Pipertaz

Pipertaz

piperacillin + tazobactam

Manufacturer:

Great Eastern Drug

Distributor:

Zuellig Pharma
Full Prescribing Info
Contents
Piperacillin sodium, tazobactam sodium.
Description
Each vial contains piperacillin sodium equivalent to piperacillin 4.0 g and tazobactam sodium equivalent to tazobactam 500 mg.
Action
Pharmacology: Pharmacodynamics: Piperacillin, a broad spectrum, semi-synthetic penicillin active against many Gram-positive and Gram-negative aerobic and anaerobic bacteria, exerts bactericidal activity by inhibition of both, septum and cell wall synthesis. Tazobactam, a triazolymethyl penicillanic acid sulfone, is an inhibitor of many beta-lactamases, including the plasmid and chromosomally mediated enzymes. The presence of tazobactam in the Pipertaz formulation enhances and extends the antibiotic spectrum of piperacillin.
Pharmacokinetics: Distribution: Both piperacillin and tazobactam are about 26% to 33% and 31% to 32% respectively bound to plasma proteins. Well into lungs, intestinal mucosa, skin, muscle, uterus, ovary, prostate, gall-bladder, and bile; penetration into cerebral spinal fluid (CSF) is low in subject with noninflamed meninges.
Metabolism: Piperacillin metabolized to minor microbiologically active desethyl metabolite. Tazobactam is metabolized to a single metabolite that lacks pharmacologic and antibacterial activities.
Excretion: Piperacillin and tazobactam are eliminated via the kidney by glomerular filtration and tubular secretion. Piperacillin is excreted rapidly as unchanged drug with 68% of the dose appearing in the urine. Tazobactam is excreted as unchanged drug, with 80% of the dose appearing in the urine. Piperacillin, Tazobactam and desethyl piperacillin also secreted into bile.
Indications/Uses
Pipertaz is indicated for the treatment of the following systemic and/or local bacterial infections in which susceptible organisms have been detected or are suspected.
Adults: Community acquired pneumonia due to Haemophilus influenzae.
Intra-abdominal infections caused by piperacillin-resistant beta-lactamase-producing strains of Escherichia coli and Bacteroides fragilis.
Skin and skin structure infections caused by piperacillin-resistant beta-lactamase-producing strains of Staphylococcus aureus.
Gynecological infections including endometritis caused by piperacillin-resistant beta-lactamase-producing strains of E. coli.
Pipertaz plus an aminoglycoside is indicated for bacterial infections in neutropenic patients.
Pseudomonas aeruginosa: When Pipertaz is used for the treatment of nosocomial infection, including pneumonia concomitant therapy with an aminoglycoside should be considered. Concomitant use of an aminoglycoside is particularly important when Pseudomonas aeruginosa is suspected as a causative organism and adjust dose as necessary; if Pseudomonas aeruginosa is not isolated, it may be possible to discontinue the aminoglycoside.
Children: CHILDREN UNDER THE AGE OF 12 YEARS: Infections in neutropenic patients CHILDREN 2-12 YEARS; In hospitalized children aged 2 to 12 years, Pipertaz is indicated for the treatment of serious intra-abdominal infections, caused by E.coli or Bacteroides species.
It has not been evaluated in this indication for pediatric patients below the age of 2 years.
Dosage/Direction for Use
Pipertaz is administered by I.V. infusion over 30 minutes. Pipertaz should be reconstituted with suitable solvent (see Reconstitution Directions as follows). The usual dose for adults is 4 g of piperacillin/0.5 g of tazobactam every 8 hours for 7 to 10 days, given as Pipertaz 4.5 g every 8 hours.
In acute infections, treatment with Pipertaz should be for a minimum of five days and continued for 48 to 72 hours beyond resolution of clinical symptoms or the fever. (See Table 1.)

Click on icon to see table/diagram/image

For patients on haemodialysis, the maximum daily dose is 2 g/0.25 g every 8 hours. In addition, because haemodialysis removes 30% - 40% of piperacillin in 4 hours, one additional dose of 0.75 g Pipertaz should be administered following each dialysis period. For patients with renal failure and hepatic insufficiency, measurement of serum levels of Pipertaz will provide additional guidance for adjusting dosage.
Neutropenic Patients: In treating neutropenic patients, full therapeutic doses of piperacillin/tazobactam and an aminoglycoside should be used. The possibility of hypokalaemia should be kept in mind in patients who have low potassium reserves, and periodic electrolyte determinations should be made in these patients.
When used in conjunction with an aminoglycoside for the treatment of nosocomial pneumonia in patients in whom Pseudomonas aeruginosa is isolated, the recommended dosage of 4.0 g of piperacillin/0.5 g tazobactam every 6 hours for 7-14 days.
Hospitalised Children with Intra-abdominal Infection: For children aged 2 to 12 years, weighing up to 40 kg, and with normal renal function, the recommended dosage is 112.5 mg/kg (100 mg piperacillin/12.5 mg tazobactam) every 8 hours. For children aged 2 to 12 years, weighing over 40 kg, and with normal renal function, follow the adult dose guidance, i.e. 4.5 g (4 g piperacillin/0.5 g tazobactam) every 8 hours.
The duration of therapy should be guided by the severity of the infection and the patient's clinical and bacteriological progress. Therapy is recommended to be a minimum of 5 days and a maximum of 14 days, considering the dose administration should continue at least 48 hours after the resolution of clinical signs and symptoms.
Children Aged 2-12 Years with Renal Insufficiency: The pharmacokinetics of piperacillin/tazobactam have not been studied in paediatric patients with renal impairment. The following dosage adjustment for paediatric patients aged 2 to 12 years with renal impairment is recommended. (See Table 2.)

Click on icon to see table/diagram/image

The dosage modification is only an approximation. Each patient must be monitored closely for signs of drug toxicity. Drug dose and interval should be adjusted accordingly.
Reconstitution Directions: Diluents for Reconstitution: Sterile Water for Injection, Bacteriostatic Water for Injection, Sodium Chloride Injection.
Each vial of 4 g/0.5 g Pipertaz should be reconstituted with at least 20 ml of one of the above diluents. Shake until dissolved.
For intravenous infusion: The reconstituted solution may be further diluted to the desired volume (e.g. 50 ml or 100 ml) with one of the reconstitution diluents or with Dextrose 5% in Water.
Pipertaz should be used immediately after reconstitution. Discard any unused portion. Vial should not be frozen after reconstitution.
Overdosage
The majority of events experienced during over dosage including nausea, vomiting and diarrhea which have also been reported with the usual recommended dosages. Patients may experience neuromuscular excitability or convulsions if higher than recommended doses are given intravenously (particularly in the presence of renal failure).
Treatment should be supportive and symptomatic according to the patients clinical presentation. No specific antidote is known. Excessive serum concentrations of either piperacillin or tazobactam may be reduced by haemodialysis.
Contraindications
The use of Pipertaz is contraindicated in patients with a history of allergic reactions to any of the penicillins, cephalosporins, or β-lactamase inhibitors.
Warnings
Serious and occasionally fatal hypersensitivity (anaphylactic/anaphylactoid including shocks) reactions have been reported in patients receiving therapy with penicillins. These reactions are more apt to occur in persons with a history of penicillin hypersensitivity or a sensitivity to multiple allergens. Before initiating therapy with piperacillin/tazobactam, careful inquiry should be made concerning previously hypersensitivity reactions to penicillins, cephalosporins, and other allergens. If an allergic reaction occurs during therapy with piperacillin/tazobactam, the antibiotic should be discontinued. Serious hypersensitivity reactions require immediate emergency measures, with adrenaline, corticosteroids and antihistamines.
Special Precautions
An open airway must be maintained. Pseudomembranous colitis has been reported with nearly all antibacterial agents, including piperacillin. Antibiotic induced pseudo-membranous colitis may be manifested by severe, persistent diarrhea which may be life-threatening. The onset of pseudomembranous colitis may occur during or after antibacterial treatment. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.
While Piperacillin/tazobactam possesses the characteristic low toxicity of the penicillin group of antibiotics, periodic assessment of organ system functions including renal and hepatic during prolonged therapy is advisable.
Leukopenia and neutropenia may occur, especially during prolonged therapy. Therefore, periodic assessment of haematopoietic function should be performed; Bleeding manifestations have occurred in some patients receiving β-lactam antibiotics. 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, the antibiotic should be discontinued and appropriate therapy instituted.
The possibility of the emergence of resistant organisms, which might cause superinfections, should be kept in mind, particularly during prolonged treatment. 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. This product contains 2.35 mEq (54 mg) of sodium per gram of piperacillin which may increase a patient's overall sodium intake. Periodic electrolyte determinations should be made in patients with low potassium reserves, and the possibility of hypokalaemia should be kept in mind with patients who have potentially low potassium reserves and who are receiving cytotoxic therapy or diuretics.
Modest elevation of indices of liver function may be observed. In patients with renal insufficiency or haemodialysis patients, the intravenous dose should be adjusted to the degree of renal function impairment. 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.
Use In Pregnancy & Lactation
Adequate studies on the use of piperacillin/tazobactam during pregnancy and the period of breast feeding are not yet available. Piperacillin/tazobactam did not affect fertility in rats and was not teratogenic in mice or rats. Piperacillin and tazobactam cross the placenta. Piperacillin is excreted in low concentrations in human milk; tazobactam concentrations in human milk have not been studied. Until further experience is available, however, pregnant or nursing women should be treated only if the therapeutic benefit outweighs the risk to the patient and the foetus.
Adverse Reactions
The adverse effect of this products: tetter, itch, diarrhea, naupathia, vomit, headache, insomnia, pain at inject part, phlebitis, edema at injected site, hematoblast reduce, fever, blood serum aminotransferase heightens, leucopenia, and reduce in platelet count.
Drug Interactions
Interactions with Other Medicines: Concurrent administration of probenecid and piperacillin/tazobactam produced a longer half-life lower renal clearance for both piperacillin and tazobactam; however, peak plasma concentrations of either medicine are unaffected.
No interaction is found between piperacillin/tazobactam and vancomycin.
Piperacillin either alone or with tazobactam did not significantly alter the pharmacokinetics of tobramycin in subjects with normal renal function and with mild or moderate renal impairment. The pharmacokinetics of piperacillin, tazobactam, and the M1 metabolite were also not significantly altered by tobramycin administration.
Whenever piperacillin/tazobactam is used concurrently with another antibiotic, especially an aminoglycoside, the drugs must not be mixed in intravenous solutions or administered concurrently due to physical incompatibility.
During simultaneous administration of high dose of heparin, oral anticoagulants and other drugs that may affect the blood coagulation system and/or the thrombocyte function, the coagulation parameter should be tested more frequently and monitored regularly.
Piperacillin, when given concomitantly with vecuronium has been implicated in the prolongation of the neuromuscular blockage of vecuronium to their mechanism of action.
Piperacillin may reduce the excretion of methotrexate; therefore, serum levels of methotrexate should be monitored in patients to avoid drug toxicity.
Pharmaceutical Incompatibilities: Pipertaz should not be mixed other medicines in a syringe or infusion bottle since compatibility has not been established. Whenever Pipertaz is used concurrently with another antibiotic (e.g. aminoglycosides), the medicines must be administered separately.
Because of chemical instability, Pipertaz should not be used with solutions containing only sodium bicarbonate. Lactated Ringer's solution is not compatible with Pipertaz. Piperatz should not be added to blood products or albumin hydrolysates.
Laboratory Tests: The administration of Pipertaz 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.
Storage
Keep in well-closed containers and store below 30°C.
Use single-dose vials immediately after reconstitution, discard any unused portion after 12 hours if stored at room temperature (30°C) or after 48 hours in refrigerated (2°C to 8°C).
MIMS Class
ATC Classification
J01CR05 - piperacillin and beta-lactamase inhibitor ; Belongs to the class of penicillin combinations, including beta-lactamase inhibitors. Used in the systemic treatment of infections.
Presentation/Packing
Powd for inj (vial) (white or almost white) x 1's.
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