Posology : מינונים

DOSAGE AND ADMINISTRATION

Adults
The dosage recommendations for TIENAM 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 TIENAM 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 4 and 5.) 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 3: INTRAVENOUS DOSAGE SCHEDULE
FOR ADULTS WITH NORMAL RENAL FUNCTION AND BODY WEIGHT 70 kg

A                                           B
Fully susceptible                              Moderately organisms including                             susceptible gram-positive                                organisms,
Type or                 and gram-negative                             primarily some Severity                    aerobes and                                   strains of of Infection                   anaerobes                                P. aeruginosa Mild                                 250 mg q6h                                 500 mg q6h (TOTAL DAILY DOSE = 1.0 g)                  (TOTAL DAILY DOSE = 2.0 g) Moderate                             500 mg q8h                                 500 mg q6h (TOTAL DAILY DOSE = 1.5 g)                  (TOTAL DAILY DOSE = 2.0 g) or                                          or
500 mg q6h                                    1 g q8h
(TOTAL DAILY DOSE = 2.0 g)                  (TOTAL DAILY DOSE = 3.0 g) Severe, life                         500 mg q6h                                    1 g q8h threatening             (TOTAL DAILY DOSE = 2.0 g)                  (TOTAL DAILY DOSE = 3.0 g) only                                                                             or 1 g q6h
(TOTAL DAILY DOSE = 4.0 g)
Uncomplicated                       250 mg q6h                                  250 mg q6h urinary tract            (TOTAL DAILY DOSE = 1.0 g)                  (TOTAL DAILY DOSE = 1.0 g) infection
Complicated                         500 mg q6h                                  500 mg q6h urinary tract            (TOTAL DAILY DOSE = 2.0 g)                  (TOTAL DAILY DOSE = 2.0 g) infection
Due to the high antimicrobial activity of TIENAM 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 TIENAM 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 TIENAM I.V. as indicated in the tables below. Creatinine clearance may be calculated from serum creatinine concentration by the following equation:
(wt. in kg) (140  age)
__________________________________________________________
Tcc (Males)            =
(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 1.0 g, 1.5 g, or 2.0 g, use the appropriate subsection of Table 4 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 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 TIENAM I. V. IN ADULT PATIENTS WITH IMPAIRED RENAL FUNCTION AND/ OR BODY WEIGHT <70 kg
If TOTAL DAILY DOSE from TABLE 3 is:
1.0 g/day                              1.5 g/day                        2.0 g/day and
Body
Weight              and creatinine clearance                            and creatinine clearance                              and creatinine clearance 2                                                   2                                                     2 (kg)                 (mL/min/1.73 m ) is:                                (mL/min/1.73 m ) is:                                  (mL/min/1.73 m ) is: 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        250           250       250              500        250           250        250               500        500           250        250 q6h        q8h          q12h       q12h             q8h        q6h           q8h       q12h               q6h        q8h           q6h       q12h 
60       250          125        250              125        250           250                  250          250   500       250          250          250 q8h          q6h       q12h              q12h       q6h           q8h                  q8h         q12h   q8h       q6h          q8h         q12h 
50       125          125          125            125        250           250               250             250   250       250          250          250 q6h          q6h          q8h           q12h        q6h           q8h              q12h            q12h   q6h       q6h          q8h         q12h 
40       125          125        125              125        250           125                  125          125   250       250          250          250 q6h          q8h       q12h             q12h        q8h           q6h                  q8h         q12h   q6h       q8h         q12h         q12h 
30       125          125        125              125        125           125                  125          125   250       125          125          125 q8h          q8h       q12h             q12h        q6h           q8h                  q8h         q12h   q8h       q6h          q8h         q12h 

TABLE 5: REDUCED INTRAVENOUS DOSAGE OF TIENAM I. V. IN ADULT PATIENTS WITH IMPAIRED RENAL FUNCTION AND/ OR BODY WEIGHT <70 kg
If TOTAL DAILY DOSE from TABLE 3 is:
3.0 g/day                                  4.0 g/day and
Body
Weight                and creatinine clearance                   and creatinine clearance 2                                          2
(kg)                   (mL/min/1.73 m ) is:                       (mL/min/1.73 m ) is: 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       500           500       500     1000       750           500       500 q8h        q6h           q8h       q12h    q6h        q8h           q6h       q12h 
60         750          500              500              500          1000         750          500        500 q8h          q8h              q8h             q12h          q8h          q8h          q8h        q12h 
50         500          500              250              250          750          500          500         500 q6h          q8h              q6h             q12h          q8h          q6h          q8h        q12h 
40         500          250              250              250          500          500          250         250 q8h          q6h              q8h             q12h          q6h          q8h          q6h        q12h 
30         250          250              250              250          500          250          250         250 q6h          q8h              q8h             q12h          q8h          q6h          q8h        q12h Patients with creatinine clearances of 6 to 20 mL/min/1.73 m2 should be treated with TIENAM 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 TIENAM I.V. unless hemodialysis is instituted within 48 hours. There is inadequate information to recommend usage of TIENAM 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 TIENAM 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, TIENAM 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 2.0 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 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.
TIENAM I.V. is not recommended in pediatric patients with CNS infections because of the risk of seizures.
TIENAM I.V. is not recommended in pediatric patients <30 kg with impaired renal function, as no data are available.

PREPARATION OF SOLUTION

Contents of the vials must be suspended and transferred to 100 mL of an appropriate infusion solution.
A suggested procedure is to add approximately 10 mL from the appropriate infusion solution (see list of diluents under COMPATIBILITY AND STABILITY) to the vial. Shake well and transfer the resulting suspension to the infusion solution container.
Benzyl alcohol as a preservative has been associated with toxicity in neonates. While toxicity has not been demonstrated in pediatric patients greater than three months of age, small pediatric patients in this age range may also be at risk for benzyl alcohol toxicity. Therefore, diluents containing benzyl alcohol should not be used when TIENAM I.V. is constituted for administration to pediatric patients in this age range.
CAUTION: THE SUSPENSION IS NOT FOR DIRECT INFUSION.
Repeat with an additional 10 mL of infusion solution to ensure complete transfer of vial contents to the infusion solution. The resulting mixture should be agitated until clear.

COMPATIBILITY AND STABILITY

Before Reconstitution:
The dry powder should be stored at room temperature (15°C - 25°C).
Reconstituted Solutions:
Solutions of TIENAM I.V. range from colorless to yellow. Variations of color within this range do not affect the potency of the product.

TIENAM I.V., as supplied in single use vials and reconstituted with the following diluents (see PREPARATION OF SOLUTION), maintains satisfactory potency for 4 hours at room temperature or for 24 hours under refrigeration (5°C). Solutions of TIENAM I.V. should not be frozen.
0.9% Sodium Chloride Injection
5% or 10% Dextrose Injection
5% Dextrose and 0.9% Sodium Chloride Injection
5% Dextrose Injection with 0.225% or 0.45% saline solution
5% Dextrose Injection with 0.15% potassium chloride solution
Mannitol 5% and 10%
TIENAM I.V. should not be mixed with or physically added to other antibiotics. However, TIENAM I.V. may be administered concomitantly with other antibiotics, such as aminoglycosides.