Tazocin

Tazocin

piperacillin + tazobactam

Manufacturer:

Pfizer
Full Prescribing Info
Contents
Piperacillin sodium, tazobactam sodium.
Description
Each 4.5-g single-dose vial contains piperacillin sodium equivalent to piperacillin 4 g and tazobactam sodium equivalent to tazobactam 0.5 g. It also contains edetate disodium dihydrate (EDTA) 1 mg and sodium 256 mg (11.17 mEq).
Indications/Uses
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 as follows: 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. The individual members of this group were studied in <10 cases.
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.
As a combination product, Tazocin is indicated only for the specified conditions previously mentioned. Infections caused by piperacillin-susceptible organisms, for which piperacillin has been shown to be effective are also amenable to Tazocin treatment due to its piperacillin content. The tazobactam component of Tazocin 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 Tazocin should not require the addition of another antibiotic.
Tazocin is useful as presumptive therapy in the indicated conditions prior to the identification of causative organisms because of its broad-spectrum bactericidal activity against gram-positive and gram-negative aerobic and anaerobic organisms.
Appropriate cultures should usually be performed before initiating antimicrobial treatment in order to isolate and identify the organisms causing the infection and to determine their susceptibility to Tazocin.
Antimicrobial therapy should be adjusted, if appropriate, once the results of culture(s) and antimicrobial susceptibility testing are known.
Adult and Children: Febrile neutropenic infections in combination with an aminoglycoside.
Dosage/Direction for Use
Adults and Children ≥12 years: General: Recommended Total Daily Dosage: Piperacillin 12 g/tazobactam 1.5 g given in divided doses every 6 or 8 hrs. Doses as high as piperacillin 18 g/tazobactam 2.25 g per day in divided doses can be used in severe infections. Neutropenia: Recommended Dose: 4.5 g (piperacillin 4 g/tazobactam 500 mg) given every 6 hrs in combination with aminoglycoside. Pediatric Neutropenia: Children 2-12 years with Normal Renal Function and Weighing <50 kg: The dose should be adjusted to piperacillin 80 mg/tazobactam 10 mg per kg administered every 6 hrs, in combination with the appropriate dose of an aminoglycoside. Children Weighing >50 kg: Follow adult dosing in combination with the appropriate dose of an aminoglycoside.
Renal Impairment: In patients with renal insufficiency or hemodialysis patients, IV dosages and administration intervals should be adjusted to the degree of renal function impairment. The recommended daily doses are as follows: See Table 1.


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For patients on hemodialysis, the maximum dose is 2.25 g every 8 hrs. In addition, because hemodialysis removes 30-40% of a Tazocin dose in 4 hrs, 1 additional dose of Tazocin 0.75 g should be administered following each dialysis period. For patients with renal failure, measurement of serum levels of piperacillin and tazobactam will provide additional guidance for adjusting dosage.
Hepatic Impairment: No dosage adjustment of piperacillin/tazobactam is necessary in patients with hepatic impairment.
Co-administration of Piperacillin/Tazobactam with Aminoglycosides: Due to the in vitro inactivation of the aminoglycoside by β-lactam antibiotics, piperacillin/tazobactam and the aminoglycoside are recommended for separate administration. Piperacillin/tazobactam 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 2.


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 2 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.
Administration: Tazocin must be given by slow IV infusion (eg, over 20-30 min) or slow IV injection (over at least 3-5 min). The usual duration of Tazocin treatment is from 7-10 days. The duration of therapy should be guided by the severity of the infection and the patient's clinical and bacteriological progress.
Overdosage
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 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
Hypersensitivity to any β-lactams (including penicillins and cephalosporins) or to β-lactamase inhibitors.
Warnings
Before initiating therapy with piperacillin/tazobactam, 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 epinephrine and other emergency measures.
Serious skin reactions eg, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported in patients receiving Tazocin (see Adverse Reactions). If a patient develops skin rash, it should be monitored closely and piperacillin/tazobactam should be discontinued if lesions progress.
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
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, Tazocin should be discontinued and appropriate therapy instituted.
Tazocin contains sodium 2.79 mEq (64 mg)/g 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.
Leukopenia and neutropenia may occur, especially during prolonged therapy. Therefore, periodic assessment of hematopoietic function should be performed.
As with treatment with other penicillins, neurological complications in the form of convulsions may occur when high doses are administered, especially in patients with impaired renal function.
Use in Patients with Hepatic Impairment: No dosage adjustment of piperacillin/tazobactam is necessary in patients with hepatic impairment.
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 the elderly: Patients >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
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 listed in CIOMS frequency categories include: 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, prolonged bleeding time), eosinophilia, haemolytic anemia. Very Rare: Agranulocytosis, positive direct Coombs' 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 blood total protein, hypokalemia.
Nervous System Disorders: Uncommon: Headache, insomnia.
Vascular Disorders: Uncommon: Hypotension, phlebitis, thrombophlebitis. Rare: Flushing.
Gastrointestinal: Common: Diarrhea, nausea, vomiting. Uncommon: Constipation, dyspepsia, jaundice, stomatitis. Rare: Abdominal pain, pseudomembranous colitis.
Hepatobiliary: 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: Pruritis, urticaria. Rare: Bullous dermatitis, erythema multiforme. Very Rare: Stevens-Johnson syndrome, toxic epidermal necrolysis.
Musculoskeletal, Connective Tissue and Bone Disorder: Rare: Arthralgia.
Renal and Urinary 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
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 non-depolarizing muscle relaxants could be prolonged in the presence of piperacillin.
During simultaneous administration of heparin, oral anticoagulants and other drugs that may affect the blood coagulation system including thrombocyte function, appropriate coagulation tests should be performed more frequently and monitored regularly (see Precautions).
Piperacillin may reduce the excretion of methotrexate; therefore, serum levels of methotrexate should be monitored in patients to avoid drug toxicity.
As with other penicillins, concurrent administration of probenecid and piperacillin/tazobactam produces a longer half-life and lower renal clearance for both piperacillin and tazobactam; however, peak plasma concentrations of either drug are unaffected.
Piperacillin, either alone or with tazobactam did not significantly alter the pharmacokinetics of tobramycin in subjects with mild or moderate renal impairment. The pharmacokinetics of piperacillin, tazobactam, and the M1 metabolite were also not significantly altered by tobramycin administration. Tazocin is not compatible with tobramycin for simultaneous co-administration via Y-site.
No pharmacokinetic interactions have been noted between piperacillin/tazobactam and vancomycin.
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
Handling: Directions for Reconstitution and Dilution for Use: IV Use Only: Reconstitute each 4.5-g vial with 20-mL volume of compatible solvent. Swirl until dissolved. When swirled constantly, reconstitution generally occurs within 5-10 min.
Compatibilities/Incompatibilities: Solutions known to be compatible with piperacillin/tazobactam sodium for reconstitution are: 0.9% Sodium chloride for injection, sterile water for injection, dextrose 5%, bacteriostatic saline/parabens, bacteriostatic water/parabens, bacteriostatic saline/benzyl alcohol and bacteriostatic water/benzyl alcohol.
The reconstituted solution may be further diluted to the desired volume (eg, 50-150 mL) with one of the compatible solvents for IV use listed as follows: 0.9% Sodium chloride for injection, sterile water for injection (maximum recommended volume of sterile water for injection per dose is 50 mL), dextrose 5%, dextran 6% in saline, lactated Ringer's solution, Hartmann’s solution, Ringer's acetate, Ringer's acetate/malate.
Whenever piperacillin/tazobactam is used concurrently with another antibiotic (eg, aminoglycosides), the drugs must be administered separately. The mixing of β-lactam antibiotics with an aminoglycoside 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.)
Piperacillin/tazobactam should not be mixed with other drugs in a syringe or infusion bottle since compatibility has not been established.
Because of chemical instability, piperacillin/tazobactam should not be used with solutions containing sodium bicarbonate only.
Piperacillin/tazobactam should not be added to blood products or albumin hydrolysates.
Before reconstitution, store Tazocin below 25°C.
Tazocin vials should be used immediately after reconstitution. For vials not used immediately after reconstitution, please follow these guidelines: Discard any unused portion after 24 hrs if stored below 25°C, but outside of the refrigerator. Discard any unused portion after 7 days, if refrigerated (between 2°-8°C). Vials should not be frozen after reconstitution.
Storage
Store below 25°C.
Shelf-Life: 36 months.
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 to off-white, sterile, single-dose, cryodessicated powd) 4.5 g x 12's.
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