Usual Adult Dose for Intraabdominal Infection

100 mg IV initial dose, followed by 50 mg IV every 12 hours
Duration of therapy: 5 to 14 days

Use: For the treatment of complicated intraabdominal infections due to susceptible isolates of Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, K pneumoniae, Enterococcus faecalis (vancomycin-susceptible isolates), Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Streptococcus anginosus group (includes S anginosus, S intermedius, and S constellatus), Bacteroides fragilis, B thetaiotaomicron, B uniformis, B vulgatus, Clostridium perfringens, and Peptostreptococcus micros

Usual Adult Dose for Skin or Soft Tissue Infection

100 mg IV initial dose, followed by 50 mg IV every 12 hours
Duration of therapy: 5 to 14 days

Comments:

• This drug is not indicated for the treatment of diabetic foot infections; a clinical trial failed to show its non-inferiority.

Use: For the treatment of complicated skin and skin structure infections due to susceptible isolates of E coli, E faecalis (vancomycin-susceptible isolates), S aureus (methicillin-susceptible and -resistant isolates), S agalactiae, S anginosus group (includes S anginosus, S intermedius, and S constellatus), S pyogenes, E cloacae, K pneumoniae, and B fragilis

Usual Adult Dose for Skin and Structure Infection

100 mg IV initial dose, followed by 50 mg IV every 12 hours
Duration of therapy: 5 to 14 days

Comments:

• This drug is not indicated for the treatment of diabetic foot infections; a clinical trial failed to show its non-inferiority.

Use: For the treatment of complicated skin and skin structure infections due to susceptible isolates of E coli, E faecalis (vancomycin-susceptible isolates), S aureus (methicillin-susceptible and -resistant isolates), S agalactiae, S anginosus group (includes S anginosus, S intermedius, and S constellatus), S pyogenes, E cloacae, K pneumoniae, and B fragilis

Usual Adult Dose for Pneumonia

100 mg IV initial dose, followed by 50 mg IV every 12 hours
Duration of therapy: 7 to 14 days

Comments:

• This drug is not indicated for the treatment of hospital-acquired or ventilator-associated pneumonia; greater mortality and decreased efficacy reported in comparative clinical trial.

Use: For the treatment of community-acquired bacterial pneumonia due to susceptible isolates of S pneumoniae (penicillin-susceptible isolates), including cases with concurrent bacteremia, Haemophilus influenzae, and Legionella pneumophila

Usual Pediatric Dose for Intraabdominal Infection

Proposed for complicated infections:
8 to 11 years: 1.2 mg/kg IV every 12 hours
Maximum dose: 50 mg/dose

12 to 17 years: 50 mg IV every 12 hours

Comments:

• Use of this drug should be avoided unless no alternative antibacterial agents are available.
• Safety and efficacy of proposed dosing regimens have not been evaluated due to observed increase in mortality associated with this drug in adult patients.
• Proposed doses based on exposures seen in pharmacokinetic trials (small numbers of pediatric patients included).

Usual Pediatric Dose for Skin and Structure Infection

Proposed for complicated infections:
8 to 11 years: 1.2 mg/kg IV every 12 hours
Maximum dose: 50 mg/dose

12 to 17 years: 50 mg IV every 12 hours

Comments:

• Use of this drug should be avoided unless no alternative antibacterial agents are available.
• Safety and efficacy of proposed dosing regimens have not been evaluated due to observed increase in mortality associated with this drug in adult patients.
• Proposed doses based on exposures seen in pharmacokinetic trials (small numbers of pediatric patients included).

Usual Pediatric Dose for Pneumonia

Proposed for community-acquired bacterial pneumonia:
8 to 11 years: 1.2 mg/kg IV every 12 hours
Maximum dose: 50 mg/dose

12 to 17 years: 50 mg IV every 12 hours

Comments:

• Use of this drug should be avoided unless no alternative antibacterial agents are available.
• Safety and efficacy of proposed dosing regimens have not been evaluated due to observed increase in mortality associated with this drug in adult patients.
• Proposed doses based on exposures seen in pharmacokinetic trials (small numbers of pediatric patients included).

Renal Dose Adjustments

No adjustment recommended.

Liver Dose Adjustments

Adult patients:

• Mild to moderate liver dysfunction (Child-Pugh A and B): No adjustment recommended.
• Severe liver dysfunction (Child-Pugh C): 100 mg IV initial dose, followed by 25 mg IV every 12 hours

Pediatric patients: Data not available

Comments:

• Caution recommended in patients with severe liver dysfunction; such patients should be monitored for treatment response.

Precautions

US BOXED WARNINGS:

• ALL-CAUSE MORTALITY: In a meta-analysis of phase 3 and 4 clinical trials, an increase in all-cause mortality was observed in patients treated with this drug versus comparator; cause of 0.6% mortality risk difference has not been established. Use of this drug should be reserved for situations when alternative therapies are not suitable.
• UNRECOGNIZED HYPOGLYCEMIA DUE TO INTERFERENCE WITH BLOOD GLUCOSE TESTING: At least 1 formulation contains maltose and may cause falsely elevated glucose readings leading to unrecognized hypoglycemia or inappropriate insulin use. Glucose testing methods that do not react with maltose should be used in patients receiving this formulation.

CONTRAINDICATIONS:
Known hypersensitivity to the active component

Safety and efficacy have not been established in patients younger than 18 years; this drug is not recommended for use in these patients.

• If no alternative antibacterial agents are available: Pediatric regimens have been suggested; this drug is not recommended for use in children younger than 8 years (due to effects on tooth development).

Consult WARNINGS section for additional precautions.

Dialysis

Hemodialysis: No adjustment recommended.
Peritoneal dialysis: Data not available

Other Comments

Administration advice:

• Reserve this drug for situations when alternative therapies are not suitable.
• Administer IV infusions over about 30 to 60 minutes; administer through a dedicated line or through a Y-site.
• If the same IV line is used for sequential infusion of several drugs, flush the line before and after infusion of this drug with an infusion solution compatible to all drugs; the manufacturer product information should be consulted.
• Duration of therapy should be guided by severity and site of infection and clinical and bacteriological progress of the patient.

Storage requirements:

• Prior to reconstitution: Store at 20C to 25C (68F to 77F); excursions permitted to 15C to 30C (59F to 86F)
• After reconstitution: May store at room temperature (not to exceed 25C [77F]) for up to 24 hours (up to 6 hours in the vial and the remaining time in the IV bag); if storage conditions exceed 25C (77F), use immediately. Alternatively, if mixed with 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP, may store refrigerated at 2C to 8C (36F to 46F) for up to 48 hours after immediate transfer of reconstituted solution into the IV bag

Reconstitution/preparation techniques:

• This drug must be reconstituted and then further diluted; the manufacturer product information should be consulted.

IV compatibility:

• Compatible IV solutions: 0.9% Sodium Chloride Injection, USP; 5% Dextrose Injection, USP; Lactated Ringer's Injection, USP
• Compatible drugs/diluents for administration through a Y-site (when used with 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP): Amikacin, dobutamine, dopamine hydrochloride (HCl), gentamicin, Lactated Ringer's, lidocaine HCl, metoclopramide, morphine, norepinephrine, potassium chloride, propofol, ranitidine HCl, theophylline, tobramycin
• Incompatible drugs: Amphotericin B, amphotericin B lipid complex, diazepam, esomeprazole, omeprazole
• The manufacturer product information should be consulted regarding compatibility of haloperidol and piperacillin-tazobactam (ethylenediaminetetraacetic acid [EDTA] formulation).

General:

• To reduce the development of drug-resistant organisms and maintain effective therapy, this drug should be used only to treat infections proven or strongly suspected to be caused by susceptible bacteria.
• Culture and susceptibility information should be considered when selecting/modifying antibacterial therapy or, if no data are available, local epidemiology and susceptibility patterns may be considered when selecting empiric therapy.
• Appropriate specimens should be obtained for bacteriological examination to isolate and identify causative organisms and determine susceptibility to this drug; may start this drug as empiric monotherapy before test results are known
• Some products may contain 100 mg lactose monohydrate or maltose monohydrate per vial; if the formulation containing maltose is substituted for another formulation, glucose testing methods that do not react with maltose should be used.

Monitoring:

• General: For treatment response in patients with severe liver dysfunction
• Hepatic: For worsening hepatic function in patients who develop abnormal liver function tests (during therapy)

Patient advice:

• Avoid missing doses and complete the entire course of therapy.
• Consult healthcare provider if severe watery or bloody diarrhea develops.