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Imipenem and Cilastatin


General


Pronunciation

(i mi PEN em & sye la STAT in)


Brand Names: U.S.

  • Primaxin I.V.

Indications


Use: Labeled Indications

Treatment of lower respiratory tract, urinary tract, intra-abdominal, gynecologic, bone and joint, skin and skin structure, endocarditis (caused by Staphylococcus aureus) and polymicrobic infections as well as bacterial septicemia. Antibacterial activity includes gram-positive bacteria (methicillin-sensitive S. aureus and Streptococcus spp), resistant gram-negative bacilli (including extended spectrum beta-lactamase-producing Escherichia coli and Klebsiella spp, Enterobacter spp, and Pseudomonas aeruginosa), and anaerobes.


Contraindications


Hypersensitivity to imipenem/cilastatin or any component of the formulation


Dosing and Administration


Dosing: Adult

Doses based on imipenem content.

Usual dosage range: Weight ≥70 kg: 250-1000 mg every 6-8 hours; maximum: 4 g/day. Note: For adults weighing <70 kg, refer to Dosing Adjustment in Renal Impairment.

Indication-specific dosing:

Burkholderia pseudomallei(melioidosis) (off-label use): IV: Initial: 20 mg/kg every 8 hours for at least 10 days (White 2003) or 25 mg/kg (up to 1 g) every 6 hours for at least 10 days (Currie 2003); continue parenteral therapy until clinical improvement then switch to oral therapy if tolerated and/or appropriate.

Intra-abdominal infections: IV:

Mild infection: 250-500 mg every 6 hours

Severe infection: 500 mg every 6 hours or 1 g every 8 hours for 4-7 days (provided source controlled). Note: Not recommended for mild-to-moderate, community-acquired intra-abdominal infections due to risk of toxicity and the development of resistant organisms (Solomkin 2010)

Liver abscess (off-label use): IV: 500 mg every 6 hours for 4-6 weeks (Ulug 2010)

Moderate infections: IV:

Fully-susceptible organisms: 500 mg every 6-8 hours

Moderately-susceptible organisms: 500 mg every 6 hours or 1 g every 8 hours

Neutropenic fever (off-label use): IV: 500 mg every 6 hours (Paul 2006)

Pseudomonas infections: IV: 500 mg every 6 hours; Note: Higher doses may be required based on organism sensitivity.

Severe infections: IV:

Fully-susceptible organisms: 500 mg every 6 hours

Moderately-susceptible organisms: 1 g every 6-8 hours

Maximum daily dose should not exceed 50 mg/kg or 4 g/day, whichever is lower

Skin and soft tissue necrotizing infections (off-label use): I.V.: 1 g every 6 to 8 hours in combination with an agent effective against MRSA (eg, vancomycin, linezolid, daptomycin) for empiric therapy of polymicrobial [mixed] infections. Continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for 48 to 72 hours (IDSA [Stevens 2014]).

Surgical site infection (intestinal or genitourinary tract surgery) (off-label use): IV: 500 mg every 6 hours (IDSA [Stevens 2014]).

Urinary tract infection, uncomplicated: IV: 250 mg every 6 hours

Urinary tract infection, complicated: IV: 500 mg every 6 hours

Mild infections:Note: Rarely a suitable option in mild infections; normally reserved for moderate-severe cases: IV:

Fully-susceptible organisms: 250 mg every 6 hours

Moderately-susceptible organisms: 500 mg every 6 hours


Dosing: Geriatric

Refer to adult dosing.


Dosing: Pediatric

Dosage based on imipenem content:

Non-CNS infections: IV: Children: >3 months: 15-25 mg/kg every 6 hours

Maximum dosage: Susceptible infections: 2 g/day; moderately-susceptible organisms: 4 g/day

Burkholderia pseudomallei (melioidosis) (off-label use): IV: Initial: 20 mg/kg every 8 hours for at least 10 days (White 2003) or 25 mg/kg (up to 1 g) every 6 hours for at least 10 days (Currie 2003); continue parenteral therapy until clinical improvement, then switch to oral therapy if tolerated and/or appropriate

Cystic fibrosis: IV: Infants, Children, and Adolescents: Up to 100 mg/kg/day divided every 6 hours; maximum dose: 4 g daily has been used. Note: Efficacy in exacerbations may be limited due to rapid development of resistance (Zobell 2013).


Dosing: Renal Impairment

IV:

Patients with a CrCl ≤5 mL/minute/1.73 m2 should not receive imipenem/cilastatin unless hemodialysis is instituted within 48 hours.

Patients weighing <30 kg with impaired renal function should not receive imipenem/cilastatin.

Reduced IV dosage regimen based on creatinine clearance and/or body weight: See table.

Intermittent hemodialysis (IHD) (administer after hemodialysis on dialysis days): Use the dosing recommendation for patients with a CrCl 6-20 mL/minute; administer dose after dialysis session and every 12 hours thereafter or 250-500 mg every 12 hours (Heintz 2009). Note: Dosing dependent on the assumption of 3 times/week, complete IHD sessions.

Peritoneal dialysis (off-label dosing): Dose as for CrCl 6-20 mL/minute (Somani 1988)

Continuous renal replacement therapy (CRRT) (Heintz 2009; Trotman 2005): Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug concentrations in relation to target trough (if appropriate). The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1-2 L/hour and minimal residual renal function) and should not supersede clinical judgment:

CVVH: Loading dose of 1 g followed by either 250 mg every 6 hours or 500 mg every 8 hours

CVVHD: Loading dose of 1 g followed by either 250 mg every 6 hours or 500 mg every 6-8 hours

CVVHDF: Loading dose of 1 g followed by either 250 mg every 6 hours or 500 mg every 6 hours

Note: Data suggest that 500 mg every 8-12 hours may provide sufficient time above MIC to cover organisms with MIC values ≤2 mg/L; however, a higher dose of 500 mg every 6 hours is recommended for resistant organisms (particularly Pseudomonas spp) with MIC ≥4 mg/L or deep-seated infections (Fish 2005).

Reduced IV dosage regimen based on creatinine clearance and/or body weight:

U.S. labeling: See table.

Imipenem and Cilastatin Dosage in Renal Impairment

Reduced IV Dosage Regimen Based on

Creatinine Clearance (mL/minute/1.73 m2) and/or Body Weight <70 kg

Body Weight (kg)

≥70

60

50

40

30

Total daily dose for normal renal function: 1 g/day

CrCl ≥71

250 mg q6h

250 mg q8h

125 mg q6h

125 mg q6h

125 mg q8h

CrCl 41-70

250 mg q8h

125 mg q6h

125 mg q6h

125 mg q8h

125 mg q8h

CrCl 21-40

250 mg q12h

250 mg q12h

125 mg q8h

125 mg q12h

125 mg q12h

CrCl 6-20

250 mg q12h

125 mg q12h

125 mg q12h

125 mg q12h

125 mg q12h

Total daily dose for normal renal function: 1.5 g/day

CrCl ≥71

500 mg q8h

250 mg q6h

250 mg q6h

250 mg q8h

125 mg q6h

CrCl 41-70

250 mg q6h

250 mg q8h

250 mg q8h

125 mg q6h

125 mg q8h

CrCl 21-40

250 mg q8h

250 mg q8h

250 mg q12h

125 mg q8h

125 mg q8h

CrCl 6-20

250 mg q12h

250 mg q12h

250 mg q12h

125 mg q12h

125 mg q12h

Total daily dose for normal renal function: 2 g/day

CrCl ≥71

500 mg q6h

500 mg q8h

250 mg q6h

250 mg q6h

250 mg q8h

CrCl 41-70

500 mg q8h

250 mg q6h

250 mg q6h

250 mg q8h

125 mg q6h

CrCl 21-40

250 mg q6h

250 mg q8h

250 mg q8h

250 mg q12h

125 mg q8h

CrCl 6-20

250 mg q12h

250 mg q12h

250 mg q12h

250 mg q12h

125 mg q12h

Total daily dose for normal renal function: 3 g/day

CrCl ≥71

1000 mg q8h

750 mg q8h

500 mg q6h

500 mg q8h

250 mg q6h

CrCl 41-70

500 mg q6h

500 mg q8h

500 mg q8h

250 mg q6h

250 mg q8h

CrCl 21-40

500 mg q8h

500 mg q8h

250 mg q6h

250 mg q8h

250 mg q8h

CrCl 6-20

500 mg q12h

500 mg q12h

250 mg q12h

250 mg q12h

250 mg q12h

Total daily dose for normal renal function: 4 g/day

CrCl ≥71

1000 mg q6h

1000 mg q8h

750 mg q8h

500 mg q6h

500 mg q8h

CrCl 41-70

750 mg q8h

750 mg q8h

500 mg q6h

500 mg q8h

250 mg q6h

CrCl 21-40

500 mg q6h

500 mg q8h

500 mg q8h

250 mg q6h

250 mg q8h

CrCl 6-20

500 mg q12h

500 mg q12h

500 mg q12h

250 mg q12h

250 mg q12h

Table has been converted to the following text.

Imipenem and Cilastatin Dosage in Renal Impairment and/or Body Weight <70 kg

Dosage in renal impairment is determined by daily dose required to treat the infection (see adult dosing), creatinine clearance (mL/minute/1.73 m2), and body weight according to the following guidelines (based on imipenem component).

Daily dosage 1 g/day:

- CrCl ≥71 mL/minute:

" “ ≥70 kg: 250 mg every 6 hours

" “ 60 kg: 250 mg every 8 hours

" “ 40-50 kg: 125 mg every 6 hours

" “ 30 kg: 125 mg every 8 hours

- CrCl 41-70 mL/minute:

" “ ≥70 kg: 250 mg every 8 hours

" “ 50-60 kg: 125 mg every 6 hours

" “ 30-40 kg: 125 mg every 8 hours

- CrCl 21-40 mL/minute:

" “ ≥60 kg: 250 mg every 12 hours

" “ 50 kg: 125 mg every 8 hours

" “ 30-40 kg: 125 mg every 12 hours

- CrCl 6-20 mL/minute:

" “ ≥70 kg: 250 mg every 12 hours

" “ 30-60 kg: 125 mg every 12 hours

Daily dosage 1.5 g/day:

- CrCl ≥71 mL/minute:

" “ ≥70 kg: 500 mg every 8 hours

" “ 60 kg: 250 mg every 6 hours

" “ 50 kg: 250 mg every 6 hours

" “ 40 kg: 250 mg every 8 hours

" “ 30 kg: 125 mg every 6 hours

- CrCl 41-70 mL/minute:

" “ ≥70 kg: 250 mg every 6 hours

" “ 50-60 kg: 250 mg every 8 hours

" “ 40 kg: 125 mg every 6 hours

" “ 30 kg: 125 mg every 8 hours

- CrCl 21-40 mL/minute:

" “ ≥60 kg: 250 mg every 8 hours

" “ 50 kg: 250 mg every 12 hours

" “ 30-40 kg: 125 mg every 8 hours

- CrCl 6-20 mL/minute:

" “ ≥50 kg: 250 mg every 12 hours

" “ 30-40 kg: 125 mg every 12 hours

Daily dosage 2 g/day:

- CrCl ≥71 mL/minute:

" “ ≥70 kg: 500 mg every 6 hours

" “ 60 kg: 500 mg every 8 hours

" “ 40-50 kg: 250 mg every 6 hours

" “ 30 kg: 250 mg every 8 hours

- CrCl 41-70 mL/minute:

" “ ≥70 kg: 500 mg every 8 hours

" “ 50-60 kg: 250 mg every 6 hours

" “ 40 kg: 250 mg every 8 hours

" “ 30 kg: 125 mg every 6 hours

- CrCl 21-40 mL/minute:

" “ ≥70 kg: 250 mg every 6 hours

" “ 50-60 kg: 250 mg every 8 hours

" “ 40 kg: 250 mg every 12 hours

" “ 30 kg: 125 mg every 8 hours

- CrCl 6-20 mL/minute:

" “ ≥40 kg: 250 mg every 12 hours

" “ 30 kg: 125 mg every 12 hours

Daily dosage 3 g/day:

- CrCl ≥71 mL/minute:

" “ ≥70 kg: 1 g every 8 hours

" “ 60 kg: 750 mg every 8 hours

" “ 50 kg: 500 mg every 6 hours

" “ 40 kg: 500 mg every 8 hours

" “ 30 kg: 250 mg every 6 hours

- CrCl 41-70 mL/minute:

" “ ≥70 kg: 500 mg every 6 hours

" “ 50-60 kg: 500 mg every 8 hours

" “ 40 kg: 250 mg every 6 hours

" “ 30 kg: 250 mg every 8 hours

- CrCl 21-40 mL/minute:

" “ ≥60 kg: 500 mg every 8 hours

" “ 50 kg: 250 mg every 6 hours

" “ 30-40 kg: 250 mg every 8 hours

- CrCl 6-20 mL/minute:

" “ ≥60 kg: 500 mg every 12 hours

" “ 30-50 kg: 250 mg every 12 hours

Daily dosage 4 g/day:

- CrCl ≥71 mL/minute:

" “ ≥70 kg: 1 g every 6 hours

" “ 60 kg: 1 g every 8 hours

" “ 50 kg: 750 mg every 8 hours

" “ 40 kg: 500 mg every 6 hours

" “ 30 kg: 500 mg every 8 hours

- CrCl 41-70 mL/minute:

" “ ≥60 kg: 750 mg every 8 hours

" “ 50 kg: 500 mg every 6 hours

" “ 40 kg: 500 mg every 8 hours

" “ 30 kg: 250 mg every 6 hours

- CrCl 21-40 mL/minute:

" “ ≥70 kg: 500 mg every 6 hours

" “ 50-60 kg: 500 mg every 8 hours

" “ 40 kg: 250 mg every 6 hours

" “ 30 kg: 250 mg every 8 hours

- CrCl 6-20 mL/minute:

" “ ≥40 kg: 500 mg every 12 hours

" “ 30-40 kg: 250 mg every 12 hours

Canadian labeling: Reduced IV dosage regimen based on creatinine clearance (mL/minute/1.73 m2) and body weight ≥70 kg (Note: The manufacturer labeling recommends further proportionate dose reductions for patients <70 kg, but does not provide specific dosing recommendations):

Mild renal impairment (CrCl 31-70 mL/minute/1.73 m2):

Fully-susceptible organisms: Maximum dosage: 500 mg every 8 hours

Less susceptible organisms (primarily some Pseudomonas strains): Maximum dosage: 500 mg every 6 hours

Moderate renal impairment (CrCl 21-30 mL/minute/1.73 m2):

Fully-susceptible organisms: Maximum dosage: 500 mg every 12 hours

Less susceptible organisms (primarily some Pseudomonas strains): Maximum dosage: 500 mg every 8 hours

Severe renal impairment (CrCl 0-20 mL/minute/1.73 m2):

Fully-susceptible organisms: Maximum dosage: 250 mg every 12 hours

Less susceptible organisms (primarily some Pseudomonas strains): Maximum dosage: 500 mg every 12 hours

Note: Patients with CrCl 6-20 mL/minute/1.73 m2 should receive 250 mg every 12 hours or 3.5 mg/kg (whichever is lower) every 12 hours for most pathogens; seizure risk may increase with higher dosing.


Dosing: Hepatic Impairment

Hepatic dysfunction may further impair cilastatin clearance in patients receiving chronic renal replacement therapy; consider decreasing the dosing frequency.


Reconstitution

IV: Prior to use, dilute dose into 100-250 mL of an appropriate solution. Imipenem is inactivated at acidic or alkaline pH. Final concentration should not exceed 5 mg/mL.


Administration

IV: Do not administer IV push. Infuse doses ≤500 mg over 20-30 minutes; infuse doses ≥750 mg over 40-60 minutes.


Dietary Considerations

Some products may contain sodium.


Storage

Imipenem/cilastatin powder for injection should be stored at <25 ‚ °C (77 ‚ °F).

IV: Reconstituted IV solutions are stable for 4 hours at room temperature and 24 hours when refrigerated. Do not freeze.


Dosage Forms/Strengths


Dosage Forms

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

Injection, powder for reconstitution: Imipenem 250 mg and cilastatin 250 mg; imipenem 500 mg and cilastatin 500 mg

Primaxin ‚ ® I.V.: Imipenem 250 mg and cilastatin 250 mg [contains sodium 18.8 mg (0.8 mEq)]; imipenem 500 mg and cilastatin 500 mg [contains sodium 37.5 mg (1.6 mEq)]


Compatibility

Variable stability (consult detailed reference) in D5W, D5LR, D51/4NS, D51/2NS, D5NS, D10W, mannitol 2.5%, mannitol 5%, mannitol 10%, NS, TPN.

Y-site administration: Incompatible with allopurinol, amiodarone, amphotericin B cholesteryl sulfate complex, azithromycin, drotrecogin alfa, etoposide phosphate, fluconazole, gemcitabine, lorazepam, meperidine, midazolam, milrinone, sargramostim, sodium bicarbonate.


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. 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: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. 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


Monitoring Parameters

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


Lab Test Interferences


Test Interactions

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


Adverse Reactions


>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% (Limited to important or life-threatening): Acute renal failure, agranulocytosis, back pain (thoracic spinal), basophilia, bilirubinuria, bone marrow depression, brain disease, candidiasis, casts in urine, change in prothrombin time, Clostridium difficile associated diarrhea, confusion, cyanosis, decreased serum sodium, dental discoloration, drug fever, dyskinesia, erythema multiforme, hallucination, hearing loss, heartburn, hematuria, hemolytic anemia, hemorrhagic colitis, hepatic failure, hepatitis (including fulminant onset), hyperchloremia, hypersensitivity, hyperventilation, hypotension, increased blood urea nitrogen, increased lactate dehydrogenase, increased serum potassium, increased urinary urobilinogen, injection site infection, jaundice, leukocytosis, leukocyturia, leukopenia, lymphocytosis, myoclonus, neutropenia, pancytopenia, positive direct Coombs test, pseudomembranous colitis, pseudomonas infection (resistant P. aeruginosa), psychiatric disturbances, Stevens-Johnson syndrome, thrombocytopenia, toxic epidermal necrolysis


Warnings/Precautions


Special Populations: Elderly

Pharmacokinetics are consistent with those expected in subjects with slight renal impairment for which no dosage alteration is considered necessary.


Warnings/Precautions

Concerns related to adverse effects:

- Anaphylaxis/hypersensitivity reactions: Serious hypersensitivity reactions, including anaphylaxis, have been reported (some without a history of previous allergic reactions to beta-lactams).

- 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.

- 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 and thrombocytopenia have been reported in patients with significant renal dysfunction.

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:

- Elderly: Lower doses (based upon renal function) are often required in the elderly.

- Pediatric: Not recommended in pediatric CNS infections due to seizure potential.


Pregnancy Risk Factor

C


Pregnancy Considerations

Teratogenic events have not been observed in animal reproduction studies. Due to pregnancy induced physiologic changes, some pharmacokinetic parameters of imipenem/cilastatin may be altered. Pregnant women have a larger volume of distribution resulting in lower serum peak levels than for the same dose in nonpregnant women. Clearance is also increased.


Actions


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.


Distribution

Rapidly and widely to most tissues and fluids including sputum, pleural fluid, peritoneal fluid, interstitial fluid, bile, aqueous humor, and bone; highest concentrations in pleural fluid, interstitial fluid, peritoneal fluid; low concentrations in CSF


Metabolism

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


Excretion

Both drugs: Urine (~70% as unchanged drug; 70% to 80% of a cilastatin dose is excreted unchanged)


Half-Life Elimination

IV: Both drugs:Prolonged with renal impairment:

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

Infants and Children: Imipenem: 1.2 hours (Blumer 1996)

Adults: 60 minutes


Protein Binding

Imipenem: 20%; cilastatin: 40%


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience nausea, vomiting, or diarrhea. Have patient report immediately to prescriber severe dizziness, passing out, seizures, confusion, chills, pharyngitis, bruising, bleeding, severe loss of strength and energy, mood changes, urinary retention, change in amount of urine passed, signs of Clostridium difficile (C. diff)-associated diarrhea (stomach pain or cramps, very loose or watery stools, or bloody stools), or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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