Generic Name: AMPICILLIN SODIUM AND SULBACTAM SODIUM
Brand Name: UNASYN
- Substance Name(s):
- AMPICILLIN SODIUM
- SULBACTAM SODIUM
Hypersensitivity 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, UNASYN should be discontinued and the appropriate therapy instituted.
Hepatotoxicity Hepatic dysfunction, including hepatitis and cholestatic jaundice has been associated with the use of UNASYN.
Hepatic toxicity is usually reversible; however, deaths have been reported.
Hepatic function should be monitored at regular intervals in patients with hepatic impairment.
Severe Cutaneous Adverse Reactions UNASYN may cause severe skin reactions, such as toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), dermatitis exfoliative, erythema multiforme, and Acute generalized exanthematous pustulosis (AGEP).
If patients develop a skin rash they should be monitored closely and UNASYN discontinued if lesions progress (see CONTRAINDICATIONS and ADVERSE REACTIONS sections).
Clostridium difficile -Associated Diarrhea Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including UNASYN, 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 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 antibacterial drug 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 antibacterial drug use not directed against C.
difficile may need to be discontinued.
Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C.
difficile , and surgical evaluation should be instituted as clinically indicated.
Drug Interactions Probenecid decreases the renal tubular secretion of ampicillin and sulbactam.
Concurrent use of probenecid with UNASYN may result in increased and prolonged blood levels of ampicillin and sulbactam.
The concurrent administration of allopurinol and ampicillin increases substantially the incidence of rashes in patients receiving both drugs as compared to patients receiving ampicillin alone.
It is not known whether this potentiation of ampicillin rashes is due to allopurinol or the hyperuricemia present in these patients.
There are no data with UNASYN and allopurinol administered concurrently.
UNASYN and aminoglycosides should not be reconstituted together due to the in vitro inactivation of aminoglycosides by the ampicillin component of UNASYN.
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.
UNASYN is an injectable antibacterial combination consisting of the semisynthetic antibacterial 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: 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: UNASYN, ampicillin sodium/sulbactam sodium parenteral combination, is available as a white to off-white dry powder for reconstitution.
UNASYN 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.
UNASYN pharmacy bulk package is a vial containing a sterile preparation of ampicillin sodium and sulbactam sodium for parenteral use that contains many single doses.
The Pharmacy Bulk Package is for use in a pharmacy admixture setting; it provides many single doses of UNASYN for addition to suitable parenteral fluids in the preparation of admixtures for intravenous infusion (see DIRECTIONS FOR USE – Directions for Proper Use of Pharmacy Bulk Package ).
Chemical Structure Chemical Structure
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 UNASYN for the treatment of skin and skin structure infections.
Of 99 pediatric patients evaluable for clinical efficacy, 60 patients received a regimen containing intravenous UNASYN, 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 UNASYN- and cefuroxime-treated patients: TABLE 2 Therapeutic Regimen Clinical Success Clinical Failure UNASYN 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.
UNASYN (ampicillin sodium/sulbactam sodium), a sterile off-white dry powder, is available in Pharmacy Bulk Package containing ampicillin sodium and sulbactam sodium equivalent to 10 g ampicillin and 5 g sulbactam × 1 (NDC 0049-0024-28).
UNASYN sterile powder is to be stored at or below 30°C (86°F) prior to reconstitution.
OTHER SIZE PACKAGES AVAILABLE UNASYN is also supplied in glass vial and piggyback bottles in the following package sizes: Vials containing 1.5 g (NDC 0049-0013-83) equivalent of UNASYN (1 g ampicillin as the sodium salt plus 0.5 g sulbactam as the sodium salt) Vials containing 3 g (NDC 0049-0014-83) equivalent of UNASYN (2 g ampicillin as the sodium salt plus 1 g sulbactam as the sodium salt) ADD-Vantage ® package of 5 vials (NDC 0049-0031-02).
Each vial containing 1.5 g (NDC 0049-0031-01) equivalent of UNASYN (1 g ampicillin as the sodium salt plus 0.5 g sulbactam as the sodium salt) are distributed by Pfizer Inc.
ADD-Vantage package of 5 vials (NDC 0049-0032-02).
Each vial containing 3 g (NDC 0049-0032-01) equivalent of UNASYN (2 g ampicillin as the sodium salt plus 1 g sulbactam as the sodium salt) are distributed by Pfizer Inc.
The 1.5 g UNASYN ADD-Vantage vials are only to be used with the ADD-Vantage Flexible Diluent Container containing 0.9% Sodium Chloride Injection, USP, 50 mL, 100 mL, or 250 mL sizes.
The 3 g UNASYN ADD-Vantage vials are only to be used with the ADD-Vantage Flexible Diluent Container containing 0.9% Sodium Chloride Injection, USP, 100 mL or 250 mL sizes.
ADD-Vantage is a registered trademark of Hospira Inc., a Pfizer company.
To report SUSPECTED ADVERSE EVENTS, contact Pfizer Inc.
at 1-800-438-1985 or FDA at 1-800-FDA-1088 or http://www.fda.gov/ for voluntary reporting of adverse reactions.
This product’s labeling may have been updated.
For the most recent prescribing information, please visit www.pfizer.com.
Rx only LAB-0018-20.0 Revised October 2020 Logo
INDICATIONS AND USAGE
UNASYN is indicated for the treatment of infections due to susceptible strains of the designated microorganisms in the conditions listed below.
Skin and Skin Structure Infections caused by beta-lactamase producing strains of Staphylococcus aureus , Escherichia coli , Efficacy for this organism in this organ system was studied in fewer than 10 infections.
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.
pneumoniae ), Bacteroides spp.
fragilis ), and Enterobacter spp.
Gynecological Infections caused by beta-lactamase producing strains of Escherichia coli, and Bacteroides spp.
While UNASYN is indicated only for the conditions listed above, infections caused by ampicillin-susceptible organisms are also amenable to treatment with UNASYN due to its ampicillin content.
Therefore, mixed infections caused by ampicillin-susceptible organisms and beta-lactamase producing organisms susceptible to UNASYN should not require the addition of another antibacterial.
Appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify the organisms causing infection and to determine their susceptibility to UNASYN.
Therapy may be instituted prior to obtaining the results from bacteriological and susceptibility studies when there is reason to believe the infection may involve any of the beta-lactamase producing organisms listed above in the indicated organ systems.
Once the results are known, therapy should be adjusted if appropriate.
To reduce the development of drug-resistant bacteria and maintain effectiveness of UNASYN and other antibacterial drugs, UNASYN should be used only to treat 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.
Pediatric Use The safety and effectiveness of UNASYN have been established for pediatric patients one year of age and older for skin and skin structure infections as approved in adults.
Use of UNASYN 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 UNASYN have not been established for pediatric patients for intra-abdominal infections.
Pregnancy 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 UNASYN.
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– PRECAUTIONS-Drug/Laboratory Test Interactions section).
Nursing Mothers Low concentrations of ampicillin and sulbactam are excreted in the milk; therefore, caution should be exercised when UNASYN is administered to a nursing woman.
INFORMATION FOR PATIENTS
Information for Patients Patients should be counseled that antibacterial drugs including UNASYN should only be used to treat bacterial infections.
They do not treat viral infections (e.g., the common cold).
When UNASYN is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed.
Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by UNASYN or other antibacterial drugs in the future.
Diarrhea is a common problem caused by antibacterials which usually ends when the antibacterial is discontinued.
Sometimes after starting treatment with antibacterials, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibacterial.
If this occurs, patients should contact their physician as soon as possible.
DOSAGE AND ADMINISTRATION
The pharmacy bulk package is for preparation of solutions for IV infusion only.
UNASYN 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 UNASYN is 1.5 g (1 g ampicillin as the sodium salt plus 0.5 g sulbactam as the sodium salt) to 3 g (2 g ampicillin as the sodium salt plus 1 g sulbactam as the sodium salt) every six hours.
This 1.5 to 3 g range represents the total of ampicillin content plus the sulbactam content of UNASYN, and corresponds to a range of 1 g ampicillin/0.5 g sulbactam to 2 g ampicillin/1 g sulbactam.
The total dose of sulbactam should not exceed 4 grams per day.
Pediatric Patients 1 Year of Age or Older The recommended daily dose of UNASYN in pediatric patients is 300 mg per kg of body weight administered via intravenous infusion in equally divided doses every 6 hours.
This 300 mg/kg/day dosage represents the total ampicillin content plus the sulbactam content of UNASYN, and corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day.
The safety and efficacy of UNASYN administered via intramuscular injection in pediatric patients have not been established.
Pediatric patients weighing 40 kg or more should be dosed according to adult recommendations, and the total dose of sulbactam should not exceed 4 grams per day.
The course of intravenous therapy should not routinely exceed 14 days.
In clinical trials, most children received a course of oral antimicrobials following initial treatment with intravenous UNASYN.
(see CLINICAL STUDIES section).
Impaired Renal Function In patients with impairment of renal function the elimination kinetics of ampicillin and sulbactam are similarly affected, hence the ratio of one to the other will remain constant whatever the renal function.
The dose of UNASYN in such patients should be administered less frequently in accordance with the usual practice for ampicillin and according to the following recommendations: TABLE 3 UNASYN Dosage Guide for Patients with Renal Impairment Creatinine Clearance (mL/min/1.73m 2 ) Ampicillin/Sulbactam Half-Life (Hours) Recommended UNASYN Dosage ≥30 1 1.5–3 g q 6h–q 8h 15–29 5 1.5–3 g q 12h 5–14 9 1.5–3 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