Prescribing Details
Description
Tazobac® is the combination of Piperacillin Sodium and Tazobactam Sodium. Piperacillin Sodium is a semisynthetic antibiotic and Tazobactam Sodium is a p-lactamase inhibitor. Piperacillin Sodium exerts bactericidal activity by inhibiting septum formation and cell wall synthesis of susceptible bacteria. In vitro, Piperacillin is active against a variety of gram-positive and gram-negative aerobic and anaerobic bacteria. Tazobactam Sodium has little clinically relevant in vitro activity against bacteria due to its reduced affinity to penicillin-binding proteins. It is, however, a p-lactamase inhibitor of the molecular class A enzymes. It varies in its ability to inhibit class II and IV (2a & 4) penicillinases. Tazobactam does not induce chromosomally-mediated P-lactamases at Tazobactam concentrations achieved with the recommended dose regimen.
Uses
No Data
Indications
Progil® is indicated for the treatment of following fungal infections-
- Invasive aspergillosis
- Candidemia (non-neutropenics) and disseminated candidiasis in skin, abdomen, kidney, bladder wall and wounds
- Esophageal candidiasis
- Serious infections caused by Scedosporium apiospermum and Fusarium species including Fusarium solani, in patients intolerant of or refractory to other therapy
Dosage and administration
Route of administration: Tazobac® should be administered by intravenous infusion over 30 minutes.
Adult patients with indications other than nosocomial pneumonia
The usual total daily dose of Tazobac® for adult patients with indications other than nosocomial pneumonia is 3.375 g every six hours [totaling 13.5 g (12.0 g piperacillin /1.5 g tazobactam)]. The usual duration of Tazobac® treatment is from 7 to 10 days.
Adult patients with nosocomial pneumonia
Initial presumptive treatment of adult patients with nosocomial pneumonia should be started with Tazobac® at a dose of 4.5 g every six hours plus an aminoglycoside, [totaling 18.0 g (16.0 g piperacillin / 2.0 g tazobactam)]. The recommended duration of Tazobac® treatment for nosocomial pneumonia is 7 to 14 days. Treatment with the aminoglycoside should be continued in patients from whom P. aeruginosa is isolated.
Pediatric patients with appendicitis/peritonitis or nosocomial pneumonia
| Recommended dose of Tazobac® in pediatric patients 2 months of age and older, weighing up to 40 kg and with normal renal function | ||
|---|---|---|
| Age | Appendicitis and/or peritonitis | Nosocomial pneumonia |
| 2 months to 9 months | 90 mg/kg (80 mg piperacillin/10 mg tazobactam) every 8 hours | 90 mg/kg (80 mg piperacillin/10 mg tazobactam) every 6 hours |
| Older than 9 months of age | 112.5 mg/kg (100 mg piperacillin/12.5 mg tazobactam) every 8 hours | 112.5 mg/kg (100 mg piperacillin/12.5 mg tazobactam) every 6 hours |
Renal impairment
Recommended dose of Tazobac® in patients with normal renal function and renal impairment (as total grams piperacillin/tazobactam) |
||
|---|---|---|
| Creatinine clearance, ml/min | All indications (except nosocomial pneumonia) | Nosocomial pneumonia |
| Greater than 40 ml/min | 3.375 g every 6 hours | 4.5 g every 6 hours |
| 20 to 40 ml/min* | 2.25 g every 6 hours | 3.375 g every 6 hours |
| Less than 20 ml/min* | 2.25 g every 8 hours | 2.25 g every 6 hours |
| Hemodialysis** | 2.25 g every 12 hours | 2.25 g every 8 hours |
| Continuous Ambulatory Peritoneal Dialysis (CAPD) | 2.25 g every 12 hours | 2.25 g every 8 hours |
| * Creatinine clearance for patients not receiving hemodialysis ** 0.75 g (0.67 g piperacillin/0.08 g tazobactam) should be administered following each hemodialysis session on hemodialysis days |
||
Directions for reconstitution and dilution for use
Prior to use, piperacillin and tazobactam 2.25 g and 4.5 g infusion must be reconstituted with sterile water for injection BP or sodium chloride BP 0.9 % w/v as per table below:
| Piperacillin / tazobactam infusion | |
|---|---|
| Vial size (piperacillin / tazobactam) | Minimum volume of diluent to be added to vial |
| 2.25 g (2 g / 0.25 g) | 10 ml |
| 4.5 g (4 g / 0.5 g) | 20 ml |
The reconstituted solution may be further diluted to 100 ml with normal saline (sodium chloride BP 0.9 % w/v) or dextrose 5 % or dextran 6 % in saline. To reduce microbiological hazard, use as soon as practicable after reconstitution. Discard any unused portion after 24 hours if stored at controlled room temperature (20°C - 25°C) or after 48 hours if stored at refrigerated temperature (2°C-8°C).
Use in pregnancy & lactation
Pregnancy: Piperacillin and tazobactam cross the placenta. This combination should only be used during pregnancy if clearly indicated, i.e. only if the expected benefit outweighs the possible risks to the pregnant woman and fetus.
Lactation: Piperacillin is excreted in human milk. Tazobactam concentrations in human milk have not been studied. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for this combination and any potential adverse effects on the breastfed child from this combination or from the underlying maternal condition.
Use in children and adolescents
The safety and effectiveness of this combination have not been established in pediatric patients less than 2 months of age.
Geriatric use
Precautions
Serious hypersensitivity reactions (anaphylactic/anaphylactoid) have been reported in patients receiving this combination. This combination should be discontinued if a reaction occurs. This combination may cause severe cutaneous adverse reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms and acute generalized exanthematous pustulosis. This combination should be discontinued for progressive rashes. Hematological effects (including bleeding, leukopenia and neutropenia) have occurred. Hematologic tests should be monitored during prolonged therapy. As with other penicillins, this combination may cause neuromuscular excitability or seizures. Patients receiving higher doses, especially in the presence of renal impairment may be at greater risk. Patients with renal impairment or seizure disorders should be monitored closely for signs and symptoms of neuromuscular excitability or seizures. Nephrotoxicity in critically ill patients has been observed. Alternative treatment options should be considered in the critically ill population. If alternative treatment options are inadequate or unavailable, renal function should be monitored during treatment with this combination. Clostridioides difficile associated diarrhea may occur. Patients should be evaluated if diarrhea occurs.
Side effects
The most common side effects are diarrhea, constipation, nausea, vomiting, dyspepsia, abdominal pain, fever, headache, insomnia, rash and pruritus.
Contraindications
This combination is contraindicated in patients with known hypersensitivity to piperacillin or tazobactam or any other component of this product. It is also contraindicated in patients with a history of allergic reactions to any of the penicillins, cephalosporins or p-lactamase inhibitors.
Drug interactions
Drug interaction with medication: Administration of this combination can significantly reduce tobramycin concentrations in hemodialysis patients. Probenecid prolongs the half-lives of piperacillin and tazobactam and should not be coadministered with this combination unless the benefit outweighs the risk. Coadministration of this combination with vancomycin may increase the incidence of acute kidney injury. Coagulation parameters should be monitored in patients receiving this combination and heparin or oral anticoagulants. This combination may prolong the neuromuscular blockade of vecuronium and other non-depolarizing neuromuscular blockers.
Drug interaction with food and others: There have been reports of positive test results using the Bio-Rad Laboratories Platelia Aspergillus EIA test in patients receiving this combination injection who were subsequently found to be free of aspergillus infection. Therefore, positive test results in patients receiving this combination should be interpreted cautiously and confirmed by other diagnostic methods. As with other penicillins, the administration of this combination may result in a false positive reaction for glucose in the urine using a copper-reduction method. It is recommended that glucose tests based on enzymatic glucose oxidase reactions be used.
Overdose
There have been reports of overdose with piperacillin/tazobactam. The majority of those events experienced, including nausea, vomiting and diarrhea have also been reported with the usual recommended doses. Patients may experience neuromuscular excitability or seizures if higher than recommended doses are given intravenously (particularly in the presence of renal failure). Treatment should be supportive and symptomatic according the patient's clinical presentation. Excessive serum concentrations of either piperacillin or tazobactam may be reduced by hemodialysis.
Preparation
No Data
Pharmaceutical precautions
No Data
Presentation
Tazobac® 2.25 g IV Infusion: Each vial contains sterile mixture of lyophilized Piperacillin 2 g as Sodium USP and Tazobactam 0.25 g as Sodium USP.
Tazobac® 4.5 g IV Infusion: Each vial contains sterile mixture of lyophilized Piperacillin 4 g as Sodium USP and Tazobactam 0.5 g as Sodium USP.
Package quantities
Storage
Store in a cool (between 20°C- 25°C) and dry place protected from light. Keep away from the reach of children.
Packing
Tazobac® 2.25 g IV Infusion: Each combipack contains 1 vial of sterile mixture of lyophilized Piperacillin 2 g as Sodium USP and Tazobactam 0.25 g as Sodium USP, 1 vial of 100 ml Salinor® (Sodium Chloride BP 0.9% w/v) as diluent, 1 infusion set, 1 disposable syringe (10 ml), 1 alcohol pad and 1 first aid bandage.
Tazobac® 4.5 g IV Infusion: Each combipack contains 1 vial of sterile mixture of lyophilized Piperacillin 4 g as Sodium USP and Tazobactam 0.5 g as Sodium USP, 1 vial of 100 ml Salinor® (Sodium Chloride BP 0.9% w/v) as diluent, 1 infusion set, 1 disposable syringe (20 ml), 1 alcohol pad and 1 first aid bandage.
