Dosing and uses of Zosyn (piperacillin-tazobactam)
Adult dosage forms and strengths
piperacillin/tazobactam
powder for injection
- (2g/250mg)/vial: 2.25g
- (3g/375mg)/vial: 3.375g
- (4g/500mg)/vial: 4.5g
- (36g/4.5g)/vial: 40.5g
Severe Infections
3.375 g (IV) q6hr; total of 13.5 g (piperacillin [12 g] per tazobactam [1.5 g]) for 7-10 days; administer over 30 min
Nosocomial Pneumonia
4.5 g IV q6 hr; add aminoglycoside; total of 18 g (piperacillin [16 g] per tazobactam [2 g]) for 7-14 days; continue aminoglycoside in P. aeruginosa patients
Community-aquired Pneumonia
3.375 g IV q6hr for 7-10 days
Diverticulitis/Intra-abdominal Abscess/ Peritonitis
3.375 g IV q6hr for 7-14 days or until clear
Complicated Intra-abdominal Infection
3.375 g IV q6hr for 4-7 days
Skin and Soft Tissue Infection
3.375 g IV q6-8hr for 7-14 days
Dosing Considerations
Dosing range
- 3.375 g IV q6hr, OR 4.5 g IV q6-8hr; not to exceed 18 g/day
Dosing Modifications
Renal impairment
- CrCl >40 mL/min: Dose adjustment not necessary
- CrCl 20-40 mL/min: 2.25 g IV q6hr, OR 3 g/0.375 g IV q6hr (for nosocomial pneumonia), OR extended infusion of 3.375 g IV over 4 hr q12hr (off-label)
- CrCl <20 mL/min: 2.25 g IV q8hr, OR 2.25 g IV q6hr (for nosocomial pneumonia)
Pediatric dosage forms and strengths
piperacillin/tazobactam
powder for injection
- (2g/250mg)/vial: 2.25g
- (3g/375mg)/vial: 3.375g
- (4g/500mg)/vial: 4.5g
- (36g/4.5g)/vial: 40.5g
Usual Dosing Range
<2 months: Safety and efficacy not established
2-9 months: 80 mg (piperacillin component)/kg q6hr
9 months and <40 kg: 100 mg (piperacillin component)/kg q8hr
>40 kg: 3.375 g (IV) q6hr; a total of 13.5 g for 7-10 days; administer over 30 min
Cystic Fibrosis (Off-label)
350-450 mg/kg/day IV/IM divided q6hr
Appendicitis, Peritonitis
<2 months: Safety and efficacy not established
2-9 months: 80 mg (piperacillin component)/kg q8hr
9 months and ≤40 kg: 100 mg (piperacillin component)/kg q8hr
>40 kg: 3.375 g (IV) q6hr for 7-10 days; administer over 30 min
Complicated Intra-abdominal Infection
200-300 mg/kg/day IV divided q6-8hr
Zosyn (piperacillin-tazobactam) adverse (side) 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
Drug reaction with eosinophilia and systemic symptoms (DRESS)
Acute generalized exanthematous pustulosis
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)
Pregnancy and lactation
Pregnancy category: B
Lactation: Low concentrations of piperacillin excreted in breast milk; tazobactam unknown; use caution
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.
Pharmacology of Zosyn (piperacillin-tazobactam)
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 time: 30 minutes following infusion
Bioavailability: 71% (piperacillin IM); 84% (tazobactam IM)
Distribution
Protein bound: Piperacillin (25-33%); tazobactam (31-32%)
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
Administration
IV Incompatibilities
Y-site: Acyclovir, alatrofloxacin, amiodarone, amphotericin B, amphotericin B cholesteryl sulfate, azithromycin, chlorpromazine, cisatracurium (at high concentrations of cisatracurium; may be compatible at low concentrations), cisplatin, dacarbazine, daunorubicin, dobutamine, doxorubicin, doxorubicin liposomal, doxycycline, droperidol, famotidine, ganciclovir, gatifloxacin, gemcitabine, haloperidol, hydroxyzine, idarubicin, minocycline, mitomycin, mitoxantrone, nalbuphine, prochlorperazine, promethazine, streptozocin, and vancomycin(?)
IV Compatibilities
Y-site (partial list): Ca-gluconate, cimetidine, clindamycin, cotrimoxazole, dexamethasone Na-phosphate, diphenhydramine, furosemide, granisetron, heparin, magnesium sulfate, metronidazole, morphine, ondansetron, KCl, ranitidine, and zidovudine
IV Preparation
Use single-dose vials immediately after reconstitution
Reconstitute with 5 mL of diluent per 1 g of piperacillin and then further dilute
Compatible diluents include NS, SW, dextran 6%, D5W, D5W with KCl 40 mEq, bacteriostatic saline, and bacteriostatic water for injection
IV Administration
Infusion over 30 min
Discontinue primary infusion, if possible, during infusion and administer aminoglycosides separately from Zosyn
Storage
Store at controlled room temperature
Reconstituted solution is stable in NS or D5W for 24 hr at room temperature and for 7 days when refrigerated
