megacilin-4gm/.5gm/vial

Indications

Piperacillin and tazobactam is indicated for the treatment of patients with moderate to severe infections caused by piperacillin-resistant, piperacillin/tazobactam susceptible, β-lactamase producing strains of the designated microorganisms in the specified conditions listed below: Appendicitis (complicated by rupture or abscess) and peritonitis caused by piperacillin-resistant, β-lactamase producing strains of Escherichia coli or the following members of the Bacteroides fragilis group: B. fragilis, B. ovatus, B. thetaiotaomicron, or B. vulgatus. Uncomplicated and complicated skin and skin structure infections, including cellulitis, cutaneous abscesses and ischemic/diabetic foot infections caused by piperacillin-resistant, β-lactamase producing strains of Staphylococcus aureus. Postpartum endometritis or pelvic inflammatory disease caused by piperacillin-resistant, β-lactamase producing strains of Escherichia coli. Community-acquired pneumonia (moderate severity only) caused by piperacillin-resistant, β-lactamase producing strains of Haemophilus influenzae. Nosocomial pneumonia (moderate to severe) caused by piperacillin-resistant, β-lactamase producing strains of Staphylococcus aureus and by piperacillin/tazobactam-susceptible Acinetobacter baumanii, Haemophilus influenzae, Klebsiella pneumoniae, and Pseudomonas aeruginosa (Nosocomial pneumonia caused by P. aeruginosa should be treated in combination with an aminoglycoside). Piperacillin and tazobactam for IV infusion is indicated only for the specified conditions listed above. Infections caused by piperacillin-susceptible organisms, for which piperacillin has been shown to be effective, are also amenable to MegacilinTM treatment due to its piperacillin content. The tazobactam component of this combination product does not decrease the activity of the piperacillin component against piperacillin-susceptible organisms. Therefore, the treatment of mixed infections caused by piperacillin-susceptible organisms and piperacillin-resistant, β-lactamase producing organisms susceptible to piperacillin and tazobactam should not require the addition of another antibiotic. MegacilinTM is useful as presumptive therapy in the indicated conditions prior to the identification of causative organisms because of its broad spectrum of bactericidal activity against gram-positive and gram-negative aerobic and anaerobic organisms.

Dosage & Administration

Piperacillin and tazobactam should be administered by intravenous infusion over 30 minutes. The usual total daily dose of Piperacillin and tazobactam for adults is 3.375 g every six hours totaling 13.5 g (12.0 g piperacillin/1.5 g tazobactam). Nosocomial Pneumonia: Initial presumptive treatment of patients with nosocomial pneumonia should start with piperacillin and tazobactam at a dosage of 4.5 g every six hours plus an aminoglycoside, totaling 18.0 g (16.0 g piperacillin/2.0 g tazobactam). Treatment with the aminoglycoside should be continued in patients from whom Pseudomonas aeruginosa is isolated. If Pseudomonas aeruginosa is not isolated, the aminoglycoside may be discontinued at the discretion of the treating physician. Due to the in vitro inactivation of the aminoglycoside by beta-lactam antibiotics, piperacillin and tazobactam and the aminoglycoside are recommended for separate administration. piperacillin and tazobactam and the aminoglycoside should be reconstituted, diluted, and administered separately when concomitant therapy with aminoglycosides is indicated. Renal Insufficiency: In patients with renal insufficiency (Creatinine Clearance > 40 mL/min), the intravenous dose of MegacilinTM (piperacillin and tazobactam for IV infusion) should be adjusted to the degree of actual renal function impairment. In patients with nosocomial pneumonia receiving concomitant aminoglycoside therapy, the aminoglycoside dosage should be adjusted according to the recommendations of the manufacturer. The recommended daily doses of Piperacillin and tazobactam for patients with renal insufficiency are as follows:

• Creatinine clearance for patients not receiving hemodialysis ** 0.75 g should be administered following each hemodialysis session on hemodialysis days for patients on hemodialysis, the maximum dose is 2.25 g every twelve hours for all indications other than nosocomial pneumonia and 2.25 g every eight hours for nosocomial pneumonia. Since hemodialysis removes 30% to 40% of the administered dose, an additional dose of 0.75 g piperacillin and tazobactam should be administered following each dialysis period on hemodialysis days. No additional dosage of piperacillin and tazobactam is necessary for CAPD patients. Duration of Therapy: The usual duration of piperacillin and tazobactam treatment is from seven to ten days. However, the recommended duration of piperacillin and tazobactam treatment of nosocomial pneumonia is 7 to 14 days. In all conditions, the duration of therapy should be guided by the severity of the infection and the patient\’s clinical and bacteriological progress. Hepatic Insufficiency: The half-life of piperacillin and of tazobactam increases by approximately 25% and 18%, respectively, in patients with hepatic cirrhosis compared to healthy subjects. However, this difference does not warrant dosage adjustment of piperacillin and tazobactam due to hepatic cirrhosis.

Side Effects

Adverse events primarily involving the skin, including rash and pruritus; the gastrointestinal system, including diarrhea, nausea, and vomiting; and allergic reactions. Adverse local reactions that were reported, irrespective of relationship to therapy with piperacillin and tazobactam were phlebitis, IV infusion site reaction, pain, inflammation, thrombophlebitis, and edema. Gastrointestinal-hepatitis, cholestatic jaundice. Hematologic-hemolytic anemia, anemia, thrombocytosis, agranulocytosis, pancytopenia. Immune-hypersensitivity reactions, anaphylactic/anaphylactoid reactions (including shock). Infections-candidal superinfections. Renal-interstitial nephritis, renal failure. Skin and Appendages-erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Precautions

Bleeding manifestations have occurred in some patients receiving β-lactam antibiotics, including piperacillin. These reactions have sometimes been associated with abnormalities of coagulation tests such as clotting time, platelet aggregation and prothrombin time, and are more likely to occur in patients with renal failure. If bleeding manifestations occur, piperacillin and tazobactam for IV infusion should be discontinued and appropriate therapy instituted. The ossibility of the emergence of resistant organisms that might cause superinfections should be kept in mind. If this occurs, appropriate measures should be taken. As with other penicillins, patients may experience neuromuscular excitability or convulsions if higher than recommended doses are given intravenously (particularly in the presence of renal failure). piperacillin and tazobactam contains a total of 2.79 mEq (64 mg) of Na+ per gram of piperacillin in the combination product. This should be considered when treating patients requiring restricted salt intake. Periodic electrolyte determinations should be performed in patients with low potassium reserves, and the possibility of hypokalemia should be kept in mind with patients who have potentially low potassium reserves and who are receiving cytotoxic therapy or diuretics. As with other semisynthetic penicillins, piperacillin therapy has been associated with an increased incidence of fever and rash in cystic fibrosis patients. In patients with creatinine clearance > 40 mL/min and dialysis patients (hemodialysis and CAPD), the intravenous dose should be adjusted to the degree of renal function impairment. Pediatric Use: Use of piperacillin and tazobactam in pediatric patients 2 months of age or older with appendicitis and/or peritonitis is supported by evidence from well-controlled studies and pharmacokinetic studies in adults and in pediatric patients. Safety and efficacy in pediatric patients less than 2 months of age have not been established. There are no dosage recommendations for piperacillin and tazobactam in pediatric patients with impaired renal function. Geriatric Use: Patients over 65 years are not at an increased risk of developing adverse effects solely because of age. However, dosage should be adjusted in the presence of renal insufficiency. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Use in Pregnancy: Pregnancy Category B. Piperacillin and tazobactam cross the placenta in humans. Use in Lactation: Piperacillin is excreted in low concentrations in human milk; tazobactam concentrations in human milk have not been studied. Caution should be exercised when piperacillin and tazobactam for IV infusion is administered to a nursing woman.

Contraindications

Piperacillin and tazobactam is contraindicated in patients with a history of allergic reactions to any of the penicillins, cephalosporins, or β-lactamase inhibitors