piperacillin/tazobactam (Rx)

Brand and Other Names:Zosyn
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

piperacillin/tazobactam

injection, lyophilized powder for reconstitution

  • (2g/250mg)/vial: 2.25g
  • (3g/375mg)/vial: 3.375g
  • (4g/500mg)/vial: 4.5g
  • (36g/4.5g)/vial: 40.5g

premix bag

  • 2.25g/50mL
  • 3.375g/50mL
  • 4.5g/100mL

Intra-abdominal Infections

Indicated for treatment of appendicitis (complicated by rupture or abscess) and peritonitis caused by beta-lactamase producing isolates of Escherichia coli or the following members of the Bacteroides fragilis group: B fragilis, B ovatus, B thetaiotaomicron, or B vulgatus

3.375 g IV q6hr (totaling 13.5 g [12 g piperacillin/1.5 g tazobactam]) for 7-10 days

Nosocomial Pneumonia

Indicated for treatment of nosocomial pneumonia (moderate to severe) caused by beta-lactamase producing isolates of Staphylococcus aureus and by piperacillin/tazobactam-susceptible Acinetobacter baumannii, Haemophilus influenzae, Klebsiella pneumoniae, and Pseudomonas aeruginosa

Nosocomial pneumonia caused by P aeruginosa should be treated in combination with an aminoglycoside

4.5 g IV q6hr (totaling 18 g [16 g piperacillin/2 g tazobactam]) for 7-14 days; continue aminoglycoside in P. aeruginosa patients

Skin and Skin Structure infections

Indicated for treatment of uncomplicated and complicated skin and skin structure infections, including cellulitis, cutaneous abscesses and ischemic/diabetic foot infections caused by beta-lactamase producing isolates of Staphylococcus aureus

3.375 g IV q6hr (totaling 13.5 g [12 g piperacillin/1.5 g tazobactam]) for 7-10 days

Female Pelvic Infections

Indicated in treatment of postpartum endometritis or pelvic inflammatory disease caused by beta-lactamase producing isolates of E coli

3.375 g IV q6hr (totaling 13.5 g [12 g piperacillin/1.5 g tazobactam]) for 7-10 days

Community-acquired Pneumonia

Indicated for the treatment of community-acquired pneumonia (moderate severity only) caused by beta-lactamase producing isolates of H influenzae

3.375 g IV q6hr (totaling 13.5 g [12 g piperacillin/1.5 g tazobactam]) for 7-10 days

Dosage Modifications

Renal impairment

  • All indications except nosocomial pneumonia
    • CrCl >40 mL/min: 3.375 g IV q6hr
    • CrCl 20-40 mL/min (without hemodialysis): 2.25 IV q6hr
    • CrCl <20 mL/min (without hemodialysis): 2.25 g IV q8hr
    • Hemodialysis: 2.25 g IV q12hr; administer an additional dose of 0.75 g (0.67 g piperacillin/0.08 g tazobactam) following each dialysis period on hemodialysis days
    • CAPD: 2.25 g IV q12hr
  • Nosocomial pneumonia
    • CrCl >40 mL/min: 4.5 g IV q6hr
    • CrCl 20-40 mL/min (without hemodialysis): 3.375 IV q6hr
    • CrCl <20 mL/min (without hemodialysis): 2.25 g IV q6hr
    • Hemodialysis: 2.25 g IV q8hr; administer an additional dose of 0.75 g (0.67 g piperacillin/0.08 g tazobactam) following each dialysis period on hemodialysis days
    • CAPD: 2.25 g IV q8hr

Hepatic impairment

  • Dosage adjustment not warranted in patients with hepatic cirrhosis

Cystic fibrosis patients

  • As with other semisynthetic penicillins, piperacillin therapy has been associated with an increased incidence of fever and rash in cystic fibrosis patients

Dosing Considerations

To reduce the development of drug-resistant bacteria and maintain the effectiveness of antibacterial drugs, use only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria

When culture and susceptibility information are available, consider selecting or modifying antibacterial therapy

In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy

Dosage Forms & Strengths

piperacillin/tazobactam

injection, lyophilized powder for reconstitution

  • (2g/250mg)/vial: 2.25g
  • (3g/375mg)/vial: 3.375g
  • (4g/500mg)/vial: 4.5g
  • (36g/4.5g)/vial: 40.5g

premix bag

  • 2.25g/50mL
  • 3.375g/50mL
  • 4.5g/100mL

Intra-abdominal Infections

Indicated for treatment of appendicitis (complicated by rupture or abscess) and/or peritonitis in adult and pediatric patients aged ≥2 months caused by beta-lactamase producing isolates of Escherichia coli or the following members of the Bacteroides fragilis group: B fragilis, B ovatus, B thetaiotaomicron, or B vulgatus

<2 months: Safety and efficacy not established

2-9 months

  • ≤40 kg: 90 mg/kg (80 mg piperacillin/10 mg tazobactam) IV q8hr  

>9 months

  • ≤40 kg: 112.5 mg/kg (100 mg piperacillin/12.5 mg tazobactam) IV q8hr  
  • >40 kg: 3.375 g IV q6hr (totaling 13.5 g [12 g piperacillin/1.5 g tazobactam]) for 7-10 days

Nosocomial Pneumonia

Indicated for treatment of nosocomial pneumonia (moderate to severe) in adult and pediatric patients aged ≥2 months caused by beta-lactamase producing isolates of Staphylococcus aureus and by piperacillin/tazobactam-susceptible Acinetobacter baumannii, Haemophilus influenzae, Klebsiella pneumoniae, and Pseudomonas aeruginosa

Nosocomial pneumonia caused by P. aeruginosa should be treated in combination with an aminoglycoside

<2 months: Safety and efficacy not established

2-9 months

  • ≤40 kg: 90 mg/kg (80 mg piperacillin/10 mg tazobactam) IV q6hr  

>9 months

  • ≤40 kg: 112.5 mg/kg (100 mg piperacillin/12.5 mg tazobactam) IV q6hr  
  • >40 kg: 4.5 g IV q6hr (totaling 18 g [16 g piperacillin/2 g tazobactam]) for 7-14 days

Dosage Modifications

Renal impairment

  • Dosage in pediatric patients with renal impairment has not been determined

Hepatic impairment

  • Dosage adjustment not warranted in patients with hepatic cirrhosis

Cystic fibrosis patients

  • As with other semisynthetic penicillins, piperacillin therapy has been associated with an increased incidence of fever and rash in patients with cystic fibrosis

Dosing Considerations

To reduce the development of drug-resistant bacteria and maintain the effectiveness of antibacterial drugs, use only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria

When culture and susceptibility information are available, consider selecting or modifying antibacterial therapy

In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy

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Interactions

Interaction Checker

and piperacillin/tazobactam

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            Adverse Effects

            >10%

            Diarrhea (7-11%)

            1-10%

            Constipation (1-8%)

            Headache (1-8%)

            Insomnia (4-7%)

            Nausea (2-7%)

            Fever (2-5%)

            Oral candidiasis (2-4%)

            Rash (2-4%)

            Vomiting (2-4%)

            Dyspepsia (3%)

            Pruritus (3%)

            Pain (2-3%)

            Hypertension (2%)

            Leukopenia (1%)

            Thrombocytopenia (1.4%)

            <1%

            Anaphylaxis

            Agranulocytosis

            Thrombocytopenia

            Eosinophilia, melena

            Leukopenia

            Positive Coombs test

            Prolonged PT and PTT

            Transient LFT and creatinine elevations

            Seizure

            Pulmonary edema

            Pulmonary embolism

            Postmarketing Reports

            Gastrointestinal: Hepatitis, jaundice

            Hematologic: Hemolytic anemia, agranulocytosis, pancytopenia

            Immune: Hypersensitivity reactions, anaphylactic/anaphylactoid reactions (including shock)

            Renal: Interstitial nephritis

            Skin and appendages: Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, dermatitis exfoliative

            Respiratory, thoracic and mediastinal disorders: Epistaxis, eosinophilic pneumonia

            Psychiatric disorders: Delirium

            Drug reaction with eosinophilia and systemic symptoms (DRESS)

            Acute generalized exanthematous pustulosis

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            Warnings

            Contraindications

            Allergy to penicillins, cephalosporins, imipenem, beta-lactamase inhibitors

            Cautions

            Risk of bleeding complications, especially in renal impairment; discontinue if thrombocytopenia or bleeding occurs

            Leukopenia/neutropenia associated with prolonged therapy; periodic assessment of hematopoietic function should be performed, especially with prolonged therapy that is ≥ 21 days

            Serious skin reactions reported, including Stevens-Johnson syndrome and toxic epidermal necrolysis, generalized exanthematous pustulosis; discontinue if reaction occurs

            Monitor renal, hepatic, and especially hematopoietic functions during prolonged treatment

            Prolonged use may result in fungal or bacterial superinfection

            Administering therapy in absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to patient and increases risk of development of drug-resistant bacteria

            Clostridium difficile associated diarrhea (CDAD) reported; if CDAD suspected or confirmed, may need to discontinue ongoing antibacterial drug use not directed against C. difficile; appropriate fluid and electrolyte management, protein supplementation may need to be implemented; antibacterial treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated

            Increased frequency of rash and fever reported in cyctic fibrosis patients receiving piperacillin

            Risk of seizures may increase in patients with history of seizures when administered at higher than recommended doses given IV in the presence of renal impairment

            Consider sodium content (2.79 mEq/g piperacillin) in patients requiring sodium restriction

            Perform periodic electrolyte determinations in patients with low potassium reserves and who are receiving cytotoxic therapy or diuretics and consider possibility of hypokalemia in patients who have potentially low potassium reserves

            Increased frequency of fever and rash reported in patients with cystic fibrosis receiving piperacillin

            Use caution in patients with renal impairment or underdeveloped kidneys due to sodium load and adverse effects of high serum concentrations of penicillin; dose adjustment may be necessary

            Patients may experience neuromuscular excitability or convulsions if higher than recommended doses are given IV (particularly in presence of renal failure); closely monitor patients with renal impairment or seizure disorders for signs and symptoms of neuromuscular excitability or convulsions (seizures)

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            Pregnancy & Lactation

            Pregnancy

            Piperacillin and tazobactam cross placenta in humans

            Insufficient data available with piperacillin and/or tazobactam in pregnant women to inform a drug-associated risk for major birth defects and miscarriage

            Animal data

            • No fetal structural abnormalities observed in rats or mice when drug administered IV during organogenesis at doses 1 to 2 times and 2 to 3 times human dose of piperacillin and tazobactam, respectively; based on body-surface area (mg/m2)
            • Fetotoxicity in presence of maternal toxicity was observed in developmental toxicity and peri/postnatal studies conducted in rats (intraperitoneal administration prior to mating and throughout gestation or from gestation day 17 through lactation day 21) at doses less than maximum recommended human daily dose based on body-surface area (mg/m2)

            Lactation

            Piperacillin is excreted in human milk; tazobactam concentrations in human milk have not been studied

            No information available on effects of piperacillin and tazobactam on breastfed child or on milk production

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Antipseudomonal penicillin plus beta-lactamase inhibitor; inhibits biosynthesis of cell wall mucopeptide synthesis by binding to 1 or more of the penicillin-binding proteins and is effective during active-multiplication stage

            Absorption

            Peak plasma concentration

            • Piperacillin: 134 mcg/mL (2.25-g dose); 242 mcg/mL (3.375-g dose); 298 mcg/mL (4.5-g dose)
            • Tazobactam: 15 mcg/mL (2.25-g dose); 24 mcg/mL (3.375-g dose); 34 mcg/mL (4.5-g dose)

            AUC

            • Piperacillin: 131 mcg⋅hr/mL (2.25-g dose); 242 mcg⋅hr/mL (3.375-g dose); 322 mcg⋅hr/mL (4.5-g dose)
            • Tazobactam: 16 mcg⋅hr/mL (2.25-g dose); 25 mcg⋅hr/mL (3.375-g dose); 39.8 mcg⋅hr/mL (4.5-g dose)

            Distribution

            Protein bound: ~30%

            Lungs, intestinal mucosa, skin, muscle, uterus, ovary, prostate, gallbladder, and bile; low CSF penetration in noninflamed meninges

            Metabolism

            Hepatic to desethyl metabolite (piperacillin) and inactive metabolite (tazobactam)

            Elimination

            Half-life: 0.7-1.2 hr

            Excretion

            • Piperacillin: Urine (68%); feces (10-20%)
            • Tazobactam: Urine (80%)
            • Both also excreted in bile

            Clearance

            • Piperacillin: 257 mL/min (2.25-g dose); 207 mL/min (3.375-g dose); 210 mL/min (4.5-g dose)
            • Tazobactam: 258 mL/min (2.25-g dose); 251 mL/min (3.375-g dose); 206 mL/min (4.5-g dose)
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            Administration

            IV Incompatibilities

            • Do not mix with other drugs in syringe or infusion bottle since compatibility has not been established
            • Not chemically stable in solutions that contain only sodium bicarbonate and solutions that significantly alter the pH
            • Do not add to blood products or albumin hydrolysates

            IV Compatibilities

            • 0.9% NaCl
            • Sterile water for injection (maximum volume: 50 mL)
            • Dextran 6% in NS
            • Dextrose 5%
            • Lactated Ringer (compatible only with reformulated piperacillin/tazobactam containing EDTA and is compatible for coadministration via a Y-site)
            • Refer to prescribing information for specific Y-site compatibility information

            Reconstitution

            Compatible for reconstitution

            • 0.9% NaCl
            • Sterile water for injection
            • Dextrose 5%
            • Bacteriostatic saline/parabens
            • Bacteriostatic water/parabens
            • Bacteriostatic saline/benzyl alcohol
            • Bacteriostatic water/benzyl alcohol

            Bulk vial

            • Reconstitute with exactly 152 mL of compatible reconstitution diluent (final concentration: 200 mg/mL of piperacillin and 25 mg/mL of tazobactam)
            • Shake well until dissolved
            • Visually inspect for particulate matter and discoloration before and during administration whenever solution and container permit

            IV Preparation

            Premix frozen bag

            • Check for minute leaks by squeezing container firmly
            • If leaks are detected, discard solution as sterility may be impaired.
            • Visually inspect product; components of solution may precipitate while frozen and will dissolve upon reaching room temperature with little or no agitation; agitate after solution has reached room temperature
            • If after visual inspection, the solution remains cloudy or if an insoluble precipitate is noted or if any seals or outlet ports are not intact, discard the container

            IV Administration

            Infuse over 30 min

            Storage

            Unopened Vials

            • Store at room temperature (20-25ºC [68-77ºF])

            Premix frozen bag

            • Unused: Freeze at -20ºC [-4ºF])
            • Thawed bag: Refrigerate at (2-8ºC [36-46ºF]) for up to 14 days or store at room temperature (20-25ºC [68-77ºF]) for up to 24 hr; do not refreeze thawed bag

            Diluted IV solutions

            • Store at room temperature (20-25ºC [68-77ºF]) for up to 24 hr, or after 1 week if refrigerated (2-8ºC [36-46ºF])

            Reconstituted single-dose vials or pharmacy bulk vials

            • Store at room temperature (20-25vC [68-77ºF]) for up to 24 hr, or after 48 hours if refrigerated (2-8ºC [36-46ºF])
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            Formulary

            FormularyPatient Discounts

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
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            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
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            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.