Dosing and uses of Primaxin (imipenem/cilastatin)
Adult dosage forms and strengths
imipenem/cilastatin
powder for injection
- 250mg/250mg
- 500mg/500mg
Lower Respiratory Tract, Skin/Skin Structure, & Gynecologic Infections
Mild to moderate: 500-750 mg IV q12hr
Intra-abdominal Infections
Mild to moderate: 250-500 mg IV q6hr
Severe: 500 mg IV q6hr or 1 g q8hr for 4-7 days, provided that infection is brought under controL
Pseudomonas Infections
500 mg IV q6hr; higher dosages may be administered, depending on organism sensitivity
Urinary Tract Infections
Uncomplicated: 250 mg IV q6hr
Complicated: 500 mg IV q6hr
Dosing Considerations
Dosages are based on imipenem component
Dosages given are for patients weighing >70 kg; use lower dosages in patients weighing <70 kg
Susceptible organisms
- Acinetobacter spp, Alcaligenes xylosoxidans, Bacteroides spp, Citrobacter spp, Clostridium spp, Enterobacter spp, Escherichia coli, Gardnerella vaginalis, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella spp, Morganella morganii, Nocardia spp, Propionibacterium spp, Proteus vulgaris, Providencia rettgeri, Pseudomonas aeruginosa, Rhodococcus equi, Serratia marcescens, Staphylococcus aureus (penicillinase-producing), Staphylococcus epidermidis, enterococci, group B/D streptococci, Streptococcus pyogenes, Streptococcus pneumoniae
Mild infections (rarely used)
- Fully susceptible organisms: 250 mg IV q6hr
- Moderately susceptible organisms: 500 mg IV q6hr
Moderate infections
- IV: Fully susceptible organisms: 500 mg IV q6-8hr
- Moderately susceptible organisms: 500 mg IV q6hr or 1 g IV q8hr
Severe infections
- Fully susceptible organisms: 500 mg IV q6hr
- Moderately susceptible organisms: 1 g IV q6-8hr; not to exceed 50 mg/kg/day or 4 g/day, whichever is lower
Dosing Modifications
Renal impairment
- CrCl ≥71 mL/min/1.73 m²: 250 mg IV q6hr
- CrCl 41-70 mL/min/1.73m²: 250 mg IV q8hr
- CrCl 21-40 mL/min/1.73 m²: 125-250 mg IV q12hr
- CrCl ≤20 mL/min/1.73 m²: 125-250 mg IV q12hr
- CrCl <5 mL/min/1.73 m²: Use IV only if hemodialysis is instituted within 48 hours
- Hemodialysis: Give supplemental dose after each dialysis, then q12hr
Pediatric dosage forms and strengths
imipenem/cilastatin
powder for injection
- 250mg/250mg
Dosages based on imipenem component
<1 week, >1.5 kg: 25 mg/kg IV q12hr for non-CNS infections
1-4 weeks, >1.5 kg: 25 mg/kg IV q8hr for non-CNS infections
4 weeks-3 months, >1.5 kg: 25 mg/kg IV q6hr for non-CNS infections
>3 months: 15-25 mg/kg IV q6hr for non-CNS infections; not to exceed 2 g/day for fully susceptible organisms or 4 g/day for moderately susceptible organisms
>12 years: 10-15 mg/kg IV q6hr for mild-to-moderate infections
Cystic fibrosis patients: Up to 100 mg/kg/day IV divided q6hr; not to exceed 4 g/day (in older children)
Primaxin (imipenem/cilastatin) adverse (side) effects
1-10%
Phlebitis (2-5%)
Eosinophilia (4%)
Miscellaneous dermatologic effects (<3%)
Potentially false-positive Coombs test (2%)
Miscellaneous hematologic effects (<2%)
Transient increase in blood urea nitrogen (BUN) or serum creatinine (<2%)
Seizures (1.5%)
Nausea, diarrhea, vomiting (1-2%)
<1%
Abnormal urinalysis
Agitation
Anaphylaxis
Anemia
Confusion (acute)
Dizziness
Dyskinesia
Emergence of resistant strains of Pseudomonas aeruginosa
Fever
Hypersensitivity
Hypotension
Elevated liver function test (LFT) results
Increased prothrombin time (PT)
Neutropenia (including agranulocytosis)
Palpitations
Pruritus
Pseudomembranous colitis
Warnings
Contraindications
Hypersensitivity to imipenem or cilastatin
Cautions
History of hypersensitivity to penicillins
Use with caution in CNS disorders (eg., history of seizures); adjust dosage in renal impairment to avoid risk of seizures; carbapenem use has been associated with seizures
Prolonged use increases risk of superinfections
Use with caution in renal impairment; adjust dosage in moderate to severe renal dysfunction
Carbapenem use may decrease serum levels of divalproex sodium or valproic acid
Combination with aminoglycosides may thwart resistant P aeruginosa
Not for use in children with CNS problems
Pregnancy and lactation
Pregnancy category: C
Lactation: Drug distributed in breast milk; use with caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Primaxin (imipenem/cilastatin)
Mechanism of action
Imipenem inhibits bacterial cell-wall synthesis by binding to penicillin-binding proteins; cilastatin prevents renal metabolism of imipenem
Distribution
Distributed rapidly and widely to most tissues and fluids, including sputum, pleural fluid, peritoneal fluid, interstitial fluid, bile, aqueous humor, reproductive organs, and bone; highest concentrations in pleural fluid, interstitial fluid, peritoneal fluid, and reproductive organs; low concentrations in CSF; crosses placenta; enters breast milk
Protein bound: Imipenem, 13-21%; cilastatin, 40%
Metabolism
Imipenem is metabolized in the kidney by dehydropeptidase 1; activity is blocked by cilastatin
Elimination
Half-life (both drugs): 60 min; prolonged with renal impairment
Excretion (both drugs): Urine (~70% as unchanged drug)
Administration
IV Incompatibilities
Solution: D5/LR, LR, sodium bicarbonate, sodium lactate (D5W and NS causes some activity loss but are recommended for short-term use)
Y-site: Allopurinol, amiodarone, amphotericin B cholesteryl sulfate, azithromycin, etoposide phosphate, fluconazole, gemcitabine, lorazepam, meperidine, midazolam, sargramostim, sodium bicarbonate
IV Preparation
Reconstitute infusion bottles with 100 mL of compatible diluent
Reconstitute vials with a portion (usually 10 mL) of IV fluid withdawn from the IV container, dissolve, and return to container; repeat
Reconstituted solutions are stable for 4 hours at room temperature and 24 hours refrigerated (4 C) in Ns
Normal color ranges from clear to yellow; these variations do not affect potency, but solution should be discarded if brown
Imipenem is inactivated at acidic or alkaline pH
IV Administration
Do not administer by IV push
Final concentration should not exceed 5 mg/mL
Infuse ≤500 mg over 20-30 minutes (15-30 minutes in children); infuse >500 mg over 40-60 min
Vial contents must be transferred to 100 mL of infusion solution
If nausea or vomiting occurs during administration, reduce infusion rate
Drug must not be mixed or physically added to other antibiotics; however, it may be administered concomitantly
