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Imipenem / Cilastatin

Pronunciation

Pronunciation: IM-i-PEN-em SYE-la-STAT-in
Class: Carbapenem antibiotic

Trade Names

Primaxin IV
- Injection, powder for solution imipenem equivalent 250 mg and cilastatin equivalent 250 mg (contains sodium 0.8 mEq)
- Injection, powder for solution imipenem equivalent 500 mg and cilastatin equivalent 500 mg (contains sodium 1.6 mEq)

Pharmacology

Imipenem inhibits bacterial cell wall synthesis. Cilastatin prevents metabolism of imipenem, resulting in increased urinary recovery and decreased renal toxicity.

Slideshow: 10 Things to Know About Antibiotic Resistance

Pharmacokinetics

Absorption

IV infusion over 20 min results in peak plasma levels of imipenem antimicrobial activity of 14 to 24 mcg/mL for the 250 mg dose, 21 to 58 mcg/mL for the 500 mg dose, and 41 to 83 mcg/mL for the 1 g dose. Plasma levels declined to less than 1 mcg/mL in 4 to 6 h.

Distribution

Protein binding is approximately 20% for imipenem and approximately 40% for cilastatin.

Metabolism

Imipenem, when administered alone, is metabolized in the kidneys by dehydropeptidase I, resulting in relatively low levels in urine. Cilastatin, an inhibitor of this enzyme, prevents renal metabolism of imipenem.

Elimination

Plasma half-life of each component is approximately 1 h. Within 10 h of administration, approximately 70% of imipenem and cilastatin is recovered in urine.

Special Populations

Renal Function Impairment

Patients with CrCl of 5 mL/min per 1.73 m 2 or less should not receive imipenem/cilastatin unless hemodialysis is instituted within 48 h.

Elderly

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

Children

IV doses of 25 mg/kg/dose in patients 3 mo to younger than 3 y and 15 mg/kg/dose in patients 3 to 12 y of age were associated with mean trough plasma concentrations of imipenem of approximately 1.1 and 0.6 mcg/mL, respectively, following multiple 60 min infusions; trough urinary concentrations of imipenem were in excess of 10 mcg/mL for both doses.

Indications and Usage

Treatment of serious infections of the lower respiratory tract and urinary tract, intra-abdominal and gynecologic infections, bacterial septicemia, bone and joint infections, skin and skin structure infections, endocarditis, and polymicrobic infections due to susceptible microorganisms.

Contraindications

Hypersensitivity to any component of this product.

Dosage and Administration

Adults

IV Base dosage on severity of infection and susceptibility of the organism. Max dose, 50 mg/kg/day or 4 g/day, whichever is less.

Mild

250 to 500 mg every 6 h.

Moderate

500 mg every 6 or 8 h or 1 g every 8 h.

Severe, life-threatening

500 mg to 1 g every 6 h or 1 g every 8 h.

UTI

250 mg every 6 h (uncomplicated UTI) or 500 mg every 6 h (complicated UTI).

Children 3 mo and older

IV 15 to 25 mg/kg every 6 hours for non-CNS infections. Max dose, 2 g/day for fully susceptible organisms, 4 g/day for infections with moderately susceptible organisms. Doses up to 90 mg/kg/day have been used in older children with cystic fibrosis.

Infants 4 wk to 3 mo (weighing at least 1.5 kg)

IV 25 mg/kg every 6 h for non-CNS infections.

Neonates 1 to 4 wk (weighing at least 1.5 kg)

IV 25 mg/kg every 8 h for non-CNS infections.

Neonates younger than 1 wk (weighing at least 1.5 kg)

IV 25 mg/kg IV every 12 hours for non-CNS infections.

Renal function impairment

Patients with CrCl less than 70 mL/min per 1.73 m 2 require dosage adjustment. Patients with CrCl of 5 mL/min per 1.73 m 2 or less should not receive imipenem/cilastatin IV unless hemodialysis is instituted within 48 h.

General Advice

  • Reduce dosage for adults weighing less than 70 kg.
  • Diluents containing benzyl alcohol should not be used when imipenem/cilastatin is constituted for administration in pediatric patients younger than 3 mo.
  • Do not mix with or physically add to antibiotics. However, it may be coadministered with other antibiotics (eg, aminoglycosides).
  • Give a 125, 250, or 500 mg dose by IV infusion over 20 to 30 min. Infuse a 750 mg or 1 g dose over 40 to 60 min. If nausea develops, slow the infusion rate. For children, give doses of 500 mg or less by IV infusion over 15 to 30 min. Give doses more than 500 mg by IV infusion over 40 to 60 min.

Storage/Stability

Store unreconstituted powder at or below 77°F.

Drug Interactions

Cyclosporine

CNS adverse effects (eg, myoclonia, seizures) may be increased.

Ganciclovir

Generalized seizures may occur; avoid use.

Probenecid

Minimal increases in imipenem levels and half-life; do not give probenecid concurrently.

Valproic acid and derivatives

Valproic acid serum concentrations may be reduced to subtherapeutic levels, resulting in loss of seizure control. Monitor valproic acid plasma concentrations and observe the patient for seizure activity. Consider adjusting the valproic acid dose as needed or using an alternative antibiotic. If imipenem/cilastatin therapy is necessary, consider supplemental anticonvulsant therapy.

Laboratory Test Interactions

May cause positive Coombs test results.

Adverse Reactions

Cardiovascular

Tachycardia (2%).

CNS

Convulsions (6%).

Dermatologic

Rash (2%).

GI

Diarrhea (4%); nausea, oral candidiasis, vomiting (2%); gastroenteritis (1%).

Genitourinary

Increased urine protein (8%); increased creatinine (5%); oliguria/anuria (2%); urine discoloration (1%); presence of RBCs, WBCs, casts, bilirubin, and urobilinogen in urine.

Hematologic

Decreased Hct (18%); decreased Hgb (15%); increased eosinophils, increased platelets (13%); decreased neutrophils (3%); platelets decreased (2%); increased monocytes, increased lymphocytes, increased basophils, increased WBCs; agranulocytosis; abnormal PT.

Hepatic

Increased AST (18%); increased ALT (11%); increased bilirubin, increased alkaline phosphatase (3%); decreased bilirubin (1%).

Local

Phlebitis/thrombophlebitis (3%); injection-site pain, irritated injection site (1%).

Metabolic

Decreased serum sodium; increased potassium and chloride.

Precautions

Monitor

Monitor patient's response to therapy; periodically monitor renal, hepatic, and hematopoietic function during prolonged therapy.


Pregnancy

Category C . Some references consider imipenem/cilastatin to be a safe and effective agent during the perinatal period.

Lactation

Excreted in breast milk.

Children

Use is not recommended in pediatric patients with CNS infections because of the risk of seizures, or in pediatric patients weighing less than 30 kg with impaired renal function because no data are available.

Elderly

Because elderly patients are more likely to have decreased renal function, select dose with caution.

Hypersensitivity

Serious and occasionally fatal anaphylactic and serious skin reactions have been reported in patients receiving beta-lactam antibiotics. Administer drug with caution to penicillin-sensitive patients because of possible cross-reactivity.

Renal Function

Dosage reduction or alteration of dosage interval is required.

Superinfection

May result in bacterial or fungal overgrowth of nonsusceptible organisms.

Clostridium difficile –associated diarrhea

Consider possibility in patients with diarrhea.

CNS effects

Myoclonic activity, confusional states, or seizures may occur. Most common in patients with CNS disorders (eg, brain lesions, history of seizures) and/or compromised renal function.

Patient Information

  • Instruct patient to report the following to health care provider: itching; rash; hives; difficulty breathing; diarrhea; black, “furry” tongue; loose, foul-smelling stools; vaginal itching or discharge.

Copyright © 2009 Wolters Kluwer Health.

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