Adult Dosing

Mild Infection

IV

• Fully susceptible organisms: 250 mg IV q6 hrs; max: 50 mg/kg or 1 g/day
• Moderately susceptible organisms: 500 mg IV q6 hrs; max: 50 mg/kg or 2 g/day

IM

• 500-750 mg IM q12 hrs depending on the severity of infection; max: 1500 mg/day
• Max duration: 14 days

Moderate Infection

IV

• Fully susceptible organisms: 500 mg IV q8 hrs; max: 50 mg/kg or 1.5 g/day
• Alt: 500 mg IV q6 hrs; max: 50 mg/kg or 2 g/day
• Moderately susceptible organisms: 500 mg IV q6 hrs; max: 50 mg/kg or 2 g/day
• Alt: 1 g IV q8 hrs; max: 50 mg/kg or 3 g/day

IM

• 500-750 mg IM q12 hrs depending on the severity of infection; max: 1500 mg/day
• Max duration: 14 days

Severe, life threatening Infection

• Fully susceptible organisms: 500 mg IV q6 hrs; max: 50 mg/kg or 2 g/day
• Moderately susceptible organisms: 1 g IV q8 hrs; max: 50 mg/kg or 3 g/day
• Alt: 1 g IV q6 hrs; max: 50 mg/kg or 4 g/day

Uncomplicated urinary tract infection

• Fully or moderately susceptible organisms: 250 mg IV q6 hrs; max: 50 mg/kg or 1 g/day

Complicated urinary tract infection

• Fully or moderately susceptible organisms: 500 mg IV q6 hrs; max: 50 mg/kg or 2 g/day

• Each 250-500 mg IV should be given by intravenous administration over 20-30 minutes and each 750-1000 mg IV should be infused over 40-60 minutes
• See package insert for dosing in patients <70 kg
• Intramuscular injection is not intended for the therapy of severe or life-threatening infections, including bacterial sepsis or endocarditis, or in instances of major physiological impairments such as shock

Pediatric Dosing

Bacterial infection, non CNS

IV

• Neonate <1 wk (weighing 1,500 g): 25 mg/kg IV q12 hrs
• Infant 1-4 wks (weighing 1,500 g): 25 mg/kg IV q8 hrs
• Infant 4 wks-3 months (weighing 1,500 g): 25 mg/kg IV q6 hrs
• Children 3 months: 15-25 mg/kg IV q6 hrs; max: 2-4 g/day

IM (>12 yrs)

• 500-750 mg IM q12 hrs depending on the severity of infection; max: 1500 mg/day
• Max duration: 14 days

• Dosage <500 mg should be given by intravenous infusion over 15-30 minutes and doses >500 mg should be infused over 40-60 minutes
• Not recommended in pediatric patients <30 kg with impaired renal function

[Outline]

• Adult Dosing
• Pediatric Dosing

• Lower respiratory tract infections
• Urinary tract infections [IV]
• Intra-abdominal infections
• Gynecologic infections
• Bacterial septicemia [IV]
• Bone and joint infections [IV]
• Skin and skin structure infections
• Endocarditis [IV]
• Polymicrobic infections [IV]

• Hypersensitivity to any of the ingredients of the product
• Hypersensitivity to local anesthetics of the amide type [IM]
• Severe shock or heart block [IM]
• Pediatric patients with CNS infections

• N/A

Renal Dose Adjustment (Based on CrCl )

Normal renal function is 1 g/day

• Body weight70 kg
• 71 mL/min/1.73 m²: 250 mg IV q6 hrs
• 41-70 mL/min/1.73 m²: 250 mg IV q8 hrs
• 21-40 mL/min/1.73 m²: 250 mg IV q12 hrs
• 6-20 mL/min/1.73 m²: 250 mg IV q12 hrs

• Body weight 60 kg
• 70 mL/min/1.73 m²: 250 mg q8 hrs
• 41-70 mL/min/1.73 m²: 125 mg q6 hrs
• 21-40 mL/min/1.73 m²: 250 mg q12 hrs
• 6-20 mL/min/1.73 m²: 125 mg q12 hrs

• Body weight 50 kg
• 70 mL/min/1.73 m²: 125 mg q6 hrs
• 41-70 mL/min/1.73 m²: 125 mg q6 hrs
• 21-40 mL/min/1.73 m²: 125 mg q8 hrs
• 6-20 mL/min/1.73 m²: 125 mg q12 hrs

• Body weight 40 kg
• 70 mL/min/1.73 m²: 125 mg q6 hrs
• 41-70 mL/min/1.73 m²: 125 mg q8 hrs
• 21-40 mL/min/1.73 m²: 125 mg q12 hrs
• 6-20 mL/min/1.73 m²: 125 mg q12 hrs

• Body weight 30 kg
• 70 mL/min/1.73 m²: 125 mg q8 hrs
• 41-70 mL/min/1.73 m²: 125 mg q8 hrs
• 21-40 mL/min/1.73 m²: 125 mg q12 hrs
• 6-20 mL/min/1.73 m²: 125 mg q12 hrs

Normal renal function is 1.5 g/day

• Body weight70 kg
• 71 mL/min/1.73 m²: 500 mg IV q8 hrs
• 41-70 mL/min/1.73 m²: 250 mg IV q6 hrs
• 21-40 mL/min/1.73 m²: 250 mg IV q8 hrs
• 6-20 mL/min/1.73 m²: 250 mg IV q12 hrs

• Body weight60 kg
• 71 mL/min/1.73 m²: 250 mg IV q6 hrs
• 41-70 mL/min/1.73 m²: 250 mg IV q8 hrs
• 21-40 mL/min/1.73 m²: 250 mg IV q8 hrs
• 6-20 mL/min/1.73 m²: 250 mg IV q12 hrs

• Body weight50 kg
• 71 mL/min/1.73 m²: 250 mg IV q6 hrs
• 41-70 mL/min/1.73 m²: 250 mg IV q8 hrs
• 21-40 mL/min/1.73 m²: 250 mg IV q12 hrs
• 6-20 mL/min/1.73 m²: 250 mg IV q12 hrs

• Body weight40 kg
• 71 mL/min/1.73 m²: 250 mg IV q8 hrs
• 41-70 mL/min/1.73 m²: 125 mg IV q6 hrs
• 21-40 mL/min/1.73 m²: 125 mg IV q8 hrs
• 6-20 mL/min/1.73 m²: 125 mg IV q12 hrs

• Body weight30 kg
• 71 mL/min/1.73 m²: 125 mg IV q6 hrs
• 41-70 mL/min/1.73 m²: 125 mg IV q8 hrs
• 21-40 mL/min/1.73 m²: 125 mg IV q8 hrs
• 6-20 mL/min/1.73 m²: 125 mg IV q12 hrs

Normal renal function is 2 g/day

• Body weight70 kg
• 71 mL/min/1.73 m²: 500 mg IV q6 hrs
• 41-70 mL/min/1.73 m²: 500 mg IV q8 hrs
• 21-40 mL/min/1.73 m²: 250 mg IV q6 hrs
• 6-20 mL/min/1.73 m²: 250 mg IV q12 hrs

• Body weight60 kg
• 71 mL/min/1.73 m²: 500 mg IV q8 hrs
• 41-70 mL/min/1.73 m²: 250 mg IV q6 hrs
• 21-40 mL/min/1.73 m²: 250 mg IV q8 hrs
• 6-20 mL/min/1.73 m²: 250 mg IV q12 hrs

• Body weight50 kg
• 71 mL/min/1.73 m²: 250 mg IV q6 hrs
• 41-70 mL/min/1.73 m²: 250 mg IV q6 hrs
• 21-40 mL/min/1.73 m²: 250 mg IV q8 hrs
• 6-20 mL/min/1.73 m²: 250 mg IV q12 hrs

• Body weight40 kg
• 71 mL/min/1.73 m²: 250 mg IV q6 hrs
• 41-70 mL/min/1.73 m²: 250 mg IV q8 hrs
• 21-40 mL/min/1.73 m²: 250 mg IV q12 hrs
• 6-20 mL/min/1.73 m²: 250 mg IV q12 hrs

• Body weight30 kg
• 71 mL/min/1.73 m²: 250 mg IV q8 hrs
• 41-70 mL/min/1.73 m²: 125 mg IV q6 hrs
• 21-40 mL/min/1.73 m²: 125 mg IV q8 hrs
• 6-20 mL/min/1.73 m²: 125 mg IV q12 hrs

Normal renal function is 3 g/day

• Body weight70 kg
• 71 mL/min/1.73 m²: 1000 mg IV q8 hrs
• 41-70 mL/min/1.73 m²: 500 mg IV q6 hrs
• 21-40 mL/min/1.73 m²: 500 mg IV q8 hrs
• 6-20 mL/min/1.73 m²: 500 mg IV q12 hrs

• Body weight60 kg
• 71 mL/min/1.73 m²: 750 mg IV q8 hrs
• 41-70 mL/min/1.73 m²: 500 mg IV q8 hrs
• 21-40 mL/min/1.73 m²: 500 mg IV q8 hrs
• 6-20 mL/min/1.73 m²: 500 mg IV q12 hrs

• Body weight50 kg
• 71 mL/min/1.73 m²: 500 mg IV q6 hrs
• 41-70 mL/min/1.73 m²: 500 mg IV q8 hrs
• 21-40 mL/min/1.73 m²: 250 mg IV q6 hrs
• 6-20 mL/min/1.73 m²: 250 mg IV q12 hrs

• Body weight40 kg
• 71 mL/min/1.73 m²: 500 mg IV q8 hrs
• 41-70 mL/min/1.73 m²: 250 mg IV q6 hrs
• 21-40 mL/min/1.73 m²: 250 mg IV q8 hrs
• 6-20 mL/min/1.73 m²: 250 mg IV q12 hrs

• Body weight30 kg
• 71 mL/min/1.73 m²: 250 mg IV q6 hrs
• 41-70 mL/min/1.73 m²: 250 mg IV q8 hrs
• 21-40 mL/min/1.73 m²: 250 mg IV q8 hrs
• 6-20 mL/min/1.73 m²: 250 mg IV q12 hrs

Normal renal function is 4 g/day

• Body weight70 kg
• 71 mL/min/1.73 m²: 1000 mg IV q6 hrs
• 41-70 mL/min/1.73 m²: 750 mg IV q8 hrs
• 21-40 mL/min/1.73 m²: 500 mg IV q6 hrs
• 6-20 mL/min/1.73 m²: 500 mg IV q12 hrs

• Body weight60 kg
• 71 mL/min/1.73 m²: 1000 mg IV q8 hrs
• 41-70 mL/min/1.73 m²: 750 mg IV q8 hrs
• 21-40 mL/min/1.73 m²: 500 mg IV q8 hrs
• 6-20 mL/min/1.73 m²: 500 mg IV q12 hrs

• Body weight50 kg
• 71 mL/min/1.73 m²: 750 mg IV q8 hrs
• 41-70 mL/min/1.73 m²: 500 mg IV q6 hrs
• 21-40 mL/min/1.73 m²: 500 mg IV q8 hrs
• 6-20 mL/min/1.73 m²: 500 mg IV q12 hrs

• Body weight40 kg
• 71 mL/min/1.73 m²: 500 mg IV q6 hrs
• 41-70 mL/min/1.73 m²: 500 mg IV q8 hrs
• 21-40 mL/min/1.73 m²: 250 mg IV q6 hrs
• 6-20 mL/min/1.73 m²: 250 mg IV q12 hrs

• Body weight30 kg
• 71 mL/min/1.73 m²: 500 mg IV q8 hrs
• 41-70 mL/min/1.73 m²: 250 mg IV q6 hrs
• 21-40 mL/min/1.73 m²: 250 mg IV q8 hrs
• 6-20 mL/min/1.73 m²: 250 mg IV q12 hrs

• 5 mL/min/1.73 m²: Contraindicated; unless hemodialysis is instituted within 48 hours
• Hemodialysis: 125-250 mg IV q12 hrs
• <20 mL/min/1.73 m²: IM contraindicated

Hepatic Dose Adjustment

• Hepatic impairment: Dose adjustments not defined

• Severe hypersensitivity reactions have been reported in patients receiving beta lactams, especially in patients with a history of sensitivity to multiple allergens, or history of penicillin hypersensitivity. Hence before initiating the therapy with cilastatin/imipenem, make careful inquiry concerning previous hypersensitivity reactions. Discontinue therapy and provide immediate emergency treatment with epinephrine, oxygen, intravenous steroids and airway management as indicated, if allergic reactions occur
• Cilastatin/imipenem can cause seizures and other CNS adverse reactions, such as confusion and myoclonic activity, especially when the recommended dosages are exceeded and/or underlying CNS disorders or compromised renal function are present. Give supplemental anticonvulsant therapy if administration of cilastatin/imipenem is necessary
• Closely follow dosing guidelines in patients with a creatinine clearance of 20 mL/min/1.73 m², whether or not undergoing hemodialysis, as they are at higher risk of seizure activity. Do not administer cilastatin/imipenem in patients with a creatinine clearance of 5 mL/min/1.73 m² unless hemodialysis is instituted within 48 hours
• Clostridium difficile associated diarrhea (CDAD) ranging from mild diarrhea to fatal colitis can occur with cilastatin/imipenem therapy as antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile
• C. difficile produces toxins A and B which contribute to CDAD. Hypertoxin producing strains causes increased morbidity and mortality since these infections can be refractory to antibiotic therapy and may require colectomy. Careful medical examination is necessary since CDAD may occur > 2 months after administration of drug
• If CDAD is suspected/confirmed, discontinue treatment and provide fluid, electrolyte, and protein supplementation along with antibiotics for C. difficile, surgical evaluation as clinically needed
• Prescribing antibiotics in the absence of proven or strongly suspected bacterial infection increases the risk of development of drug-resistant bacteria
• Prolonged use of cilastatin/imipenem can result in overgrowth of nonsusceptible organisms. Provide appropriate treatment if superinfection occurs during therapy
• Monitor organ system functions, including renal, hepatic, and hematopoietic periodically during prolonged therapy

Cautions: Use cautiously in

• Renal impairment
• Hepatic impairment
• CNS disorder
• History or risk of seizure
• History of hypersensitivity to beta lactams
• Hypersensitivity to multiple allergens

Primaxin interacts with :

	Depakene
	Stavzor
	Valproic Acid

Pregnancy Category:C

Breastfeeding: Single maternal doses of imipenem up to 500 mg produce low levels in milk that are not expected to cause adverse effects in breastfed infants. Hence acceptable during breastfeeding. Disruption of the infant's gastrointestinal flora, resulting in diarrhea or thrush has been reported occasionally with beta-lactams, but these effects have not been adequately evaluated. This data is based upon LactMed database (available at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT last accessed 28 March 2011). Manufacturer advises caution.

• CNS: Seizure, dizziness, somnolence
• CV: Hypotension
• GI: Nausea, diarrhea, vomiting, pseudomembranous colitis, hemorrhagic colitis, hepatitis
• HEMA: Pancytopenia
• DERM: Rash, pruritus, urticaria, angioneurotic edema, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme
• GU: Oliguria, acute renal failure
• LOCAL: Phlebitis/thrombophlebitis, pain, erythema, vein induration
• MISC: Fever, anaphylactic reaction, superinfection
• LABS: Increased liver function tests, increased BUN and creatinine

Imipenem

• Anti-Bacterial agent; binds to penicillin binding proteins thus inhibiting the cell wall synthesis of various gram-positive and gram-negative bacteria
• Metabolized in kidney
• Renally excreted 70%
• Half-life: 1 hr

Cilastatin

• Protease inhibitor; inhibits renal dehydropeptidase-I thereby blocking the metabolism and thus the inactivation of imipenem so that antibacterial levels of imipenem can be attained in the urine. Also prevents the metabolism of leukotriene D4 to leukotriene E4
• Metabolism: Unknown
• Renally excreted 70%
• Half-life: 1 hr

US Trade Name(s)

• Primaxin

US Availability

cilastatin/imipenem (generic)

• PWDR for INJ: [250 mg/250 mg]/vial
• PWDR for INJ: [500 mg/500 mg]/vial

Primaxin (cilastatin/imipenem)

• PWDR for INJ: [250 mg/250 mg]/vial
• PWDR for INJ: [500 mg/500 mg]/vial

Canadian Trade Name(s)

• Primaxin

Canadian Availability

Primaxin (cilastatin/imipenem )

• PWDR for INJ: [250 mg/250 mg]/vial
• PWDR for INJ: [500 mg/500 mg]/vial

UK Trade Name(s)

• Primaxin

UK Availability

Primaxin (cilastatin/imipenem )

• PWDR for INJ: [500 mg/500 mg]/vial

Australian Trade Name(s)

• Primaxin

Australian Availability

Primaxin (cilastatin/imipenem )

• PWDR for INJ: [500 mg/500 mg]/vial

[Outline]

Antimicrobials

Antibiotics

Carbapenems

Infectious Disease

Antibiotics

Carbapenems