Zosyn

Generic Name: Piperacillin Sodium and Tazobactam Sodium
Class: Extended-spectrum Penicillins
Chemical Name: [2S - [2α,5α,6β(S*)]] - 6 - [[[[(4 - Ethyl - 2,3 - dioxo - 1 - piperazinyl)carbonyl]amino]phenylacetyl]amino] - 3,3 - dimethyl - 7 - oxo - 4 - thia - 1 - azabicyclo[3.2.0]heptane - 2 - carboxylic acid monosodium salt
Molecular Formula: C₂₃H₂₇N₅O₇S•Na
CAS Number: 59703-84-3

Introduction

Antibacterial; β-lactam antibiotic; fixed combination of piperacillin (an extended-spectrum penicillin) and tazobactam (a β-lactamase inhibitor).^{1 3 5 6 7 9 12 33 35}

Uses for Zosyn

Gynecologic and Obstetric Infections

Treatment of postpartum endometritis or pelvic inflammatory disease (PID) caused by β-lactamase-producing Escherichia coli resistant to piperacillin but susceptible to piperacillin and tazobactam.^{1 21 33 34 35}

Intra-abdominal Infections

Treatment of appendicitis (complicated by rupture or abscess) and peritonitis caused by β-lactamase-producing E. coli resistant to piperacillin but susceptible to piperacillin and tazobactam or caused by Bacteroides fragilis, B. ovatus, B. thetaiotaomicron, or B. vulgatus.^{1 12 13 14 33 35}

Respiratory Tract Infections

Treatment of moderately severe community-acquired pneumonia (CAP) caused by β-lactamase-producing Haemophilus influenzae resistant to piperacillin but susceptible to piperacillin and tazobactam.^{1 33 35}

For empiric treatment of CAP in adults with risk factors for Pseudomonas aeruginosa, IDSA and ATS recommend a combination regimen that includes an antipneumococcal, antipseudomonal β-lactam (piperacillin and tazobactam, cefepime, imipenem, meropenem) and ciprofloxacin or levofloxacin; one of these β-lactams, an aminoglycoside, and azithromycin; or one of these β-lactams, an aminoglycoside, and an antipneumococcal fluoroquinolone.⁴¹ If Ps. aeruginosa has been identified by appropriate microbiologic testing, these experts recommend treatment with a regimen that includes an antipseudomonal β-lactam (cefepime, ceftazidime, aztreonam, imipenem, meropenem, piperacillin, ticarcillin) and ciprofloxacin, levofloxacin, or an aminoglycoside.⁴¹

Treatment of moderate to severe nosocomial pneumonia caused by β-lactamase-producing S. aureus resistant to piperacillin but susceptible to piperacillin and tazobactam or caused by Acinetobacter baumanii, H. influenzae, Klebsiella pneumoniae, or Ps. aeruginosa resistant to piperacillin but susceptible to piperacillin and tazobactam.^{1 33 34 35} For nosocomial pneumonia caused by Ps. aeruginosa, used in conjunction with an aminoglycoside or fluoroquinolone with antipseudomonal activity (e.g., ciprofloxacin, levofloxacin).^{1 33 34 35}

For initial empiric treatment of hospital-acquired pneumonia, ventilator-associated pneumonia, or health-care associated pneumonia in adults who are severely ill or have late-onset disease or risk factors for multidrug-resistant bacteria, ATS, IDSA, and other clinicians recommend an antipseudomonal cephalosporin (cefepime, ceftazidime), antipseudomonal penicillin (piperacillin and tazobactam, ticarcillin and clavulanate), or an antipseudomonal carbapenem (imipenem, meropenem) used in conjunction with an aminoglycoside (amikacin, gentamicin, tobramycin) or antipseudomonal fluoroquinolone (ciprofloxacin, levofloxacin).^{34 42} In hospitals where oxacillin-resistant (methicillin-resistant) Staphylococcus is common or if there are risk factors for these strains, the initial regimen also should include vancomycin or linezolid.^{34 42}

Septicemia

Treatment of septicemia† caused by susceptible gram-negative bacteria. For initial empiric treatment of life-threatening sepsis, used in conjunction with vancomycin with or without an aminoglycoside.³⁴

Skin and Skin Structure Infections

Treatment of uncomplicated and complicated skin and skin structure infections (including cellulitis, cutaneous abscess, ischemic/diabetic foot infections) caused by β-lactamase-producing Staphylococcus aureus resistant to piperacillin but susceptible to piperacillin and tazobactam.^{1 12 15 33 35}

Urinary Tract Infections (UTIs)

Treatment of UTIs† in hospitalized patients; used with or without an aminoglycoside.³⁴

Zosyn Dosage and Administration

Administration

Administer by IV infusion.^{1 33 35}

IV Administration

Piperacillin and tazobactam should not be admixed with other drugs (e.g., in a syringe or infusion bottle) and should not be added to blood products or albumin hydrolysates.^{1 33 35}

If concomitant use of an aminoglycoside is indicated (e.g., for treatment of nosocomial pneumonia), piperacillin and tazobactam and the aminoglycoside should be administered separately.^{1 33 35}

In certain situations when simultaneous coadministration of piperacillin and tazobactam and an aminoglycoside via Y-site infusion is considered necessary, this can be accomplished using only certain dosages of amikacin or gentamicin, only certain formulations of piperacillin and tazobactam (Zosyn) containing edetate disodium dihydrate (EDTA), and only certain acceptable diluents.^{1 33 35} (See Tables.) For Y-site coadministration, do not use any formulations of piperacillin and tazobactam other than those specified in the tables and do not use tobramycin or any aminoglycoside other than amikacin or gentamicin.^{1 33 35} Coadministration via Y-site infusion in any manner other than that specified in the tables may result in inactivation of the aminoglycoside.^{1 33 35}

Based on amikacin dosage of 10–15 mg/kg daily given in 2 divided doses or gentamicin dosage of 3–5 mg/kg daily given in 3 divided doses; higher dosage or once-daily dosage has not been evaluated for Y-site compatibility.

Table 1. Y-site Compatibility for Zosyn (with EDTA) in Single-dose Vials and Bulk Vials133

Aminoglycoside	Zosyn Dosage (g)	Zosyn Diluent (mL)	Aminoglycoside Concentration Range (mg/mL)	Acceptable Diluents
Amikacin	2.25, 3.375, 4.5	50, 100, 150	1.75–7.5	0.9% sodium chloride injection or 5% dextrose injection
Gentamicin	2.25, 3.375, 4.5	100, 150	0.7–3.32	0.9% sodium chloride injection

Based on amikacin dosage of 10–15 mg/kg daily given in 2 divided doses or gentamicin dosage of 3–5 mg/kg daily given in 3 divided doses; higher dosage or once-daily dosage has not been evaluated for Y-site compatibility.

Frozen Zosyn injections in Galaxy containers that contain 3.375 g/50 mL are not compatible with gentamicin and should not be used for Y-site coadministration with gentamicin.

Table 2. Y-site Compatibility for Zosyn (with EDTA) Frozen Injections in Galaxy Containers 35

Aminoglycoside	Zosyn Dosage (g)	Aminoglycoside Concentration Range (mg/mL)	Acceptable Diluents
Amikacin	2.25, 3.375, 4.5	1.75–7.5	0.9% sodium chloride injection or 5% dextrose injection
Gentamicin	2.25 or 4.5	0.7–3.32	0.9% sodium chloride injection

Reconstitution and Dilution

Reconstitute Zosyn single-dose vials containing 2 g of piperacillin and 0.25 g of tazobactam, 3 g of piperacillin and 0.375 g of tazobactam, or 4 g of piperacillin and 0.5 g of tazobactam by adding 10, 15, or 20 mL, respectively, of 0.9% sodium chloride injection, sterile water for injection, 5% dextrose injection, bacteriostatic water for injection (with parabens or benzyl alcohol), or bacteriostatic sodium chloride injection (with parabens or benzyl alcohol).¹ Shake thoroughly until contents are dissolved.¹ Reconstituted solutions should be diluted further to the desired volume (usually 50–150 mL) with 0.9% sodium chloride injection, sterile water for injection (maximum recommended volume is 50 mL), 5% dextrose injection, or 6% dextrose in 0.9% sodium chloride.^{1 33} Lactated Ringer's injection is compatible with and can be used to dilute reconstituted solutions of Zosyn (with EDTA), but cannot be used to dilute piperacillin and tazobactam preparations that do not contain EDTA.^{1 33}

ADD-Vantage vials containing Zosyn should be diluted according to the manufacturer’s labeling.¹

Reconstitute Zosyn pharmacy bulk vials containing 36 g of piperacillin and 4.5 g of tazobactam by adding 152 mL of a compatible IV solution (see Solution Compatibility under Stability) to provide a solution containing 200 mg/mL of piperacillin and 25 mg/mL of tazobactam.³³ Pharmacy bulk vials of the drug are not intended for direct IV infusion; prior to administration, solutions reconstituted in the pharmacy bulk vial must be further diluted with a compatible IV solution.³³

Thaw the commercially available injection (frozen) of Zosyn in Galaxy containers at room temperature (20–25°C) or in a refrigerator (2–8°C); do not force thaw by immersion in a water bath or by exposure to microwave radiation.³⁵ A precipitate may have formed in the frozen injection, but should dissolve with little or no agitation after reaching room temperature.³⁵ Discard thawed injection if an insoluble precipitate is present or if container seals or outlet ports are not intact.³⁵ Additives should not be introduced into the injection.³⁵ The injections should not be used in series connections with other plastic containers, since such use could result in air embolism from residual air being drawn from the primary container before administration of fluid from the secondary container is complete.³⁵

Rate of Administration

Administer by IV infusion over 30 minutes.^{1 33 35}

Dosage

Available as a fixed combination of piperacillin sodium and tazobactam sodium in an 8:1 ratio; dosage usually expressed in terms of the total of the piperacillin and tazobactam content of the fixed combination (i.e., grams of Zosyn).^{1 33 35} Potency of both piperacillin sodium and tazobactam sodium are expressed in terms of the bases.^{1 33 35}

Pediatric Patients

Intra-abdominal Infections

Appendicitis and/or Peritonitis

IV

Children 2 months to <9 months of age: 80 mg/kg of piperacillin and 10 mg/kg of tazobactam every 8 hours.^{1 33 35}

IV

Children ≥9 months of age weighing ≤40 kg: 100 mg/kg of piperacillin and 12.5 mg/kg of tazobactam every 8 hours.^{1 33 35}

IV

Children weighing >40 kg: 3.375 g (3 g of piperacillin and 0.375 g of tazobactam) every 6 hours.^{1 33 35}

Adults

Gynecologic and Obstetric Infections

IV

3.375 g (3 g of piperacillin and 0.375 g of tazobactam) every 6 hours for 7–10 days.^{1 33 35}

Intra-abdominal Infections

IV

3.375 g (3 g of piperacillin and 0.375 g of tazobactam) every 6 hours for 7–10 days.^{1 33 35}

Respiratory Tract Infections

IV

3.375 g (3 g of piperacillin and 0.375 g of tazobactam) every 6 hours for 7–10 days.^{1 33 35}

Nosocomial Pneumonia

IV

4.5 g (4 g of piperacillin and 0.5 g of tazobactam) every 6 hours for 7–14 days; used in conjunction with an aminoglycoside.^{1 33 35}

The aminoglycoside should be continued for the duration of treatment in patients in whom Ps. aeruginosa is isolated; if nosocomial pneumonia is not caused by Ps. aeruginosa, the aminoglycoside may be discontinued at the discretion of the clinician, taking into account severity of the infection and the patient’s clinical and bacteriologic progress.^{1 33 35}

Skin and Skin Structure Infections

IV

3.375 g (3 g of piperacillin and 0.375 g of tazobactam) every 6 hours for 7–10 days.^{1 33 35}

Special Populations

Hepatic Impairment

No dosage adjustment required in patients with hepatic impairment.^{1 3 12 33 35}

Serum half-lives of piperacillin and tazobactam are prolonged in patients with hepatic cirrhosis;^{1 3 33 35} not considered clinically important.^{1 3 12 33 35}

Renal Impairment

Dosage adjustment recommended in adults with Cl_cr ≤40 mL/minute and in adults undergoing hemodialysis or CAPD.^{1 7 12 33 35} No dosage recommendations for pediatric patients with renal impairment.^{1 33 35}

In adults with nosocomial pneumonia and renal impairment who are receiving concomitant aminoglycoside therapy, dosage of the aminoglycoside should be adjusted according to the recommendations for that drug.^{1 33 35}

Table 3. Dosage for Adults with Renal Impairment13335

Clcr (mL/min)	Daily Dosage (Except Nosocomial Pneumonia)	Daily Dosage (Nosocomial Pneumonia)
20–40	2.25 g every 6 hours	3.375 g every 6 hours
<20	2.25 g every 8 hours	2.25 g every 6 hours
Hemodialysis Patients	2.25 g every 12 hours; also give 0.75 g after each hemodialysis session	2.25 g every 8 hours; also give 0.75 g after each hemodialysis session
CAPD Patients	2.25 g every 12 hours	2.25 g every 8 hours

Cautions for Zosyn

Contraindications

• 
  

  Hypersensitivity to any penicillin, cephalosporin, or β-lactamase inhibitor.^{1 33 35}

  
  

Warnings/Precautions

Warnings

Clostridium difficile-associated Diarrhea and Colitis (CDAD)

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile.^{1 33 35 36 37 38 39 40} C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) has been reported with nearly all anti-infectives, including piperacillin and tazobactam, and may range in severity from mild diarrhea to fatal colitis.^{1 33 35 36 37 38 39 40} Hyper toxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.^{1 33 35}

Consider CDAD if diarrhea develops during or after therapy and manage accordingly.^{1 33 35 36 37 38 39 40} Careful medical history is necessary since CDAD has been reported to occur as late as 2 months or longer after anti-infective therapy is discontinued.^{1 33 35 36 37 38 39 40}

If CDAD is suspected or confirmed, piperacillin and tazobactam may need to be discontinued.^{1 33 35 36 37 38 39 40} Some mild cases may respond to discontinuance alone.^{36 37 38 39 40} Manage moderate to severe cases with fluid, electrolyte, and protein supplementation, anti-infective therapy active against C. difficile (e.g., oral metronidazole or vancomycin), and surgical evaluation when clinically indicated.^{1 33 35 36 37 38 39 40}

Sensitivity Reactions

Hypersensitivity Reactions

Serious and occasionally fatal hypersensitivity reactions, including anaphylaxis, reported with penicillins.^{1 33 35}

Prior to initiation of therapy, make careful inquiry regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other drugs.^{1 33 35} Partial cross-allergenicity occurs among penicillins and other β-lactam antibiotics including cephalosporins and cephamycins.^{1 33 35}

If a severe hypersensitivity reaction occurs, discontinue immediately and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, maintenance of an adequate airway and oxygen).^{1 33 35}

General Precautions

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of piperacillin and tazobactam and other antibacterials, use only for treatment of infections proven or strongly suspected to be caused by susceptible bacteria.^{1 33 35}

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.^{1 33 35} In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.^{1 33 35}

Hematologic Effects

Bleeding manifestation reported with some β-lactam antibiotics, including piperacillin.^{1 33 35} These reactions have sometimes been associated with abnormal coagulation tests (e.g., clotting time, platelet aggregation, PT) and are most likely to occur in patients with renal failure.^{1 33 35}

Periodically evaluate hematologic function, especially with prolonged treatment (i.e., ≥21 days).^{1 33 35}

If bleeding manifestations occur, discontinue piperacillin and tazobactam and institute appropriate measures.^{1 33 35}

Nervous System Effects

Neuromuscular excitability or seizures reported with some penicillins when higher than recommended dosage used (especially in patients with renal failure).^{1 33 35}

Sodium Content and Electrolyte Imbalance

Fixed-combination of piperacillin and tazobactam contains 2.79 mEq (64 mg) of sodium per g of piperacillin.^{1 33} (See Geriatric Use under Cautions.)

Consider sodium content when used in patients requiring restricted salt intake.^{1 33 35}

Determine electrolyte concentrations periodically in patients with low potassium reserves; consider possibility of hypokalemia in those with potentially low potassium reserves who are receiving cytotoxic therapy or diuretics.^{1 33 35}

Cystic Fibrosis Patients

Possibility of increased incidence of fever and rash.^{1 33 35}

Laboratory Monitoring

Periodically assess organ system functions, including renal, hepatic, and hematopoietic, during prolonged therapy.² Monitoring hematopoietic function is especially important when duration is ≥21 days (see Hematologic Effects under Cautions).^{1 33 35}

Specific Populations

Pregnancy

Category B.^{1 33 35}

Lactation

Piperacillin distributed into milk; not known whether tazobactam is distributed into milk.^{1 33 35} Use with caution.^{1 33 35}

Pediatric Use

Use for treatment of appendicitis and/or peritonitis in pediatric patients ≥2 months of age is supported by evidence from well-controlled studies and pharmacokinetic studies in adults and pediatric patients.^{1 33 35}

Safety and efficacy not established in pediatric patients <2 months of age.^{1 33 35}

Geriatric Use

Piperacillin and tazobactam contains sodium (see Sodium Content and Electrolyte Imbalance under Cautions).^{1 33 35} Patients receiving the usual IV dosage will receive 768 or 1024 mg (33.5 or 44.6 mEq) of sodium daily.^{1 33} Geriatric patients may respond to salt loading with blunted natriuresis;^{1 33 35} this may be clinically important with regard to such diseases as congestive heart failure.^{1 33 35}

Select dosage with caution (usually starting at low end of dosage range) because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.^{1 33 35}

Substantially eliminated by kidneys; risk of toxicity may be greater in patients with impaired renal function.^{1 33 35} Assess renal function periodically since geriatric patients are more likely to have renal impairment.^{1 33 35}

No dosage adjustments except those related to renal function.^{1 33 35} (See Renal Impairment under Dosage and Administration.)

Hepatic Impairment

Serum half-lives of piperacillin and tazobactam are prolonged in patients with hepatic cirrhosis;^{1 3 33 35} not considered clinically important.^{1 3 12 33 35}

No dosage adjustment required in patients with hepatic impairment.^{1 3 12 33 35}

Renal Impairment

Dosage adjustments recommended in adults with Cl_cr ≤40 mL/minute and in those undergoing hemodialysis or CAPD.^{1 33 35} No dosage recommendations in pediatric patients with impaired renal function.^{1 33 35} (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Adults: GI effects (diarrhea, constipation, nausea); headache; insomnia; fever; dermatologic reactions (rash, pruritus).^{1 33 35}

Pediatric patients with severe intra-abdominal infections (including appendicitis and/or peritonitis): Diarrhea, fever, vomiting, local reaction, abscess, sepsis, abdominal pain, infection, bloody diarrhea, pharyngitis, constipation, increased AST.^{1 33 35}

Interactions for Zosyn

Specific Drugs and Laboratory Tests

Drug or Test	Interaction	Comments
Aminoglycosides	Substantial inactivation of aminoglycosides can occur if combined with piperacillin in vitro1 33 35 Amikacin and gentamicin: Compatible in vitro with formulations of piperacillin and tazobactam (Zosyn) containing EDTA and can be used for simultaneous Y-site administration under specific conditions1 33 35 (see Administration under Dosage and Administration) Tobramycin: Not compatible in vitro with piperacillin and tazobactam, including formulations of Zosyn containing EDTA1 33 35 Studies using piperacillin indicate clinically important decreases in aminoglycoside concentrations if the drugs are administered concomitantly in patients with end-stage renal disease (ESRD) requiring hemodialysis; effect may vary depending on the specific aminoglycoside1 33 35 Tobramycin: Sequential administration of Zosyn and tobramycin in patients with normal or mild to moderate renal impairment does not appear to significantly affect tobramycin pharmacokinetics, but tobramycin concentrations may be significantly altered in those with ESRD requiring hemodialysis 1 33 35	Monitor aminoglycoside concentrations1 33 35 If simultaneous coadministration of piperacillin and tazobactam and an aminoglycoside via Y-site infusion is considered necessary, use only certain dosages of amikacin or gentamicin, only certain formulations of piperacillin and tazobactam (Zosyn) containing EDTA, and only certain acceptable diluents1 33 35 (see Administration under Dosage and Administration)
Anticoagulants (oral anticoagulant, heparin)		Monitor coagulation parameters more frequently if used concomitantly with high doses of heparin, oral anticoagulants, or other drugs that affect blood coagulation or thrombocyte function1 33 35
Methotrexate	Possible decreased renal clearance of methotrexate and increased risk of methotrexate adverse effects1 33 35	Determine serum methotrexate concentrations and monitor for signs and symptoms of methotrexate toxicity1 33 35
Neuromuscular blocking agents (vecuronium)	Prolonged neuromuscular blockade reported when vecuronium used with piperacillin; could also occur with piperacillin and tazobactam1 33 35 Because of similar mechanism of action, possibility of prolonged neuromuscular blockade with piperacillin and other nondepolarizing muscle relaxants1 33 35
Probenecid	Prolonged piperacillin and tazobactam half-lives1 33 35
Tests for Aspergillus	Possible false-positive results in Platelia Aspergillus EIA test1 33 35	Use caution when interpreting such tests and confirm diagnosis of Aspergillus infection using other diagnostic methods1 33 35
Tests for glucose	Possible false-positive reactions in urine glucose tests using copper reduction (e.g., Clinitest)1 33 35	Use glucose tests based on enzymatic glucose oxidase reactions (e.g., Diastix, Tes-Tape)1 33 35
Vancomycin	No evidence of pharmacokinetic interaction1 33 35

Zosyn Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentrations attained immediately after completion of IV infusion.^{1 33 35}

Piperacillin plasma concentrations with the fixed-combination of piperacillin and tazobactam are similar to those attained with equivalent doses of piperacillin administered alone.^{1 33 35}

Distribution

Extent

Both piperacillin and tazobactam widely distributed into tissues and body fluids, including intestinal mucosa, gallbladder, lung, female reproductive tissues (uterus, ovary, fallopian tube), interstitial fluid, and bile.^{1 33 35}

Only low concentrations of piperacillin and tazobactam distributed into CSF.^{1 33 35}

Both piperacillin and tazobactam cross the placenta.^{1 33 35} Piperacillin is distributed into milk; not known whether tazobactam is distributed into milk.^{1 33 35}

Plasma Protein Binding

Both piperacillin and tazobactam approximately 30% bound to plasma proteins.^{1 33 35}

Elimination

Metabolism

Piperacillin metabolized to a minor microbiologically active desethyl metabolite.^{1 33 35} Tazobactam metabolized to a single metabolite that lacks pharmacologic and antibacterial activity.^{1 33 35}

Elimination Route

Piperacillin, tazobactam, and their metabolites eliminated principally in urine by glomerular filtration and active tubular secretion; also excreted in bile.^{1 33 35}

68% of piperacillin dose eliminated unchanged in urine; 80% of tazobactam dose eliminated unchanged drug in urine.^{1 33 35}

Half-life

Plasma half-live of piperacillin and of tazobactam range from 0.7–1.2 hours.^{1 33 35}

Special Populations

Patients with cirrhosis: Half-life of piperacillin and tazobactam increased by approximately 25 and 18%, respectively, compared with patients with normal hepatic function.^{1 33 35}

Patients with renal impairment: Half-lives of piperacillin and tazobactam increase with decreasing Cl_cr.^{1 33 35} In those with Cl_cr <20 mL/minute, half-life of piperacillin is 2 times higher and half-life of tazobactam is 4 times higher compared with patients with normal renal function.^{1 33 35}

Pediatric patients: Clearance of piperacillin and tazobactam in children 9 months to 12 years of age is comparable to that reported in adults.^{1 33 35} Piperacillin clearance in children 2–9 months of age is estimated to be 80% of that value;^{1 33 35} clearance is slower in patients <2 months of age compared to older children.^{1 33 35}

Stability

Storage

Parenteral

Powder for Injection

20–25°C.^{1 33}

Reconstituted single-dose vials should be used immediately after reconstitution; any unused injection should be discarded after 24 hours if stored at 20–25°C or after 48 hours if refrigerated at 2–8°C.¹

ADD-Vantage vials prepared using 0.9% sodium chloride or 5% dextrose are stable for 24 hours at room temperature; these reconstituted solutions should not be refrigerated or frozen.¹

Reconstituted bulk vials should be discarded after 24 hours if stored at 20–25°C or after 48 hours if refrigerated at 2–8°C.³³ Do not freeze.³³

Injection (Frozen)

-20° C or lower.³⁵ Thawed solutions of the commercial frozen injection are stable for 24 hours at room temperature (20–25°C) or 14 days at 2–8°C.³⁵

Do not refreeze after thawing.³⁵

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Solution Compatibility

If sterile water for injection is used for dilution, the maximum recommended volume is 50 mL.^{1 33}

Lactated Ringer’s injection is compatible with Zosyn (with EDTA), but is incompatible with and should not be used to reconstitute or dilute piperacillin and tazobactam preparations that do not contain EDTA.^{1 33}

Chemically unstable in solutions containing only sodium bicarbonate and solutions that alter pH.^{1 33 35}

Compatible
Dextran 6% in sodium chloride 0.9%1 33
Dextrose 5%1 33 35
Sodium chloride 0.9%1 33 35
Ringer’s injection, lactated (compatible only with Zosyn containing EDTA)1 33

Drug Compatibility

Y-site CompatibilityHID

Compatible
Amikacin (compatible only with Zosyn containing EDTA)1 33 35
Aminophylline
Aztreonam
Bivalirudin
Bleomycin sulfate
Bumetanide
Buprenorphine HCl
Butorphanol tartrate
Calcium gluconate
Carboplatin
Carmustine
Cefepime HCl
Cimetidine HCl
Clindamycin phosphate
Co-trimoxazole
Cyclophosphamide
Cytarabine
Dexamethasone sodium phosphate
Dexmedetomidine HCl
Diphenhydramine HCl
Docetaxel
Dopamine HCl
Enalaprilat
Etoposide
Etoposide phosphate
Fenoldopam mesylate
Floxuridine
Fluconazole
Fludarabine phosphate
Fluorouracil
Furosemide
Gentamicin (compatible only with Zosyn containing EDTA)1 33 35
Gallium nitrate
Granisetron HCl
Heparin sodium
Hetastarch in lactated electrolyte injection (Hextend)
Hydrocortisone sodium phosphate
Hydrocortisone sodium succinate
Hydromorphone HCl
Ifosfamide
Lansoprazole
Leucovorin calcium
Linezolid
Lorazepam
Magnesium sulfate
Mannitol
Meperidine HCl
Mesna
Methotrexate sodium
Methylprednisolone sodium succinate
Metoclopramide HCl
Metronidazole
Milrinone lactate
Morphine sulfate
Ondansetron HCl
Potassium chloride
Ranitidine HCl
Remifentanil HCl
Sargramostim
Sodium bicarbonate
Thiotepa
Vinblastine sulfate
Vincristine sulfate
Zidovudine
Incompatible
Acyclovir sodium
Amiodarone HCl
Amphotericin B
Amphotericin B cholesteryl sulfate complex
Azithromycin
Chlorpromazine HCl
Cisplatin
Dacarbazine
Daunorubicin HCl
Dobutamine HCl
Doxorubicin HCl
Doxorubicin HCl liposome injection
Doxycycline hyclate
Drotrecogin alfa (activated)
Droperidol
Famotidine
Ganciclovir sodium
Gemcitabine HC