Skip to main content

Imipenem and Cilastatin

Medically reviewed by Drugs.com. Last updated on Aug 17, 2020.

Pronunciation

(i mi PEN em & sye la STAT in)

Index Terms

  • Cilastatin and Imipenem
  • Imipemide
  • Imipenem/Cilastatin
  • Primaxin I.M. [DSC]

Dosage Forms

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

Brand Names: U.S.

  • Primaxin I.V.

Pharmacologic Category

  • Antibiotic, Carbapenem

Pharmacology

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.

Metabolism

Imipenem is metabolized in the kidney by dehydropeptidase I; cilastatin prevents imipenem metabolism by this enzyme

Excretion

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

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

Protein Binding

Imipenem: ~20%; cilastatin: ~40%

Use: Labeled Indications

Blood stream infection (gram-negative bacteremia): Treatment of blood stream 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.

Off Label Uses

Cystic fibrosis, acute pulmonary exacerbation

Clinical experience suggests the utility of imipenem/cilastatin in the treatment of acute pulmonary exacerbation of cystic fibrosis [Chmiel 2014], [Simon 2020].

Diabetic foot infection, moderate to severe

Data from a double-blind, randomized study support the use of imipenem/cilastatin in the treatment of diabetic foot infection [Grayson 1994].

Based on the Infectious Diseases Society of America (IDSA) clinical practice guidelines for the diagnosis and treatment of diabetic foot infections, imipenem/cilastatin is effective and recommended in the management of moderate to severe diabetic foot infection, especially infections caused by resistant organisms [IDSA [Lipsky 2012]].

Melioidosis (Burkholderia pseudomallei infection)

Data from a randomized, open-label study support the use of imipenem/cilastatin in the treatment of severe melioidosis [Simpson 1999].

Mycobacterial (nontuberculous, rapidly growing) infection

Based on American Thoracic Society, European Respiratory Society, European Society of Clinical Microbiology and Infectious Diseases, and IDSA guidelines for the treatment of nontuberculous mycobacterial pulmonary disease, imipenem/cilastatin, as part of a multidrug regimen, is effective and recommended for the treatment of nontuberculous mycobacterial disease attributed to rapidly growing mycobacteria [Daley 2020].

Neutropenic enterocolitis (typhlitis)

Clinical experience suggests the utility of imipenem/cilastatin in the treatment of neutropenic enterocolitis [Wong Kee Song 2020].

Neutropenic fever, high-risk patients with cancer (empiric therapy)

In a meta-analysis of 12 randomized controlled trials, imipenem/cilastatin monotherapy was shown to be effective for treatment of neutropenic fever [Paul 2006].

Based on the IDSA guidelines for the use of antimicrobial agents in neutropenic patients with cancer, an antipseudomonal beta-lactam antibiotic such as imipenem/cilastatin is effective and recommended for initial empiric treatment of high-risk patients who require hospitalization [Freifeld 2011].

Nocardiosis, severe

Data from a limited number of patients studied retrospectively suggest that imipenem/cilastatin maybe be beneficial in the treatment of pulmonary nocardiosis [Ott 2019]. Clinical experience also suggests the utility of imipenem/cilastatin in the management of nocardiosis [Spelman 2020], [Wilson 2012].

Peritonitis, treatment (patients undergoing peritoneal dialysis)

Based on the International Society for Peritoneal Dialysis peritonitis recommendations, imipenem/cilastatin is an effective and recommended agent in the management of peritonitis in patients undergoing peritoneal dialysis [Li 2016].

Sepsis/septic shock (broad-spectrum empiric therapy, including P. aeruginosa)

Clinical experience suggests the utility of imipenem/cilastatin in the treatment of sepsis and septic shock [Moehring 2020a], [Schmidt 2020].

Skin and soft tissue necrotizing infection

Based on the IDSA guidelines for the diagnosis and management of skin and soft tissue infections, imipenem/cilastatin, in combination with an agent effective against methicillin-resistant S. aureus, is an effective and recommended empiric treatment for polymicrobial necrotizing infections of the skin, fascia, and muscle [Stevens 2014].

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.

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 2020; 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 2020).

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 oral step-down therapy) is 4 to 7 days following adequate source control (Gomi 2018; SIS [Mazuski 2017]; SIS/IDSA [Solomkin 2010]); for infections managed without surgical or percutaneous intervention, a longer duration may be necessary (Barshak 2020; Pemberton 2020). 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 2020; 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 2020; 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 2020). 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.

Durationof 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 P. aeruginosa infection. Patients should be clinically stable with normal vital signs prior to discontinuation (ATS/IDSA [Metlay 2019]).

Hospital-acquired or ventilator-associated pneumonia: For empiric therapy 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 as part of an appropriate combination regimen. Duration of therapy varies based on disease severity and response to therapy; treatment is typically given for 7 days, (IDSA/ATS [Kalil 2016]) but a longer course may be required for severe or complicated infection or for P. aeruginosa infection (Kanj 2020c). Note: Some experts prefer the extended infusion method, particularly in those who are critically ill (Ibrahim 2017; Klompas 2020; 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 2020d).

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 2020d; Nichols 1995).

Urinary tract infection, complicated (including pyelonephritis):

Note: Reserve for critically ill patients or for patients with risk factor(s) for MDR pathogens, including ESBL-producing organisms and P. aeruginosa (Hooton 2020).

IV: 500 mg every 6 hours. Switch to an appropriate oral regimen once symptoms improve, if culture and susceptibility results allow. Duration of therapy depends on the antimicrobial chosen to complete the regimen and ranges from 5 to 14 days (Hooton 2020; Sims 2017).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

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.

Reconstitution

Reconstitute vials with approximately 10 mL of NS, D5W, D5NS, D51/2NS, or D51/4NS. Shake well and transfer to 100 mL of an appropriate infusion solution; repeat transfer with an additional 10 mL of infusion solution to ensure complete transfer of vial contents to the infusion solution. Agitate resulting mixture until clear. Solutions range from colorless to yellow.

Administration

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.

Dietary Considerations

Some products may contain sodium.

Storage

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.

Drug Interactions

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). 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. 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). 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. Consider therapy modification

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

Probenecid: May increase the serum concentration of Imipenem. 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. 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. 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. Consider therapy modification

Test Interactions

Interferes with urinary glucose determination using Clinitest®; positive Coombs' [direct]

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 (formerly Clostridium) 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

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).

Monitoring Parameters

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

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).

Patient Education

What is this drug used for?

• It is used to treat bacterial infections.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Nausea

• Vomiting

• Fatigue

• Diarrhea

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Severe dizziness

• Passing out

• Seizures

• Confusion

• Injection site irritation

Clostridioides (formerly Clostridium) difficile-associated diarrhea like abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools.

• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes.

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.