Carbapenems

Complicated intra-abdominal infections
Complicated urinary tract infections, including pyelonephritis

DOSAGE AND ADMINISTRATION

Creatinine clearance can be estimated from serum creatinine using the Cockcroft-Gault formula.

DOSAGE FORMS AND STRENGTHS
250 mg single-use vial, 500 mg single-use vial

INVANZ is indicated in adults for the prophylaxis of surgical site infection following elective colorectal surgery.

DOSAGE AND ADMINISTRATION
Do not mix or co-infuse INVANZ with other medications. Do not use diluents containing dextrose (a-D-glucose).

INVANZ should be infused over 30 minutes in both the Treatment and Prophylactic regimens.

Dosing considerations should be made in adults with advanced or end-stage renal impairment and those on hemodialysis.

Treatment regimen:
Adults and pediatric patients 13 years of age and older. The dosage should be 1 gram once a day intravenously or intramuscularly.

Patients 3 months to 12 years of age should be administered 15 mg/kg twice daily (not to exceed 1 g/day intravenously or intramuscularly.)

Intravenous infusion may be administered in adults and pediatrics for up to 14 days or intramuscular injection for up to 7 days.

Prophylaxis regimen for adults:
1 gram single dose given 1 hour prior to elective colorectal surgery.

Patients with Renal Impairment
INVANZ may be used for the treatment of infections in adult patients with renal impairment. In patients whose creatinine clearance is >30 mL/min/1.73 m2, no dosage adjustment is necessary. Adult patients with severe renal impairment (creatinine clearance ≤30 mL/min/1.73 m2) and end-stage renal disease (creatinine clearance ≤10 mL/min/1.73 m2) should receive 500 mg daily. A supplementary dose of 150 mg is recommended if ertapenem is administered within 6 hours prior to hemodialysis. There are no data in pediatric patients with renal impairment.

Patients on Hemodialysis:
When adult patients on hemodialysis are given the recommended daily dose of 500 mg of INVANZ within 6 hours prior to hemodialysis, a supplementary dose of 150 mg is recommended following the hemodialysis session. If INVANZ is given at least 6 hours prior to hemodialysis, no supplementary dose is needed. There are no data in patients undergoing peritoneal dialysis or hemofiltration. There are no data in pediatric patients on hemodialysis.

When only the serum creatinine is available, the following formula (see below) may be used to estimate creatinine clearance. The serum creatinine should represent a steady state of renal function.
 
Creatinine clearance can be estimated from serum creatinine using the Cockcroft-Gault formula.

DOSAGE FORMS AND STRENGTHS
Vial 1 gram.
ADD-Vantage® vial: 1 gram.

1. Lower respiratory tract infections. Staphylococcus aureus (penicillinase-producing strains), Acinetobacter species, Enterobacter species, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae², Klebsiella species, Serratia marcescens

2. Urinary tract infections (complicated and uncomplicated). Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing strains)² , Enterobacter species, Escherichia coli, Klebsiella species, Morganella morganii² , Proteus vulgaris² , Providencia rettgeri² , Pseudomonas aeruginosa

3. Intra-abdominal infections. Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing strains)² , Staphylococcus epidermidis, Citrobacter species, Enterobacter species, Escherichia coli, Klebsiella species, Morganella morganii² , Proteus species, Pseudomonas aeruginosa, Bifidobacterium species, Clostridium species, Eubacterium species, Peptococcus species, Peptostreptococcus species, Propionibacterium species² , Bacteroides species including B. fragilis, Fusobacterium species

4. Gynecologic infections. Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing strains)2 , Staphylococcus epidermidis, Streptococcus agalactiae (Group B streptococci), Enterobacter species² , Escherichia coli, Gardnerella vaginalis, Klebsiella species² , Proteus species, Bifidobacterium species² , Peptococcus species² , Peptostreptococcus species, Propionibacterium species2 , Bacteroides species including B. fragilis

5. Bacterial septicemia. Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing strains), Enterobacter species, Escherichia coli, Klebsiella species, Pseudomonas aeruginosa, Serratia species2 , Bacteroides species including B. fragilis²

6. Bone and joint infections. Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing strains), Staphylococcus epidermidis, Enterobacter species, Pseudomonas aeruginosa

7. Skin and skin structure infections. Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing strains), Staphylococcus epidermidis, Acinetobacter species, Citrobacter species, Enterobacter species, Escherichia coli, Klebsiella species, Morganella morganii, Proteus vulgaris, Providencia rettgeri² , Pseudomonas aeruginosa, Serratia species, Peptococcus species, Peptostreptococcus species, Bacteroides species including B. fragilis, Fusobacterium species²

8. Endocarditis. Staphylococcus aureus (penicillinase-producing strains)

9. Polymicrobic infections. PRIMAXIN I.V. is indicated for polymicrobic infections including those in which S. pneumoniae (pneumonia, septicemia), S. pyogenes (skin and skin structure), or nonpenicillinase-producing S. aureus is one of the causative organisms. However, monobacterial infections due to these organisms are usually treated with narrower spectrum antibiotics, such as penicillin G.

[2.  Efficacy for this organism in this organ system was studied in fewer than 10 infections.]

PRIMAXIN I.V. is not indicated in patients with meningitis because safety and efficacy have not been established.

For Pediatric Use information, see PRECAUTIONS, Pediatric Use, and DOSAGE AND ADMINISTRATION sections.

Because of its broad spectrum of bactericidal activity against gram-positive and gram-negative aerobic and anaerobic bacteria, PRIMAXIN I.V. is useful for the treatment of mixed infections and as presumptive therapy prior to the identification of the causative organisms.

Although clinical improvement has been observed in patients with cystic fibrosis, chronic pulmonary disease, and lower respiratory tract infections caused by Pseudomonas aeruginosa, bacterial eradication may not necessarily be achieved.

As with other beta-lactam antibiotics, some strains of Pseudomonas aeruginosa may develop resistance fairly rapidly during treatment with PRIMAXIN I.V. During therapy of Pseudomonas aeruginosa infections, periodic susceptibility testing should be done when clinically appropriate.

Infections resistant to other antibiotics, for example, cephalosporins, penicillin, and aminoglycosides, have been shown to respond to treatment with PRIMAXIN I.V.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of PRIMAXIN I.V. and other antibacterial drugs, PRIMAXIN I.V. should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

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

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.

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:

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

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

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
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. (See PRECAUTIONS.)

Pediatric Patients
See package insert for 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 2.0 g per day, and of infections with moderately susceptible organisms (primarily some strains of P. aeruginosa) is 4.0 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 gms), 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.

PRIMAXIN I.V. is not recommended in pediatric patients with CNS infections because of the risk of seizures.

PRIMAXIN I.V. is not recommended in pediatric patients<30 kg with impaired renal function, as no data are available.

Complicated skin and skin structure infections (adult patients and pediatric patients ≥ 3 months only).
Complicated intra-abdominal infections (adult patients and pediatric patients ≥ 3 months only).
Bacterial meningitis (pediatric patients ≥ 3 months only).

DOSAGE AND ADMINISTRATION
Adults

The recommended dose of MERREM I.V. is 500 mg given every 8 hours for skin and skin structure infections and 1 g given every 8 hours for intra-abdominal infections. MERREM I.V. should be administered by intravenous infusion over approximately 15 to 30 minutes. Doses of 1 g may also be administered as an intravenous bolus injection (5 to 20 mL) over approximately 3-5 minutes.

Use in Adults with Renal Impairment
Dosage should be reduced in patients with creatinine clearance less than 51 mL/min. (see dosing table below).

Recommended MERREM I.V.
Dosage Schedule for Adults With Impaired Renal Function .

When only serum creatinine is available, the following formula (Cockcroft and Gault equation) may be used to estimate creatinine clearance.

There is inadequate information regarding the use of MERREM I.V. in patients on hemodialysis.

There is no experience with peritoneal dialysis.

Use in Adults With Hepatic Insufficiency
No dosage adjustment is necessary in patients with impaired hepatic function.

Use in Elderly Patients
No dosage adjustment is required for elderly patients with creatinine clearance values above 50 mL/min.

Use in Pediatric Patients
For pediatric patients from 3 months of age and older, the MERREM I.V. dose is 10, 20 or 40 mg/kg every 8 hours (maximum dose is 2 g every 8 hours), depending on the type of infection (complicated skin and skin structure, intra-abdominal or meningitis). (See dosing table below.) Pediatric patients weighing over 50 kg should be administered MERREM I.V. at a dose of 500 mg every 8 hours for complicated skin and skin structure infections, 1 g every 8 hours for intra-abdominal infections and 2 g every 8 hours for meningitis. MERREM I.V. should be given as intravenous infusion over approximately 15 to 30 minutes or as an intravenous bolus injection (5 to 20 mL) over approximately 3-5 minutes.

Recommended MERREM I.V. Dosage Schedule for Pediatrics with Normal Renal Function

There is no experience in pediatric patients with renal impairment.