Ampicillin And Sulbactam

Ampicillin and sulbactam for injection 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.

Ampicillin and sulbactam for injection may be administered by deep intramuscular injection. (See Preparation for Intramuscular Injection.)

The recommended adult dosage of ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection, 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 ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. The safety and efficacy of ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection. (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 ampicillin and sulbactam for injection in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:

Ampicillin And Sulbactam For Injection Dosage Guide
For Patients With Renal Impairment Creatinine Clearance (mL/min/1.73m2) Ampicillin/ Sulbactam
Half-Life (Hours)

Recommended

Ampicillin And Sulbactam
For Injection Dosage ≥ 30 1 1.5-3 g q 6 h-q 8 h 15-29 5 1.5-3 g q 12 h 5-14 9 1.5-3 g q 24 h

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

Ampicillin and sulbactam for injection 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.

Ampicillin and sulbactam for injection may be administered by deep intramuscular injection. (See Preparation for Intramuscular Injection.)

The recommended adult dosage of ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection, 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 ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. The safety and efficacy of ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection. (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 ampicillin and sulbactam for injection in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:

Ampicillin And Sulbactam For Injection Dosage Guide
For Patients With Renal Impairment Creatinine Clearance
(mL/min/1.73m2) Ampicillin/ Sulbactam
Half-Life (Hours)

Recommended

Ampicillin And Sulbactam
For Injection Dosage ≥ 30 1 1.5-3 g q 6 h-q 8 h 15-29 5 1.5-3 g q 12 h 5-14 9 1.5-3 g q 24 h

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

Ampicillin and sulbactam for injection 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.

Ampicillin and sulbactam for injection may be administered by deep intramuscular injection. (See Preparation for Intramuscular Injection .)

The recommended adult dosage of ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection, 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 ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. The safety and efficacy of ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection. (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 ampicillin and sulbactam for injection in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:

Ampicillin And Sulbactam For Injection Dosage Guide For
Patients With Renal Impairment Creatinine Clearance (mL/min/1.73m2) Ampicillin/ Sulbactam Half-Life (Hours)

Recommended

Ampicillin And Sulbactam
For Injection Dosage ≥ 30 1 1.5-3 g q 6 h-q 8 h 15-29 5 1.5-3 g q 12 h 5-14 9 1.5-3 g q 24 h

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

Ampicillin and sulbactam for injection may be used for parenteral administration. THE INTENT OF THIS PHARMACY BULK PACKAGE IS FOR PREPARATION OF SOLUTIONS FOR IV INFUSION ONLY.

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.

The recommended adult dosage of ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection, 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 ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. The safety and efficacy of ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection. (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 ampicillin and sulbactam for injection in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:

Ampicillin And Sulbactam For Injection Dosage Guide
For Patients With Renal Impairment
Creatinine Clearance
(mL/min/1.73 m2) Ampicillin/Sulbactam
Half-Life (Hours) Recommended
Ampicillin And Sulbactam
For Injection Dosage ≥30 1 1.5-3.0 g q 6 h-q 8 h 15-29 5 1.5-3.0 g q 12 h 5-14 9 1.5-3.0 g q 24 h

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) x (140 – age)
72 x serum creatinine Females 0.85 x above value

Ampicillin and sulbactam for injection may be used for parenteral administration. THE INTENT OF THIS PHARMACY BULK PACKAGE IS FOR PREPARATION OF SOLUTIONS FOR IV INFUSION ONLY.

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.

The recommended adult dosage of ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection, 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 ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. The safety and efficacy of ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection. (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 ampicillin and sulbactam for injection in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:

Ampicillin And Sulbactam For Injection Dosage Guide
For Patients With Renal Impairment Creatinine Clearance (mL/min/1.73 m2) Ampicillin/Sulbactam
Half-Life (Hours)

Recommended

Ampicillin And Sulbactam
For Injection Dosage ≥ 30 1 1.5-3.0 g q 6 h-q 8 h 15-29 5 1.5-3.0 g q 12 h 5-14 9 1.5-3.0 g q 24 h

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

Ampicillin and sulbactam for injection may be used for parenteral administration. THE INTENT OF THIS PHARMACY BULK PACKAGE IS FOR PREPARATION OF SOLUTIONS FOR IV INFUSION ONLY.

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.

The recommended adult dosage of ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection, 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 ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. The safety and efficacy of ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection. (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 ampicillin and sulbactam for injection in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:

Ampicillin And Sulbactam For Injection Dosage Guide For Patients With Renal Impairment Creatinine Clearance (mL/min/1.73 m2) Ampicillin/Sulbactam
Half-Life (Hours)

Recommended

Ampicillin And Sulbactam
For Injection Dosage ≥ 30 1 1.5-3.0 g q 6 h-q 8 h 15-29 5 1.5-3.0 g q 12 h 5-14 9 1.5-3.0 g q 24 h

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

Ampicillin and Sulbactam for Injection, USP 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 to 15 minutes or can also be delivered in greater dilutions with 50 to 100 mL of a compatible diluent as an intravenous infusion over 15 to 30 minutes.

Ampicillin and Sulbactam for Injection, USP may be administered by deep intramuscular injection (see Preparation for Intramuscular Injection).

The recommended adult dosage of Ampicillin and Sulbactam for Injection, USP 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 Ampicillin and Sulbactam for Injection, USP 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 Ampicillin and Sulbactam for Injection, USP 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 Ampicillin and Sulbactam for Injection, USP, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. The safety and efficacy of Ampicillin and Sulbactam for Injection, USP 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 Ampicillin and Sulbactam for Injection, USP (see CLINICAL STUDIES).

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 Ampicillin and Sulbactam for Injection, USP in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:

Ampicillin and Sulbactam for Injection, USP Dosage Guide For Patients With Renal Impairment Creatinine Clearance (mL/min/1.73m2 Ampicillin/Sulbactam Half-Life (Hours) Recommended Ampicillin and Sulbactam for Injection, USP Dosage ≥30 1 1.5 to 3 g q 6h to q 8h 15 to 29 5 1.5 to 3 g q 12h 5 to 14 9 1.5 to 3 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 weight (kg) ×(140 - age) 72 × serum creatinine Females 0.85 × above value COMPATIBILITY, RECONSTITUTION AND STABILITY:

Ampicillin and Sulbactam for Injection, USP sterile powder is to be stored at 20o to 25oC (68o to 77oF) [see USP Controlled Room Temperature] prior to reconstitution.

When concomitant therapy with aminoglycosides is indicated, Ampicillin and Sulbactam for Injection, USP 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

Ampicillin and Sulbactam for Injection, USP 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 gram and 3.0 gram vials: Initially, vials for intravenous use may be reconstituted with Sterile Water for Injection to yield solutions containing 375 mg Ampicillin and Sulbactam for Injection, USP per mL (250 mg ampicillin/125 mg sulbactam per mL). An appropriate volume should then be immediately diluted with the following suitable parenteral diluents to yield solutions containing 3 to 45 mg Ampicillin and Sulbactam for Injection, USP per mL (2 to 30 mg ampicillin/1 to 15 mg sulbactam/per mL). Reconstitution of Ampicillin and Sulbactam for Injection, USP at the specified concentrations, with these diluents provides 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) Ampicillin and Sulbactam for Injection, USP Use Periods Sterile Water for Injection 45 (30/15) 8 hrs @ 25°C 45 (30/15) 48 hrs @ 4°C 30 (20/10) 72 hrs @ 4°C 0.9% Sodium Chloride Injection 45 (30/15) 8 hrs @ 25°C 45 (30/15) 48 hrs @ 4°C 30 (20/10) 72 hrs @ 4°C 5% Dextrose injection 30 (20/10) 2 hrs @ 25°C 30 (20/10) 4 hrs @ 4°C 3 (2/1) 4 hrs @ 25°C Lactated Ringer’s Injection 45 (30/15) 8 hrs @ 25°C 45 (30/15) 24 hrs @ 4°C M/6 Sodium Lactate Injection 45 (30/15) 8 hrs @ 25°C 45 (30/15) 8 hrs @ 4°C 5% Dextrose in 0.45% Saline 3 (2/1) 4 hrs @ 25°C 15 (10/5) 4 hrs @ 4°C 10% Invert Sugar 3 (2/1) 4 hrs @ 25°C 30 (20/10) 3 hrs @ 4°C Preparation for Intramuscular Injection

1.5 gram and 3 gram 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 Ampicillin and Sulbactam per mL (250 mg ampicillin/125 mg sulbactam per mL). Note: Use only freshly prepared solutions and administer within one hour after preparation.

Ampicillin and Sulbactam for Injection, USP Vial Size Volume of Diluent to be Added Withdrawal Volume* 1.5 g 3.2 mL 4 mL 3 g 6.4 mL 8 mL

*There is sufficient excess present to allow withdrawal and administration of the stated volumes.

Ampicillin and Sulbactam for Injection, USP 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 to 15 minutes or can also be delivered in greater dilutions with 50 to 100 mL of a compatible diluent as an intravenous infusion over 15 to 30 minutes.

Ampicillin and Sulbactam for Injection, USP may be administered by deep intramuscular injection (see Preparation for Intramuscular Injection).

The recommended adult dosage of Ampicillin and Sulbactam for Injection, USP 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 Ampicillin and Sulbactam for Injection, USP 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 Ampicillin and Sulbactam for Injection, USP 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 Ampicillin and Sulbactam for Injection, USP, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. The safety and efficacy of Ampicillin and Sulbactam for Injection, USP 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 Ampicillin and Sulbactam for Injection, USP (see CLINICAL STUDIES).

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 Ampicillin and Sulbactam for Injection, USP in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:

Ampicillin and Sulbactam for Injection, USP Dosage Guide For Patients With Renal Impairment Creatinine Clearance (mL/min/1.73m2 Ampicillin/Sulbactam Half-Life (Hours) Recommended Ampicillin and Sulbactam for Injection, USP Dosage ≥30 1 1.5 to 3 g q 6h to q 8h 15 to 29 5 1.5 to 3 g q 12h 5 to 14 9 1.5 to 3 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 weight (kg) ×(140 - age) 72 × serum creatinine Females 0.85 × above value COMPATIBILITY, RECONSTITUTION AND STABILITY:

Ampicillin and Sulbactam for Injection, USP sterile powder is to be stored at 20o to 25oC (68o to 77oF) [see USP Controlled Room Temperature] prior to reconstitution.

When concomitant therapy with aminoglycosides is indicated, Ampicillin and Sulbactam for Injection, USP 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

Ampicillin and Sulbactam for Injection, USP 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 gram and 3.0 gram vials: Initially, vials for intravenous use may be reconstituted with Sterile Water for Injection to yield solutions containing 375 mg Ampicillin and Sulbactam for Injection, USP per mL (250 mg ampicillin/125 mg sulbactam per mL). An appropriate volume should then be immediately diluted with the following suitable parenteral diluents to yield solutions containing 3 to 45 mg Ampicillin and Sulbactam for Injection, USP per mL (2 to 30 mg ampicillin/1 to 15 mg sulbactam/per mL). Reconstitution of Ampicillin and Sulbactam for Injection, USP at the specified concentrations, with these diluents provides 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) Ampicillin and Sulbactam for Injection, USP Use Periods Sterile Water for Injection 45 (30/15) 8 hrs @ 25°C 45 (30/15) 48 hrs @ 4°C 30 (20/10) 72 hrs @ 4°C 0.9% Sodium Chloride Injection 45 (30/15) 8 hrs @ 25°C 45 (30/15) 48 hrs @ 4°C 30 (20/10) 72 hrs @ 4°C 5% Dextrose injection 30 (20/10) 2 hrs @ 25°C 30 (20/10) 4 hrs @ 4°C 3 (2/1) 4 hrs @ 25°C Lactated Ringer’s Injection 45 (30/15) 8 hrs @ 25°C 45 (30/15) 24 hrs @ 4°C M/6 Sodium Lactate Injection 45 (30/15) 8 hrs @ 25°C 45 (30/15) 8 hrs @ 4°C 5% Dextrose in 0.45% Saline 3 (2/1) 4 hrs @ 25°C 15 (10/5) 4 hrs @ 4°C 10% Invert Sugar 3 (2/1) 4 hrs @ 25°C 30 (20/10) 3 hrs @ 4°C Preparation for Intramuscular Injection

1.5 gram and 3 gram 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 Ampicillin and Sulbactam per mL (250 mg ampicillin/125 mg sulbactam per mL). Note: Use only freshly prepared solutions and administer within one hour after preparation.

Ampicillin and Sulbactam for Injection, USP Vial Size Volume of Diluent to be Added Withdrawal Volume* 1.5 g 3.2 mL 4 mL 3 g 6.4 mL 8 mL

*There is sufficient excess present to allow withdrawal and administration of the stated volumes.

Ampicillin and Sulbactam for Injection is administered intravenously.

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.

The recommended adult dosage of Ampicillin and Sulbactam for Injection 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 Ampicillin and Sulbactam for Injection, 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 Ampicillin and Sulbactam for Injection 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 Ampicillin and Sulbactam for Injection, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. 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 Ampicillin and Sulbactam for Injection. (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 Ampicillin and Sulbactam in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:

TABLE 5. Ampicillin and Sulbactam for Injection Dosage Guide for Patients with Renal Impairment Creatinine Clearance
(mL/min/1.73m2) Ampicillin/Sulbactam
Half-Life (Hours) Recommended Ampicillin and Sulbactam Dosage

≥ 30

1

1.5-3 g q 6h-q 8h

15-29

5

1.5-3 g q 12h

5-14

9

1.5-3 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

weight (kg) x (140 - age)

72 x serum creatinine

Females

0.85 x above value

COMPATIBILITY, RECONSTITUTION AND STABILITY

Ampicillin and Sulbactam for Injection sterile powder is to be stored at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature.] prior to reconstitution.

When concomitant therapy with aminoglycosides is indicated, Ampicillin and Sulbactam and aminoglycosides should be reconstituted and administered separately, due to the in vitro inactivation of aminoglycosides by any of the aminopenicillins.

DIRECTIONS FOR USE

1.5 g ADD-Vantage® Vials: Ampicillin and Sulbactam for Injection 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: Ampicillin and Sulbactam for Injection 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.

Ampicillin and Sulbactam for Injection 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 section. Reconstitution of Ampicillin and Sulbactam for Injection, at the specified concentration, with 0.9% Sodium Chloride Injection, USP provides stable solutions for the time period indicated below:

TABLE 6. Diluent Maximum Concentration
(mg/mL)
ampicillin and sulbactam Use Periods

0.9% Sodium Chloride Injection, USP

30 (20/10)

8 hrs at 25°C

In 0.9% Sodium Chloride Injection, USP

The final diluted solution of Ampicillin and Sulbactam for Injection should be completely administered within 8 hours in order to assure proper potency.

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.

Ampicillin and sulbactam for injection 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.

Ampicillin and sulbactam for injection may be administered by deep intramuscular injection. (See Preparation for Intramuscular Injection.)

The recommended adult dosage of ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection, 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 ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. The safety and efficacy of ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection. (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 ampicillin and sulbactam for injection in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:

Ampicillin And Sulbactam For Injection Dosage Guide
For Patients With Renal Impairment Creatinine Clearance (mL/min/1.73m2) Ampicillin/ Sulbactam
Half-Life (Hours) RecommendedAmpicillin And Sulbactam
For Injection Dosage ≥ 30 1 1.5-3 g q 6 h-q 8 h 15-29 5 1.5-3 g q 12 h 5-14 9 1.5-3 g q 24 h

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

Ampicillin and sulbactam for injection 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 to 15 minutes or can also be delivered in greater dilutions with 50 to 100 mL of a compatible diluent as an intravenous infusion over 15 to 30 minutes.

Ampicillin and sulbactam for injection may be administered by deep intramuscular injection. (See DIRECTIONS FOR USE-Preparation for Intramuscular Injection section.)

The recommended adult dosage of ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection, 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 ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. The safety and efficacy of ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection. (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 ampicillin and sulbactam for injection in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:

TABLE 5 Ampicillin And Sulbactam For Injection Dosage Guide for Patients with Renal Impairment Creatinine Clearance
(mL/min/1.73m2) Ampicillin/Sulbactam
Half-Life (Hours) Recommended Ampicillin And Sulbactam For Injection Dosage ≥ 30 1 1.5 to 3 g q 6 h to q 8 h 15 to 29 5 1.5 to 3 g q 12 h 5 to 14 9 1.5 to 3 g q 24 h

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) x (140 - age) 72 x serum creatinine Females 0.85 x above value

DOSAGE AND ADMINISTRATION:

Ampicillin and Sulbactam for Injection, USP 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 to 15 minutes or can also be delivered, in greater dilutions with 50 to 100 mL of a compatible diluent as an intravenous infusion over 15 to 30 minutes.

Ampicillin and Sulbactam for Injection, USP may be administered by deep intramuscular injection (see Preparation tor Intramuscular Injection).

The recommended adult dosage of Ampicillin and Sulbactam for Injection, USP 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 Ampicillin and Sulbactam for Injection, USP, 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 Ampicillin and Sulbactam for Injection, USP 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 Ampicillin and Sulbactam for Injection, USP, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. The safety and efficacy of Ampicillin and Sulbactam for Injection, USP 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 Ampicillin and Sulbactam for Injection, USP (see CLINICAL STUDIES).

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 Ampicillin and Sulbactam for Injection, USP in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:

Ampicillin and Sulbactam for Injection, USP Dosage Guide For Patients With Renal Impairment Creatinine
Clearance
(mL/min/1.73m2) Ampicillin/Sulbactam
Half-Life (Hours) Recommended
Ampicillin and Sulbactam
for Injection, USP
Dosage ≥ 30 1 1.5 to 3 g q 6h-q 8h 15-29 5 1.5 to 3 g q 12h 5-14 9 1.5 to 3 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 Weight (kg) x (140 - age) 72 x serum creatinine Females 0.85 x above value

DOSAGE AND ADMINISTRATION:

Ampicillin and Sulbactam for Injection, USP may be used for parenteral administration (following dilution). THE INTENT OF THIS PHARMACY BULK PACKAGE IS FOR PREPARATION OF SOLUTIONS FOR IV INFUSION ONLY.

For IV administration, the dose can be given by slow intravenous injection over at least 10 to 15 minutes or can also be delivered, in greater dilutions with 50 to 100 mL of a compatible diluent as an intravenous infusion over 15 to 30 minutes.

The recommended adult dosage of ampicillin and sulbactam 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 Ampicillin and Sulbactam for Injection, USP 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 Ampicillin and Sulbactam for Injection, USP 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 ampicillin and sulbactam for injection, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. 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 Ampicillin and Sulbactam for Injection, USP (see CLINICAL STUDIES).

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 Ampicillin and Sulbactam for Injection in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:

Ampicillin and Sulbactam for Injection, USP Dosage Guide For Patients With Renal Impairment Creatinine
Clearance
(mL/min/1.73m2) Ampicillin/Sulbactam
Half-Life (Hours) Recommended
Ampicillin and Sulbactam
for Injection, USP
Dosage ≥ 30 1 1.5 to 3g q6h-q8h 15-29 5 1.5 to 3g q12h 5-14 9 1.5 to 3g q24h

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) x (140 - age) 72 x serum creatinine Females 0.85 x above value

Ampicillin and Sulbactam for Injection may be administered by IV route.

For IV administration, the dose can be given by slow intravenous injection over at least 10 to 15 minutes or can also be delivered in greater dilutions with 50 to 100 mL of a compatible diluent as an intravenous infusion over 15 to 30 minutes.

The recommended adult dosage of ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection, 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 ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. The safety and efficacy of ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection. (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 ampicillin and sulbactam in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:

TABLE 5

Ampicillin and Sulbactam for Injection Dosage Guide for Patients
with Renal Impairment

Creatinine Clearance
(mL/min/1.73 m2)

Ampicillin/Sulbactam
Half-Life (Hours)

Recommended
Ampicillin and Sulbactam Dosage 

≥30

1

1.5 g to 3 g q 6h to q 8h

15 to 29

5

1.5 g to 3 g q 12h

5 to 14

9

1.5 g to 3 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       weight (kg) × (140 – age)
                   72 × serum creatinine

Females      0.85 × above value

Ampicillin and Sulbactam for Injection 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.

Ampicillin and Sulbactam for Injection may be administered by deep intramuscular injection. (See DIRECTIONS FOR USE-Preparation for Intramuscular Injection section.)

The recommended adult dosage of Ampicillin and Sulbactam for Injection 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 Ampicillin and Sulbactam for Injection, 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 Ampicillin and Sulbactam for Injection 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 Ampicillin and Sulbactam for Injection, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. The safety and efficacy of Ampicillin and Sulbactam for Injection 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 Ampicillin and Sulbactam for Injection. (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 Ampicillin and Sulbactam in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:

TABLE 5. Ampicillin and Sulbactam for Injection Dosage Guide for Patients with Renal Impairment Creatinine Clearance
(mL/min/1.73m2) Ampicillin/Sulbactam
Half-Life (Hours) Recommended Ampicillin and Sulbactam Dosage

≥ 30

1

1.5-3 g q 6h-q 8h

15-29

5

1.5-3 g q 12h

5-14

9

1.5-3 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

weight (kg) x (140 - age)

72 x serum creatinine

Females

0.85 x above value

COMPATIBILITY, RECONSTITUTION AND STABILITY

Ampicillin and Sulbactam for Injection sterile powder is to be stored at 20 to 25°C (68 to 77°F) [See USP Controlled Room Temperature.] prior to reconstitution.

When concomitant therapy with aminoglycosides is indicated, Ampicillin and Sulbactam 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

Ampicillin and Sulbactam for Injection 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

Reconstitution of Ampicillin and Sulbactam for Injection, 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 6. Diluent Maximum Concentration
(mg/mL)
ampicillin and 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)

2 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

Initially, the vials may be reconstituted with Sterile Water for Injection to yield solutions containing 375 mg Ampicillin and Sulbactam 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 Ampicillin and Sulbactam per mL (2 to 30 mg ampicillin/1 to 15 mg sulbactam/per mL).

Preparation for Intramuscular Injection 1.5 g and 3 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 ampicillin and sulbactam per mL (250 mg ampicillin/ 125 mg sulbactam per mL).

Note: Use only freshly prepared solutions and administer within one hour after preparation.

Ampicillin and Sulbactam Vial Size Volume of Diluent to be Added Withdrawal Volume* * There is sufficient excess present to allow withdrawal and administration of the stated volumes.

1.5 g

3.2 mL

4 mL

3 g

6.4 mL

8 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.

Ampicillin and sulbactam for injection may be used for parenteral administration. THE INTENT OF THIS PHARMACY BULK PACKAGE IS FOR PREPARATION OF SOLUTIONS FOR IV INFUSION ONLY.

Ampicillin and sulbactam for injection should be administered 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.

The recommended adult dosage of ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection, 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 ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. The safety and efficacy of ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection. (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 ampicillin and sulbactam for injection in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:

TABLE 5 Ampicillin and Sulbactam for Injection Dosage Guide for Patients With Renal Impairment  Creatinine Clearance
(mL/min/1.73m2)  Ampicillin/Sulbactam
Half-Life (Hours)  Recommended
Ampicillin and Sulbactam
for Injection Dosage   ≥ 30   1   1.5 to 3 g q 6 h-q 8 h   15 to 29   5   1.5 to 3 g q 12 h   5 to 14   9   1.5 to 3 g q 24 h

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) x (140 – age)
72 x serum creatinine   Females   0.85 x above value

Carefully consider the potential benefits and risks of flurbiprofen tablets USP and other treatment options before deciding to use flurbiprofen tablets USP. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).

After observing the response to initial therapy with flurbiprofen tablets USP, the dose and frequency should be adjusted to suit an individual patient's needs.

For relief of the signs and symptoms of rheumatoid arthritis or osteoarthritis, the recommended starting dose of flurbiprofen tablets USP is 200 to 300 mg per day, divided for administration two, three, or four times a day. The largest recommended single dose in a multiple-dose daily regimen is 100 mg.

Ampicillin and sulbactam for injection may be used for parenteral administration. THE INTENT OF THIS PHARMACY BULK PACKAGE IS FOR PREPARATION OF SOLUTIONS FOR IV INFUSION ONLY.

Ampicillin and sulbactam for injection should be administered 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.

The recommended adult dosage of ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection, 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 ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. The safety and efficacy of ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection. (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 ampicillin and sulbactam for injection in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:

TABLE 5 Ampicillin and Sulbactam for Injection Dosage Guide for Patients With Renal Impairment Creatinine Clearance (mL/min/1.73m2) Ampicillin/Sulbactam
Half-Life (Hours) Recommended Ampicillin and Sulbactam
for Injection Dosage ≥ 30 1 1.5 to 3 g q 6 h-q 8 h 15 to 29 5 1.5 to 3 g q 12 h 5 to 14 9 1.5 to 3 g q 24 h

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

Ampicillin and sulbactam for injection 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.

Ampicillin and sulbactam for injection may be administered by deep intramuscular injection. (See DIRECTION FOR USE-Preparation for Intramuscular Injection section.)

The recommended adult dosage of ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection, 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 ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. The safety and efficacy of ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection. (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 ampicillin and sulbactam for injection in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:

TABLE 5 Ampicillin and Sulbactam for Injection Dosage Guide for Patients With Renal Impairment  Creatinine Clearance
(mL/min/1.73m2)  Ampicillin/Sulbactam
Half-Life (Hours)   Recommended Ampicillin and Sulbactam
for Injection Dosage  ≥30  1  1.5 to 3 g q 6 h-q 8 h  15 to 29  5  1.5 to 3 g q 12 h  5 to 14  9  1.5 to 3 g q 24 h

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

Ampicillin and Sulbactam for Injection 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.

Ampicillin and Sulbactam for Injection may be administered by deep intramuscular injection. (See DIRECTIONS FOR USE-Preparation for Intramuscular Injection section.)

The recommended adult dosage of Ampicillin and Sulbactam for Injection 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 Ampicillin and Sulbactam for Injection, 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 Ampicillin and Sulbactam for Injection 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 Ampicillin and Sulbactam for Injection, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. The safety and efficacy of Ampicillin and Sulbactam for Injection 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 Ampicillin and Sulbactam for Injection. (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 Ampicillin and Sulbactam in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:

TABLE 5. Ampicillin and Sulbactam for Injection Dosage Guide for Patients with Renal Impairment Creatinine Clearance
(mL/min/1.73m2) Ampicillin/Sulbactam
Half-Life (Hours) Recommended Ampicillin and Sulbactam Dosage

≥ 30

1

1.5-3 g q 6h-q 8h

15-29

5

1.5-3 g q 12h

5-14

9

1.5-3 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

weight (kg) x (140 - age)

72 x serum creatinine

Females

0.85 x above value

COMPATIBILITY, RECONSTITUTION AND STABILITY

Ampicillin and Sulbactam for Injection sterile powder is to be stored at 20 to 25°C (68 to 77°F) [See USP Controlled Room Temperature.] prior to reconstitution.

When concomitant therapy with aminoglycosides is indicated, Ampicillin and Sulbactam 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

Ampicillin and Sulbactam for Injection 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

Reconstitution of Ampicillin and Sulbactam for Injection, 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 6. Diluent Maximum Concentration
(mg/mL)
ampicillin and 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)

2 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

Initially, the vials may be reconstituted with Sterile Water for Injection to yield solutions containing 375 mg Ampicillin and Sulbactam 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 Ampicillin and Sulbactam per mL (2 to 30 mg ampicillin/1 to 15 mg sulbactam/per mL).

Preparation for Intramuscular Injection 1.5 g and 3 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 ampicillin and sulbactam per mL (250 mg ampicillin/ 125 mg sulbactam per mL).

Note: Use only freshly prepared solutions and administer within one hour after preparation.

Ampicillin and Sulbactam Vial Size Volume of Diluent to be Added Withdrawal Volume* * There is sufficient excess present to allow withdrawal and administration of the stated volumes.

1.5 g

3.2 mL

4 mL

3 g

6.4 mL

8 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.

Dosage should be adjusted according to the severity of the pain and the response of the patient. It may occasionally be necessary to exceed the usual dosage recommended below in cases of more severe pain or in those patients who have become tolerant to the analgesic effect of opioids. If pain is constant, the opioid analgesic should be given at regular intervals on an around-the-clock schedule. Oxycodone and acetaminophen tablets, USP are given orally.

Oxycodone and acetaminophentablets, USP 7.5 mg/325 mg

The usual adult dosage is one tablet every 6 hours as needed for pain. The total daily dose of acetaminophen, USP should not exceed 4 grams.

 Strength  Maximal Daily Dose  Oxycodone and acetaminophen tablets, USP 7.5 mg/325 mg  8 Tablets

Cessation of Therapy

In patients treated with oxycodone and acetaminophen tablets, USP for more than a few weeks who no longer require therapy, doses should be tapered gradually to prevent signs and symptoms of withdrawal in the physically dependent patient.

Ampicillin and Sulbactam for Injection is administered intravenously.

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.

The recommended adult dosage of Ampicillin and Sulbactam for Injection 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 Ampicillin and Sulbactam for Injection, 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 Ampicillin and Sulbactam for Injection 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 Ampicillin and Sulbactam for Injection, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. 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 Ampicillin and Sulbactam for Injection. (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 Ampicillin and Sulbactam in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:

TABLE 5. Ampicillin and Sulbactam for Injection Dosage Guide for Patients with Renal Impairment Creatinine Clearance
(mL/min/1.73m2) Ampicillin/Sulbactam
Half-Life (Hours) Recommended Ampicillin and Sulbactam Dosage

≥ 30

1

1.5-3 g q 6h-q 8h

15-29

5

1.5-3 g q 12h

5-14

9

1.5-3 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

weight (kg) x (140 - age)

72 x serum creatinine

Females

0.85 x above value

COMPATIBILITY, RECONSTITUTION AND STABILITY

Ampicillin and Sulbactam for Injection sterile powder is to be stored at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature.] prior to reconstitution.

When concomitant therapy with aminoglycosides is indicated, Ampicillin and Sulbactam and aminoglycosides should be reconstituted and administered separately, due to the in vitro inactivation of aminoglycosides by any of the aminopenicillins.

DIRECTIONS FOR USE

1.5 g ADD-Vantage® Vials: Ampicillin and Sulbactam for Injection 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: Ampicillin and Sulbactam for Injection 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.

Ampicillin and Sulbactam for Injection 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 section. Reconstitution of Ampicillin and Sulbactam for Injection, at the specified concentration, with 0.9% Sodium Chloride Injection, USP provides stable solutions for the time period indicated below:

TABLE 6. Diluent Maximum Concentration
(mg/mL)
ampicillin and sulbactam Use Periods

0.9% Sodium Chloride Injection, USP

30 (20/10)

8 hrs at 25°C

In 0.9% Sodium Chloride Injection, USP

The final diluted solution of Ampicillin and Sulbactam for Injection should be completely administered within 8 hours in order to assure proper potency.

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.

Ampicillin and sulbactam may be administered by either the intravenous or the intramuscular routes.

For IV administration, the dose can be given by slow intravenous injection over at least 10 to 15 minutes or can also be delivered, in greater dilutions with 50 to 100 mL of a compatible diluent as an intravenous infusion over 15 to 30 minutes.

Ampicillin and sulbactam may be administered by deep intramuscular injection. (See Preparation for Intramuscular Injection.)

Pediatric Patients One Year of Age or Older

The recommended daily dose of ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. The safety and efficacy of ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection (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 ampicillin and sulbactam for injection in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:

Table 5: Ampicillin and Sulbactam for Injection Dosage Guide for Patients With Renal Impairment Creatinine Clearance
(mL/min/1.73m2) Ampicillin/Sulbactam
Half-Life (Hours) Recommended
Ampicillin and Sulbactam
for Injection Dosage

≥30

1

1.5 g to 3 g q 6h to q 8h

15 to 29

5

1.5 g to 3 g q 12h

5 to 14

9

1.5 g to 3 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 weight (kg) × (140 - age)

72 × serum creatinine

Females

0.85 × above value

Carefully consider the potential benefits and risks of Salsalate tablet, USP and other treatment options before deciding to use Salsalate tablet, USP. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).

After observing the response to initial therapy with Salsalate tablet, USP, the dose and frequency should be adjusted to suit an individual patient's needs. Salsalate is indicated for relief of the signs and symptoms of rheumatoid arthritis, osteoarthritis and related rheumatic disorder.

Adults: The usual dosage is 3000 mg daily, given in divided doses as follows:

1) two doses of two 750 mg tablets; 2) two doses of three 500 mg tablets; or 3) three doses of two 500 mg tablets. Some patients, e.g., the elderly, may require a lower dosage to achieve therapeutic blood concentrations and to avoid the more common side effects such as auditory.

Alleviation of symptoms is gradual, and full benefit may not be evident for 3 to 4 days, when plasma salicylate levels have achieved steady state. There is no evidence for development of tissue tolerance (tachyphylaxis), but salicylate therapy may induce increased activity of metabolizing liver enzymes, causing a greater rate of salicyluric acid production and excretion, with a resultant increase in dosage requirement for maintenance of therapeutic serum salicylate levels.

Children: Dosage recommendations and indications for salsalate use in children have not been established.

Cattle fed in confinement for slaughter

Virginiamycin required mg/hd/day

Virginiamycin (g/tons) of complete feed (90% dry matter basis)

Improved feed efficiency

70–240

11.0–16.0

Reduction of incidence of liver abscesses

85–240

13.5–16.0

Increased rate of weight gain

100–340

16.0–22.5

Caution: Not for use in animals intended for breeding.

Type B Medicated Feeds for cattle fed in confinement for slaughter—Thoroughly mix the following amounts of V-Max Type A Medicated Article to make 1 ton of Type B Medicated Feed to provide the concentrations shown in Table 1. An intermediate blending step, consistent with the mixing equipment specifications, should be performed to ensure adequate mixing.

Table 1. Type B Medicated Feed

lb of V-Max Type A Medicated Article per ton of supplement

Virginiamycin concentration in Type B Medicated Feed (g/ton)

1.1

2.2

4.4

8.8

22.0

44.0

250

500

1,000

2,000

5,000

10,000

Type C Medicated Feed

The Type B Medicated Feed must be diluted to a Type C Medicated Feed before being fed. Prepare a Type B Medicated Feed as described above. Thoroughly mix the V-Max Type B Medicated Feed to make 1 ton of Type C Medicated Feed to provide 11.0–22.5 g of virginiamycin per ton of complete feed on a 90% dry matter basis using the examples provided in Table 2.

Table 2. Type C Medicated Feed

lb of a 500g/ton Type B Medicated Feed per ton of complete feed

lb of a 1,000 g/ton Type B Medicated Feed per ton of complete feed

lb of a 5,000 g/ton Type B Medicated Feed per ton of complete feed

lb of a 10,000 g/ton Type B Medicated Feed per ton of complete feed

Virginiamycin concentration in complete feed 90% dry matter basis (g/ton)

44

22

4.4

2.2

11.0

54

27

5.4

2.7

13.5

64

32

6.4

3.2

16.0

90

45

9.0

4.5

22.5

Feed continuously as sole ration

Sildenafil Tablets

The recommended dose of sildenafil is 20 mg three times a day. Administer sildenafil doses 4–6 hours apart.

In the clinical trial no greater efficacy was achieved with the use of higher doses. Treatment with doses higher than 20 mg three times a day is not recommended.

Ampicillin and sulbactam for injection is administered by the IV route.

For IV administration, the dose can be given by slow intravenous injection over at least 10 to 15 minutes or can also be delivered, in greater dilutions with 50 to 100 mL of a compatible diluent as an intravenous infusion over 15 to 30 minutes.

The recommended adult dosage of ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection, 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 ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. The safety and efficacy of ampicillin and sulbactam for injection 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 ampicillin and sulbactam for injection. (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 ampicillin and sulbactam in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:

TABLE 5 Ampicillin and Sulbactam Dosage Guide for Patients With Renal Impairment Creatinine Clearance
(mL/min/1.73 m2) Ampicillin/Sulbactam
Half-Life (Hours) Recommended
Ampicillin and Sulbactam
for Injection Dosage ≥30
1
1.5 to 3 g q 6 h to q 8 h
15 to 29
5
1.5 to 3 g q 12 h
5 to 14
9
1.5 to 3 g q 24 h

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

Ampicillin and sulbactam for injection sterile powder is to be stored at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature] prior to reconstitution.

When concomitant therapy with aminoglycosides is indicated, ampicillin and sulbactam 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

Ampicillin and sulbactam for injection sterile powder for intravenous 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 g infusion bottles: Ampicillin and sulbactam for injection sterile powder in infusion bottles may be reconstituted directly to the desired concentrations using any of the following parenteral diluents. Reconstitution of ampicillin and sulbactam for injection, 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 6 Maximum Concentration
(mg/mL) Diluent Ampicillin and
Sulbactam for Injection 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

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.

Ampicillin and Sulbactam for Injection 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.

Ampicillin and Sulbactam for Injection may be administered by deep intramuscular injection (see DIRECTIONS FOR USE - Preparation for Intramuscular Injection section). The recommended adult dosage of Ampicillin and Sulbactam for Injection 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 Ampicillin and Sulbactam for Injection, 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 Ampicillin and Sulbactam for Injection 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 Ampicillin and Sulbactam for Injection, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. The safety and efficacy of Ampicillin and Sulbactam for Injection 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 sshould not routinely exceed 14 days. In clinical trials, most children received a course of ooral antimicrobials following initial treatment with intravenous Ampicillin and Sulbactam ffor Injection (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 Ampicillin and Sulbactam for Injection in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:

TABLE 5 Ampicillin And Sulbactam For Injection Dosage Guide for Patients With Renal Impairment Creatinine Clearance (mL/min/1.73m2) Ampicillin/ Sulbactam Half-Life (Hours) Recommended
Ampicillin/Sulbactam Dosage ≥ 30 1 1.5-3 g q 6 h-q 8h 15-29 5 1.5-3 g q 12h 5-14 9 1.5-3 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 weight (kg) × (140 - age)
72 × serum creatinine Females 0.85 × above value

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Ampicillin and Sulbactam for Injection may be used for parenteral administration.

THE INTENT OF THE PHARMACY BULK PACKAGE IS FOR PREPARATION OFSOLUTIONS FOR IV INFUSION ONLY.

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.

The recommended adult dosage of Ampicillin and Sulbactam 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 Ampicillin and Sulbactam for Injection, 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 Ampicillin and Sulbactam for Injection 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 Ampicillin and Sulbactam for Injection, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. The safety and efficacy of Ampicillin and Sulbactam for Injection 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 Ampicillin and Sulbactam for Injection (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 Ampicillin and Sulbactam for Injection in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:

TABLE 5 Ampicillin and Sulbactam For Injection Dosage Guide for Patients With Renal Impairment Creatinine Clearance (mL/min/1.73m2) Ampicillin/ Sulbactam Half-Life (Hours) Recommended
Ampicillin And Sulbactam For Injection Dosage ≥ 30 1 1.5-3 g q 6h-q 8h 15-29 5 1.5-3 g q 12h 5-14 9 1.5-3 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 weight (kg) × (140 - age)
72 × serum creatinine Females 0.85 × above value

The pharmacy bulk package is for preparation of solutions for IV infusion only. Ampicillin and Sulbactam for Injection should be administered 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.

The recommended adult dosage of Ampicillin and Sulbactam for Injection 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 Ampicillin and Sulbactam for Injection, 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 Ampicillin and Sulbactam for Injection 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 Ampicillin and Sulbactam for Injection, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. 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 Ampicillin and Sulbactam for Injection. (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 Ampicillin and Sulbactam in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:

TABLE 5.

Ampicillin and Sulbactam for Injection Dosage Guide for Patients with Renal Impairment Creatinine Clearance
(mL/min/1.73m2) Ampicillin/Sulbactam
Half-Life (Hours) Recommended Ampicillin and Sulbactam Dosage

≥ 30

1

1.5-3 g q 6h-q 8h

15-29

5

1.5-3 g q 12h

5-14

9

1.5-3 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

weight (kg) x (140 ˗ age)

72 x serum creatinine

Females

0.85 x above value

COMPATIBILITY, RECONSTITUTION AND STABILITY

When concomitant therapy with aminoglycosides is indicated, Ampicillin and Sulbactam and aminoglycosides should be reconstituted and administered separately, due to the in vitro inactivation of aminoglycosides by any of the aminopenicillins.

Intravenous Administration
DIRECTIONS FOR USE Directions for Proper Use of Pharmacy Bulk Package

Ampicillin and Sulbactam for Injection sterile powder for intravenous 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. Ampicillin and Sulbactam concentrations between 3 and 45 mg (2 to 30 mg ampicillin/1 to 15 mg sulbactam/mL) are recommended for intravenous use.

The 15 gram bottle may be reconstituted with either 92 mL Sterile Water for Injection or 0.9% Sodium Chloride Injection. The diluent should be added in two separate aliquots in a suitable work area, such as a laminar flow hood. Add 50 mL of solution, shake to dissolve. Then add an additional 42 mL and shake. The solution should be allowed to stand after dissolution to allow any foaming to dissipate in order to permit visual inspection for complete solubilization. The resultant solution will have a final concentration of approximately 100 mg/mL ampicillin and 50 mg/mL sulbactam. The closure may be penetrated only one time after reconstitution, if needed, using a suitable sterile transfer device or dispensing set that allows for measured dispensing of the contents.

After reconstitution, use within two hours if stored at room temperature, or within four hours if stored under refrigeration.

Reconstituted Bulk Solution Should Not be Used For Direct Infusion

If the reconstituted bulk solution is stored for less than one hour at 20 to 25°C (68 to 77°F) [See USP Controlled Room Temperature] prior to further dilution, the use periods indicated in Table 6 apply for the diluted solutions.

If the bulk solution is stored for one to two hours at 20 to 25°C (68 to 77°F) [See USP Controlled Room Temperature] and then diluted with Sterile Water for Injection or 0.9% Sodium Chloride Injection to the following concentrations, the use periods indicated in Table 7 apply.

Any unused portions of solution that remain after the indicated time periods should be discarded.

TABLE 6. Diluent Maximum Concentration
(mg/mL)
ampicillin and sulbactam Use Periods

Sterile Water for Injection

45 (30/15)

8 hrs at 21°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 21°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 21°C

30 (20/10)

4 hrs at 4°C

3 (2/1)

2 hrs at 21°C

Lactated Ringer's Injection

45 (30/15)

8 hrs at 21°C

45 (30/15)

24 hrs at 4°C

M/6 Sodium Lactate Injection

45 (30/15)

8 hrs at 21°C

45 (30/15)

12 hrs at 4°C

5% Dextrose in 0.45% Saline

3 (2/1)

4 hrs at 21°C

15 (10/5)

4 hrs at 4°C

10% Invert Sugar

3 (2/1)

4 hrs at 21°C

30 (20/10)

3 hrs at 4°C

Table 7.

IV Solution

Maximum Concentration

(mg/mL) Ampicillin/Sulbactam

Use Period

Sterile Water for Injection, USP

45 (30/15)

4 hrs at 21°C

45 (30/15)

24 hrs at 4°C

0.9% Sodium Chloride Injection, USP

45 (30/15)

4 hrs at 21°C

45 (30/15)

24 hrs at 4°C

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.

The pharmacy bulk package is for preparation of solutions for IV infusion only. Ampicillin and Sulbactam for Injection should be administered 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.

The recommended adult dosage of Ampicillin and Sulbactam for Injection 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 Ampicillin and Sulbactam for Injection, 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 Ampicillin and Sulbactam for Injection 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 Ampicillin and Sulbactam for Injection, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day. 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 Ampicillin and Sulbactam for Injection. (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 Ampicillin and Sulbactam in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations:

TABLE 5.

Ampicillin and Sulbactam for Injection Dosage Guide for Patients with Renal Impairment Creatinine Clearance
(mL/min/1.73m2) Ampicillin/Sulbactam
Half-Life (Hours) Recommended Ampicillin and Sulbactam Dosage

≥ 30

1

1.5-3 g q 6h-q 8h

15-29

5

1.5-3 g q 12h

5-14

9

1.5-3 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

weight (kg) x (140 ˗ age)

72 x serum creatinine

Females

0.85 x above value

COMPATIBILITY, RECONSTITUTION AND STABILITY

When concomitant therapy with aminoglycosides is indicated, Ampicillin and Sulbactam and aminoglycosides should be reconstituted and administered separately, due to the in vitro inactivation of aminoglycosides by any of the aminopenicillins.

Intravenous Administration
DIRECTIONS FOR USE Directions for Proper Use of Pharmacy Bulk Package

Ampicillin and Sulbactam for Injection sterile powder for intravenous 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. Ampicillin and Sulbactam concentrations between 3 and 45 mg (2 to 30 mg ampicillin/1 to 15 mg sulbactam/mL) are recommended for intravenous use.

The 15 gram bottle may be reconstituted with either 92 mL Sterile Water for Injection or 0.9% Sodium Chloride Injection. The diluent should be added in two separate aliquots in a suitable work area, such as a laminar flow hood. Add 50 mL of solution, shake to dissolve. Then add an additional 42 mL and shake. The solution should be allowed to stand after dissolution to allow any foaming to dissipate in order to permit visual inspection for complete solubilization. The resultant solution will have a final concentration of approximately 100 mg/mL ampicillin and 50 mg/mL sulbactam. The closure may be penetrated only one time after reconstitution, if needed, using a suitable sterile transfer device or dispensing set that allows for measured dispensing of the contents.

After reconstitution, use within two hours if stored at room temperature, or within four hours if stored under refrigeration.

Reconstituted Bulk Solution Should Not be Used For Direct Infusion

If the reconstituted bulk solution is stored for less than one hour at 20 to 25°C (68 to 77°F) [See USP Controlled Room Temperature] prior to further dilution, the use periods indicated in Table 6 apply for the diluted solutions.

If the bulk solution is stored for one to two hours at 20 to 25°C (68 to 77°F) [See USP Controlled Room Temperature] and then diluted with Sterile Water for Injection or 0.9% Sodium Chloride Injection to the following concentrations, the use periods indicated in Table 7 apply.

Any unused portions of solution that remain after the indicated time periods should be discarded.

TABLE 6. Diluent Maximum Concentration
(mg/mL)
ampicillin and sulbactam Use Periods

Sterile Water for Injection

45 (30/15)

8 hrs at 21°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 21°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 21°C

30 (20/10)

4 hrs at 4°C

3 (2/1)

2 hrs at 21°C

Lactated Ringer's Injection

45 (30/15)

8 hrs at 21°C

45 (30/15)

24 hrs at 4°C

M/6 Sodium Lactate Injection

45 (30/15)

8 hrs at 21°C

45 (30/15)

12 hrs at 4°C

5% Dextrose in 0.45% Saline

3 (2/1)

4 hrs at 21°C

15 (10/5)

4 hrs at 4°C

10% Invert Sugar

3 (2/1)

4 hrs at 21°C

30 (20/10)

3 hrs at 4°C

Table 7.

IV Solution

Maximum Concentration

(mg/mL) Ampicillin/Sulbactam

Use Period

Sterile Water for Injection, USP

45 (30/15)

4 hrs at 21°C

45 (30/15)

24 hrs at 4°C

0.9% Sodium Chloride Injection, USP

45 (30/15)

4 hrs at 21°C

45 (30/15)

24 hrs at 4°C

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.

2.1 Important Administration Instructions Administer SIRTURO by directly observed therapy (DOT). Use SIRTURO only in combination with other anti-mycobacterial drugs [see Dosage and Administration (2.3)]. Emphasize the need for compliance with full course of therapy. 2.2 Required Testing Prior to Administration

Prior to treatment with SIRTURO, obtain the following:

Susceptibility information for the background regimen against M. tuberculosis isolate if possible [see Dosage and Administration (2.3)] ECG [see Warnings and Precautions (5.2)] Serum potassium, calcium, and magnesium concentrations [see Warnings and Precautions (5.2)] Liver enzymes [see Warnings and Precautions (5.3)] 2.3 Recommended Dosage in Combination Therapy

Only use SIRTURO in combination with at least 3 other drugs to which the patient's MDR-TB isolate has been shown to be susceptible in vitro. If in vitro testing results are unavailable, SIRTURO treatment may be initiated in combination with at least 4 other drugs to which the patient's MDR-TB isolate is likely to be susceptible.

The recommended dosage of SIRTURO is 400 mg orally once daily for the first two weeks, followed by 200 mg orally three times per week (with at least 48 hours between doses) for 22 weeks (total duration of 24 weeks).

The SIRTURO tablet should be swallowed whole with water and taken with food.

If a dose is missed during the first 2 weeks of treatment, do not administer the missed dose (skip the dose and then continue the daily dosing regimen). From Week 3 onwards, if a 200 mg dose is missed, administer the missed dose as soon as possible, and then resume the 3 times a week dosing regimen.