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تعداد ایتم قابل مشاهده باقیمانده : 4 مورد

Imipenem and cilastatin: Drug information

Imipenem and cilastatin: Drug information
(For additional information see "Imipenem and cilastatin: Patient drug information" and see "Imipenem and cilastatin: Pediatric drug information")

For abbreviations and symbols that may be used in Lexicomp (show table)
Brand Names: US
  • Primaxin I.V.
Brand Names: Canada
  • Imipenem and Cilastatin for Injection;
  • Imipenem and Cilastatin for Injection, USP;
  • Primaxin;
  • RAN-Imipenem-Cilastatin
Pharmacologic Category
  • Antibiotic, Carbapenem
Dosing: Adult

Note: Doses based on imipenem component. Infusion method: Dosing is presented based on the traditional infusion method over 30 minutes, unless otherwise specified.

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 (Ibrahim 2017; Lim 2018; Lipš 2014). 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) (Lipš 2014; SCCM [Rhodes 2017]).

Note: Extended infusion method is largely based on pharmacokinetic and pharmacodynamic modeling data. 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 (Ibrahim 2017; Jaruratanasirikul 2015; Lim 2018).

Indication-specific dosing:

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 (Corcione 2019; IDSA [Mermel 2009]).

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 (Kanj 2020a; Kanj 2020b; Moehring 2020a; SCCM [Rhodes 2017]).

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 (Moehring 2020a; Yahav 2019). Longer durations may be warranted in immunocompromised patients (IDSA [Freifeld 2011]; Oriol 2017).

Cystic fibrosis, acute pulmonary exacerbation (off-label use):

Note: For empiric or targeted treatment of P. aeruginosa or other gram-negative bacilli (Chmiel 2014; Simon 2020).

IV: 500 mg to 1 g every 6 hours, most often given as part of an appropriate combination regimen (Chmiel 2014; Flume 2009). Note: Some experts use the extended infusion method to optimize exposure (Simon 2020). Duration is usually 10 days to 3 weeks or longer based on clinical response (Flume 2009; Simon 2020).

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 (IDSA [Lipsky 2012]).

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 (Grayson 1994; IDSA [Lipsky 2012]; Saltoglu 2010; Weintrob 2020).

Intra-abdominal infection, health care-associated or high-risk community-acquired infection:

Note: For community-acquired infection, reserve for severe infection or patients at high risk of adverse outcome and/or resistance (Barshak 2021; SIS/IDSA [Solomkin 2010]).

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 (Gomi 2018; SIS [Mazuski 2017]; SIS/IDSA [Solomkin 2010]; Vollmer 2021).

Other intra-abdominal infection (eg, cholangitis, complicated cholecystitis, perforated appendix, 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 (Gomi 2018; Sawyer 2015; SIS [Mazuski 2017]); for diverticulitis or uncomplicated appendicitis managed without intervention, duration is 7 to 10 days (Barshak 2021; Pemberton 2021). Note: For patients who are critically ill or at high risk for infection with drug-resistant pathogens, some experts favor the extended infusion method (Barshak 2021; WSES [Sartelli 2017]).

Melioidosis (Burkholderia pseudomallei infection) (alternative agent) (off-label use):

Initial intensive therapy: IV: 25 mg/kg up to 1 g every 6 to 8 hours for 10 to 14 days (Currie 2003; Simpson 1999); a longer duration may be necessary depending on disease severity and site of infection (Currie 2003; Inglis 2006). Some experts prefer meropenem over imipenem (Currie 2021; Inglis 2006; Wiersinga 2018) and recommend adding sulfamethoxazole/trimethoprim for patients with focal disease of the CNS, prostate, bone, joint, skin, or soft tissue (Currie 2021). Note: Following the course of parenteral therapy, eradication therapy with oral antibiotics for ≥12 weeks is recommended (Currie 2003; Inglis 2006).

Mycobacterial (nontuberculous, rapidly growing) infection (off-label use):

IV: 500 mg to 1 g twice daily (AST-IDCOP [Longworth 2019]; BTS [Haworth 2017]; Floto 2016); some experts also suggest these doses up to 3 times daily (ATS/ERS/ESCMID/IDSA [Daley 2020]). 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 (AST-IDCOP [Longworth 2019]; ATS/ERS/ESCMID/IDSA [Daley 2020]; BTS [Haworth 2017]; Floto 2016; Griffith 2020).

Neutropenic enterocolitis (typhlitis) (alternative agent) (off-label use):

Note: Reserve for patients colonized or infected with a resistant gram-negative bacillus, such as an extended-spectrum beta-lactamase (ESBL)-producing organism (Wong Kee Song 2020).

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 (IDSA [Freifeld 2011]; Wong Kee Song 2020).

Neutropenic fever, high-risk patients with cancer (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) (IDSA [Freifeld 2011]); some experts use an ANC cutoff of <500 cells/mm3 to define high-risk patients (Wingard 2020).

IV: 500 mg every 6 hours (Paul 2006) 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 (IDSA [Freifeld 2011]; Wingard 2020). Some experts prefer the extended infusion method, particularly in patients who are critically ill (Jaruratanasirikul 2015; Moehring 2020b; SCCM [Rhodes 2017]; Wingard 2020).

Nocardiosis, severe (off-label use):

Note: Due to concerns for resistance, susceptibility testing should be performed on isolates (CDC 2016).

IV: 500 mg every 6 hours as part of an appropriate combination regimen (Spelman 2020). 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]) (Ott 2019; Spelman 2020; Wilson 2012).

Peritonitis, treatment (patients receiving peritoneal dialysis) (alternative agent for pathogens resistant to other agents) (off-label use):

Note: Intraperitoneal administration is preferred to IV administration unless the patient has sepsis (ISPD [Li 2016]). Consider a 25% dose increase (for intermittent or continuous dosing) in patients with significant residual renal function (urine output >100 mL/day) (ISPD [Li 2010]; ISPD [Li 2016]; Mancini 2018; Szeto 2018).

Intermittent (every other exchange): Intraperitoneal: 500 mg added to the dialysate solution with every other exchange; allow to dwell ≥6 hours (Anwar 1995; ISPD [Li 2016]; Szeto 2018).

Continuous (with every exchange) (dose is per liter of dialysate): Intraperitoneal: Loading dose: 250 mg/L with first exchange of dialysate; maintenance dose: 50 mg/L with each subsequent exchange of dialysate (ISPD [Li 2016]; Lui 1994).

Duration of therapy: ≥3 weeks for patients with adequate clinical response (Burkart 2020; ISPD [Li 2016]).

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 (ATS/IDSA [Metlay 2019]; Ramirez 2020).

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, P. aeruginosa, Acinetobacter spp.) (Corcione 2019; IDSA/ATS [Kalil 2016]):

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 (IDSA/ATS [Kalil 2016]). Note: Some experts prefer extended infusion for critical illness or when treating a susceptible organism with an elevated minimum inhibitory concentration (Ibrahim 2017; Klompas 2021; Moehring 2020b; SCCM [Rhodes 2017]).

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) (Jaruratanasirikul 2015; Moehring 2020a; Schmidt 2020). Initiate therapy as soon as possible once there is recognition of sepsis or septic shock. Usual duration of treatment is dependent on underlying source but is typically 7 to 10 days or longer depending upon clinical response. Discontinue if a noninfectious etiology is identified (SCCM [Rhodes 2017]; Schmidt 2020). Note: Some experts prefer the extended infusion method (Moehring 2020b; SCCM [Rhodes 2017]).

Skin and soft tissue infection:

Note: Reserve for patients with or at risk for pathogens resistant to other agents, including P. aeruginosa (Corcione 2019; Pakyz 2009).

Necrotizing infection (off-label use): IV: 1 g every 6 to 8 hours as part of an appropriate combination regimen. Continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for ≥48 hours (IDSA [Stevens 2014]; Kanj 2021).

Non-necrotizing infection (moderate to severe infection, select surgical site infections [intestinal, GU tract]): IV: 500 mg every 6 hours. Usual duration is 10 to 14 days based on clinical response (IDSA [Stevens 2014]; Kanj 2021; Nichols 1995).

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 (Hooton 2021; IDSA [Tamma 2020]).

IV: 500 mg every 6 hours. Switch to an appropriate oral regimen once symptoms improve if culture and susceptibility results allow. Total duration of therapy ranges from 5 to 14 days and depends on clinical response and the antimicrobial chosen to complete the regimen (Hooton 2021; Sims 2017).

Dosing: Renal Impairment: Adult

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.

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 (Bilbao-Meseguer 2018; Udy 2010).

IV: 1 g every 6 hours (expert opinion)

Hemodialysis, intermittent (thrice weekly): Dialyzable (55% imipenem, 63% cilastatin [Konishi 1991]):

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 (Alarabi 1990; Heintz 2009).

Peritoneal dialysis: IV: 250 to 500 mg every 12 hours (Chan 1991; Somani 1988; expert opinion).

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 (Heintz 2009; Trotman 2005; expert opinion).

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 (expert opinion).

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% (Lewis 2016); however, risk of neurotoxicity (eg, seizures) is significantly higher. Therefore, use of an alternative antimicrobial agent may be preferred.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Pediatric

(For additional information see "Imipenem and cilastatin: Pediatric drug information")

Note: Dosage recommendations are based on imipenem component.

General dosing, susceptible infection; severe infections (Red Book [AAP 2018]): Infants, Children, and Adolescents: IV: 60 to 100 mg/kg/day divided every 6 hours; maximum daily dose: 4,000 mg/day

Burkholderia pseudomallei (melioidosis): Infants, Children, and Adolescents: IV: Initial: 60 to 100 mg/kg/day divided every 6 to 8 hours for at least 10 days; maximum daily dose: 4,000 mg/day; continue parenteral therapy until clinical improvement, then switch to oral therapy if tolerated and/or appropriate (Currie 2003; White 2003)

Febrile neutropenia, empiric therapy: Limited data available: Children and Adolescents: IV: 60 mg/kg/day divided every 6 hours (Caselli 2012; Erbey 2009; Riikonen 1991); some centers use doses as high as 100 mg/kg/day; maximum daily dose: 4,000 mg/day

Intra-abdominal infection, complicated: Infants, Children, and Adolescents: IV: 60 to 100 mg/kg/day divided every 6 hours; maximum dose: 500 mg (Solomkin 2010)

Non-tuberculosis mycobacterium, cystic fibrosis: Infants, Children, and Adolescents: IV: 15 to 20 mg/kg/dose every 12 hours; maximum dose: 1,000 mg/dose (USCFF/ECFS [Floto 2016])

Peritonitis (peritoneal dialysis): Infants, Children, and Adolescents: Intraperitoneal: Continuous: Loading dose: 250 mg per liter of dialysate; maintenance dose: 50 mg per liter (ISPD [Warady 2012])

Pulmonary exacerbation, cystic fibrosis: Infants, Children, and Adolescents: IV: 100 mg/kg/day divided every 6 hours; maximum daily dose: 4,000 mg/day; efficacy may be limited due to rapid development of resistance (Döring 2000; Zobell 2012)

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Renal Impairment: Pediatric

Infants, Children, and Adolescents: IV:

Manufacturer's labeling: Patient weight <30 kg and impaired renal function (not defined): Use not recommended

The following adjustments have been recommended (Aronoff 2007): Note: Renally adjusted dose recommendations are based on doses of 60 to 100 mg/kg/day divided every 6 hours.

GFR 30 to 50 mL/minute/1.73 m2: Administer 7 to 13 mg/kg/dose every 8 hours

GFR 10 to 29 mL/minute/1.73 m2: Administer 7.5 to 12.5 mg/kg/dose every 12 hours

GFR <10 mL/minute/1.73 m2: Administer 7.5 to 12.5 mg/kg/dose every 24 hours

Intermittent hemodialysis (IHD): Dialysis: Moderately dialyzable (20% to 50%): 7.5 to 12.5 mg/kg/dose every 24 hours (administer after hemodialysis on dialysis days)

Peritoneal dialysis (PD): 7.5 to 12.5 mg/kg/dose every 24 hours

Continuous renal replacement therapy (CRRT): 7 to 13 mg/kg/dose every 8 hours

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Geriatric

Refer to adult dosing.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, powder for reconstitution:

Primaxin I.V.: imipenem 250 mg and cilastatin 250 mg [sodium] [DSC]; imipenem 500 mg and cilastatin 500 mg [sodium]

Injection, powder for reconstitution (preservative free):

Generic: imipenem 250 mg and cilastatin 250 mg; imipenem 500 mg and cilastatin 500 mg

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

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

Administration: Adult

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 (Ibrahim 2017; Lipš 2014). Note: Must consider imipenem/cilastatin limited room temperature stability if using extended infusions.

Administration: Pediatric

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.

Use: Labeled Indications

Bloodstream infection (gram-negative bacteremia): Treatment of bloodstream infection caused by Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing), Escherichia coli, Klebsiella species, Pseudomonas aeruginosa, Serratia species, Enterobacter species, and Bacteroides species (including Bacteroides fragilis).

Bone and joint infections: Treatment of bone and joint infections caused by E. faecalis, S. aureus (penicillinase-producing), Staphylococcus epidermidis, Enterobacter species, and P. aeruginosa.

Gynecologic infections: Treatment of gynecologic infections caused by E. faecalis, S. aureus (penicillinase-producing), S. epidermidis, Streptococcus agalactiae (group B streptococci), E. coli, Klebsiella species, Proteus species, Enterobacter species, Bifidobacterium species, Bacteroides species (including B. fragilis), Gardnerella vaginalis, Peptococcus species, Peptostreptococcus species, and Cutibacterium species.

Intra-abdominal infection, health care-associated or high-risk community-acquired infection: Treatment of intra-abdominal infections caused by E. faecalis, S. aureus (penicillinase-producing), S. epidermidis, E. coli, Klebsiella species, Enterobacter species, Proteus species, Morganella morganii, P. aeruginosa, Citrobacter species, Clostridium species, Bacteroides species (including B. fragilis), Fusobacterium species, Peptococcus species, Peptostreptococcus species, Eubacterium species, Cutibacterium species, and Bifidobacterium species.

Pneumonia: Treatment of pneumonia caused by S. aureus (penicillinase-producing), E. coli, Klebsiella species, Enterobacter species, Haemophilus influenzae, Haemophilus parainfluenzae, Acinetobacter species, and Serratia marcescens.

Skin and soft tissue infection: Treatment of skin and soft tissue infections caused by E. faecalis, S. aureus (penicillinase-producing), S. epidermidis, E. coli, Klebsiella species, Enterobacter species, Proteus vulgaris, Providencia rettgeri, M. morganii, P. aeruginosa, Serratia species, Citrobacter species, Acinetobacter species, Bacteroides species (including B. fragilis), Fusobacterium species, Peptococcus species, and Peptostreptococcus species.

Urinary tract infection (complicated and uncomplicated): Treatment of uncomplicated and complicated urinary tract infections caused by E. faecalis, S. aureus (penicillinase-producing), E. coli, Klebsiella species, Enterobacter species, P. vulgaris, P. rettgeri, M. morganii, and P. aeruginosa.

Use: Off-Label: Adult

Cystic fibrosis, acute pulmonary exacerbation; Diabetic foot infection, moderate to severe; Melioidosis (Burkholderia pseudomallei infection); Mycobacterial (nontuberculous, rapidly growing) infection; Neutropenic enterocolitis (typhlitis); Neutropenic fever, high-risk patients with cancer (empiric therapy); Nocardiosis, severe; Peritonitis, treatment (patients undergoing peritoneal dialysis); Sepsis/septic shock (broad-spectrum empiric therapy, including P. aeruginosa); Skin and soft tissue necrotizing infection

Medication Safety Issues
Sound-alike/look-alike issues:

Imipenem may be confused with ertapenem, meropenem, doripenem

Primaxin may be confused with Premarin, Primacor

Adverse Reactions

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

Contraindications

Hypersensitivity to imipenem/cilastatin or any component of the formulation

Documentation of allergenic cross-reactivity for carbapenems, penicillins, and cephalosporins is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Warnings/Precautions

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. Not recommended in pediatric patients <30 kg with impaired renal function (no data available).

Metabolism/Transport Effects

None known.

Drug Interactions

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): May enhance the neurotoxic effect of Imipenem. Imipenem may decrease the serum concentration of CycloSPORINE (Systemic). Imipenem may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy

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

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. 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

Pregnancy Considerations

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).

Breast-Feeding Considerations

Imipenem is present in breast milk (Ito 1988; Chung 2002).

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Imipenem is not one of the preferred antibiotics used for the management of cystic fibrosis in lactating females; however, when a safer alternative is not available, imipenem is the preferred carbapenem antibiotic. Due to poor oral bioavailability, exposure to a breastfed infant is expected to be limited (Panchaud 2016).

Dietary Considerations

Some products may contain sodium.

Monitoring Parameters

Periodic renal, hepatic, and hematologic function tests; monitor for signs of anaphylaxis during first dose

Mechanism of Action

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.

Pharmacodynamics and Pharmacokinetics

Distribution:

Lung: Epithelial lining fluid:plasma ratio: 44%, varies with time (van Hasselt 2016).

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: Both drugs: Prolonged with renal impairment:

Neonates: Imipenem: 1.7 to 2.4 hours; Cilastatin: 3.9 to 6.3 hours (Freij 1985).

Infants and children: Imipenem: 1.2 hours (Blumer 1996).

Adults: ~60 minutes.

Excretion: Both drugs: Urine (~70% as unchanged drug).

Pharmacodynamics and Pharmacokinetics: Additional Considerations

Anti-infective considerations:

Parameters associated with efficacy:

Time dependent, associated with time free drug concentration (fT) > minimum inhibitory concentration (MIC).

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).

Pricing: US

Solution (reconstituted) (Imipenem-Cilastatin Intravenous)

250 mg (per each): $7.80 - $16.43

500 mg (per each): $15.00 - $32.86

Solution (reconstituted) (Primaxin IV Intravenous)

500-500 mg (per each): $39.18

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Amanam (LB);
  • Anipen (PH);
  • Arzobema (MX);
  • Bacquire (ZW);
  • Bacqure (TH);
  • Bidinam (VN);
  • Bionam (TH);
  • Cilanem (BH, JO, LB);
  • Cilapenem (KR);
  • Cispenam (BD);
  • Imcitin (TH);
  • Imenam (TW);
  • Imicila Alvogen (TH);
  • Imiclast (ID);
  • Iminem (BD);
  • Iminen (MX);
  • Imipen (PH);
  • Imivex (PH);
  • Inem (BD, CL, PY);
  • Junte (CN);
  • Minem (TH);
  • Nemcis (VN);
  • Nimedine (MT);
  • Pelascap (ID);
  • Pelastin IV (ID);
  • Penam (PH);
  • Plastin (PH);
  • Premax (JO);
  • Prepenem (HK, KR, TH);
  • Primax (BD);
  • Primaxin (AU, GB, GR, MT, NZ);
  • Primaxin IV (BB, BM, BS, BZ, GY, JM, SR, TT);
  • Sianem (TH);
  • Supernem (TW);
  • Supranem (EG);
  • Talispenem (VN);
  • Tenacid (IT);
  • Tienam (AE, BD, BE, BG, BR, CH, CL, CN, CO, CY, CZ, EC, EE, EG, ET, FI, FR, HK, ID, IE, IL, IN, IT, JO, JP, KW, LB, LT, LU, LV, MX, MY, NL, NO, PE, PH, PK, PL, PT, RO, RU, SA, SE, SG, SK, TH, TR, TW, UA, VN);
  • Tiesilan (CO, EC);
  • Timipen (ID);
  • Tipem (KR);
  • Vexpinem (PH);
  • Zienam (AR, AT, DE, PY, UY, VE)


For country abbreviations used in Lexicomp (show table)

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