Unasyn (Ampicillin Sodium / Sulbactam Sodium) - Indications and Dosage

INDICATIONS AND USAGE

UNASYN is indicated for the treatment of infections due to susceptible strains of the designated microorganisms in the conditions listed below.

Skin and Skin Structure Infections caused by beta-lactamase producing strains of Staphylococcus aureus, Escherichia coli, [ Efficacy for this organism in this organ system was studied in fewer than 10 infections.] Klebsiella spp. (including K. pneumoniae ), Proteus mirabilis, Bacteroides fragilis, Enterobacter spp., and Acinetobacter calcoaceticus.

NOTE: For information on use in pediatric patients see PRECAUTIONS–Pediatric Use and CLINICAL STUDIES sections.

Intra-Abdominal Infections caused by beta-lactamase producing strains of Escherichia coli, Klebsiella spp. (including K. pneumoniae ), Bacteroides spp. (including B. fragilis), and Enterobacter spp.

Gynecological Infections caused by beta-lactamase producing strains of Escherichia coli, and Bacteroides spp. (including B. fragilis ).

While UNASYN is indicated only for the conditions listed above, infections caused by ampicillin-susceptible organisms are also amenable to treatment with UNASYN due to its ampicillin content. Therefore, mixed infections caused by ampicillin-susceptible organisms and beta-lactamase producing organisms susceptible to UNASYN should not require the addition of another antibiotic.

Appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify the organisms causing infection and to determine their susceptibility to UNASYN.

Therapy may be instituted prior to obtaining the results from bacteriological and susceptibility studies, when there is reason to believe the infection may involve any of the beta-lactamase producing organisms listed above in the indicated organ systems. Once the results are known, therapy should be adjusted if appropriate.

To reduce the development of drug-resistant bacteria and maintain effectiveness of UNASYN and other antibacterial drugs, UNASYN 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

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 Preparation for Intramuscular Injection.)

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:

UNASYN Dosage Guide For Patients With Renal Impairment

Creatinine Clearance (mL/min/1.73m2)	Ampicillin/Sulbactam Half-Life (Hours)	Recommended UNASYN Dosage
≥30	1	1.5–3.0 g q 6h-q 8h
15–29	5	1.5–3.0 g q 12h
5–14	9	1.5–3.0 g 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         wei g ht (k g) × (140 – a g e)
                         72 × serum creatinine

     Females     0.85 × above value

COMPATIBILITY, RECONSTITUTION AND STABILITY

UNASYN sterile powder is to be stored at or below 30°C (86°F) prior to reconstitution.

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.)

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

1.5 g ADD-Vantage® Vials: UNASYN in the ADD-Vantage® system is intended as a single dose for intravenous administration after dilution with the ADD-Vantage® Flexible Diluent Container containing 50 mL, 100 mL or 250 mL of 0.9% Sodium Chloride Injection, USP.

3 g ADD-Vantage® Vials: UNASYN in the ADD-Vantage® system is intended as a single dose for intravenous administration after dilution with the ADD-Vantage® Flexible Diluent Container containing 100 mL or 250 mL of 0.9% Sodium Chloride Injection, USP.

UNASYN in the ADD-Vantage® system is to be reconstituted with 0.9% Sodium Chloride Injection, USP only. See INSTRUCTIONS FOR USE OF THE ADD-Vantage® VIAL. Reconstitution of UNASYN, at the specified concentration, with 0.9% Sodium Chloride Injection, USP provides stable solutions for the time period indicated below:

Diluent	Maximum Concentration (mg/mL) UNASYN (Ampicillin/Sulbactam)	Use Period
0.9% Sodium Chloride Injection	30 (20/10)	8 hrs @ 25°C

In 0.9% Sodium Chloride Injection, USP

The final diluted solution of UNASYN should be completely administered within 8 hours in order to assure proper potency.

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.

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

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.

HOW SUPPLIED

UNASYN (ampicillin sodium/sulbactam sodium) is supplied as a sterile off-white dry powder in glass vials and piggyback bottles. The following packages are available:

Vials containing 1.5 g (NDC 0049-0013-83) equivalent of UNASYN (1 g ampicillin as the sodium salt plus 0.5 g sulbactam as the sodium salt)

Vials containing 3 g (NDC 0049-0014-83) equivalent of UNASYN (2 g ampicillin as the sodium salt plus 1 g sulbactam as the sodium salt)

Bottles containing 1.5 g (NDC 0049-0022-83) equivalent of UNASYN (1 g ampicillin as the sodium salt plus 0.5 g sulbactam as the sodium salt)

Bottles containing 3 g (NDC 0049-0023-83) equivalent of UNASYN (2 g ampicillin as the sodium salt plus 1 g sulbactam as the sodium salt)

Pharmacy Bulk Package containing 15 g (NDC 0049-0024-28) equivalent of UNASYN (10 g ampicillin as the sodium salt plus 5 g sulbactam as the sodium salt)

ADD-Vantage® vials containing 1.5 g (NDC 0049-0031-83) equivalent of UNASYN (1 g ampicillin as the sodium salt plus 0.5 g sulbactam as the sodium salt) are distributed by Pfizer Inc.

ADD-Vantage® vials containing 3 g (NDC 0049-0032-83) equivalent of UNASYN (2 g ampicillin as the sodium salt plus 1 g sulbactam as the sodium salt) are distributed by Pfizer Inc.

The 1.5 g UNASYN ADD-Vantage® vials are only to be used with Abbott Laboratories' ADD-Vantage® Flexible Diluent Container containing 0.9% Sodium Chloride Injection, USP, 50 mL, 100 mL, or 250 mL sizes.

The 3 g UNASYN ADD-Vantage® vials are only to be used with Abbott Laboratories' ADD-Vantage® Flexible Diluent Container containing 0.9% Sodium Chloride Injection, USP, 100 mL or 250 mL sizes.

INSTRUCTIONS FOR USE OF THE ADD-Vantage® VIAL

To Open Diluent Container

Peel overwrap from the corner and remove container. Some opacity of the plastic due to moisture absorption during the sterilization process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually.

To Assemble Vial and Flexible Diluent Container: (Use Aseptic Technique)

1. Remove the protective covers from the top of the vial and the vial port on the diluent container as follows:
   a.To remove the breakaway vial cap, swing the pull ring over the top of the vial and pull down far enough to start the opening (see Figure 1), pull the ring approximately half way around the cap and then pull straight up to remove the cap (see Figure 2).

NOTE: Do not access vial with syringe.

• b.To remove the vial port cover, grasp the tab on the pull ring, pull up to break the three tie strings, then pull back to remove the cover. (See Figure 3.)

NOTE: Once vial is sealed, do not attempt to remove. (See Figure 4.)

• 3.Recheck the vial to assure that it is tight by trying to turn it further in the direction of assembly.
  
  
• 4.Label appropriately.

          

                                      
                                     Fig. 3                                                    Fig. 4