r than 10 infections. while ampicillin and sulbactam for injection 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 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 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 ampicillin and sulbactam for injection. 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 and other antibacterial drugs, ampicillin and sulbactam for injection 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.

itored at regular intervals in patients with hepatic impairment. severe cutaneous adverse reactions ampicillin and sulbactam 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 ampicillin and sulbactam 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 ampicillin and sulbactam, 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 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.

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 3 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) × (140 – age) 72 × serum creatinine females 0.85 × above value

ical lymphocytosis has been observed in one pediatric patient receiving ampicillin and sulbactam. adverse laboratory changes adverse laboratory changes without regard to drug relationship that were reported during clinical trials were: hepatic: increased ast (sgot), alt (sgpt), alkaline phosphatase, and ldh. hematologic: decreased hemoglobin, hematocrit, rbc, wbc, neutrophils, lymphocytes, platelets and increased lymphocytes, monocytes, basophils, eosinophils, and platelets. blood chemistry: decreased serum albumin and total proteins. renal: increased bun and creatinine. urinalysis: presence of rbc’s and hyaline casts in urine. postmarketing experience in addition to adverse reactions reported from clinical trials, the following have been identified during post-marketing use of ampicillin sodium/sulbactam sodium or other products containing ampicillin. because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. these events have been chosen for inclusion due to a combination of their seriousness, frequency, or potential causal connection to ampicillin sodium/sulbactam sodium. blood and lymphatic system disorders: hemolytic anemia, thrombocytopenic purpura, and agranulocytosis have been reported. these reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena. some individuals have developed positive direct coombs tests during treatment with ampicillin and sulbactam, as with other beta-lactam antibacterials. gastrointestinal disorders: abdominal pain, cholestatic hepatitis, cholestasis, hyperbilirubinemia, jaundice, abnormal hepatic function, melena, gastritis, stomatitis, dyspepsia, black “hairy” tongue, and clostridium difficile associated diarrhea (see contraindications and warnings sections). general disorders and administration site conditions: injection site reaction immune system disorders: serious and fatal hypersensitivity (anaphylactic) reactions (see warnings section), acute myocardial ischemia with or without myocardial infarction may occur as part of an allergic reaction. nervous system disorders: convulsion and dizziness renal and urinary disorders: tubulointerstitial nephritis respiratory, thoracic and mediastinal disorders: dyspnea skin and subcutaneous tissue disorders: toxic epidermal necrolysis, stevens-johnson syndrome, angioedema, acute generalized exanthematous pustulosis (agep), erythema multiforme, exfoliative dermatitis, and urticaria (see contraindications and warnings sections). to report suspected adverse reactions, contact mylan at 1-877-446-3679 (1-877-4-info-rx) or fda at 1-800-fda-1088 or www.fda.gov/medwatch for voluntary reporting of adverse reactions.

ention 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 is administered to a nursing woman. pediatric use: the safety and effectiveness of ampicillin and sulbactam 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 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 have not been established for pediatric patients for intra-abdominal infections.

nd sulbactam are excreted unchanged in the urine during the first 8 hours after administration of ampicillin and sulbactam to individuals with normal renal function. somewhat higher and more prolonged serum levels of ampicillin and sulbactam can be achieved with the concurrent administration of probenecid. in patients with impaired 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 (see dosage and administration section). ampicillin has been found to be approximately 28% reversibly bound to human serum protein and sulbactam approximately 38% reversibly bound. the following average levels of ampicillin and sulbactam were measured in the tissues and fluids listed: table 1 concentration of ampicillin and sulbactam in various body tissues and fluids fluid or tissue dose (grams) ampicillin/sulbactam concentration (mcg/ml or mcg/g) ampicillin/sulbactam peritoneal fluid 0.5/0.5 iv 7/14 blister fluid (cantharides) 0.5/0.5 iv 8/20 tissue fluid 1/0.5 iv 8/4 intestinal mucosa 0.5/0.5 iv 11/18 appendix 2/1 iv 3/40 penetration of both ampicillin and sulbactam into cerebrospinal fluid in the presence of inflamed meninges has been demonstrated after iv administration of ampicillin and sulbactam. the pharmacokinetics of ampicillin and sulbactam in pediatric patients receiving ampicillin and sulbactam are similar to those observed in adults. immediately after a 15-minute infusion of 50 to 75 mg ampicillin and sulbactam/kg body weight, peak serum and plasma concentrations of 82 to 446 mcg ampicillin/ml and 44 to 203 mcg sulbactam/ml were obtained. mean half-life values were approximately 1 hour.

ired 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.