Adults
The dosage recommendations for Imipenem and Cilastatin for Injection 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 Imipenem and Cilastatin for Injection 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 3 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 4 and 5.)
Dosage regimens in column A of Table 3 are recommended for infections caused by fully susceptible organisms which represent the majority of pathogenic species. Dosage regimens in column B of Table 3 are recommended for infections caused by organisms with moderate susceptibility to imipenem, primarily some strains of P. aeruginosa.
TABLE 3: 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 = 1g)
500 mg q6h
(TOTAL DAILY DOSE = 2g)
Moderate
500 mg q8h
(TOTAL DAILY DOSE = 1.5g)
or
500 mg q6h
(TOTAL DAILY DOSE = 2g)
500 mg q6h
(TOTAL DAILY DOSE = 2g)
or
1 g q8h
(TOTAL DAILY DOSE = 3g)
Severe, life
threatening
only
500 mg q6h
(TOTAL DAILY DOSE = 2g)
1 g q8h
(TOTAL DAILY DOSE = 3g)
or
1 g q6h
(TOTAL DAILY DOSE = 4g)
Uncomplicated
urinary tract
infection
250 mg q6h
(TOTAL DAILY DOSE = 1g)
250 mg q6h
(TOTAL DAILY DOSE = 1g)
Complicated
urinary tract
infection
500 mg q6h
(TOTAL DAILY DOSE = 2g)
500 mg q6h
(TOTAL DAILY DOSE = 2g)
Due to the high antimicrobial activity of Imipenem and Cilastatin for Injection I.V., it is recommended that the maximum total daily dosage not exceed 50 mg/kg/day or 4 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 Imipenem and Cilastatin for Injection I.V. at doses up to 90 mg/kg/day in divided doses, not exceeding 4 g/day.
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 Imipenem and Cilastatin for Injection I.V. as indicated in the tables below. Creatinine clearance may be calculated from serum creatinine concentration by the following equation:
Tcc (Males) = (wt. in kg) (140 – age)
(72) (creatinine in mg/dL)
Tcc (Females) = 0.85 × above value
To determine the dose for adults with impaired renal function and/or reduced body weight:
1. Choose a total daily dose from Table 3 based on infection characteristics.
2. a) If the total daily dose is 1 g, 1.5 g, or 2 g, use the appropriate subsection of Table 4
and continue with step 3.
b) If the total daily dose is 3 g or 4 g, use the appropriate subsection of Table 5 and
continue with step 3.
3. From Table 4 or 5:
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 4: REDUCED INTRAVENOUS DOSAGE OF IMIPENEM AND CILASTATIN FOR INJECTION I.V. IN ADULT PATIENTS WITH IMPAIRED RENAL FUNCTION AND/OR BODY WEIGHT <70 kg
And
Body
Weight
(kg)
is:
If TOTAL DAILY DOSE from TABLE 3 is:
1 g/day
1.5 g/day
2 g/day
and creatinine clearance
(mL/min/1.73 m2) 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
≥71
41-70
21-40
6-20
then the reduced dosage regimen (mg) is:
then the reduced dosage regimen (mg) is:
then the reduced dosage regimen (mg) is:
≥70
250
q6h
250
q8h
250
q12h
250
q12h
500
q8h
250
q6h
250
q8h
250
q12h
500
q6h
500
q8h
250
q6h
250
q12h
60
250
q8h
125
q6h
250
q12h
125
q12h
250
q6h
250
q8h
250
q8h
250
q12h
500
q8h
250
q6h
250
q8h
250
q12h
50
125
q6h
125
q6h
125
q8h
125
q12h
250
q6h
250
q8h
250
q12h
250
q12h
250
q6h
250
q6h
250
q8h
250
q12h
40
125
q6h
125
q8h
125
q12h
125
q12h
250
q8h
125
q6h
125
q8h
125
q12h
250
q6h
250
q8h
250
q12h
250
q12h
30
125
q8h
125
q8h
125
q12h
125
q12h
125
q6h
125
q8h
125
q8h
125
q12h
250
q8h
125
q6h
125
q8h
125
q12h
TABLE 5: REDUCED INTRAVENOUS DOSAGE OF IMIPENEM AND CILASTATIN FOR INJECTION I.V. IN ADULT PATIENTS WITH IMPAIRED RENAL FUNCTION AND/OR BODY WEIGHT <70 kg
And
Body
Weight
(kg)
is:
If TOTAL DAILY DOSE from TABLE 3 is:
3 g/day
4 g/day
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 Imipenem and Cilastatin for Injection 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 Imipenem and Cilastatin for Injection I.V. unless hemodialysis is instituted within 48 hours. There is inadequate information to recommend usage of Imipenem and Cilastatin for Injection I.V. for patients undergoing peritoneal dialysis.
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 Imipenem and Cilastatin for Injection 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, Imipenem and Cilastatin for Injection I.V. is recommended only when the benefit outweighs the potential risk of seizures. (See PRECAUTIONS.)
Pediatric Patients
See PRECAUTIONS, Pediatric Patients.
For pediatric patients ≥3 months of age, the recommended dose for non-CNS infections is 15-25 mg/kg/dose administered every six hours. Based on studies in adults, the maximum daily dose for treatment of infections with fully susceptible organisms is 2 g per day, and of infections with moderately susceptible organisms (primarily some strains of P. aeruginosa) is 4 g/day. Higher doses (up to 90 mg/kg/day in older children) have been used in patients with cystic fibrosis.
For pediatric patients ≤3 months of age (weighing ≥1,500 g), the following dosage schedule is recommended for non-CNS infections:
<1 wk of age: 25 mg/kg every 12 hrs
1-4 wks of age: 25 mg/kg every 8 hrs
4 wks-3 mos. of age: 25 mg/kg every 6 hrs.
Doses less than or equal to 500 mg should be given by intravenous infusion over 15 to 30 minutes. Doses greater than 500 mg should be given by intravenous infusion over 40 to 60 minutes.
Imipenem and Cilastatin for Injection I.V. is not recommended in pediatric patients with CNS infections because of the risk of seizures.
Imipenem and Cilastatin for Injection I.V. is not recommended in pediatric patients <30 kg with impaired renal function, as no data are available.
