Viccillin-SX 1500

Sultamicillin (ampicillin sodium and sulbactam sodium).

Each vial contains ampicillin 1000 mg and sulbactam 500 mg.
Ampicillin sodium is derived from the penicillin nucleus, 6-aminopenicillanic acid. It is D(-)-α-aminobenzyl penicillin sodium salt and has a molecular weight of 371.39.
Sulbactam sodium is a derivative of the basic penicillin nucleus. It is sodium penicillanate sulfone and is an off-white crystalline powder that is highly soluble in water. The molecular weight is 255.22.
Sultamicillin is a combination of ampicillin sodium and sulbactam sodium.

Biochemical studies with cell-free bacterial system have shown sulbactam to be an irreversible inhibitor of several important β-lactamases that occur in penicillin-resistant organisms. It possesses significant antibacterial activity only against Neisseriaceae, Acinetobacter calcoaceticus, Bacteroides sp, Branhamella catarrhalis and Pseudomonas cepacia. The potential for sulbactam sodium is preventing the destruction of penicillins and cephalosporins by resistant organisms was confirmed in whole organism studies using resistant strains, in which sulbactam sodium exhibited marked synergistic effects with penicillins and cephalosporins. Since sulbactam also binds to some penicillin-binding proteins, some sensitive strains are rendered more susceptible to the combination than to the β-lactam antibiotic alone.
The bactericidal component of the combination is ampicillin which like benzyl penicillin, acts against sensitive organisms during the stage of active multiplication by the inhibition of biosynthesis of cell wall mucopeptide.
Viccillin-SX 1500 powder for injection is effective against a wide range of gram-positive and gram-negative bacteria including: Staphylococcus aureus and S. epidermidis (including penicillin-resistant and some methicillin-resistant strains); Streptococcus pneumoniae, Streptococcus faecalis and other Streptococcus spp; Haemophilus influenzae and H. parainfluenzae (both β-lactamase positive and negative strains); Branhamella catarrhalis; anaerobes, including Bacteroides fragilis and related species; Escherichia coli, Klebsiella spp, Proteus spp (both indole-positive and negative), Morganelli morganii, Citrobacter spp, Enterobacter spp, Neisseria meningitidis and Neisseria gonorrhoeae.
Ampicillin/sulbactam 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 IV or IM administration and both components have a half-life of approximately 1 hr. Most of the ampicillin/sulbactam is excreted unchanged in the urine.

Infections caused by susceptible microorganisms. Typical indications are upper and lower respiratory tract infections including sinusitis, otitis media and epiglottis; 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. Viccillin-SX 1500 powder for injection may also be administered perioperatively to reduce the incidence of postoperative wound infections in patients undergoing abdominal or pelvic surgery, in which peritoneal contamination may be present. In termination of pregnancy of cesarean section, Viccillin-SX 1500 powder for injection may be used prophylactically to reduce post-operative sepsis.

Viccillin-SX 1500 powder for injection can be administered by either IV or IM routes. The following dilutions may be used (see Table 1).


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Usual Dose Range: 1.5-12 g/day in divided doses every 6 or 8 hrs up to a maximum daily dosage of sulbactam 4 g. Less severe infections may be treated on a 12-hr interval schedule. (See Table 2.)


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Dosage: Children, Infants and Neonates: 150 mg/kg/day (corresponding to sulbactam 50 mg/kg/day and ampicillin 100 mg/kg/day) every 6 or 8 hrs in accordance with the usual practice for ampicillin. In neonates during the 1st week of life (especially pre-terms), dosing is usually every 12 hrs. 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 hrs after pyrexia and other abnormal signs have resolved. Treatment is normally given for 5-14 days but the treatment period may be extended or additional ampicillin may be administered in severely ill cases.
Patients with Severe Impairment of Renal Function (creatinine clearance <30 mL/min): The elimination kinetics of sulbactam and ampicillin are similarly affected and hence the plasma ratio of one to the other will remain constant. The dose of Viccillin-SX 1500 powder for injection in such patients should be administered less frequently in accordance with the usual practice of ampicillin. In treating patients on restricted sodium intake, it should be noted that 1500 mg of Viccillin-SX 1500 powder for injection contains approximately 115 mg (5 mmol) of sodium.
Prophylaxis of Surgical Infections: 1.5-3 g of Viccillin-SX 1500 powder for injection 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 6-8 hrly; administration is usually stopped 24 hrs after the majority of surgical procedures, unless a therapeutic course of Viccillin-SX 1500 powder for injection is indicated.
Administration: For IV administration, Viccillin-SX 1500 powder for injection should be reconstituted with sterile water for injection or any compatible solution and allowed to stand to allow any foaming to dissipate to permit visual inspection for complete dissolution. The dose can be given by bolus injection over a minimum of 3 min or can be used in greater dilutions either as a bolus or as an IV infusion over 15-30 min. Meiji ampicillin sodium/sulbactam sodium parenteral may also be administered by deep IM injection. If pain is experienced, 0.5% sterile solution for injection of anhydrous lignocaine HCl may be used for reconstitution of the powder.

Neurological adverse reactions, including convulsions, may occur with the affainment of high CSF levels of β-lactams. Ampicillin may be removed from circulation by hemodialysis. The molecular weight, degree of protein-binding and pharmacokinetic profile of sulbactam suggest that this compound may also be removed by hemodialysis.

Individuals with a history of an allergic reaction to any of the penicillins and sulbactam.

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy. These reaction 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, Viccillin-SX 1500 should be discontinued and the appropriate therapy instituted.
Serious anaphylactic reactions require immediate emergency treatment with adrenaline. Oxygen, IV steroid and airway management, including intubations, should be administered as indicated.
Use in pregnancy & lactation: Animal reproduction studies have revealed no evidence of impaired fertility or harm to the fetus due to ampicillin and sulbactam. However, safety for use in pregnancy and lactation has not been established.

As with any antibiotic preparation, constant observation for signs of overgrowth of nonsusceptible organisms including fungi, is essential. Should superinfection occur, Viccillin-SX 1500 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.

Animal reproduction studies have revealed no evidence of impaired fertility or harm to the fetus due to ampicillin and sulbactam. However, 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 IM route of administration. A small number of patients may develop phlebitis after IV administration.
Gastrointestinal: The most common were nausea, vomiting and diarrhea.
Skin/Skin Structure: The most common were rash, itching and other skin reactions.
Haematopoietic and Lymphatic Systems: Anemia, thrombocytopenia, eosinophilia and leucopenia have been reported during therapy with sulbactam sodium/ampicillin sodium. These reactions are reversible on discontinuation of therapy and are believed to be sensitivity reactions.
Hepatic: Transient elevations of alanine and aspartic transaminases have been observed.
It is expected that the adverse reactions associated with the use of ampicillin will be occasionally observed.
Since infectious mononucleosis is viral in origin, ampicillin should not be used in the treatment. A high percentage of patients with mononucleosis who receive ampicillin develop a skin rash.

Probenecid decreases the renal tubular secretion of ampicillin and sulbactam. Concurrent use of probenecid with Viccillin-SX 1500 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 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 Viccillin-SX 1500 and allopurinol administered concurrently, Viccillin-SX 1500 and allopurinol aminoglycosides should not be reconstituted together due to the in vitro inactivation of aminoglycosides by the ampicillin component of Viccillin-SX 1500.
Administration of Viccillin-SX 1500 will result in high urine concentration of ampicillin. High urine concentrations of ampicillin may result in false-positive reactions when testing for presence of glucose in urine using Clinitest, Benedict's solution or Fehling's solution. It is recommended that glucose based on enzymatic glucose oxidase reactions (eg, clinistix or tes-tape) be used. Following administration of ampicillin to pregnant women, a transient decrease in plasma concentration of total conjugated estriol, estriol-glucoronide, conjugated estrone and estradiol has been noted. This effect may also occur with Viccillin-SX 1500.
Stability and Compatibility: Sulbactam sodium is compatible with most IV solutions but ampicillin sodium and hence Viccillin-SX 1500 powder for injection is less stable in solutions containing dextrose or other carbohydrates and should not be mixed with blood products or protein hydrolysates. Ampicillin and hence Viccillin-SX 1500 powder for injection is incompatible with aminoglycosides and should not be physically mixed in the same container. The concentrated solution for IM administration should be used within 1 hr of reconstitution. Time periods for use in different diluents for IV infusion are as follows (see Table 3).


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Store in a dry place (below 30°C). Protect from light. After reconstitution, the concentrated solution is stable in the room temperature (25±2°C) within 1 hr and stable in refrigerator (below 5°C) within 24 hrs.
Shelf-Life: 2 years.

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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