for pathogens resistant to other agents, including P. aeruginosa (Ref). Often used as part of an appropriate combination regimen (Ref).
Necrotizing infection (off-label use): IV: 1 g every 6 to 8 hours. Continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for ≥48 hours (Ref).
Non-necrotizing infection: IV: 500 mg every 6 hours. Usual duration (including oral step-down therapy) is 5 to 14 days based on severity and clinical response (Ref).
Urinary tract infection, complicated (pyelonephritis or urinary tract infection with systemic signs/symptoms):
Note: Reserve for critically ill patients or for patients with risk factor(s) for MDR pathogens, including ESBL-producing organisms and P. aeruginosa (Ref).
IV: 500 mg every 6 hours. Switch to an appropriate oral regimen once symptoms improve if culture and susceptibility results allow (Ref). Total duration of therapy ranges from 5 to 14 days; for patients with symptomatic improvement within the first 48 to 72 hours of therapy, some experts recommend shorter courses of 5 to 10 days (or 7 to 10 days if therapy is completed with imipenem/cilastatin) (Ref).
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Note: Doses based on imipenem component.
Altered kidney function: IV:
Imipenem Dosage Adjustments (Intermittent Infusion Method) for Altered Kidney Functiona,b | |||
---|---|---|---|
CrClc (mL/minute) |
If the usual recommended dose is 500 mg every 6 hours |
If the usual recommended dose is 1 g every 8 hours |
If the usual recommended dose is 1 g every 6 hoursd |
a Recommended doses are based on expert opinion derived from Gibson 1985; Verbist 1986; Yoshizawa 2012. Note: Recommendations may vary considerably compared to the manufacturer’s labeling. | |||
b Patients with acute kidney injury may have increased non-renal clearance compared to patients with chronic kidney disease. Monitor patients closely and consider an increased dose or alternative agent if the patient does not respond to therapy (Mueller 1993). | |||
c CrCl determined using Cockcroft-Gault formula. | |||
d Designed to achieve a pharmacodynamic target of ≥40% fT > MIC for an MIC of 4 mg/L (Yoshizawa 2012). | |||
e The more frequent dosing regimen may decrease the risk of toxicity in this population (Yoshizawa 2012). | |||
≥60 to <130 |
No dosage adjustment necessary |
No dosage adjustment necessary |
No dosage adjustment necessary |
≥30 to <60 |
250 mg every 6 hours or 500 mg every 8 hours |
500 mg every 8 hours |
500 mg every 6 hours |
≥15 to <30e |
250 mg every 8 hours or 500 mg every 12 hours |
250 mg every 8 hours or 500 mg every 12 hours |
250 mg every 6 hours |
<15 |
Do not administer imipenem/cilastatin unless hemodialysis is instituted within 48 hours. |
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Young patients (<55 years of age) admitted post-trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).
IV: 1 g every 6 hours (Ref).
Hemodialysis, intermittent (thrice weekly): Dialyzable (55% imipenem, 63% cilastatin (Ref)):
IV: 250 to 500 mg every 12 hours, depending on infection type and severity. When scheduled dosing falls on dialysis days, one of the doses should be scheduled to be given after dialysis, if possible (Ref).
Peritoneal dialysis: IV: 250 to 500 mg every 12 hours (Ref).
CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection) and consideration of initial loading doses. Close monitoring of response and adverse reactions (eg, neurotoxicity) due to drug accumulation is important.
IV: 1 g as a single dose, followed by 250 mg every 6 hours or 500 mg every 6 to 8 hours (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection) and consideration of initial loading doses. Close monitoring of response and adverse reactions (eg, neurotoxicity) due to drug accumulation is important.
IV: 500 mg to 1 g as a single dose, followed by 250 mg every 6 hours or 500 mg every 8 hours with one of the doses scheduled to be given after PIRRT on PIRRT days when possible (Ref).
Note: Recommended doses may reduce risk of neurotoxicity but may not achieve PK/PD targets. Monte Carlo simulations suggest doses of 750 mg every 6 hours or 1 g every 8 hours are necessary to achieve a PK/PD target of fT 4 × MIC >40% (Ref); however, risk of neurotoxicity (eg, seizures) is significantly higher. Therefore, use of an alternative antimicrobial agent may be preferred.
There are no dosage adjustments provided in the manufacturer's labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%
Hematologic & oncologic: Decreased hematocrit (infants and children 3 months to 12 years: 18%; neonates and infants <3 months: 2%), decreased hemoglobin (infants and children 3 months to 12 years: 15%), eosinophilia (neonates, infants, and children to 12 years: 9% to 13%), thrombocythemia (infants and children 3 months to 12 years: 13%; neonates and infants <3 months: 4%)
Hepatic: Increased serum AST (infants and children 3 months to 12 years: 18%; neonates and infants <3 months: 6%), increased serum ALT (infants and children 3 months to 12 years: 11%; neonates and infants <3 months: 3%)
1% to 10%:
Cardiovascular: Phlebitis (2% to 3%), tachycardia (neonates and infants ≤3 months: 2%; adults <1%)
Central nervous system: Seizure (neonates and infants ≤3 months: 6%; adults <1%)
Dermatologic: Skin rash (≤2%)
Gastrointestinal: Diarrhea (neonates, infants, and children to 12 years: 3% to 4%; adults 2%), nausea (2%), oral candidiasis (neonates and infants ≤3 months: 2%), vomiting (≤1% to 2%), gastroenteritis (≤1%)
Genitourinary: Proteinuria (infants and children 3 months to 12 years: 8%), urine discoloration (≤1%), oliguria (neonates and infants ≤3 months: 2%; adults <1%)
Hematologic & oncologic: Neutropenia (infants and children 3 months to 12 years: 3%; adults <1%), decreased platelet count (neonates and infants <3 months: 2%), increased hematocrit (neonates and infants <3 months: 1%)
Hepatic: Increased serum alkaline phosphatase (neonates and infants <3 months: 3%), increased serum bilirubin (neonates and infants <3 months: 3%), decreased serum bilirubin (neonates and infants <3 months: 1%)
Local: Irritation at injection site (infants, children, and adolescents 3 months to 16 years: 1%)
Renal: Increased serum creatinine (neonates and infants <3 months: 5%)
<1%, postmarketing and/or case reports: Abdominal pain, acute renal failure, agitation, agranulocytosis, anaphylaxis, angioedema, back pain (thoracic spinal), basophilia, bilirubinuria, bone marrow depression, brain disease, candidiasis, casts in urine, change in prothrombin time, chest discomfort, Clostridioides difficile-associated diarrhea, confusion, cyanosis, decreased serum sodium, dental discoloration, dizziness, drowsiness, drug fever, dysgeusia, dyskinesia, dyspnea, erythema at injection site, erythema multiforme, fever, flushing, glossitis, hallucination, headache, hearing loss, heartburn, hematuria, hemolytic anemia, hemorrhagic colitis, hepatic failure, hepatitis (including fulminant onset), hyperchloremia, hyperhidrosis, hypersensitivity, hyperventilation, hypotension, increased blood urea nitrogen, increased lactate dehydrogenase, increased monocytes, increased serum potassium, increased urinary urobilinogen, induration at injection site, injection site infection, jaundice, leukocytosis, leukocyturia, leukopenia, lymphocytosis, myoclonus, neutropenia, pain at injection site, palpitations, pancytopenia, paresthesia, polyarthralgia, polyuria, positive direct Coombs' test, pruritus, pruritus vulvae, pseudomembranous colitis, pseudomonas infection (resistant P. aeruginosa), psychiatric disturbances, sialorrhea, skin changes (texture), sore throat, Stevens-Johnson syndrome, thrombocytopenia, tinnitus, tongue changes (papillar hypertrophy), tongue discoloration, toxic epidermal necrolysis, tremor, urticaria, vertigo, weakness
Hypersensitivity to imipenem/cilastatin or any component of the formulation.
Concerns related to adverse effects:
• CNS effects: Carbapenems have been associated with CNS adverse effects, including confusional states and seizures (myoclonic); use caution with CNS disorders (eg, brain lesions and history of seizures) and adjust dose in renal impairment to avoid drug accumulation, which may increase seizure risk. However, there have been reports of adverse CNS effects in patients who had no recognized or documented underlying CNS disorder or compromised renal function.
• Hypersensitivity reactions: Serious hypersensitivity/anaphylactic reactions have been reported, including fatalities; may be more common in patients with a history of sensitivity to multiple allergens. Patients with a history of penicillin hypersensitivity may experience severe hypersensitivity reactions when treated with other beta-lactams; carefully inquire about previous hypersensitivity reactions to penicillins, cephalosporins, other beta-lactams, and other allergens. Serious anaphylactic reactions require immediate discontinuation and supportive care as clinically indicated.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment required in patients with moderate to severe renal dysfunction. Increased seizure risk has been reported in patients with significant renal dysfunction. Do not use in patients with CrCl ≤15 mL/minute unless hemodialysis is instituted within 48 hours. For patients on hemodialysis, use is recommended only when the benefit outweighs the potential risk of seizures.
Concurrent drug therapy issues:
• Valproic acid and derivatives: Carbapenems, including imipenem, may decrease the serum concentration of divalproex sodium/valproic acid increasing the risk of breakthrough seizures. Concurrent use of carbapenem antibiotics with divalproex sodium/valproic acid is generally not recommended. Alternative antimicrobial agents should be considered, but if a concurrent carbapenem is necessary, consider additional antiseizure medication.
Special populations:
• Pediatric: Not recommended in pediatric CNS infections due to seizure potential.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution:
Primaxin I.V.: Imipenem 500 mg and cilastatin 500 mg
Injection, powder for reconstitution (preservative free):
Generic: Imipenem 250 mg and cilastatin 250 mg; Imipenem 500 mg and cilastatin 500 mg
Yes
Solution (reconstituted) (Imipenem-Cilastatin Intravenous)
250 mg (per each): $7.80 - $17.99
500 mg (per each): $15.00 - $35.98
Solution (reconstituted) (Primaxin IV Intravenous)
500-500 mg (per each): $39.18
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Injection, powder for reconstitution:
Primaxin: imipenem 500 mg and cilastatin 500 mg
RAN-Imipenem-Cilastatin: imipenem 250 mg and cilastatin 250 mg; imipenem 500 mg and cilastatin 500 mg
Generic: imipenem 250 mg and cilastatin 250 mg; imipenem 500 mg and cilastatin 500 mg
Sodium content: 250 mg vial contains 0.8 mEq; 500 mg vial contains 1.6 mEq
IV: Administer by IV intermittent infusion; doses ≤500 mg may be infused over 20 to 30 minutes; doses >500 mg should be infused over 40 to 60 minutes. If nausea and/or vomiting occur during administration, decrease the rate of IV infusion.
IV: For IV infusion only; do not administer IV push. Infuse doses ≤500 mg over 20 to 30 minutes; infuse doses >500 mg over 40 to 60 minutes. If nausea and/or vomiting occur during administration, decrease the rate of IV infusion.
Extended-infusion administration (off-label method): Administer over 3 hours (Ref). Note: Must consider imipenem/cilastatin limited room temperature stability if using extended infusions.
Intraperitoneal (off-label route): May administer intermittently (1 exchange daily; allow to dwell ≥6 hours) or continuously (with every exchange) (Ref).
Store intact vials at <25°C (77°F). Reconstituted solution is stable for 4 hours at room temperature or 24 hours when refrigerated at 5°C (41°F). Do not freeze.
Treatment of lower respiratory tract, urinary tract, intra-abdominal, gynecologic, bone and joint, septicemias, endocarditis, and skin and skin structure infections due to susceptible bacteria (FDA approved in all ages); has also been used for the treatment of peritonitis in patients with peritoneal catheters and as empiric therapy for neutropenic fever.
Imipenem may be confused with ertapenem, meropenem, doripenem
Primaxin may be confused with Premarin, Primacor
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination
CycloSPORINE (Systemic): Imipenem may enhance the neurotoxic effect of CycloSPORINE (Systemic). Risk C: Monitor therapy
Fecal Microbiota (Live) (Oral): May diminish the therapeutic effect of Antibiotics. Risk X: Avoid combination
Fecal Microbiota (Live) (Rectal): Antibiotics may diminish the therapeutic effect of Fecal Microbiota (Live) (Rectal). Risk X: Avoid combination
Ganciclovir-Valganciclovir: May enhance the adverse/toxic effect of Imipenem. Specifically, the risk of seizures may be increased. Management: Avoid concomitant use of these agents unless the prospective benefits of therapy outweigh the risks. Risk D: Consider therapy modification
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Mycophenolate: Antibiotics may decrease serum concentrations of the active metabolite(s) of Mycophenolate. Specifically, concentrations of mycophenolic acid (MPA) may be reduced. Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Imipenem. Risk C: Monitor therapy
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Valproate Products: Carbapenems may decrease the serum concentration of Valproate Products. Management: Concurrent use of carbapenem antibiotics with valproic acid is generally not recommended. Alternative antimicrobial agents should be considered, but if a concurrent carbapenem is necessary, consider additional anti-seizure medication. Risk D: Consider therapy modification
Some products may contain sodium.
Imipenem and cilastatin cross the placenta (Cho 1988; Heikkilä 1992)
Due to pregnancy-induced physiologic changes, some pharmacokinetic parameters of imipenem/cilastatin may be altered (Heikkilä 1992).
Imipenem is not one of the preferred antibiotics for the management of cystic fibrosis in pregnant females; however, it may be used when a safer alternative is not available (Panchaud 2016).
Periodic kidney, liver, and hematologic function tests; changes in bowel movement frequency. Monitor for signs of anaphylaxis and CNS effects.
Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs); which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested. Cilastatin prevents renal metabolism of imipenem by competitive inhibition of dehydropeptidase along the brush border of the renal tubules.
Distribution:
Lung: Epithelial lining fluid:plasma ratio: 44%, varies with time (van Hasselt 2016).
Vd:
Neonates (GA 31 to 42 weeks; PNA ≤10 days): Imipenem: 0.538 ± 0.105 L/kg; Cilastatin: 0.246 ± 0.05 L/kg (Freij 1985).
Children ≥2 years: Imipenem: 0.656 ± 0.122 L/kg (Jacobs 1984).
Protein binding: Imipenem: ~20%; cilastatin: ~40%.
Metabolism: Imipenem is metabolized in the kidney by dehydropeptidase I; cilastatin prevents imipenem metabolism by this enzyme.
Half-life elimination: IV:
Neonates (GA 31 to 42 weeks; PNA ≤10 days): Mean range: Imipenem: 1.7 to 2.4 hours; Cilastatin: 3.9 to 6.4 hours (Freij 1985).
Children ≥2 years: Imipenem: 1.2 hours (Jacobs 1984).
Adults (both drugs): ~60 minutes.
Excretion: Both drugs: Urine (~70% as unchanged drug).
Anti-infective considerations:
Parameters associated with efficacy:
Time dependent, associated with time free drug concentration (fT) > minimum inhibitory concentration (MIC).
Infusion specific:
Standard infusion and up to 4 hours extended infusion: Goal: 40% to 70% fT > MIC (Hong 2023).
Continuous infusion: Goal: 100% fT > MIC with concentrations that exceed up to 4 to 8 times free drug over the steady-state concentration (fCss) (Hong 2023).
Organism specific:
P. aeruginosa: Goal: ≥40% fT > MIC (bactericidal) (Ong 2007).
Population specific:
Critically ill patients in the ICU: Minimum goal: ≥50% fT > MIC; preferred goal: ≥100% fT > MIC (Abdul-Aziz 2020; Al-Shaer 2020; Roberts 2014); some experts favor ≥100% fT > 4 times the MIC (Guilhaumou 2019).
Expected drug exposure in patients with normal renal function:
Cmax (peak):
Children 2 to 12 years of age: 25 mg/kg IV (15-minute infusion), single dose: Imipenem: 33.47 mg/L (Jacobs 1984).
Adults:
500 mg IV, single dose: Imipenem: 21 to 58 mg/L; cilastatin: 31 to 49 mg/L.
1 g IV, single dose: Imipenem: 41 to 83 mg/L; cilastatin: 56 to 88 mg/L.
Critical illness: 1 g every 8 hours (30-minute infusion), steady state: Imipenem: 44.2 ± 13.26 mg/L; 500 mg every 6 hours (3-hour infusion), steady state: Imipenem: 9.25 ± 3.47 mg/L (Lipš 2014).
Postantibiotic effect: Minimal bacterial killing continues after imipenem concentration falls below the MIC of targeted pathogen and varies based on the organism:
S. aureus: 1.1 to 1.8 hours (Nadler 1989; Odenholt 1998).
P. aeruginosa: 1.2 to 2.6 hours (Nadler 1989).
Other gram-negative organisms (eg, Enterobacter cloacae, E. coli, H. influenzae, M. morganii, S. marcescens): ≤0.4 hours (Nadler 1989; Odenholt 1998).
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