Ampicillin and sulbactam

Adult Patients

UNASYN is generally well tolerated. The following adverse reactions have been reported in clinical trials.

Pain at IM injection site – 16%

Pain at IV injection site – 3%

Thrombophlebitis – 3%

Phlebitis – 1.2%

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 UNASYN demonstrate a similar adverse events profile to those observed in adult patients. Additionally, atypical lymphocytosis has been observed in one pediatric patient receiving UNASYN.

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 postmarketing use of UNASYN 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 UNASYN.

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 UNASYN, as with other beta-lactam antibacterials.

Cholestatic hepatitis, cholestasis, hyperbilirubinemia, jaundice, abnormal hepatic function, gastritis, stomatitis, black "hairy" tongue and Clostridium difficile associated diarrhea (see CONTRAINDICATIONS and WARNINGS).

Injection site reaction

Serious and fatal hypersensitivity (anaphylactic) reactions (See WARNINGS).

Convulsion

Tubulointerstitial nephritis

Toxic epidermal necrolysis, Stevens-Johnson syndrome, and acute generalized exanthematous pustulosis (AGEP), urticaria, erythema multiforme, and exfoliative dermatitis (see CONTRAINDICATIONS and WARNINGS).

Antibiotic medicines can cause diarrhea, which may be a sign of a new infection. If you have diarrhea that is watery or bloody, call your doctor. Do not use anti-diarrhea medicine unless your doctor tells you to.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• diarrhea that is watery or bloody;

• thrush (white patches inside your mouth or throat);

• sudden weakness or ill feeling, fever, chills, sore throat, mouth sores, red or swollen gums, trouble swallowing;

• liver problems--nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or

• severe skin reaction--fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Common side effects may include:

• swollen, black, or "hairy" tongue;

• mild or occasional diarrhea;

• vaginal itching or discharge;

• mild skin rash; or

• pain, swelling, bruising, or irritation around the IV needle.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

• Unasyn

Administer around-the-clock to promote less variation in peak and trough serum levels.

IV: Administer by slow injection over 10 to 15 minutes or as an IV infusion over 15 to 30 minutes. Ampicillin and gentamicin should not be mixed in the same IV tubing.

Some penicillins (eg, ampicillin, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate aminoglycosides in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent Y-site administration should be avoided.

IM: Inject deep I.M. into large muscle mass; a concentration of 375 mg/mL ampicillin/sulbactam (250 mg ampicillin/125 mg sulbactam per mL) is recommended; may be diluted in sterile water or lidocaine 0.5% or lidocaine 2% for I.M. administration.

Also see Ampicillin.

>10%: Local: Pain at injection site (IM; 16%)

1% to 10%:

Cardiovascular: Thrombophlebitis (3%), phlebitis (1%)

Dermatologic: Skin rash (<2%)

Gastrointestinal: Diarrhea (3%)

Local: Pain at injection site (IV; 3%)

<1% (Limited to important or life-threatening): Acute generalized exanthematous pustulosis, agranulocytosis, anemia, basophilia, candidiasis, casts in urine (hyaline), chest pain, chills, cholestasis, cholestatic hepatitis, clostridium difficile associated diarrhea, convulsions, decreased neutrophils, decreased serum albumin, decreased serum total protein, dysuria, edema, eosinophilia, erythema, erythema multiforme, erythrocyturia, exfoliative dermatitis, gastritis, glossitis, hairy tongue, headache, hemolytic anemia, hepatic insufficiency, hepatitis, hyperbilirubinemia, hypersensitivity reaction, immune thrombocytopenia, increased blood urea nitrogen, increased lactate dehydrogenase, increased liver enzymes, increased monocytes, increased serum creatinine, injection site reaction, interstitial nephritis, lymphocytopenia, lymphocytosis (abnormal), nausea, positive direct Coombs test, pruritus, pseudomembranous colitis, Stevens-Johnson syndrome, stomatitis, thrombocythemia, thrombocytopenia, urinary retention, urticaria

Adverse events have not been observed in animal reproduction studies. Both ampicillin and sulbactam cross the placenta. Maternal use of penicillins has generally not resulted in an increased risk of birth defects. When used during pregnancy, pharmacokinetic changes have been observed with ampicillin alone (refer to the Ampicillin monograph for details). Ampicillin/sulbactam may be considered for prophylactic use prior to cesarean delivery (consult current guidelines).

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience diarrhea or injection site pain. Have patient report immediately to prescriber vaginal yeast infection, signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes), thrush, or signs of Clostridium difficile (C. diff)-associated diarrhea (abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Do not use this medication if you are allergic to ampicillin and sulbactam or to any other penicillin antibiotic, such as:

• amoxicillin (Amoxil, Amoxicot, Biomox, Dispermox, Trimox);
• carbenicillin (Geocillin);
• dicloxacillin (Dycill, Dynapen);
• oxacillin (Bactocill); or
• penicillin (Beepen-VK, Ledercillin VK, Pen-V, Pen-Vee K, Pfizerpen, V-Cillin K, Veetids, and others).

Before using ampicillin and sulbactam, tell your doctor if you are allergic to any drugs (especially cephalosporins such as Ceclor, Ceftin, Duricef, Keflex, and others), or if you have:

• kidney disease;
• a bleeding or blood clotting disorder;
• mononucleosis (also called "mono");
• a history of diarrhea caused by taking antibiotics; or
• a history of any type of allergy.

If you have any of these conditions, you may need a dose adjustment or special tests to safely use this medication.

FDA pregnancy category B. This medication is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

Ampicillin and sulbactam can make birth control pills less effective, which may result in pregnancy. Before using ampicillin and sulbactam, tell your doctor if you use birth control pills.

Ampicillin and sulbactam can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

US CDC Recommendations: 3 g IV every 6 hours

Comments:
-The dose is expressed as the total of ampicillin content plus sulbactam content (in a constant 2:1 ratio).
-This drug plus doxycycline are recommended as an alternative parenteral regimen; effective against Chlamydia trachomatis, Neisseria gonorrhoeae, and anaerobes in patients with tubo-ovarian abscess.
-At least 24 hours of direct inpatient observation recommended for patients with tubo-ovarian abscesses.
-Oral therapy can generally be started within 24 to 48 hours after clinical improvement.
-The patient's sexual partner(s) should also be evaluated/treated.
-Current guidelines should be consulted for additional information.

Safety and efficacy for the treatment of skin and skin structure infections have not been established in patients younger than 1 year. Safety and efficacy for the treatment of intraabdominal infections have not been established in patients younger than 18 years. Safety and efficacy of IM administration have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Data not available

Comments: Both components may be removed from circulation by hemodialysis.

Administration advice:
-For IM use: Administer by deep IM injection; use only freshly prepared solutions and administer within 1 hour after preparation.
-For IV use: Administer by slow IV injection over at least 10 to 15 minutes or administer (diluted with 50 to 100 mL compatible diluent) as IV infusion over 15 to 30 minutes; consult the manufacturer product information and administer within the recommended time periods according to package (e.g., glass vial, ADD-Vantage[R] vial), diluent, concentration, and storage temperature.
-Do not exceed total sulbactam dose of 4 g/day.
-Do not use ampicillin antibiotics to treat mononucleosis due to high incidence of skin rashes.
-If concomitant aminoglycoside therapy is indicated, reconstitute and administer each product separately; aminopenicillins inactivate aminoglycosides in vitro.

Storage requirements:
-Prior to reconstitution: Store sterile powder at or below 30C (86F)

Reconstitution/preparation techniques:
-For IM injection: Vials for IM use may be reconstituted with Sterile Water for Injection USP, 0.5% Lidocaine Hydrochloride Injection USP, or 2% Lidocaine Hydrochloride Injection USP; the manufacturer product information should be consulted further guidance.
-For IV use: The manufacturer product information should be consulted.

IV compatibility:
-Compatible diluents for vials, piggyback bottles, pharmacy bulk package: Sterile Water for Injection, 0.9% Sodium Chloride Injection, 5% Dextrose Injection, Lactated Ringer's Injection, M/6 Sodium Lactate Injection, 5% Dextrose in 0.45% Saline, 10% Invert Sugar
-Compatible diluent for ADD-Vantage(R) vials: 0.9% Sodium Chloride Injection USP

General:
-Unless otherwise specified, the dose is expressed as the total of ampicillin content (as the sodium salt) plus sulbactam content (as the sodium salt); the 1.5 g dose corresponds to 1 g ampicillin plus 500 mg sulbactam; the 3 g dose corresponds to 2 g ampicillin plus 1 g sulbactam.
-Culture and susceptibility studies are recommended prior to therapy to isolate and identify infecting organisms and to establish susceptibility to this drug.
-This drug is only indicated for skin and skin structure infections, intraabdominal infections, and gynecological infections; however, infections due to ampicillin-susceptible organisms also respond to this drug due to its ampicillin content; should not need to add another antibacterial for mixed infections caused by ampicillin-susceptible organisms and beta-lactamase-producing organisms susceptible to this drug.

Patient advice:
-Avoid missing doses and complete the entire course of therapy.