Tazocin

Tazocin

piperacillin + tazobactam

Manufacturer:

Pfizer

Distributor:

Zuellig Pharma
Full Prescribing Info
Contents
Piperacillin sodium, tazobactam sodium.
Description
Each vial contains sterile piperacillin sodium equivalent to piperacillin 4 g and sterile tazobactam sodium equivalent to tazobactam 500 mg.
Each vial of piperacillin/tazobactam reformulation contains a total of 2.79 mEq (64 mg) of sodium per gram of piperacillin.
Tazocin also contains edetate disodium dihydrate (EDTA) 1 mg/vial. It contains no preservatives.
Action
Pharmacology: Piperacillin, a broad-spectrum, semisynthetic 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 triazolylmethyl penicillanic acid sulphone, is a potent inhibitor of many β-lactamases, in particular, the plasmid-mediated enzymes which commonly cause resistance to penicillins and cephalosporins including 3rd-generation cephalosporins. The presence of tazobactam in the Tazocin formulation enhances and extends the antibiotic spectrum of piperacillin to include many β-lactamases-producing bacteria normally resistant to it and other β-lactam antibiotics. Thus, Tazocin combines the properties of a broad-spectrum antibiotic and a β-lactamase inhibitor.
Microbiology: Tazocin is highly active against piperacillin-sensitive microorganisms as well as many β-lactamase-producing, piperacillin-resistant microorganisms.
Gram-Negative Bacteria: Most plasmid-mediated β-lactamase-producing and non-β-lactamase-producing strains of Escherichia coli, Klebsiella sp (including K. oxytoca, K. pneumoniae), Proteus sp (including Proteus vulgaris, Proteus mirabilis), Salmonella and Shigella spp, Neisseria gonorrhoeae, Neisseria meningitidis, Moraxella sp (including M. catarrhalis), Haemophilus sp (including H. influenzae, H. parainfluenzae), Pasteurella multocida, Yersinia and Campylobacter spp, Gardnerella vaginalis. Many chromosomally-mediated β-lactamase-producing and non-β-lactamase-producing strains of Enterobacter sp (including E. cloacae, E. aerogenes), Citrobacter sp (including C. freundii, C. diversus), Providencia sp, Morganella morganii, Serratia sp (including S. marcescens, S. liquefaciens), Pseudomonas aeruginosa and other Pseudomonas sp (including P. cepacia, P. fluorescens), Xanthomonas maltophilia, Acinetobacter sp.
Gram-Positive Bacteria: β-Lactamase-producing and non-β-lactamase-producing strains of streptococci (S. pneumoniae, S. pyogenes, S. bovis, S. agalactiae, S. viridans, group C, group G), enterococci (E. faecalis), Staphylococcus aureus (not methicillin-resistant S. aureus), S. saprophyticus, S. epidermidis (coagulase-negative staphylococci), corynebacteria, Listeria monocytogenes, Nocardia sp.
Anaerobic Bacteria: β-Lactamase-producing and non-β-lactamase-producing anaerobes eg, Bacteroides sp (including B. bivius, B disiens, B. capillosus, B. melaninogenicus, B. oralis), the Bacteroides fragilis group (including B. fragilis, B. vulgatus, B. distasonis, B. ovatus, B. thetaiotaomicron, B. uniformis, B. asaccharolyticus), as well as Peptostreptococcus and Fusobacterium spp, Eubacterium group, Clostridia sp (including C. difficile, C. perfringens), Veillonella and Actinomyces spp.
Indications/Uses
Treatment of the following systemic and/or local bacterial infections in which susceptible organisms have been detected or are suspected:
Lower respiratory tract infections; urinary tract infections (complicated and uncomplicated); intra-abdominal infections; skin and skin structure infections; bacterial septicaemia.
Polymicrobic Infections: Tazocin is indicated for polymicrobic infections including those where aerobic and anaerobic organisms are suspected (intra-abdominal, skin and skin structure, lower respiratory tract).
Tazocin, in combination with an aminoglycoside, is indicated for bacterial infections in neutropenic adults or children.
In hospitalized children 2-12 years, piperacillin/tazobactam is indicated for the treatment of intra-abdominal infections including appendicitis complicated by rupture or abscess, peritonitis and biliary infections. It has not been evaluated in this indication for pediatric patients <2 years.
While Tazocin is indicated only for the conditions previously mentioned, infections caused by piperacillin-susceptible organisms are also amenable to Tazocin treatment due to its piperacillin content. Therefore, treatment of mixed infections caused by piperacillin-susceptible organisms and β-lactamase-producing organisms susceptible to Tazocin should not require the addition of another antibiotic.
Tazocin is particularly useful in the treatment of mixed infections and in presumptive therapy prior to the availability of the results of sensitivity tests because of its broad spectrum of activity.
Tazocin acts synergistically with aminoglycosides against certain strains of Pseudomonas aeruginosa. Combined therapy has been successful, especially in patients with impaired host defenses. Both drugs should be used in full therapeutic doses. As soon as results of culture and susceptibility tests become available, antimicrobial therapy should be adjusted if necessary.
Dosage/Direction for Use
Neutropenic patients with signs of infection (eg, fever) should receive immediate empirical antibiotic therapy before laboratory results are available.
Adults and Children Receiving the Adult Dose: The usual dosage for adults and children receiving the adult dose with normal renal function is 4.5 g Tazocin (piperacillin 4 g and tazobactam 0.5 g) given every 8 hrs.
The total daily dose depends on the severity and localization of the infection and can vary from 2.25-4.5 g Tazocin (piperacillin 2-4 g and tazobactam 0.25-0.5 g) administered every 6 or 8 hrs.
Elderly: Tazocin may be used at the same dose levels as adults except in cases of renal impairment (see as follows).
Neutropenia: Recommended Dose: 4.5 g Tazocin (piperacillin 4 g and tazobactam 0.5 g) given every 6 hrs in combination with an aminoglycoside.
Pediatric Neutropenia: For children with normal renal function, the dose should be adjusted to 90 mg/kg (piperacillin 80 mg/tazobactam 10 mg) administered every 6 hrs in combination with an aminoglycoside, not exceeding 4.5 g Tazocin (piperacillin 4 g and tazobactam 0.5 g) given every 6 hrs.
Intra-Abdominal Infections: Hospitalized Children 2-12 years with Normal Renal Function: Weighing up to 40 kg: Recommended Dose: 112.5 mg/kg (piperacillin 100 g/tazobactam 12.5 g) every 8 hrs; >40 kg: Follow the adult dose guidance ie, 4.5 g (piperacillin 4 g/tazobactam 0.5 g) every 8 hrs.
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 that dose administration should continue at least 48 hrs after the resolution of clinical signs and symptoms.
Renal Insufficiency: Adults and Children Receiving the Adult Dose: In adults and children receiving the adult dose with renal insufficiency and haemodialysis patients, the IV dosages and administration intervals should be adjusted to the degree of actual renal function impairment. The suggested daily doses are as follows: (See Table 1.)

Click on icon to see table/diagram/image

For patients on haemodialysis, the maximum daily dose is 8 g/1 g Tazocin. In addition, because haemodialysis removes 30-50% of piperacillin in 4 hrs, 1 additional dose of 2 g/250 mg Tazocin should be administered following each dialysis period. For patients with renal failure and hepatic insufficiency, measurement of serum levels of Tazocin will provide additional guidance for adjusting dosage.
Children with Renal Insufficiency <40 kg: IV dosage should be adjusted to the degree of actual renal impairment.
Children with Renal Insufficiency 2-12 years: The pharmacokinetics of piperacillin/tazobactam have not been studied in pediatric patients with renal impairment. The following dosage adjustment for pediatric patients with renal impairment 2-12 years is recommended (see Table 2).

Click on icon to see table/diagram/image

This 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.
Children <50 kg on Hemodialysis: Recommended Dose: 45 mg/kg every 8 hrs.
Duration of Therapy: In acute infections, treatment with Tazocin should be continued for 48 hrs beyond the resolution of clinical symptoms or fever.
Administration: Tazocin may be given by slow IV injection (over at least 3-5 min) or by slow IV infusion (over 20-30 min).
Reconstitution Directions: IV Injection: Each vial of Tazocin 4.5 g should be reconstituted with 20 mL of one of the following diluents:
Diluents for Reconstitution: 0.9% Sodium Chloride for Injection; Sterile Water for Injection; Dextrose 5%; Bacteriostatic Saline/Parabens; Bacteriostatic Water/Parabens; Bacteriostatic Saline/Benzyl Alcohol; Bacteriostatic Water/Benzyl Alcohol; Lactated Ringer's Solution..
Shake until dissolved. IV injection should be given over 3-5 min.
IV Infusion: Each vial of Tazocin 4.5 g should be reconstituted with at least 20 mL of one of the reconstitution diluents.
The reconstituted solution may be further diluted to the desired volume (eg, 50-150 mL) with one of the compatible solvents for IV use as follows: 0.9% Sodium Chloride for Injection; Sterile Water for Injection+; Dextrose 5%; and Dextran 6% in Saline.
+Maximum recommended volume of Sterile Water for Injection per dose is 50 mL.
Co-Administration of Piperacillin/Tazobactam with Aminoglycosides: Due to in vitro inactivation of the aminoglycosides by β-lactam antibiotics, piperacillin/tazobactam and the aminoglycoside are recommended for separate administration. Piperacillin/tazobactam and the aminoglycoside should be reconstituted and diluted separately when concomitant therapy with aminoglycosides is indicated (see Cautions for Usage).
In circumstances where co-administration is preferred, the reformulated piperacillin/tazobactam-containing EDTA supplied in vials is compatible for simultaneous co-administration via y-site infusion only with the following aminoglycosides under the following conditions. (See Table 3.)

Click on icon to see table/diagram/image

Compatibility of piperacillin/tazobactam with other aminoglycosides has not been established. Only the concentration and diluents for amikacin and gentamicin with the dosages of piperacillin/tazobactam listed in Table 3 have been established as compatible for co-administration via y-site infusion.
Simultaneous co-administration via y-site in any manner other than previously mentioned, may result in inactivation of the aminoglycoside by piperacillin/tazobactam.
Overdosage
Symptoms: There have been post-marketing 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 dosages. Patients may experience neuromuscular excitability or convulsions if higher than recommended doses are given IV (particularly in the presence of renal failure).
Treatment: No specific antidote is known.
Treatment should be supportive and symptomatic according to the patient's clinical presentation. Excessive serum concentrations of either piperacillin or tazobactam may be reduced by hemodialysis.
Contraindications
Patients with a history of hypersensitivity to any of the β-lactams (including penicillins and cephalosporins) or to β-lactamase inhibitors.
Warnings
Before initiating therapy with Tazocin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins and other allergens. Serious and occasionally fatal hypersensitivity [anaphylactic/anaphylactoid (including shock)] reactions have been reported in patients receiving therapy with penicillins, including piperacillin/tazobactam. These reactions are more likely to occur in persons with a history of sensitivity to multiple allergens. Serious hypersensitivity reactions require the discontinuation of the antibiotic, and may require administration of adrenaline and other emergency measures.
There have been reports of patients with a history of penicillin hypersensitivity who have experienced severe reactions when treated with a cephalosporin.
Antibiotic-induced pseudomembranous colitis may be manifested by severe, persistent diarrhea which may be life-threatening. The onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment.
Special Precautions
While Tazocin possesses the characteristic low toxicity of the penicillin group of antibiotics, periodic assessment of organ system functions including renal, hepatic and haematopoietic during prolonged therapy is advisable.
Bleeding manifestations have occurred in some patients receiving β-lactam antibiotics. These reactions have sometimes been associated with abnormalities of coagulation tests eg, 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.
During prolonged therapy, leukopenia and neutropenia may occur; therefore, periodic assessment of hematopoietic function should be performed.
In case of severe, persistent diarrhoea, the possibility of antibiotic-induced, life-threatening pseudomembranous colitis must be taken into consideration. Therefore, Tazocin must be discontinued immediately in such cases and suitable therapy be initiated (eg, oral metronidazole or oral vancomycin). Preparations which inhibit peristalsis are contraindicated.
As with other antibiotics, the possibility of emergence of resistant organisms, which might cause superinfections, should be kept in mind particularly during prolonged treatment. Microbiological follow-up may be required to detect any important superinfection. If this occurs, appropriate measures should be taken.
Tazocin contains 2.79 mEq (64 mg) of sodium per gram of piperacillin which may increase a patient's overall sodium intake. Hypokalemia may occur in patients with low potassium reserves or who are receiving concomitant medications that may lower potassium levels; periodic electrolyte determinations may be advisable in such patients. Modest elevation of indices of liver function may be observed.
Antimicrobials used in high doses for short periods to treat gonorrhoea may mask or delay the symptoms of incubating syphilis. Therefore, prior to treatment, patients with gonorrhea should also be evaluated for syphilis. Specimens for darkfield examination should be obtained from patients with any suspected primary lesion, and serologic tests should be made for a minimum of 4 months.
Use in Patients with Hepatic Impairment: No dosage adjustment of Tazocin is necessary.
Use in Patients with Renal Impairment: In patients with renal insufficiency or hemodialysis patients, the IV dose should be adjusted to the degree of renal function impairment.
Use in Pregnancy: Studies in mice and rats have not demonstrated any embryotoxic or teratogenic effects of the piperacillin-tazobactam combination. There are no adequate and well-controlled studies with the piperacillin-tazobactam combination or with piperacillin or tazobactam alone in pregnant women. Piperacillin and tazobactam cross the placenta. Pregnant women should be treated only if the expected benefit outweighs the possible risks to the pregnant woman and fetus.
Use in Lactation: Piperacillin is excreted in low concentrations in human milk; tazobactam concentrations in human milk have not been studied. Women who are breastfeeding should be treated only if the expected benefit outweighs the possible risks to the woman and child.
Use In Pregnancy & Lactation
Use in Pregnancy: Studies in mice and rats have not demonstrated any embryotoxic or teratogenic effects of the piperacillin-tazobactam combination. There are no adequate and well-controlled studies with the piperacillin-tazobactam combination or with piperacillin or tazobactam alone in pregnant women. Piperacillin and tazobactam cross the placenta. Pregnant women should be treated only if the expected benefit outweighs the possible risks to the pregnant woman and fetus.
Use in Lactation: Piperacillin is excreted in low concentrations in human milk; tazobactam concentrations in human milk have not been studied. Women who are breastfeeding should be treated only if the expected benefit outweighs the possible risks to the woman and child.
Adverse Reactions
Adverse reactions are listed in CIOMS frequency categories: Very common: ≥10%; common: ≥1%; uncommon: ≥0.1% and <1%; rare: ≥0.01% and <0.1%; very rare: <0.01%.
Infections and Infestations: Uncommon: Candidal superinfection.
Blood and Lymphatic System: Uncommon: Leukopenia, neutropenia, thrombocytopenia. Rare: Anemia, bleeding manifestations (including purpura, epistaxis and prolonged bleeding time), eosinophilia, haemolytic anemia. Very Rare: Agranulocytosis, positive Coombs' direct test, pancytopenia, prolonged partial thromboplastin time, prolonged prothrombin time, thrombocytosis.
Immune System Disorders: Uncommon: Hypersensitivity reaction. Rare: Anaphylactic/anaphylactoid reaction (including shock).
Metabolism and Nutrition Disorders: Very Rare: Decreased blood albumin, decreased blood glucose, decreased total blood protein, hypokalemia.
Nervous System Disorders: Uncommon: Headache, insomnia.
Vascular System Disorders: Uncommon: Hypotension, phlebitis, thrombophlebitis. Rare: Flushing.
Gastrointestinal System Disorders: Common: Diarrhea, nausea, vomiting. Uncommon: Constipation, dyspepsia, jaundice, stomatitis. Rare: Abdominal pain, pseudomembranous colitis.
Hepatobiliary System Disorders: Uncommon: Increased alanine aminotransferase, increased aspartate aminotransferase. Rare: Increased bilirubin, increased blood alkaline phosphatase, increased γ-glutamyltransferase, hepatitis.
Skin and Subcutaneous Tissue Disorders: Common: Rash. Uncommon: Pruritus, urticaria. Rare: Bullous dermatitis, erythema multiforme. Very Rare: Stevens-Johnson syndrome, toxic epidermal necrolysis.
Musculoskeletal, Connective Tissue and Bone Disorders: Rare: Arthralgia.
Renal and Urinary System Disorders: Uncommon: Increased blood creatinine. Rare: Interstitial nephritis, renal failure. Very Rare: Increased blood urea nitrogen.
General Disorders and Administration Site Conditions: Uncommon: Fever, injection site reaction. Rare: Rigors.
Piperacillin therapy has been associated with an increased incidence of fever and rash in cystic fibrosis patients.
Drug Interactions
As with other penicillins, concurrent administration of probenecid and piperacillin/tazobactam produced a longer half-life and lower renal clearance for both piperacillin and tazobactam. However, peak plasma concentrations of either drug are unaffected. No pharmacokinetic interaction is found between Tazocin and either vancomycin or tobramycin.
Compatibility of piperacillin/tazobactam with other aminoglycosides has not been established. Only the concentration and diluents for amikacin and gentamicin with the dosages of piperacillin/tazobactam listed in the table have been established as compatible for co-administration via y-site infusion.
Simultaneous co-administration via y-site in any manner other than listed previously may result in inactivation of the aminoglycoside by piperacillin/tazobactam.
During simultaneous administration of heparin, oral anticoagulants and other drugs which may affect the blood coagulation system, including thrombocyte function, appropriate coagulation tests should be performed more frequently and monitored regularly.
Piperacillin when used concomitantly with vecuronium has been implicated in the prolongation of the neuromuscular blockade of vecuronium. Due to their similar mechanism of action, it is expected that the neuromuscular blockade produced by any of the nondepolarizing muscle relaxants could be prolonged in the presence of piperacillin.
Piperacillin may reduce the excretion of methotrexate; therefore, serum levels of methotrexate should be monitored in patients to avoid drug toxicity.
Interference with Laboratory and Other Diagnostic Tests: As with other penicillins, the administration of piperacillin/tazobactam 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.
There have been reports of positive test results using the Bio-Rad Laboratories Platelia Aspergillus EIA test in patients receiving piperacillin/tazobactam injection who were subsequently found to be free of Aspergillus infection. Cross-reactions with non-Aspergillus polysaccharides and polyfuranoses with Bio-Rad Laboratories Platelia Aspergillus EIA test have been reported. Therefore, positive test results in patients receiving piperacillin/tazobactam should be interpreted cautiously and confirmed by other diagnostic methods.
Caution For Usage
Tazocin should not be mixed with other drugs in a syringe or infusion bottle since compatibility has not been established.
Whenever Tazocin is used concurrently with another antibiotic (eg, aminoglycosides), the drugs must be administered separately.
The mixing of beta-lactam antibiotics with aminoglycosides in vitro can result in substantial inactivation of the aminoglycoside. However, amikacin and gentamicin were determined to be compatible with piperacillin/tazobactam in vitro in certain diluents at specific concentrations (see Dosage & Administration).
Because of chemical instability, Tazocin should not be used with solutions containing only sodium bicarbonate.
Lactated Ringer's solution is only compatible with piperacillin/tazobactam EDTA reformulation.
Tazocin should not be added to blood products or albumin hydrolysates.
Storage
Before reconstitution, store Tazocin vials below 25°C. Tazocin vials should be used immediately after reconstitution. For vials not used immediately after reconstitution, follow these guidelines: Discard any unused portion after 24 hrs if stored below 25°C, but outside the refrigerator.
Discard any unused portion after 48 hrs, if refrigerated (between 2-8°C).
Vials should not be frozen after reconstitution.
Diluted solutions prepared for IV use are stable for 24 hrs when stored under refrigeration (2-8°C) in IV bags or syringes. Unused solution should be discarded.
Once further diluted to desired volume (50 or 150 mL) with 5% dextrose injection or with 0.9% sodium chloride injection, or with sterile water for injection, Tazocin has demonstrated chemical stability up to 24 hrs at room temperature (15-25°C) and up to 1 week at refrigerated temperature (2-8°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) 4.5 g (white to off-white, sterile, lyophilized powd) x 12's.
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