(pi PER a sil in & ta zoe BAK tam)
- Piperacillin and Tazobactam Sodium
- Piperacillin Sodium and Tazobactam Sodium
- Piperacillin Sodium/Tazobactam
- Piperacillin/Tazobactam Sod
- Tazobactam and Piperacillin
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Note: 8:1 ratio of piperacillin sodium/tazobactam sodium
Infusion [premixed iso-osmotic solution]:
Zosyn: 2.25 g: Piperacillin 2 g and tazobactam 0.25 g (50 mL) [contains edetate disodium, sodium 128 mg (5.58 mEq)]
Zosyn: 3.375 g: Piperacillin 3 g and tazobactam 0.375 g (50 mL) [contains edetate disodium, sodium 192 mg (8.38 mEq)]
Zosyn: 4.5 g: Piperacillin 4 g and tazobactam 0.5 g (100 mL) [contains edetate disodium, sodium 256 mg (11.17 mEq)]
Injection, powder for reconstitution: 2.25 g: Piperacillin 2 g and tazobactam 0.25 g; 3.375 g: Piperacillin 3 g and tazobactam 0.375 g; 4.5 g: Piperacillin 4 g and tazobactam 0.5 g; 40.5 g: Piperacillin 36 g and tazobactam 4.5 g
Zosyn: 2.25 g: Piperacillin 2 g and tazobactam 0.25 g [contains edetate disodium, sodium 130 mg (5.68 mEq)]
Zosyn: 3.375 g: Piperacillin 3 g and tazobactam 0.375 g [contains edetate disodium, sodium 195 mg (8.52 mEq)]
Zosyn: 4.5 g: Piperacillin 4 g and tazobactam 0.5 g [contains edetate disodium, sodium 260 mg (11.36 mEq)]
Zosyn: 40.5 g: Piperacillin 36 g and tazobactam 4.5 g [contains edetate disodium, sodium 2304 mg (100.4 mEq); bulk pharmacy vial]
Brand Names: U.S.
- Antibiotic, Penicillin
Piperacillin inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs); which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested. Piperacillin exhibits time-dependent killing. Tazobactam inhibits many beta-lactamases, including staphylococcal penicillinase and Richmond-Sykes types 2, 3, 4, and 5, including extended spectrum enzymes; it has only limited activity against class 1 beta-lactamases other than class 1C types.
Well into lungs, intestinal mucosa, uterus, ovary, fallopian tube, interstitial fluid, gallbladder, and bile; penetration into CSF is low in subjects with noninflamed meninges; Vd: Children and Adults: 0.243 L/kg
Piperacillin: 6% to 9% to desethyl metabolite (weak activity)
Tazobactam: ~22% to inactive metabolite
Clearance of both piperacillin and tazobactam are directly proportional to renal function; Infants and Children 9 months to 12 years: 5.64 mL/minute/kg
Piperacillin: Urine (68% as unchanged drug); feces (10% to 20%)
Tazobactam: Urine (80% as unchanged drug; remainder as inactive metabolite)
Time to Peak
Immediately following completion of 30-minute infusion
Note: Pediatric data: Reed 1994
Infants 2 to 5 months: 1.4 hours
Infants and Children 6 to 23 months: 0.9 hour
Children 2 to 12 years: 0.7 hour
Adults: 0.7 to 1.2 hours
Metabolite: 1 to 1.5 hours
Infants 2 to 5 months: 1.6 hours
Infants and Children 6 to 23 months: 1 hour
Children 2 to 12 years: 0.8 to 0.9 hour
Adults: 0.7 to 0.9 hour
Piperacillin: ~26% to 33%; Tazobactam: 31% to 32%
Special Populations: Renal Function Impairment
Half-life increases 2-fold for piperacillin and 4-fold for tazobactam in patients with CrCl <20 mL/minute.
Use: Labeled Indications
Intra-abdominal infections: Treatment of appendicitis complicated by rupture or abscess and peritonitis caused by beta-lactamase-producing strains of Escherichia coli, Bacteroides fragilis, Bacteroides ovatus, Bacteroides thetaiotaomicron, or Bacteroides vulgatus.
Pelvic infections: Treatment of postpartum endometriosis or pelvic inflammatory disease caused by beta-lactamase-producing strains of E. coli.
Pneumonia, community-acquired: Treatment of moderate severity community-acquired pneumonia (CAP) caused by beta-lactamase-producing strains of Haemophilus influenzae. Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) guidelines only recommend piperacillin/tazobactam for CAP caused by P. aeruginosa or due to aspiration (Mandell 2007).
Pneumonia, hospital-acquired (nosocomial): Treatment of moderate to severe hospital-acquired (nosocomial) pneumonia caused by beta-lactamase-producing strains of Staphylococcus aureus and by piperacillin/tazobactam-susceptible Acinetobacter baumanii, H. influenzae, Klebsiella pneumoniae, and Pseudomonas aeruginosa.
Skin and skin structure infections: Treatment of skin and skin structure infections, including cellulitis, cutaneous abscesses, and ischemic/diabetic foot infections caused by beta-lactamase–producing strains of S. aureus.
Off Label Uses
Bite wound infections (animal)
Based on the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and management of skin and soft tissue infections (SSTI), piperacillin and tazobactam is an effective and recommended treatment of animal bite wound infections
Endocarditis, treatment (pediatric)
Based on the American Heart Association (AHA) Scientific Statement for Infective Endocarditis in Childhood, piperacillin and tazobactam, in combination with an aminoglycoside, is effective and recommended for the treatment of infective endocarditis due to gram-negative bacilli in children and adolescents.
Skin and soft tissue necrotizing infections
Based on the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and management of skin and soft tissue infections (SSTI), piperacillin and tazobactam, in combination with vancomycin (or linezolid or daptomycin), is effective and recommended for the empiric treatment of necrotizing infections of the skin, fascia, and muscle caused by polymicrobial [mixed] infections.
Based on the American Society of Health-System Pharmacists (ASHP), the Infectious Diseases Society of America (IDSA), the Surgical Infection Society (SIS), and the Society of Healthcare Epidemiology of America (SHEA) guidelines for antimicrobial prophylaxis in surgery, piperacillin and tazobactam (in combination with cefotaxime and ampicillin) is effective and recommended for administration prior to liver transplantation for surgical prophylaxis.
Surgical site infections
Based on the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and management of skin and soft tissue infections (SSTI), piperacillin and tazobactam is an effective and recommended option for treatment of surgical site infections occurring after surgery of the intestinal or genitourinary tract. Systemic antibacterials are not routinely indicated for surgical site infections, but may be beneficial (in conjunction with suture removal plus incision and drainage) in patients with significant systemic response (eg, temperature >38.5ºC, heart rate >110 beats per minute, erythema/induration extending >5 cm from incision, WBC >12,000/mm3)
Additional Off-Label Uses
Bone and joint infections; Complicated intra-abdominal infections; Cystic fibrosis exacerbations; Septicemia; Urinary tract infections
Hypersensitivity to penicillins, cephalosporins, beta-lactamase inhibitors, or any component of the formulation
Note: Dosing presented is based on traditional infusion method (IV infusion over 30 minutes) unless otherwise specified as the extended infusion method (IV infusion over 4 hours [off-label method]).
Usual dosage range: IV: 3.375 g every 6 hours or 4.5 g every 6 to 8 hours; maximum: 18 g daily
Extended infusion method (off-label dosing): 3.375 to 4.5 g IV over 4 hours every 8 hours (Kim 2007; Shea 2009); an alternative regimen of 4.5 g IV over 3 hours every 6 hours has also been described (Kim 2007)
Appendicitis, diverticulitis, intra-abdominal abscess, peritonitis: IV: 3.375 g every 6 hours for 7 to 10 days
Community-acquired pneumonia (CAP): IV: 3.375 g every 6 hours for 7 to 10 days. Note: IDSA/ATS guidelines only recommend piperacillin/tazobactam for CAP caused by P. aeruginosa or due to aspiration (Mandell 2007).
Hospital-acquired or ventilator-associated: IV: 4.5 g every 6 hours for 7 days; may consider shorter or longer duration depending on rate of clinical improvement. Administration as an extended infusion may be considered. When used as empiric therapy, use in combination with an agent active against MRSA (unless coverage of MSSA only is appropriate) with or without an additional antipseudomonal agent (dependent on patient and institution-specific risk factors) (Kalil 2016).
Skin and soft tissue infection: IV: 3.375 g every 6 hours for 7 to 10 days. Note: For severe diabetic foot infections, recommended treatment duration is up to 4 weeks depending on severity of infection and response to therapy (Lipsky 2012).
Necrotizing infections (off-label use): IV:3.375 g every 6 to 8 hours (in combination with vancomycin for empiric therapy); continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for 48 to 72 hours (IDSA [Stevens 2014]).
Bite wound infection (animal) (off-label use): IV: 3.375 g every 6 to 8 hours (IDSA [Stevens 2014])
Intra-abdominal infection, complicated (off-label use): IV: 3.375 g every 6 hours for 4 to 7 days (provided source controlled). Note: Increase to 3.375 g every 4 hours or 4.5 g every 6 hours if P. aeruginosa is suspected. Not recommended for mild-to-moderate, community-acquired intra-abdominal infections due to risk of toxicity and the development of resistant organisms (Solomkin 2010).
Surgical (perioperative) prophylaxis (off-label use): IV: 3.375 g within 60 minutes prior to surgery. Doses may be repeated in 2 hours if procedure is lengthy or if there is excessive blood loss (Bratzler 2013).
Surgical site infections (intestinal or genitourinary tract) (off-label use): IV: 3.375 g every 6 hours or 4.5 g every 8 hours (IDSA [Stevens 2014])
Refer to adult dosing.
Note: Piperacillin and tazobactam is a combination product; each 3.375 g vial contains 3 g piperacillin sodium and 0.375 g tazobactam sodium in an 8:1 ratio. Dosage recommendations in pediatric patients are based on the piperacillin component. Dosing presented is based on traditional infusion method (IV infusion over 30 minutes) unless otherwise specified as the extended infusion method (IV infusion over 4 hours [off-label method]).
Usual dosage range: IV:
Infants 2 to 9 months: 80 mg piperacillin/kg/dose every 8 hours (Red Book [AAP] 2012):
Infants >9 months, Children, and Adolescents: 100 mg piperacillin/kg/dose every 8 hours (maximum dose: 16 g piperacillin/day) (Red Book [AAP] 2012):
Children and Adolescents: Extended-infusion method: Limited data available: 100 mg piperacillin/kg/dose infused over 4 hours 3 times daily. Dosing based on a prospective, observational study (n=332) in a single children's hospital comparing the extended interval method to traditional dosing (Nichols 2012).
Indication-specific dosing: Infants, Children, and Adolescents: Note: In pediatric patients, dosage recommendations are based on the piperacillin component. Dosing is presented in mg/kg/dose and mg/kg/day; use caution.
Infants 2 to 9 months: IV: 80 mg piperacillin/kg/dose every 8 hours
Infants >9 months, Children, and Adolescents ≤40 kg: IV: 100 mg piperacillin/kg/dose every 8 hours (maximum: 3,000 mg piperacillin/dose)
Children and Adolescents >40 kg: Refer to adult dosing.
Cystic fibrosis, pseudomonal lung infections (off-label use):
Standard dosing: IV: 240 to 400 mg piperacillin/kg/day divided every 8 hours (Kliegman, 2011); others have used 350 to 400 mg/kg/day divided every 4 hours in early piperacillin trials (Zobell, 2013)
High-dose: Limited data available: IV: 450 mg piperacillin/kg/day divided every 4 to 6 hours or 600 mg piperacillin/kg/day divided every 4 hours has been described from early studies of piperacillin alone; usual maximum daily dose: 18 to 24 g piperacillin/day. Note: Piperacillin doses >600 mg/kg/day or an extended duration of therapy (>14 days) have been associated with dose-related adverse effects including serum sickness, immune-mediated hemolytic anemia and bone marrow suppression (Zobell 2013).
Endocarditis, treatment (off-label use): Children and Adolescents: IV: 240 mg piperacillin/kg/day divided every 8 hours in combination with an aminoglycoside for at least 6 weeks; maximum daily dose: 18 g piperacillin/day (AHA [Baltimore 2015])
Intra-abdominal infection, complicated (off-label use): IV: 200 to 300 mg piperacillin/kg/day divided every 6 to 8 hours (maximum dose: 12 g piperacillin/day) (Solomkin, 2010).
Skin and soft tissue necrotizing infections (off-label use): IV: 60 to 75 mg piperacillin/kg every 6 hours (in combination with vancomycin for empiric therapy); continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for 48 to 72 hours. (IDSA [Stevens 2014])
Surgical (perioperative) prophylaxis (off-label use): Note: Doses may be repeated in 2 hours if procedure is lengthy or if there is excessive blood loss (Bratzler 2013): IV:
Infants 2 to 9 months: 80 mg piperacillin/kg within 60 minutes prior to surgical incision (maximum: 3,000 mg piperacillin/dose)
Infants >9 months, Children, and Adolescents ≤40 kg: 100 mg piperacillin/kg within 60 minutes prior to surgical incision (maximum: 3,000 mg piperacillin/dose).
Children and Adolescents >40 kg: Refer to adult dosing.
Dosing: Renal Impairment
Traditional infusion method (ie, IV infusion over 30 minutes): Manufacturer’s labeling:
CrCl >40 mL/minute: No dosage adjustment necessary.
CrCl 20 to 40 mL/minute: Administer 2.25 g every 6 hours (3.375 g every 6 hours for hospital-acquired or ventilator-associated pneumonia)
CrCl <20 mL/minute: Administer 2.25 g every 8 hours (2.25 g every 6 hours for hospital-acquired or ventilator-associated pneumonia)
Note: Some clinicians suggest adjusting the dose at CrCl ≤20 mL/minute (rather than CrCl <40 mL/minute) in patients receiving either traditional or extended-infusion methods, particularly if treating serious gram-negative infections (empirically or definitively) (Patel 2010).
Extended infusion method (off-label dosing): CrCl ≤20 mL/minute: 3.375 g IV over 4 hours every 12 hours (Patel 2010)
End-stage renal disease (ESRD):
Intermittent hemodialysis (IHD): 2.25 g every 12 hours (2.25 g every 8 hours for hospital-acquired or ventilator-associated pneumonia); Hemodialysis removes 30% to 40% of a piperacillin/tazobactam dose. Note: Dosing dependent on the assumption of 3 times/week, complete IHD sessions. Administer scheduled doses after hemodialysis on dialysis days; if next regularly scheduled dose is not due right after dialysis session, administer an additional dose of 0.75 g after the dialysis session.
Peritoneal dialysis (PD): 2.25 g every 12 hours (2.25 g every 8 hours for hospital-acquired or ventilator-associated pneumonia); peritoneal dialysis removes 6% of piperacillin and 21% of tazobactam.
Continuous renal replacement therapy (CRRT) (Heintz 2009; Trotman 2005): Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug concentrations in relation to target trough (if appropriate). The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1 to 2 L/hour and minimal residual renal function) and should not supersede clinical judgment (Trotman 2005):
CVVH: 2.25 to 3.375 g every 6 to 8 hours
CVVHD: 2.25 to 3.375 g every 6 hours
CVVHDF: 3.375 g every 6 hours
Note: Higher dose of 3.375 g should be considered when treating resistant pathogens (especially Pseudomonas spp); alternative recommendations suggest dosing of 4.5 g every 8 hours (Valtonen 2001); regardless of regimen, there is some concern of tazobactam (TAZ) accumulation, given its lower clearance relative to piperacillin (PIP). Some clinicians advocate dosing with PIP to alternate with PIP/TAZ, particularly in CVVH-dependent patients, to lessen this concern.
Infants, Children, and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling; however, the following adjustments have been recommended (Aronoff, 2007): Dosing based on a usual dose of 200 to 300 mg piperacillin/kg/day in divided doses every 6 hours.
GFR >50 mL/minute/1.73 m2: No dosage adjustment necessary.
GFR 30 to 50 mL/minute/1.73 m2: 35 to 50 mg piperacillin/kg/dose every 6 hours
GFR <30 mL/minute/1.73 m2: 35 to 50 mg piperacillin/kg/dose every 8 hours
End-stage renal disease (ESRD) on intermittent hemodialysis (IHD): Hemodialysis removes 30% to 40% of a piperacillin/tazobactam dose: 50 to 75 mg piperacillin/kg/dose every 12 hours
Peritoneal dialysis (PD): Peritoneal dialysis removes 21% of tazobactam and 6% of piperacillin: 50 to 75 mg piperacillin/kg/dose every 12 hours
Continuous renal replacement therapy (CRRT): 35 to 50 mg piperacillin/kg/dose every 8 hours
Dosing: Hepatic Impairment
No dosage adjustment necessary.
Galaxy containers: Thaw at 20°C to 25°C (68°F to 77°F) or 2°C to 8°C (36°F to 46°F). Do not thaw in microwave or by bath immersion.
Vials: Reconstitute single-dose vials with 10 mL of diluent (2.25 g vial), 15 mL of diluent (3.375 g vial), or 20 mL of diluent (4.5 g vial); further dilute in D5W or NS to a volume of 50 to 150 mL. Reconstitute pharmacy bulk vials with 152 mL of diluent to yield a concentration of piperacillin 200 mg/mL and tazobactam 25 mg/mL; transfer reconstituted solution and further dilute in D5W or NS to a volume of 50 to 150 mL. Note: If using sterile water for injection for dilution, the maximum recommended volume per dose is 50 mL for single-dose and bulk vials
IV: Administer by IV infusion over 30 minutes. For extended infusion administration (off-label dosing), administer over 3-4 hours (Kim 2007; Shea 2009).
Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate aminoglycosides in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered. Note: Reformulated Zosyn containing EDTA has been shown to be compatible in vitro for Y-site infusion with amikacin and gentamicin diluted in NS or D5W (applies only to specific concentrations and varies by product; consult manufacturer’s labeling). Reformulated Zosyn containing EDTA is not compatible with tobramycin.
Some products may contain sodium.
Vials: Store intact vials at 20°C to 25°C (68°F to 77°F). Use single-dose or bulk vials immediately after reconstitution. Discard any unused portion after 24 hours if stored at 20°C to 25°C (68°F to 77°F) or after 48 hours if stored at 2°C to 8°C (36°F to 46°F). Do not freeze vials after reconstitution. Stability in D5W or NS has been demonstrated for up to 24 hours at room temperature and up to 1 week at refrigerated temperature. Stability in an ambulatory IV infusion pump has been demonstrated for a period of 12 hours at room temperature.
Galaxy containers: Store at or below -20°C (-4°F). The thawed solution is stable for 14 days at 2°C to 8°C (36°F to 46°F) or 24 hours at 20°C to 25°C (68°F to 77°F). Do not refreeze.
Acemetacin: May increase the serum concentration of Penicillins. Monitor therapy
Aminoglycosides: Penicillins may decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Consider therapy modification
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Avoid combination
Flucloxacillin: Piperacillin may increase the serum concentration of Flucloxacillin. Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy
Methotrexate: Penicillins may increase the serum concentration of Methotrexate. Monitor therapy
Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Monitor therapy
Probenecid: May increase the serum concentration of Penicillins. Management: Avoid the routine use of penicillins and probenecid, but this combination may be used advantageously in select cases with careful monitoring. Monitor for toxic effects of penicillins if probenecid is initiated or the dose is increased. Consider therapy modification
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification
Tetracyclines: May diminish the therapeutic effect of Penicillins. Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification
Vancomycin: Piperacillin may enhance the nephrotoxic effect of Vancomycin. Monitor therapy
Vecuronium: Piperacillin may enhance the neuromuscular-blocking effect of Vecuronium. Monitor therapy
Vitamin K Antagonists (eg, warfarin): Penicillins may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy
Positive Coombs' [direct] test; false positive reaction for urine glucose using copper-reduction method (Clinitest); may result in false positive results with the Platelia Aspergillus enzyme immunoassay (EIA); confirm with other diagnostic methods.
Also see piperacillin monograph.
>10%: Gastrointestinal: Diarrhea (11%)
1% to 10%:
Cardiovascular: Phlebitis (1%), flushing (≤1%), hypotension (≤1%), thrombophlebitis (≤1%)
Central nervous system: Headache (8%), insomnia (7%), rigors (≤1%)
Dermatologic: Skin rash (4%), pruritus (3%), purpura (≤1%)
Endocrine & metabolic: Hypoglycemia (≤1%)
Gastrointestinal: Constipation (8%), nausea (7%), dyspepsia (3%), vomiting (3%), abdominal pain (1%), pseudomembranous colitis (≤1%)
Hypersensitivity: Anaphylaxis (≤1%)
Infection: Candidiasis (2%)
Local: Injection site reaction (≤1%)
Neuromuscular & skeletal: Arthralgia (≤1%), myalgia (≤1%)
Respiratory: Epistaxis (≤1%)
Miscellaneous: Fever (2%)
Frequency not defined:
Endocrine & metabolic: Decreased serum albumin, decreased serum glucose, decreased serum total protein, electrolyte disturbance (increases and decreases in sodium, potassium, and calcium), hyperglycemia, hypokalemia, increased gamma-glutamyl transferase
Hematologic & oncologic: Decreased hematocrit, decreased hemoglobin, eosinophilia, leukopenia, neutropenia, positive direct Coombs test, prolonged bleeding time, prolonged partial thromboplastin time, prolonged prothrombin time, thrombocythemia, thrombocytopenia
Hepatic: Increased serum alkaline phosphatase, increased serum ALT, increased serum AST, increased serum bilirubin
Renal: Increased blood urea nitrogen, increased serum creatinine, renal failure (in critically ill patients)
<1%, postmarketing, and/or case reports: Acute generalized exanthemous pustulosis, agranulocytosis, anaphylactoid reaction, Clostridium difficile-associated diarrhea, convulsions, DRESS syndrome, eosinophilic pneumonitis, erythema multiforme, exfoliative dermatitis, hemolytic anemia, hepatitis, hypersensitivity reaction, interstitial nephritis, jaundice, pancytopenia, shock, Stevens-Johnson syndrome, toxic epidermal necrolysis
Concerns related to adverse effects:
• Anaphylactoid/hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactic/anaphylactoid) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity or history of sensitivity to multiple allergens. Discontinue treatment and institute appropriate therapy if an allergic reaction occurs.
• Dermatologic effects: Serious skin reactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), acute exanthematous pustulosis, and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported. If a skin rash develops, monitor closely. Discontinue if lesions progress.
• Electrolyte abnormalities: Sodium content (2.84 mEq per gram of piperacillin) should be considered in patients requiring sodium restriction. Assess electrolytes periodically in patients with low potassium reserves, especially those receiving cytotoxic therapy or diuretics.
• Hematologic effects: Prothrombin time, platelet aggregation, and clotting time abnormalities have been reported with piperacillin and particularly in patients with renal impairment. Discontinue if thrombocytopenia or bleeding occurs. Leukopenia/neutropenia may occur; appears to be reversible and most frequently associated with prolonged administration. Assess hematologic parameters periodically, especially with prolonged (≥21 days) use.
• Superinfection: Use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
• Cystic fibrosis: An increased frequency of fever and rash has been reported in patients with cystic fibrosis receiving piperacillin.
• Renal impairment: Use with caution in patients with renal impairment or in hemodialysis patients. Dosage adjustment recommended.
• Seizure disorders: Use with caution in patients with a history of seizure disorder; high levels, particularly in the presence of renal impairment, may increase risk of seizures.
• Critically ill patients: Use of piperacillin and tazobactam in critically ill patients may delay renal recovery as compared to other beta-lactam antibacterial drugs; consider alternative treatment options in critically ill patients. If alternative treatment options are inadequate or unavailable, closely monitor renal function.
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Creatinine, BUN, CBC with differential, PT, PTT, serum electrolytes, LFTs, urinalysis; signs of bleeding; monitor for signs of anaphylaxis during first dose
Piperacillin and tazobactam both cross the placenta and are found in the fetal serum, placenta, amniotic fluid, and fetal urine. When used during pregnancy, the clearance and volume of distribution of piperacillin/tazobactam are increased; half-life and AUC are decreased (Bourget, 1998). Piperacillin/tazobactam is approved for the treatment of postpartum gynecologic infections, including endometritis or pelvic inflammatory disease, caused by susceptible organisms.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience headache, nausea, diarrhea, constipation, or insomnia. Have patient report immediately to prescriber signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), bruising, bleeding, seizures, extra muscle movement, signs of Clostridium difficile (C. diff)-associated diarrhea (abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools), pharyngitis, signs of infection, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
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- Drug class: beta-lactamase inhibitors
Other brands: Zosyn