Ampicillin-Sulbactam

Ampicillin-Sulbactam
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Turky Alkathery, M.D. [2]

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Overview

Ampicillin-Sulbactam is a combination of the common penicillin-derived antibiotic ampicillin and sulbactam, an inhibitor of bacterial beta-lactamase that is FDA approved for the treatment of infection caused by: Staphylococcus aureus, Escherichia coli, Klebsiella spp (including K. pneumoniae ), Proteus mirabilis, Bacteroidesfragilis, Enterobacter spp. and Acinetobacter calcoaceticus. Common adverse reactions include pain at IV injection site, thrombophlebitis and phlebitis.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Indications

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,* Bacteroidesfragilis,* 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 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, 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 infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Dosage

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.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Ampicillin-Sulbactam in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Ampicillin-Sulbactam in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Indications

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

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).

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Ampicillin-Sulbactam in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Ampicillin-Sulbactam in pediatric patients.

Contraindications

The use of Ampicillin and Sulbactam for Injection is contraindicated in individuals with a history of serious hypersensitivity reactions (e.g., anaphylaxis or Stevens-Johnson syndrome) to ampicillin, sulbactam or to other beta-lactam antibacterial drugs (e.g., penicillins and cephalosporins).

Ampicillin and Sulbactam for Injection is contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with Ampicillin and Sulbactam for Injection.

Warnings

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, Ampicillin and Sulbactam for Injection should be discontinued and the appropriate therapy instituted.

Hepatotoxicity Hepatic dysfunction, including hepatitis and cholestatic jaundice has been associated with the use of Ampicillin and Sulbactam for Injection. Hepatic toxicity is usually reversible; however, deaths have been reported. Hepatic function should be monitored at regular intervals in patients with hepatic impairment.

Clostridium difficile-Associated Diarrhea 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 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.

Precautions

General A high percentage of patients with mononucleosis who receive ampicillin develop a skin rash. Thus, ampicillin class antibacterials should not be administered to patients with mononucleosis. In patients treated with Ampicillin and Sulbactam the possibility of superinfections with mycotic or bacterial pathogens should be kept in mind during therapy. If superinfections occur (usually involving Pseudomonas or Candida), the drug should be discontinued and/or appropriate therapy instituted. Prescribing Ampicillin and Sulbactam for Injection in the absence of proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Information for Patients Patients should be counseled that antibacterial drugs including Ampicillin and Sulbactam for Injection should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Ampicillin and Sulbactam for Injection 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 Ampicillin and Sulbactam for Injection 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.

Adverse Reactions

Clinical Trials Experience

Adult Patients Ampicillin and Sulbactam for Injection is generally well tolerated. The following adverse reactions have been reported in clinical trials.

Local Adverse Reactions

Pain at IV injection site – 3% Thrombophlebitis – 3% Phlebitis – 1.2% Systemic Adverse Reactions

The most frequently reported adverse reactions were diarrhea in 3% of the patients and rash in less than 2% of the patients.

Additional systemic reactions reported in less than 1% of the patients were: itching, nausea, vomiting, candidiasis, fatigue, malaise, headache, chest pain, flatulence, abdominal distension, glossitis, urine retention, dysuria, edema, facial swelling, erythema, chills, tightness in throat, substernal pain, epistaxis and mucosal bleeding.

Pediatric Patients Available safety data for pediatric patients treated with Ampicillin and Sulbactam demonstrate a similar adverse events profile to those observed in adult patients. Additionally, atypical 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 and Sulbactam for Injection 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 and Sulbactam for Injection.

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 for Injection, as with other beta-lactam antibacterials.

Gastrointestinal Disorders: Cholestatic hepatitis, cholestasis, hyperbilirubinemia, jaundice, abnormal hepatic function, gastritis, stomatitis, black “hairy” tongue and Clostridium difficile associated diarrhea (see CONTRAINDICATIONSand WARNINGSsections).

General Disorders and Administration Site Conditions: Injection site reaction

Immune System Disorders: Serious and fatal hypersensitivity (anaphylactic) reactions (See WARNINGSsection)

Nervous System Disorders: Convulsion.

Renal and Urinary Disorders: Tubulointerstitial nephritis.

Skin and Subcutaneous Tissue Disorders: Toxic epidermal necrolysis, Stevens-Johnson syndrome, and acute generalised exanthematous pustulosis (AGEP), urticaria, erythema multiforme, and exfoliative dermatitis (see CONTRAINDICATIONSsection).

Drug Interactions

Probenecid decreases the renal tubular secretion of ampicillin and sulbactam. Concurrent use of probenecid with Ampicillin and Sulbactam 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 Ampicillin and Sulbactam and allopurinol administered concurrently. Ampicillin and Sulbactam and aminoglycosides should not be reconstituted together due to the in vitro inactivation of aminoglycosides by the ampicillin component of Ampicillin and Sulbactam. Drug/Laboratory Test Interactions Administration of Ampicillin and Sulbactam will result in high urine concentration of ampicillin. High urine concentrations of ampicillin may result in false positive reactions when testing for the presence of glucose in urine using Clinitest™, Benedict's Solution or Fehling's Solution. It is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as Clinistix™ or Testape™) be used. Following administration of ampicillin to pregnant women, a transient decrease in plasma concentration of total conjugated estriol, estriol-glucuronide, conjugated estrone and estradiol has been noted. This effect may also occur with Ampicillin and Sulbactam.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): 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. 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.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Ampicillin-Sulbactam in women who are pregnant.

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 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 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.

The safety and effectiveness of Ampicillin and Sulbactam for Injection have not been established for pediatric patients for intra-abdominal infections.

Geriatic Use

There is no FDA guidance on the use of Ampicillin-Sulbactam in geriatric settings.

Gender

There is no FDA guidance on the use of Ampicillin-Sulbactam with respect to specific gender populations.

Race

There is no FDA guidance on the use of Ampicillin-Sulbactam with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Ampicillin-Sulbactam in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Ampicillin-Sulbactam in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Ampicillin-Sulbactam in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Ampicillin-Sulbactam in patients who are immunocompromised.

Administration and Monitoring

Administration

• Intravenous.

Monitoring

There is limited information regarding Ampicillin-Sulbactam Monitoring in the drug label.

IV Compatibility

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.

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.

Pharmacology

There is limited information regarding Ampicillin-Sulbactam Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Ampicillin-Sulbactam Mechanism of Action in the drug label.

Structure

There is limited information regarding Ampicillin-Sulbactam Structure in the drug label.

Pharmacodynamics

There is limited information regarding Ampicillin-Sulbactam Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Ampicillin-Sulbactam Pharmacokinetics in the drug label.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies in animals have not been performed to evaluate carcinogenic or mutagenic potential.

Clinical Studies

There is limited information regarding Ampicillin-Sulbactam Clinical Studies in the drug label.

How Supplied

Ampicillin and Sulbactam for Injection, USP (ampicillin sodium/sulbactam sodium) is supplied as a sterile white to yellowish dry powder in ADD-Vantage® Vials as follows:

Each 1.5 grams ADD-Vantage® vial contains 1.5 g Ampicillin and Sulbactam for Injection, USP (equivalent to 1 g ampicillin as the sodium salt plus 0.5 g sulbactam as the sodium salt).

NDC 0409-2689-01-packed in trays of 10 vials.

Each 3 grams ADD-Vantage® vial contains 3 g Ampicillin and Sulbactam for Injection, USP (equivalent to 2 g ampicillin as the sodium salt plus 1 g sulbactam as the sodium salt).

NDC 0409-2987-03-packed in trays of 10 vials.

The 1.5 g Ampicillin and Sulbactam for Injection, USP ADD-Vantage® vials are only to be used with an ADD-Vantage® Flexible Diluent Container containing 0.9% Sodium Chloride Injection, USP, 50 mL, 100 mL or 250 mL sizes.

The 3 g Ampicillin and Sulbactam for Injection, USP ADD-Vantage® vials are only to be used with an ADD-Vantage® Flexible Diluent Container containing 0.9% Sodium Chloride Injection, USP, 100 mL or 250 mL sizes.

Storage

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.

Images

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Patient Counseling Information

There is limited information regarding Ampicillin-Sulbactam Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Ampicillin-Sulbactam interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Ampicillin-Sulbactam Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Ampicillin-Sulbactam Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.