Posology : מינונים

DOSAGE AND ADMINISTRATION
UNASYN®     may be administered by either the IV or the IM routes.
For IV administration, the dose can be given by slow intravenous injection over at least 10–15 minutes or can also be delivered in greater dilutions with 50–100 mL of a compatible diluent as an intravenous infusion over 15–30 minutes.

UNASYN® may be administered by deep intramuscular injection (see DIRECTIONS FOR USE-Preparation for Intramuscular Injection section).

The recommended adult dosage of UNASYN® is 1.5 g (1 g ampicillin as the sodium salt plus 0.5 g sulbactam as the sodium salt) to 3 g (2 g ampicillin as the sodium salt plus 1 g sulbactam as the sodium salt) every six hours. This 1.5 to 3 g range represents the total of 
ampicillin content plus the sulbactam content of UNASYN®, and corresponds to a range of 1 g ampicillin/0.5 g sulbactam to 2 g ampicillin/1 g sulbactam. The total dose of sulbactam should not exceed 4 grams per day.

Pediatric Patients 1 Year of Age or Older: The recommended daily dose of UNASYN® in pediatric patients is 300 mg per kg of body weight administered via intravenous infusion in equally divided doses every 6 hours. This 300 mg/kg/day dosage represents the total ampicillin content plus the sulbactam content of UNASYN®, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. The safety and efficacy of UNASYN® administered via intramuscular injection in pediatric patients have not been established. Pediatric patients weighing 40 kg or more should be dosed according to adult recommendations, and the total dose of sulbactam should not exceed 4 grams per day. The course of intravenous therapy should not routinely exceed 14 days.
In clinical trials, most children received a course of oral antimicrobials following initial treatment with intravenous UNASYN® (see CLINICAL STUDIES section).

Impaired Renal Function
In patients with impairment of renal function the elimination kinetics of ampicillin and sulbactam are similarly affected, hence the ratio of one to the other will remain constant whatever the renal function. The dose of UNASYN® in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:

TABLE 3
UNASYN® Dosage Guide for Patients with Renal Impairment
Creatinine Clearance  Ampicillin/Sulbactam           Recommended
(mL/min/1.73m ) 2      Half-Life (Hours)           UNASYN® Dosage

≥30                              1                     1.5-3 g q 6h-q 8h 15-29                             5                       1.5-3 g q 12h 5-14                             9                       1.5-3g q 24h 
When only serum creatinine is available, the following formula (based on sex, weight, and age of the patient) may be used to convert this value into creatinine clearance. The serum creatinine should represent a steady state of renal function.

Males          weight (kg) × (140 – age)
72 × serum creatinine

Females        0.85 × above value

COMPATIBILITY, RECONSTITUTION AND STABILITY
UNASYN® sterile powder is to be stored below 25°C prior to reconstitution.

The expiry date of the product is indicated on the packaging materials 
When concomitant therapy with aminoglycosides is indicated, UNASYN® and aminoglycosides should be reconstituted and administered separately, due to the in vitro inactivation of aminoglycosides by any of the aminopenicillins.


DIRECTIONS FOR USE
General Dissolution Procedures
UNASYN® sterile powder for intravenous and intramuscular use may be reconstituted with any of the compatible diluents described in this insert. Solutions should be allowed to stand after dissolution to allow any foaming to dissipate in order to permit visual inspection for complete solubilization.
Preparation for Intravenous Use
1.5 g and 3.0 g Bottles: UNASYN® sterile powder in piggyback units may be reconstituted directly to the desired concentrations using any of the following parenteral diluents. Reconstitution of UNASYN®, at the specified concentrations, with these diluents provide stable solutions for the time periods indicated in the following table: (After the indicated time periods, any unused portions of solutions should be discarded).

TABLE 4
Maximum Concentration
(mg/mL)
Diluent                              UNASYN®(Ampicillin/Sulbactam)               Use Periods Sterile Water for Injection                   45 (30/15)                         8 hrs at 25°C 45 (30/15)                        48 hrs at 4°C
30 (20/10)                        72 hrs at 4°C
0.9% Sodium Chloride Injection                45 (30/15)                         8 hrs at 25°C 45 (30/15)                        48 hrs at 4°C
30 (20/10)                        72 hrs at 4°C
5% Dextrose Injection                         30 (20/10)                         2 hrs at 25°C 30 (20/10)                         4 hrs at 4°C
3 (2/1)                           4 hrs at 25°C
Lactated Ringer’s Injection                   45 (30/15)                         8 hrs at 25°C 45 (30/15)                        24 hrs at 4°C
M/6 Sodium Lactate Injection                  45 (30/15)                         8 hrs at 25°C 45 (30/15)                         8 hrs at 4°C
5% Dextrose in 0.45% Saline                    3 (2/1)                           4 hrs at 25°C 15 (10/5)                          4 hrs at 4°C
10% Invert Sugar                               3 (2/1)                           4 hrs at 25°C 30 (20/10)                         3 hrs at 4°C

If piggyback bottles are unavailable, standard vials of UNASYN® sterile powder may be 
used. Initially, the vials may be reconstituted with Sterile Water for Injection to yield solutions containing 375 mg UNASYN® per mL (250 mg ampicillin/125 mg sulbactam per mL). An appropriate volume should then be immediately diluted with a suitable parenteral diluent to yield solutions containing 3 to 45 mg UNASYN® per mL (2 to 30 mg ampicillin/1 to 15 mg sulbactam/per mL).

Preparation for Intramuscular Injection
1.5 g and 3.0 g Standard Vials: Vials for intramuscular use may be reconstituted with Sterile Water for Injection USP, 0.5% Lidocaine Hydrochloride Injection USP or 2% Lidocaine Hydrochloride Injection USP. Consult the following table for recommended volumes to be added to obtain solutions containing 375 mg UNASYN® per mL (250 mg ampicillin/125 mg sulbactam per mL). Note: Use only freshly prepared solutions and administer within one hour after preparation.

TABLE 5
UNASYN®                                Volume of Diluent                           Withdrawal Vial Size                              to be Added                                Volume* 1.5 g                                     3.2 mL                                    4.0 mL 3.0 g                                     6.4 mL                                    8.0 mL *There is sufficient excess present to allow withdrawal and administration of the stated volumes.

Animal Pharmacology: While reversible glycogenosis was observed in laboratory animals, this phenomenon was dose- and time-dependent and is not expected to develop at the therapeutic doses and corresponding plasma levels attained during the relatively short periods of combined ampicillin/sulbactam therapy in man.