piperacillin sodium
Pipracil

Available forms
Available by prescription only
Infusion: 2 g, 3 g, 4 g
Injection: 2 g, 3 g, 4 g

Indications and dosages
 Infections caused by susceptible organisms. Adults and children older than age 12: Serious infection: 12 to 18 g daily I.V. in divided doses q 4 to 6 hours. Uncomplicated urinary tract infection (UTI) and community-acquired pneumonia: 6 to 8 g/day I.V. in divided doses q 6 to 12 hours. Complicated UTI: 8 to 16 g daily I.V. in divided doses q 6 to 8 hours. Uncomplicated gonorrhea: 2 g I.M. as a single dose. Maximum daily dose is 24 g.
Children ages 1 month to 12 years: 50 mg/kg I.V. over 30 minutes q 4 hours.
 Prophylaxis of surgical infections. Adults: Intra-abdominal surgery: 2 g I.V. before surgery, 2 g during surgery, and 2 g q 6 hours after surgery for no longer than 24 hours. Vaginal hysterectomy: 2 g I.V. before surgery, 2 g 6 hours after first dose then 2 g 12 hours after second dose. Cesarean section: 2 g I.V. after cord is clamped; then 2 g q 4 hours for two doses. Abdominal hysterectomy: 2 g I.V. before surgery, 2 g in postanesthesia care unit, and 2 g after 6 hours.
≡ Dosage adjustment. For adults with renal impairment, see below.

Urinary tract infection Creatinine clearance (ml/min) Uncomplicated Complicated Serious systemic infection 20-40 * 3 g q 8 hr 4 g q 8 hr < 20 3 g q 12 hr 3 g q 12 hr 4 g q 12 hr *No dosage adjustment necessary

Pharmacodynamics
Antibiotic action: Bactericidal. Adheres to bacterial penicillin-binding proteins, thus inhibiting bacterial cell wall synthesis. Extended-spectrum penicillins are more resistant to inactivation by certain beta-lactamases, especially those produced by gram-negative organisms, but are still liable to inactivation by certain others. Because of the potential for rapid development of bacterial resistance, drug shouldn’t be used as a sole drug in the treatment of an infection.
 Piperacillin’s spectrum of activity includes many gram-negative aerobic and anaerobic bacilli, many gram-positive and gram-negative aerobic cocci, and some gram-positive aerobic and anaerobic bacilli. Piperacillin may be effective against some strains of carbenicillin-resistant and ticarcillin-resistant gram-negative bacilli. Piperacillin is more active against Pseudomonas aeruginosa than are other extended-spectrum penicillins.

Pharmacokinetics
Absorption: Rapidly and almost completely absorbed within the first hour after I.M. administration.
Distribution: Distributed widely after parenteral administration; penetrates minimally into uninflamed meninges and slightly into bone and sputum. 16% to 22% protein-bound; crosses the placental barrier.
Metabolism: None significant.
Excretion: 42% to 90% excreted in urine by renal tubular secretion and glomerular filtration; also excreted in bile and breast milk. Elimination half-life in adults is about 1/2 to 1 1/2 hours; in extensive renal impairment, half-life extended to about 2 to 6 hours; in combined hepatorenal dysfunction, half-life may extend from 11 to 32 hours. Drug is removed by hemodialysis but not by peritoneal dialysis.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug or other penicillins. Use cautiously in patients with other drug allergies (especially to cephalosporins), bleeding tendencies, uremia, or hypokalemia.

Interactions
Drug-drug. Aminoglycoside antibiotics: Has synergistic bactericidal effects against Pseudomonas aeruginosa, Escherichia coli, Klebsiella, Citrobacter, Enterobacter, Serratia, and Proteus mirabilis. However, drugs are physically and chemically incompatible; inactivated when mixed or given together. Don’t give together.
Clavulanic acid, sulbactam, tazobactam: Has synergistic bactericidal effect against certain beta-lactamase-producing bacteria. May be used together for this effect.
Hormonal contraceptives: Decreases efficacy. Suggest other means of contraception.
Methotrexate: Large doses of penicillins may interfere with renal tubular secretion of methotrexate; causes delayed elimination and elevated serum levels of methotrexate. Monitor patient for toxicity.
Probenecid: Blocks tubular secretion of piperacillin, raising serum levels of drug. Probenecid may be used for this purpose.
Vecuronium: Prolongs neuromuscular blockade. Monitor patient closely.

Adverse reactions
CNS: seizures, headache, dizziness, fatigue.
CV: vein irritation, phlebitis.
GI: nausea, diarrhea, vomiting, pseudomembranous colitis.
GU: interstitial nephritis.
Hematologic: bleeding (with high doses), neutropenia, eosinophilia, leukopenia, thrombocytopenia.
Metabolic: hypokalemia, hypernatremia.
Musculoskeletal: prolonged muscle relaxation.
Skin: pain at injection site.
Other: hypersensitivity reactions (edema, fever, chills, rash, pruritus, urticaria, anaphylaxis), overgrowth of nonsusceptible organisms.

Effects on lab test results
• May increase ALT, AST, alkaline phosphatase, LDH, and sodium levels. May decrease potassium level.
• May increase eosinophil count. May decrease hemoglobin, hematocrit, and platelet, WBC, and granulocyte counts.

Overdose and treatment
Overdose may cause neuromuscular hypersensitivity and seizures resulting from CNS irritation by high drug levels.
 A 4- to 6-hour hemodialysis will remove 10% to 50% of drug.

Special considerations
• Piperacillin is usually given with another antibiotic such as an aminoglycoside in life-threatening situations.
• Drug may be more suitable than carbenicillin or ticarcillin for patients on salt-free diets; piperacillin contains only 1.85 mEq of sodium per gram.
• Drug may be administered by direct I.V. injection, given slowly over at least 5 minutes; chest discomfort occurs if injection is given too rapidly.
• Patients with cystic fibrosis are most susceptible to fever or rash from piperacillin.
• Use reduced dosage in patients with creatinine clearance below 40 ml/minute.
• Monitor serum electrolytes, especially potassium.
• Monitor neurologic status. High serum levels of this drug may cause seizures. • Monitor CBC, differential, and platelets. Drug may cause thrombocytopenia. Observe patient carefully for signs of occult bleeding.
• Because drug is dialyzable, patients undergoing hemodialysis may need dosage adjustments.
• Drug may falsely decrease serum aminoglycoside levels; drug may cause positive Coombs’ tests.
Breast-feeding patients
• Drug appears in breast milk. Use cautiously in breast-feeding women.
Pediatric patients
• Safe use in children younger than age 12 hasn’t been established.
Geriatric patients
• Half-life may be prolonged in elderly patients because of impaired renal function.

Patient education
• Tell patient to report adverse reactions promptly.
• Advise patient to limit salt intake during therapy because drug contains 1.85 mEq of sodium/g.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use