Piperacillin Sodium / Tazobactam Sodium

Pronunciation: (PI-per-a-SIL-in SO-dee-um/TAZ-oh-BAK-tam SO-dee-um)Class: Antibiotic, Extended-spectrum penicillin

Trade Names:Zosyn- Injection, powder for solution piperacillin 2 g and tazobactam 0.25 g- Injection, powder for solution piperacillin 3 g and tazobactam 0.375 g- Injection, powder for solution piperacillin 4 g and tazobactam 0.5 g- Injection, powder for solution piperacillin 36 g and tazobactam 4.5 g (bulk)- Injection, solution piperacillin 2 g and tazobactam 0.25 g- Injection, solution piperacillin 3 g and tazobactam 0.375 g- Injection, solution piperacillin 4 g and tazobactam 0.5 g

Tazocin (Canada)

Pharmacology

Inhibits bacterial cell wall mucopeptide synthesis.

Indications and Usage

Treatment of moderate to severe infections caused by piperacillin-resistant, piperacillin/tazobactam–susceptible, beta-lactamase–producing strains of microorganisms in the following conditions: appendicitis (complicated by rupture or abscess), uncomplicated and complicated skin and skin structure infections, peritonitis, postpartum endometritis or pelvic inflammatory disease, community-acquired pneumonia (moderate severity only), nosocomial pneumonia (moderate to severe).

Contraindications

History of allergic reactions to penicillins, cephalosporins, or beta-lactamase inhibitors; hypersensitivity to any component of the product.

Dosage and Administration

Administer by IV infusion over 30 min.

Nosocomial PneumoniaAdults

IV Start with 4.5 g every 6 h plus an aminoglycoside (administered separately) for 7 to 14 days.

Healthy Renal Function (CrCl 90 mL/min or more)Adults

IV 3.375 g every 6 h, totaling 13.5 g (piperacillin 12 g/tazobactam 1.5 g), for 7 to 10 days.

Children 2 mo of age and older

IV Piperacillin 80 mg/tazobactam 10 mg per kg every 8 h. Children weighing more than 40 kg with healthy renal function should receive the adult dose.

Children 2 mo of age and older with appendicitis and/or peritonitis

IV Children between 2 and 9 mo of age – piperacillin 80 mg/tazobactam 10 mg per kg every 8 h. Children 9 mo of age and older weighing up to 40 kg – piperacillin 100 mg/tazobactam 12.5 mg per kg every 8 h. Children weighing more than 40 kg – Administer the adult dose.

Renal Function ImpairmentAdults CrCl more than 40 mL/min

IV 4.5 g every 6 h (nosocomial pneumonia). 3.375 g every 6 h (other indications).

CrCl 20 to 40 mL/min

IV 3.375 g every 6 h (nosocomial pneumonia). 2.25 g every 6 h (other indications).

CrCl less than 20 mL/min

IV 2.25 g every 6 h (nosocomial pneumonia). 2.25 g every 8 h (other indications).

There are no dosage recommendations for children with renal function impairment.

HemodialysisAdults

IV Max dosage is 2.25 g every 8 h for nosocomial pneumonia and every 12 h for other indications, plus 1 additional dose of 0.75 g following each dialysis period.

Continuous Ambulatory Peritoneal Dialysis (CAPD)Adults

IV 2.25 g every 8 h for nosocomial pneumonia and every 12 h for other indications.

Elderly

Start at the low end of the dose range.

General Advice

• For IV infusion only. Not for intradermal, subcutaneous, IM, IV bolus, or intra-arterial administration. May be used in ambulatory IV infusion pump.
• Multiple concentrations are available for reconstitution. Ensure proper concentration is being used.
• If using ADD-Vantage antibiotic vial, carefully follow manufacturer's instructions for assembling vial and flexible 50 or 100 mL diluent container, reconstituting drug, and preparing for administration.
• If using regular vial with powder for injection, reconstitute with sterile or bacteriostatic water for injection, sterile or bacteriostatic sodium chloride for injection, or dextrose 5% injection. Add 5 mL diluent per gram of piperacillin being reconstituted and swirl until dissolved.
• Further dilute reconstituted solution with compatible diluent to prescribed volume (eg, 50 to 150 mL).
• Piperacillin/tazobactam in Galaxy containers should not be used in children who require less than the adult dose.

Storage/Stability

• Store powder for injection at controlled room temperature (68° to 77°F). Use reconstituted solution immediately or dilute for infusion. Discard any unused portion after 24 h if stored at room temperature or after 48 h if stored in refrigerator (36° to 46°F). Do not freeze vials after reconstitution.
• Diluted solution in IV bags is stable for up to 24 h at room temperature and up to 7 days if refrigerated.
• Admixed solution in the ADD-Vantage system is stable for up to 24 h at room temperature. Do not refrigerate or freeze the admixed ADD-Vantage system solution after reconstitution.
• Diluted solution in ambulatory IV infusion pump is stable for up to 12 h.
• Store premixed frozen solutions at or below 4°F. Thaw at room temperature (72°F) or in refrigerator (39°F). Do not force thaw by immersion in water baths or by microwave irradiation. Thawed solution is stable for 24 h at room temperature or 7 days if refrigerated. Do not refreeze thawed solutions.

Drug Interactions

Aminoglycosides

May form microbiologically inactive complexes; do not mix in the same container.

Anticoagulants/Heparin

Frequently monitor coagulation parameters.

Methotrexate

May reduce Cl of methotrexate.

Probenecid

Increases and prolongs half-life of penicillin levels.

Vecuronium

Neuromuscular blockade may be prolonged.

Incompatibility

Ringer's lactate solution.

Laboratory Test Interactions

False-positive reaction for glucose in the urine using a copper-reduction method (eg, Clinitest ) but not with enzyme-based tests (eg, Diastix , Tes-Tape ). False-positive results for Aspergillus have been reported using the Bio-Rad Laboratories' Platelia Aspergillus EIA test.

Adverse Reactions

The incidences stated for the following adverse reactions were reported with piperacillin/tazobactam administration alone. Adverse reactions occurring with administration of piperacillin/tazobactam in combination with other antibiotics (eg, an aminoglycoside) are not included. Adverse reactions occurring in children are similar to those reported in adults.

Cardiovascular

Hypertension (2%).

CNS

Headache (8%); insomnia (7%); agitation (2%); anxiety, dizziness (1%).

Dermatologic

Rash, including bullous, eczematoid, maculopapular, and urticarial (4%); pruritus (3%); erythema multiforme, Stevens-Johnson syndrome, TEN (postmarketing).

EENT

Rhinitis (1%).

GI

Diarrhea (11%); constipation (8%); nausea (7%); dyspepsia, vomiting (3%); stool changes (2%); abdominal pain (1%).

Genitourinary

Interstitial nephritis, renal failure (postmarketing).

Hematologic-Lymphatic

Agranulocytosis, anemia, hemolytic anemia, pancytopenia, thrombocytosis (postmarketing).

Hepatic

Cholestatic jaundice, hepatitis (postmarketing).

Hypersensitivity

Anaphylactic/anaphylactoid reactions (including shock), hypersensitivity reactions (postmarketing).

Local

Phlebitis (1%).

Respiratory

Dyspnea (1%).

Miscellaneous

Fever, moniliasis, pain (2%); chest pain, edema (1%); candidal superinfections (postmarketing).

Precautions

Monitor Periodically assess hematopoietic function, especially with prolonged therapy (ie, 21 days or more). Perform periodic electrolyte determinations in patients with low potassium reserves.

Pregnancy

Category B .

Lactation

Piperacillin

Excreted in low concentrations in human milk.

Tazobactam

Undetermined.

Children

Safety and efficacy not established in children younger than 2 mo of age.

Elderly

Use with caution, usually starting at the low end of the dosage range, because of the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant diseases or other drug therapy.

Hypersensitivity

Serious and sometimes fatal hypersensitivity reactions have occurred.

Renal Function

Adjust dose accordingly.

Superinfection

Prolonged use of antibiotics may result in bacterial or fungal overgrowth of nonsusceptible microorganisms.

Bleeding abnormalities

Hemorrhagic manifestations associated with abnormalities of coagulation tests (bleeding time, platelet aggregation, PT) may occur. Abnormalities revert to normal when drug is discontinued.

Neuromuscular excitability/convulsions

May occur if higher than recommended doses are used.

Patients with cystic fibrosis

May experience higher incidence of adverse reactions when treated with piperacillin.

Prophylactic use

Is unlikely to provide benefit and may increase risk of development of drug-resistant bacteria.

Pseudomembranous colitis

May occur because of overgrowth of Clostridium difficile ; consider the possibility in patients in whom diarrhea develops.

Sodium content

Product contains 2.79 mEq (64 mg) of sodium; consider this when treating patients requiring restricted sodium intake.

Overdosage

Symptoms

Convulsions, diarrhea, nausea, neuromuscular excitability, vomiting.

Patient Information

• Advise patient or caregiver that medication will be prepared by health care provider and administered in a health care setting.
• Review dosing schedule and prescribed length of therapy with patient. Advise patient that dose, dosing frequency, and duration of therapy are dependent on site of infection, severity of infection, and response to treatment.
• Advise patient or caregiver to immediately inform health care provider if injection-site pain or redness, skin rash, hives, itching, or shortness of breath occur during treatment.
• Advise patient or caregiver to report the following signs of superinfection to health care provider: black “furry” tongue, foul-smelling stools, vaginal itching or discharge, white patches in mouth.
• Warn patient or caregiver that diarrhea containing blood or pus may be a sign of a serious disorder and, if noted after discharge, to seek medical care and not to treat at home.

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