Imipenem/cilastin

Usual Dosing (Adults)

DOSAGE AND ADMINISTRATION
Adults
The dosage recommendations for PRIMAXIN I.V. represent the quantity of imipenem to be administered. An equivalent amount of cilastatin is also present in the solution. Each 125 mg, 250 mg, or 500 mg dose should be given by intravenous administration over 20 to 30 minutes. Each 750 mg or 1000 mg dose should be infused over 40 to 60 minutes. In patients who develop nausea during the infusion, the rate of infusion may be slowed.

The total daily dosage for PRIMAXIN I.V. should be based on the type or severity of infection and given in equally divided doses based on consideration of degree of susceptibility of the pathogen(s), renal function, and body weight. Adult patients with impaired renal function, as judged by creatinine clearance ≤70 mL/min/1.73 m2, require adjustment of dosage as described in the succeeding section of these guidelines.

Intravenous Dosage Schedule for Adults with Normal Renal Function and Body Weight ≥70 kg
Doses cited in Table I are based on a patient with normal renal function and a body weight of 70 kg. These doses should be used for a patient with a creatinine clearance of ≥71 mL/min/1.73 m2 and a body weight of ≥70 kg. A reduction in dose must be made for a patient with a creatinine clearance of ≤70 mL/min/1.73 m2 and/or a body weight less than 70 kg. (See Tables II and III.)

Dosage regimens in column A of Table I are recommended for infections caused by fully susceptible organisms which represent the majority of pathogenic species. Dosage regimens in column B of Table I are recommended for infections caused by organisms with moderate susceptibility to imipenem, primarily some strains of P. aeruginosa.

TABLE I: INTRAVENOUS DOSAGE SCHEDULE FOR ADULTS WITH NORMAL RENAL FUNCTION AND BODY WEIGHT ≥70 kg

Type or Severity of Infection	A Fully susceptible organisms including gram-positive and gram-negative aerobes and anaerobes	B MODERATELY SUSCEPTIBLE ORGANISMS, PRIMARILY SOME STRAINS OF P. aeruginosa
Mild	250 mg q6h (TOTAL DAILY DOSE = 1.0g)	500 mg q6h (TOTAL DAILY DOSE = 2.0g)
Moderate	500 mg q8h (TOTAL DAILY DOSE = 1.5g) or 500 mg q6h (TOTAL DAILY DOSE = 2.0g)	500 mg q6h (TOTAL DAILY DOSE = 2.0g) or 1 g q8h (TOTAL DAILY DOSE = 3.0g)
Severe, life threatening only	500 mg q6h (TOTAL DAILY DOSE = 2.0g)	1 g q8h (TOTAL DAILY DOSE = 3.0g) or 1 g q6h (TOTAL DAILY DOSE = 4.0g)
Uncomplicated urinary tract infection	250 mg q6h (TOTAL DAILY DOSE = 1.0g)	250 mg q6h (TOTAL DAILY DOSE = 1.0g)
Complicated urinary tract infection	500 mg q6h (TOTAL DAILY DOSE = 2.0g)	500 mg q6h (TOTAL DAILY DOSE = 2.0g)

Due to the high antimicrobial activity of PRIMAXIN I.V., it is recommended that the maximum total daily dosage not exceed 50 mg/kg/day or 4.0 g/day, whichever is lower. There is no evidence that higher doses provide greater efficacy. However, patients over twelve years of age with cystic fibrosis and normal renal function have been treated with PRIMAXIN I.V. at doses up to 90 mg/kg/day in divided doses, not exceeding 4.0 g/day.

Renal Dosing

Reduced Intravenous Schedule for Adults with Impaired Renal Function and/or Body Weight <70 kg

Patients with creatinine clearance of ≤70 mL/min/1.73 m2 and/or body weight less than 70 kg require dosage reduction of PRIMAXIN I.V. as indicated in the tables below. Creatinine clearance may be calculated from serum creatinine concentration by the following equation:

Creatinine clearance for males =	[140-age (years)]× [body wt (kg)] 72 × [serum creatinine (mg/dL)]
Creatinine clearance for females =	[140-age (years)]× [body wt (kg)]× 0.85 72 × [serum creatinine (mg/dL)]

To determine the dose for adults with impaired renal function and/or reduced body weight:
1. Choose a total daily dose from Table I based on infection characteristics.
2. a) If the total daily dose is 1.0 g, 1.5 g, or 2.0 g, use the appropriate subsection of Table II and continue with step 3.
b) If the total daily dose is 3.0 g or 4.0 g, use the appropriate subsection of Table III and continue with step 3.
3. From Table II or III:
a) Select the body weight on the far left which is closest to the patient's body weight (kg).
b) Select the patient's creatinine clearance category.
c) Where the row and column intersect is the reduced dosage regimen.

TABLE II: REDUCED INTRAVENOUS DOSAGE OF PRIMAXIN I.V. IN ADULT PATIENTS WITH IMPAIRED RENAL FUNCTION AND/OR BODY WEIGHT <70 kg

If TOTAL DAILY DOSE from TABLE I is:

1.0 g/day

1.5 g/day

2.0 g/day

And Body Weight (kg) is:

and creatinine clearance (mL/min/1.73 m2) is:

≥71

41-70

21-40

6-20

≥71

41-70

21-40

6-20

≥71

41-70

21-40

6-20

then the reduced dosage regimen (mg) is:

≥70

250
q6h

250
q8h

250
q12h

500
q8h

250
q6h

250
q8h

250
q12h

500
q6h

500
q8h

250
q6h

250
q12h

250
q8h

125
q6h

250
q12h

125
q12h

250
q6h

250
q8h

250
q12h

500
q8h

250
q6h

250
q8h

250
q12h

125
q6h

125
q8h

125
q12h

250
q6h

250
q8h

250
q12h

250
q6h

250
q8h

250
q12h

125
q6h

125
q8h

125
q12h

250
q8h

125
q6h

125
q8h

125
q12h

250
q6h

250
q8h

250
q12h

125
q8h

125
q12h

125
q6h

125
q8h

125
q12h

250
q8h

125
q6h

125
q8h

125
q12h

TABLE III: REDUCED INTRAVENOUS DOSAGE OF PRIMAXIN I.V. IN ADULT PATIENTS WITH IMPAIRED RENAL FUNCTION AND/OR BODY WEIGHT <70 kg

If TOTAL DAILY DOSE from TABLE I is:
	3.0 g/day				4.0 g/day
And Body Weight (kg) is:	and creatinine clearance (mL/min/1.73 m2) is:				and creatinine clearance (mL/min/1.73 m2) is:
	≥71	41-70	21-40	6-20	≥71	41-70	21-40	6-20
	then the reduced dosage regimen (mg) is:				then the reduced dosage regimen (mg) is:
≥70	1000 q8h	500 q6h	500 q8h	500 q12h	1000 q6h	750 q8h	500 q6h	500 q12h
60	750 q8h	500 q8h	500 q8h	500 q12h	1000 q8h	750 q8h	500 q8h	500 q12h
50	500 q6h	500 q8h	250 q6h	250 q12h	750 q8h	500 q6h	500 q8h	500 q12h
40	500 q8h	250 q6h	250 q8h	250 q12h	500 q6h	500 q8h	250 q6h	250 q12h
30	250 q6h	250 q8h	250 q8h	250 q12h	500 q8h	250 q6h	250 q8h	250 q12h

Patients with creatinine clearances of 6 to 20 mL/min/1.73 m2 should be treated with PRIMAXIN I.V. 125 mg or 250 mg every 12 hours for most pathogens. There may be an increased risk of seizures when doses of 500 mg every 12 hours are administered to these patients.

Patients with creatinine clearance ≤5 mL/min/1.73 m2 should not receive PRIMAXIN I.V. unless hemodialysis is instituted within 48 hours. There is inadequate information to recommend usage of PRIMAXIN I.V. for patients undergoing peritoneal dialysis.

Hemodialysis

Hemodialysis
When treating patients with creatinine clearances of ≤5 mL/min/1.73 m2 who are undergoing hemodialysis, use the dosage recommendations for patients with creatinine clearances of 6-20 mL/min/1.73 m2. (See Reduced Intravenous Dosage Schedule for Adults with Impaired Renal Function and/or Body Weight <70 kg.) Both imipenem and cilastatin are cleared from the circulation during hemodialysis. The patient should receive PRIMAXIN I.V. after hemodialysis and at 12 hour intervals timed from the end of that hemodialysis session. Dialysis patients, especially those with background CNS disease, should be carefully monitored; for patients on hemodialysis, PRIMAXIN I.V. is recommended only when the benefit outweighs the potential risk of seizures.

Reference(s)

National Institutes of Health, U.S. National Library of Medicine, DailyMed Database.
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