Posology : מינונים

4.2.     Posology and method of administration
Piperacillin/Tazobactam Panpharma should be administered by intravenous infusion over 30 minutes.
Neutropenic patients with signs of infection (e.g., fever) should receive immediate empirical antibiotic therapy before laboratory results are available.
Adults and adolescents (over 12 years)
The usual dosage for adults and juveniles with normal renal function is 4.5 g piperacillin/tazobactam given every eight hours.
For nosocomial pneumonia and bacterial infections in neutropenic patients, the recommended dose is 4 g piperacillin/ 0.5 g tazobactam administered every 6 hours. This regimen may also be applicable to treat patients with other indicated infections when particularly severe.
Nosocomial Pneumonia
Initial presumptive treatment of patients with nosocomial pneumonia should start with Piperacillin/ Tazobactam Panpharma at a dosage of 4.5 g every six hours plus an aminoglycoside, totaling 18.0 g (16.0 g piperacillin/2.0 g tazobactam). Treatment with the aminoglycoside should be continued in patients from whom Pseudomonas aeruginosa is isolated. If Pseudomonas aeruginosa is not isolated, the aminoglycoside may be discontinued at the discretion of the treating physician.
Due to the in vitro inactivation of the aminoglycoside by beta-lactam antibiotics, Piperacillin/Tazobactam Panpharma and the aminoglycoside are recommended for separate administration.
Renal Insufficiency: Adults
In patients with renal insufficiency (Creatinine Clearance ≤40 mL/min), the intravenous dose of Piperacillin/Tazobactam Panpharma (piperacillin and tazobactam for injection) should be adjusted to the degree of actual renal function impairment. In patients with nosocomial pneumonia receiving concomitant aminoglycoside therapy, the aminoglycoside dosage should be adjusted according to the recommendations of the manufacturer. The recommended daily doses of Piperacillin/ Tazobactam Panpharma for patients with renal insufficiency are as follows:
Recommended Dosing of Piperacillin/Tazobactam Panpharma in Patients with Normal Renal Function and Renal Insufficiency (As total grams piperacillin/tazobactam).
TABLE 1
Renal Function
All Indications (except nosocomial
(Creatinine Clearance,                                                      Nosocomial Pneumonia pneumonia) mL/min)
>40 mL/min                No dose adjustment necessary                      4.5 q 6 h 20-40 mL/min*          Maximum dose suggested: 4.5 g q 8 h                  3.375 q 6 h
<20 mL/min*           Maximum dose suggested: 4.5 g q 12 h                  2.25 q 6 h Hemodialysis**                       2.25 q 12 h                             2.25 q 8 h CAPD                             2.25 q 12 h                             2.25 q 8 h * Creatinine clearance for patients not receiving hemodialysis
** 0.75 g should be administered following each hemodialysis session on hemodialysis days For patients on hemodialysis, the maximum dose is 2.25 g every twelve hours for all indications other than nosocomial pneumonia and 2.25 g every eight hours for nosocomial pneumonia. Since hemodialysis removes 30% to 40% of the administered dose, an additional dose of 0.75 g Piperacillin/Tazobactam Panpharma should be administered following each dialysis period on hemodialysis days. No additional dosage of Piperacillin/Tazobactam Panpharma is necessary for CAPD patients.
Duration of Therapy
The usual duration of Piperacillin/Tazobactam Panpharma treatment for most indications is in the range of 5-14 days. However, the recommended duration of Piperacillin/Tazobactam Panpharma treatment of nosocomial pneumonia is 7 to 14 days. In all conditions, the duration of therapy should be guided by the severity of the infection and the patient’s clinical and bacteriological progress.
Pediatric Patients (2-12 years of age)
For children with appendicitis older than 2 years and/or peritonitis, weighing up to 40 kg, and with normal renal function, the recommended Piperacillin/Tazobactam Panpharma dosage is 100 mg piperacillin/12.5 mg tazobactam per kilogram of body weight, every 8 hours. Pediatric patients weighing over 40 kg and with normal renal function should receive the adult dose.
The following table summarizes the treatment frequency and the dose per body weight for pediatric patients 2-12 years of age by indication or condition:
TABLE 2
Dose per weight and treatment frequency             Indication / condition 80 mg Piperacillin / 10 mg Tazobactam per kg        Neutropenic children with fever suspected to be body weight / every 6 hours                         due to bacterial infections* 100 mg Piperacillin / 12.5 mg Tazobactam per kg     Complicated intra-abdominal infections* body weight / every 8 hours
* Not to exceed the maximum 4 g / 0.5 g per dose over 30 minutes


Renal impairment
The intravenous dose should be adjusted to the degree of actual renal impairment as follows (each patient must be monitored closely for signs of substance toxicity; medicinal product dose and interval should be adjusted accordingly):
TABLE 3
Creatinine        clearance    Piperacillin/Tazobactam Panpharma (recommended dose) (mL/min)
>50                            No dose adjustment needed.
>50                            70 mg piperacillin / 8.75 mg tazobactam / kg every 8 hours.


For children on hemodialysis, one additional dose of 40 mg piperacillin / 5 mg tazobactam / kg should be administered following each dialysis period.
Geriatric Use
Patients over 65 years are not at an increased risk of developing adverse effects solely because of age. However, dosage should be adjusted in the presence of renal insufficiency. (See DOSAGE AND ADMINISTRATION.)
In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Piperacillin/Tazobactam Panpharma contains 54 mg (2.35 mEq) of sodium per gram of piperacillin in the combination product. At the usual recommended doses, patients would receive between 648 and 864 mg/day (28.2 and 37.6 mEq) of sodium. The geriatric population may respond with a blunted natriuresis to salt loading. This may be clinically important with regard to such diseases as congestive heart failure.
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.