Sultacillin

Ampicillin sodium, sulbactam sodium.

500 mg/250 mg: Each vial contains Ampicillin (as sodium), USP 500 mg, Sulbactam (as sodium), USP 250 mg.
1 g/500 mg: Each vial contains Ampicillin (as sodium), USP 1g, Sulbactam (as sodium), USP 500 mg.

Pharmacology: Pharmacodynamics: Biochemical studies with cell-free bacterial systems have shown sulbactam to be an irreversible inhibitor of most important beta-lactamases that occur in penicillin resistant organism. It possesses significant antibacterial activity only against Neisseriaceae, Acinetobacter calcoaceticus, Bacteroides sp., Branhamella catarrhalis and Pseudomonas cepacia. The potential for sulbactam sodium's preventing the destruction of penicillins and cephalosporins by resistant organism was confirmed in whole-organism studies using resistant strains, in which sulbactam sodium exhibited marked synergistic effects with penicillin and cephalosporins. Since sulbactam also binds to some penicillin-binding proteins, some sensitive strains are rendered more susceptible to the combination than to the beta-lactam antibiotics alone.
The bactericidal component of the combination is ampicillin which, like benzyl penicillin, acts against sensitive organism during the stage of active multiplication by the inhibition of biosynthesis of cell-wall mucopeptide. Ampicillin sodium/Sulbactam sodium IM/IV is effective against a wide range of Gram-positive and Gram-negative bacteria including: Staphylococcus aureus and epidermidis (including penicillin-resistant and some methicillin-resistant strains); Streptococcus pneumoniae, Streptococcus faecalis and other Streptococcus species; Haemophilus influenzae and parainfluenzae (both beta-lactamase positive and negative strains); Branhamella catarrhalis, anaerobes, including Bacteroides fragilis and related species; Escherichia coli, Klebsiella species, Proteus species (both indole-positive and indole-negative), Morganelli morganii, Citrobacter species, Enterobacter species, Neisseria meningitis and Neisseria gonorrheae.
Pharmacokinetics: Ampicillin sodium/Sulbactam sodium IM/IV diffuses readily into most body tissues and fluids in the human. Penetration into brain and spinal fluid is low except when meninges are inflamed. High concentrations of ampicillin and sulbactam are achieved in the blood following intravenous or intramuscular administration and both components have a half life of approximately 1 hour. Most of the Ampicillin sodium/Sulbactam sodium IM/IV is excreted unchanged in the urine.

Sulbactam sodium/Ampicillin sodium IM/IV is indicated for infections caused by susceptible microorganisms. Typical indications are upper and lower respiratory tract infections including sinusitis, otitis media and epiglottitis; bacterial pneumonias; urinary tract infections and pyelonephritis; intra-abdominal infections including peritonitis, cholecystitis, endometritis and pelvic cellulitis; bacterial septicemia; skin, soft tissue, bone and joint infections and gonococcal infections. Sulbactam sodium/Ampicillin sodium IM/IV may also be administered peri-operatively to reduce the incidence of post-operative wound infections in patients undergoing abdominal or pelvic surgery, in which peritoneal contamination may be present. In termination of pregnancy or cesarean section, Ampicillin sodium/Sulbactam sodium IM/IV may be used prophylactically to reduce post-operative sepsis.

Ampicillin sodium/Sulbactam sodium IM/IV can be administered by either intravenous or intramuscular routes.
The following dilutions may be used. (See Table 1.)

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For intravenous administration, Ampicillin sodium/Sulbactam sodium IM/IV should be reconstituted with sterile water for injection or any compatible solution (see Instructions for use under Cautions for Usage.) To ensure complete dissolution, allow foaming to dissipate in order to visually inspect. The dose can be given by bolus injection over a minimum of 3 minutes or can be used in greater dilutions as intravenous infusion over 15-30 minutes. Ampicillin sodium/Sulbactam sodium parenteral may also be administered by deep intramuscular injection; if pain is experienced, 0.5% sterile solution for injection of lignocaine hydrochloride anhydrous may be used for reconstitution of the powder.
Use in Adults: The usual dosage range of Ampicillin sodium/Sulbactam sodium IM/IV is 1.5 g (1 g ampicillin and 0.5 g sulbactam) to 12 g (8 g ampicillin and 4 g sulbactam) per day in divided doses every 6 or 8 hours up to a maximum daily dosage of 12 g (8 g ampicillin and 4 g sulbactam). Less severe infections may be treated on an every-12-hours schedule. (See Table 2.)

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More or less frequent dosing may be indicated depending on the severity of the illness and the renal function of the patient. Treatment is usually continued until 48 hours after pyrexia and other abnormal signs have been resolved. Treatment is normally given for 5 to 14 days, but the treatment period may be extended or additional Ampicillin may be administered in severely ill cases.
In treating patients on restricted sodium intake, it should be noted that 1,500 mg (1 g ampicillin and 0.5 g sulbactam) of Ampicillin sodium/Sulbactam sodium IM/IV contains approximately 115 mg (5 mmol) of sodium. For the prophylaxis of surgical infections, 1.5 g (1g ampicillin and 0.5 g sulbactam). 3 g (2 g ampicillin and 1 g sulbactam) of Ampicillin sodium/Sulbactam sodium IM/IV should be given at induction of anesthesia, which allows sufficient time to achieve effective serum and tissue concentrations during the procedure. The dose may be repeated every 6-8 hours. Administration is usually stopped 24 hours after on the majority of surgical procedures, unless a therapeutic course of Ampicillin sodium/Sulbactam sodium IM/IV is indicated. In the treatment of uncomplicated gonorrhea, Ampicillin sodium/Sulbactam sodium IM/IV can be given as a single dose of 1.5 g (1 g ampicillin and 0.5 g sulbactam). Concomitant probenecid 1 g orally should be administered in order to prolong plasma concentrations of Ampicillin and Sulbactam.
Use in Children, Infant and Neonates: The dosage of Ampicillin sodium/Sulbactam sodium IM/IV for most infections in children, infants and neonates is 150 mg/kg/day (corresponding to ampicillin 100 mg/kg/day and sulbactam 50 mg/kg/day). In children, infants and neonates, dosing is usually every 6 or 8 hours in accordance with the usual practice for ampicillin. In neonates during the first week of life (especially preterms), the recommended dose is 75 mg/kg/day (corresponding to 50 mg/kg/day ampicillin and 25 mg/kg/day sulbactam) in divided doses every 12 hours.
Use in Patients with Renal Impairment: In patients with severe impairment of renal function (creatinine clearance <30 mL/min), the elimination kinetics of ampicillin and sulbactam are similarly affected and hence the plasma ratio of one to the other will remain constant. The dose of Ampicillin sodium/Sulbactam sodium IM/IV in such patients should be administered less frequently in accordance with the usual practice for ampicillin.

Limited information is available on the acute toxicity of ampicillin sodium and sulbactam sodium in humans. Overdose of the drug would be expected to produce manifestations that are principally extensions of the adverse reactions reported with the drug. The fact that high CSF concentrations of β-lactam antibiotics may cause neurologic effects, including seizures, should be considered. Because ampicillin and sulbactam are both removed from the circulation by hemodialysis, these procedures may enhance elimination of the drug from the body if overdosage occurs in patients with impaired renal function.

This combination is contraindicated in individuals with a history of an allergic reaction to any of the penicillins.

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy including Ampicillin sodium/Sulbactam sodium IM/IV. These reactions are more apt to occur in individuals with a history of penicillin hypersensitivity who have experienced severe reactions when treated with cephalosporins. Before therapy with the penicillin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins and other allergens. If an allergic reaction occurs, the drug should be discontinued and the appropriate therapy instituted. Serious anaphylactic reactions require immediate emergency treatment with epinephrine. Oxygen, intravenous steroids and airway management, including intubation, should be administered as indicated.
As with any antibiotic preparation, constant observation for signs of overgrowth of nonsusceptible organism, including fungi, is essential. Should superinfection occurs, the drug should be discontinued and/or appropriate therapy instituted. As with any potent systemic agent, it is advisable to check periodically for organ system dysfunction during extended therapy; this includes renal, hepatic and hematopoietic systems. This is particularly important in neonates, especially when premature, and other infants. Since infectious mononucleosis is viral in origin, Ampicillin sodium/Sulbactam sodium IM/IV should not be used in its treatment. A high percentage of patients with mononucleosis who received ampicillin have developed a skin rash.

Animal reproduction studies have revealed no evidence of fertility impairment or harm to the fetus due to ampicillin and sulbactam. Sulbactam crosses the placental barrier. Safety for use in pregnancy and lactation has not been established.

As with other parenteral antibiotics, the principal side effect observed is injection site pain, especially associated with the intramuscular route of administration. A small number of patients may develop phlebitis or an injection-site reaction after intravenous administration.
Body as a Whole: anaphylactoid reaction and anaphylactic shock.
Central and Peripheral Nervous: rare reports of convulsions.
Gastrointestinal: nausea, vomiting, diarrhea and pseudomembranous colitis.
Hematopoietic and Lymphatic: anemia, hemolytic anemia, thrombocytopenia and leukopenia have been reported during therapy with ampicillin sodium/sulbactam sodium. These reactions are reversible on discontinuation of therapy and are believed to be sensitivity reactions.
Liver/Biliary: transient elevations of ALT (SGPT) and AST (SGOT) transaminases, bilirubinemia, abnormal hepatic function and jaundice.
Skin/skin structure: rash, itching, other skin reactions, rare reports of Stevens Johnson syndrome, epidermal necrolysis and erythema multiforme.
Urinary: rare reports of interstitial nephritis.
Adverse reactions associated with the use of ampicillin alone may be observed with Ampicillin sodium/Sulbactam sodium IM/IV.

Allopurinol: The concurrent administration of allopurinol and ampicillin substantially increases the incidence of rashes in patients receiving both drugs as compared with patients receiving ampicillin alone.
Aminoglycosides: Mixing ampicillin with aminoglycosides in vitro has resulted in substantial mutual inactivation. If these groups of antibacterial are to be administered concurrently, they should be administered at separate sites at least 1 hour apart.
Anticoagulants: Parenteral penicillin can produce alterations in platelet aggregation and coagulation test. These effects may be additive with anticoagulants.
Bacteriostatic drugs (Chloramphenicol, erythromycin, sulfonamides and tetracyclines): Bacteriostatic drugs may interfere with the bactericidal effect of penicillin; it is best to avoid concurrent therapy.
Estrogen- containing oral contraceptives: There have been case reports of reduced oral contraceptive effectiveness in women taking ampicillin resulting in unplanned pregnancy. Patients should be given the option to use an alternate or additional method of contraception while taking ampicillin.
Methotrexate: Concurrent use with penicillins has resulted in decreased clearance of methotrexate toxicity. Patients should be closely monitored. Leucovorin dosages may need to be increased and administered for longer periods of time.
Probenecid: Probenecid decreased renal tubular secretion of ampicillin and sulbactam when used concurrently. This effect results in increased and prolonged serum concentrations, prolonged elimination half-life, and increased risk of toxicity.
Laboratory Test Interactions: False positive glycosuria may be observed in urinalysis using Benedict's reagent, Fehling's reagent, and Clinitest. Following administration of ampicillin to pregnant women, a transient decrease in plasma concentration of total conjugated estriol, estriol-glucuronide, conjugated estrone has been noted. This effect may also occur with ampicillin sodium/sulbactam sodium IM/IV.

Incompatibilities: Ampicillin sodium/Sulbactam sodium IM/IV and aminoglycosides should be reconstituted and administered separately because they are chemically and physically incompatible and become inactivated when mixed.
Instructions for Use: Sulbactam sodium is compatible with most intravenous solutions, but ampicillin sodium and hence Ampicillin sodium/Sulbactam sodium IM/IV is less stable in solutions containing dextrose or other carbohydrates, and should not be mixed with blood products or protein hydrolysates. Ampicillin and hence Ampicillin sodium/Sulbactam sodium IM/IV is incompatible with aminoglycosides and should not be physically mixed in the same container (see Dosage & Administration). The concentrated solution for intramuscular administration should be used within 1 hour of reconstitution. Time periods for use with different diluents for intravenous infusion are as follows: (See Table 3.)

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Store at temperatures not exceeding 30°C.

Penicillins

J01CR01 - ampicillin and beta-lactamase inhibitor ; Belongs to the class of penicillin combinations, including beta-lactamase inhibitors. Used in the systemic treatment of infections.

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