Ampicillin 1000 MG / Sulbactam 500 MG Injection
WARNINGS
SERIOUS AND OCCASIONALLY FATAL HYPERSENSITIVITY (ANAPHYLACTIC) REACTIONS HAVE BEEN REPORTED IN PATIENTS ON PENICILLIN THERAPY.
THESE REACTIONS ARE MORE APT TO OCCUR IN INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY AND/OR HYPERSENSITIVITY REACTIONS TO MULTIPLE ALLERGENS.
THERE HAVE BEEN REPORTS OF INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY WHO HAVE EXPERIENCED SEVERE REACTIONS WHEN TREATED WITH CEPHALOSPORINS.
BEFORE THERAPY WITH A PENICILLIN, CAREFUL INQUIRY SHOULD BE MADE CONCERNING PREVIOUS HYPERSENSITIVITY REACTIONS TO PENICILLINS, CEPHALOSPORINS, AND OTHER ALLERGENS.
IF AN ALLERGIC REACTION OCCURS, AMPICILLIN AND SULBACTAM FOR INJECTION SHOULD BE DISCONTINUED AND THE APPROPRIATE THERAPY INSTITUTED.
SERIOUS ANAPHYLACTOID REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH EPINEPHRINE.
OXYGEN, INTRAVENOUS STEROIDS, AND AIRWAY MANAGEMENT, INCLUDING INTUBATION, SHOULD ALSO BE ADMINISTERED AS INDICATED.
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including ampicillin and sulbactam for injection, and may range in severity from mild diarrhea to fatal colitis.
Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C.
difficile .
C.
difficile produces toxins A and B which contribute to the development of CDAD.
Hypertoxin producing strains of C.
difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy.
CDAD must be considered in all patients who present with diarrhea following antibiotic use.
Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C.
difficile may need to be discontinued.
Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C.
difficile , and surgical evaluation should be instituted as clinically indicated.
OVERDOSAGE
Neurological adverse reactions, including convulsions, may occur with the attainment of high CSF levels of beta-lactams.
Ampicillin may be removed from circulation by hemodialysis.
The molecular weight, degree of protein binding and pharmacokinetics profile of sulbactam suggest that this compound may also be removed by hemodialysis.
DESCRIPTION
Ampicillin and Sulbactam for Injection, USP is an injectable antibacterial combination consisting of the semisynthetic antibiotic ampicillin sodium and the beta-lactamase inhibitor sulbactam sodium for intravenous and intramuscular administration.
Ampicillin sodium is derived from the penicillin nucleus, 6-aminopenicillanic acid.
Chemically, it is monosodium (2S, 5R, 6R)-6-[(R)-2-amino-2-phenylacetamido]-3, 3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate and has a molecular weight of 371.39.
Its chemical formula is C 16 H 18 N 3 NaO 4 S.
The structural formula is: Structure of Ampicillin Sulbactam sodium is a derivative of the basic penicillin nucleus.
Chemically, sulbactam sodium is sodium penicillinate sulfone; sodium (2S, 5R)-3,3-dimethyl-7-oxo-4-thia- 1-azabicyclo [3.2.0] heptane-2-carboxylate 4,4-dioxide.
Its chemical formula is C 8 H 10 NNaO 5 S with a molecular weight of 255.22.
The structural formula is: Structure of Sulbactum Ampicillin and Sulbactam for Injection, USP, ampicillin sodium/sulbactam sodium parenteral combination, is available as a white to off-white dry powder for reconstitution.
Ampicillin and Sulbactam for Injection, USP dry powder is freely soluble in aqueous diluents to yield pale yellow to yellow solutions containing ampicillin sodium and sulbactam sodium equivalent to 250 mg ampicillin per mL and 125 mg sulbactam per mL.
The pH of the solutions is between 8.0 and 10.0.
Dilute solutions (up to 30 mg ampicillin and 15 mg sulbactam per mL) are essentially colorless to pale yellow.
The pH of dilute solutions remains the same.
1.5 g of Ampicillin and Sulbactam for Injection, USP (1 g ampicillin as the sodium salt plus 0.5 g sulbactam as the sodium salt) parenteral contains approximately 115 mg (5 mEq) of sodium.
3 g of Ampicillin and Sulbactam for Injection, USP (2 g ampicillin as the sodium salt plus 1 g sulbactam as the sodium salt) parenteral contains approximately 230 mg (10 mEq) of sodium.
Structure of Ampicillin Structure of Sulbactum
CLINICAL STUDIES
Skin and Skin Structure Infections in Pediatric Patients: Data from a controlled clinical trial conducted in pediatric patients provided evidence supporting the safety and efficacy of ampicillin and sulbactam for injection for the treatment of skin and skin structure infections.
Of 99 pediatric patients evaluable for clinical efficacy, 60 patients received a regimen containing intravenous ampicillin and sulbactam, and 39 patients received a regimen containing intravenous cefuroxime.
This trial demonstrated similar outcomes (assessed at an appropriate interval after discontinuation of all antimicrobial therapy) for ampicillin and sulbactam – and cefuroxime-treated patients: TABLE 4: Therapeutic Regimen Clinical Success Clinical Failure Ampicillin and Sulbactam 51/60 (85%) 9/60 (15%) Cefuroxime 34/39 (87%) 5/39 (13%) Most patients received a course of oral antimicrobials following initial treatment with intravenous administration of parenteral antimicrobials.
The study protocol required that the following three criteria be met prior to transition from intravenous to oral antimicrobial therapy: 1) receipt of a minimum of 72 hours of intravenous therapy; 2) no documented fever for prior 24 hours; and 3) improvement or resolution of the signs and symptoms of infection.
The choice of oral antimicrobial agent used in this trial was determined by susceptibility testing of the original pathogen, if isolated, to oral agents available.
The course of oral antimicrobial therapy should not routinely exceed 14 days.
HOW SUPPLIED
Ampicillin and Sulbactam for Injection, USP is supplied as a sterile off-white dry powder in glass vials.
The following packages are available: Vials containing 1.5 g equivalent of Ampicillin and Sulbactam for Injection, USP (1 g ampicillin as the sodium salt plus 0.5 g sulbactam as the sodium salt) Box of 10 vials NDC 76126-273-10 Vials containing 3 g equivalent of Ampicillin and Sulbactam for Injection, USP (2 g ampicillin as the sodium salt plus 1 g sulbactam as the sodium salt) Box of 10 vials NDC 76126-035-10 Ampicillin and Sulbactam for Injection, USP sterile powder is to be stored at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature] prior to reconstitution.
INDICATIONS AND USAGE
Ampicillin and sulbactam for Injection, USP is indicated for the treatment of infections due to susceptible strains of the designated microorganisms in the conditions listed below.
Skin and Skin Structure Infections caused by beta-lactamase producing strains of Staphylococcus aureus , Escherichia coli ,* Klebsiella spp.* (including K.
pneumoniae* ), Proteus mirabilis ,* Bacteroides fragilis ,* Enterobacter spp.,* and Acinetobacter calcoaceticus.* NOTE: For information on use in pediatric patients see PRECAUTIONS–Pediatric Use and CLINICAL STUDIES sections.
Intra-Abdominal Infections caused by beta-lactamase producing strains of Escherichia coli , Klebsiella spp.
(including K.
pneumoniae* ), Bacteroides spp.
(including B.
fragilis ), and Enterobacter spp.* Gynecological Infections caused by beta-lactamase producing strains of Escherichia coli,* and Bacteroides spp.* (including B.
fragilis* ).
* Efficacy for this organism in this organ system was studied in fewer than 10 infections.
While ampicillin and sulbactam for injection, USP is indicated only for the conditions listed above, infections caused by ampicillin-susceptible organisms are also amenable to treatment with ampicillin and sulbactam for injection, USP due to its ampicillin content.
Therefore, mixed infections caused by ampicillin-susceptible organisms and beta-lactamase producing organisms susceptible to ampicillin and sulbactam for injection, USP should not require the addition of another antibiotic.
Appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify the organisms causing infection and to determine their susceptibility to ampicillin and sulbactam for injection, USP.
Therapy may be instituted prior to obtaining the results from bacteriological and susceptibility studies, when there is reason to believe the infection may involve any of the beta-lactamase producing organisms listed above in the indicated organ systems.
Once the results are known, therapy should be adjusted if appropriate.
To reduce the development of drug-resistant bacteria and maintain effectiveness of ampicillin and sulbactam for injection, USP and other antibacterial drugs, ampicillin and sulbactam for injection, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.
When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy.
In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
PREGNANCY
Pregnancy Pregnancy Category B: Reproduction studies have been performed in mice, rats, and rabbits at doses up to ten (10) times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to ampicillin and sulbactam for injection.
There are, however, no adequate and well controlled studies in pregnant women.
Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
(See–Drug/Laboratory Test Interactions.) Labor and Delivery: Studies in guinea pigs have shown that intravenous administration of ampicillin decreased the uterine tone, frequency of contractions, height of contractions, and duration of contractions.
However, it is not known whether the use of ampicillin and sulbactam for injection in humans during labor or delivery has immediate or delayed adverse effects on the fetus, prolongs the duration of labor, or increases the likelihood that forceps delivery or other obstetrical intervention or resuscitation of the newborn will be necessary.
Nursing Mothers: Low concentrations of ampicillin and sulbactam are excreted in the milk; therefore, caution should be exercised when ampicillin and sulbactam for injection is administered to a nursing woman.
Pediatric Use: The safety and effectiveness of ampicillin and sulbactam for injection have been established for pediatric patients one year of age and older for skin and skin structure infections as approved in adults.
Use of ampicillin and sulbactam for injection in pediatric patients is supported by evidence from adequate and well-controlled studies in adults with additional data from pediatric pharmacokinetic studies, a controlled clinical trial conducted in pediatric patients and post-marketing adverse events surveillance.
(See CLINICAL PHARMACOLOGY , INDICATIONS AND USAGE , ADVERSE REACTIONS , DOSAGE AND ADMINISTRATION , and CLINICAL STUDIES sections.) The safety and effectiveness of ampicillin and sulbactam for injection have not been established for pediatric patients for intra-abdominal infections.
DOSAGE AND ADMINISTRATION
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 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: TABLE 5:Ampicillin and Sulbactam for Injection Dosage Guide For Patients With Renal Impairment Creatinine Clearance (mL/min/1.73m 2 ) Ampicillin/Sulbactam Half-Life (Hours) Recommended Ampicillin and Sulbactam for Injection 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) 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 for injection 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 1.5 g and 3 g Vials : 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).
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 @ 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 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 per mL (250 mg ampicillin/125 mg sulbactam per mL).
Note: Use only freshly prepared solutions and administer within one hour after preparation.
TABLE 7: Ampicillin and Sulbactam for Injection 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.
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.