Piperacillin Sodium

Trade Names:Pipracil- Powder for injection (contains 1.85 mEq [42.5 mg] sodium/g) 2 g- Powder for injection 3 g- Powder for injection 4 g

Trade Names:Piperacillin- Powder for injection 40 g (bulk)

Pharmacology

Inhibits bacterial cell wall mucopeptide synthesis.

Pharmacokinetics

Absorption

Not absorbed orally; rapidly absorbed IM. T _max is 30 min (IM) and immediately after completion (IV). C _max is 412 mcg/mL (IV).

Distribution

Widely distributed in human tissues and body fluids, including bone, prostate, and heart; reaches high concentrations in bile. Penetrates CSF in the presence of inflamed meninges. Protein binding is 16%. Vd is 0.23 L/kg. It crosses the placenta and distributes into breast milk.

Metabolism

Liver.

Elimination

Urine (60% to 80% unchanged), partially biliary. Serum t _½ is 36 to 72 min; elimination t _½ is 54 to 63 min.

Special Populations

Elimination t _½ is increased 2-fold in mild to moderate impairment, 5- to 6-fold in severe impairment.

Indications and Usage

Treatment of intra-abdominal, urinary tract, gynecologic, and lower respiratory tract infections; septicemia; skin and skin structure infections; bone and joint infections; gonococcal urethritis; surgical prophylaxis; treatment of infection caused by susceptible microorganisms, including infections caused by Streptococcus and Pseudomonas species.

Contraindications

Hypersensitivity to penicillins or cephalosporins.

Dosage and Administration

IM / IV 3 to 4 g every 4 to 6 h (max, 24 g/day).

IV 12 to 18 g/day (200 to 300 mg/kg/day) in divided doses every 4 to 6 h (max daily dose, 24 g/day).

IV 8 to 16 g/day (125 to 200 mg/kg/day) in divided doses every 6 to 8 h.

IM / IV 6 to 8 g/day (100 to 125 mg/kg/day) in divided doses every 6 to 12 h.

IM 2 g as a one time dose; give 1 g of probenecid 30 min prior to injection.

IV 2 g just prior to surgery, 2 g during surgery, and 2 g every 6 h postsurgery for not more than 24 h.

IV 2 g just prior to surgery, 2 g 6 h later, 2 g 12 h after first dose.

IV 2 g after cord is clamped, 2 g 4 h later, 2 g 8 h after first dose.

IV 2 g just prior to surgery, 2 g on return to recovery room, 2 g 6 h later.

3 g every 8 h (9 g/day).

4 g every 8 h (12 g/day).

3 g every 12 h (6 g/day).

4 g every 12 h (8 g/day).

Max dose, 6 g/day (2 g every 8 h); give 1 g additional dose after each dialysis.

General Advice

For IM or IV administration only. Not for intradermal, subcutaneous, or intra-arterial administration.

• Reconstitute powder for injection with sterile or bacteriostatic water for injection, sterile or bacteriostatic sodium chloride for injection, 5% dextrose injection, 5% dextrose in 0.9% sodium chloride injection, or 0.5% to 1% lidocaine hydrochloride solution (without epinephrine). Add 2 mL of diluent/g of piperacillin being reconstituted and shake well until dissolved. Reconstituted solution contains 1 g piperacillin per 2.5 mL.
• Do not administer if solution is cloudy, discolored, or contains particulate matter.
• Administer promptly after reconstitution by deep IM injection into large muscle mass. Preferred site of injection is upper outer quadrant of the buttock. Deltoid area may be used but only if well developed and with caution to avoid radial nerve injury. Do not inject into the lower or mid-third of the upper arm.
• Do not exceed 2 g of reconstituted piperacillin/injection at any one site.
• Discard any unused solution. Do not save for future use.

• Reconstitute powder for injection with sterile or bacteriostatic water for injection, sterile or bacteriostatic sodium chloride for injection, 5% dextrose injection, or 5% dextrose in 0.9% sodium chloride injection. Add at least 5 mL of diluent/g of piperacillin being reconstituted and shake well until dissolved.
• Further dilute reconstituted solution with compatible diluent to prescribed volume (eg, 50 or 100 mL).
• Do not administer if solution is cloudy, discolored, or contains particulate matter.
• For direct IV bolus injection, administer reconstituted solution over a 3- to 5-min period to help avoid vein irritation.
• For IV infusion, administer as intermittent infusion over 30 min by direct injection or through a Y-type IV infusion set already in place. If using Y-type IV infusion set, temporarily discontinue administration of any other solution during infusion of piperacillin.

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.

Drug Interactions

May inactivate aminoglycosides in vitro; do not mix in same IV solution. May be used in combination for synergy.

May increase bleeding risks by prolonging bleeding time.

Synergism or antagonism may develop.

May reduce efficacy of oral contraceptives. Use additional form of contraception during piperacillin therapy.

Synergism or antagonism may develop.

May increase bleeding risks of heparin by prolonging bleeding time.

Serum concentrations may be elevated by piperacillin, increasing the risk of toxicity.

Piperacillin serum concentrations may be increased by probenecid.

May impair bactericidal effects of piperacillin.

Action of vecuronium may be potentiated, producing protracted respiratory depression.

Laboratory Test Interactions

May cause false-positive urine glucose test results with Benedict solution, Fehling solution, or Clinitest tablets but not with enzyme-based tests (eg, Clinistix , Tes-tape ); false-positive direct Coombs test result in certain patient groups; positive direct antiglobulin tests; false-positive protein reactions with sulfosalicylic acid and boiling test, acetic acid test, biuret reaction and nitric acid test but not with the bromphenol blue test ( Multi-Stix ). False-positive results for Aspergillus have been reported using the Bio-Rad Laboratories' Platelia Aspergillus EIA Test with piperacillin/tazobactam.

Adverse Reactions

CNS

Dizziness; fatigue; convulsions; hallucinations; lethargy; neuromuscular irritability; prolonged muscle relaxation; headache; seizures.

Dermatologic

Ecchymosis.

GI

Diarrhea or bloody diarrhea; nausea; pseudomembranous colitis; rectal bleeding; vomiting.

Genitourinary

Elevated creatinine or BUN; interstitial nephritis (hematuria, hyaline casts, oliguria, proteinuria, pyuria).

Hematologic

Agranulocytosis; eosinophilia; hemolytic anemia; leukopenia; neutropenia; prolongation of bleeding and prothrombin time; reduced Hgb or Hct; thrombocytopenia; pancytopenia.

Hepatic

Cholestatic hepatitis; elevated AST, ALT, LDH, and bilirubin.

Metabolic

Hypokalemia.

Miscellaneous

Deep vein thrombosis; hematomas; hypersensitivity reactions (eg, erythema multiforme, skin rashes, urticaria, vesicular eruptions); pain and erythema at injection site; vein irritation; toxic epidermal necrolysis; Stevens-Johnson syndrome; fever; thrombophlebitis; pruritus.

Precautions

Pregnancy

Category B .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established.

Elderly

Use with caution because of the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy.

Hypersensitivity

Reactions range from mild to life-threatening. Administer cautiously to cephalosporin-sensitive patients because of possible crossreactivity.

Renal Function

Dosage adjustment required.

Superinfection

May result in bacterial or fungal overgrowth of nonsusceptible organisms.

Bleeding abnormalities

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

Cystic fibrosis patients

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 caused by overgrowth of clostridia. Consider possibility in patients with diarrhea.

Overdosage

Symptoms

Agitation, confusion, asterixis, hallucinations, stupor, coma, seizures, hyperexcitability.

Patient Information

• Advise patient or caregiver that medication will be prepared by a 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 signs of superinfection to health care provider: black “furry” tongue, white patches in mouth, foul-smelling stools, vaginal itching or discharge.
• 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 if noted and not treat at home.

Copyright © 2009 Wolters Kluwer Health.