Dosing & Uses
Dosage Forms & Strengths
powder for injection
- 2g
- 3g
- 4g
- 40g
Usual Dosage Range
IV: 3-4 g/dose q4-6hr; not to exceed 24 g/24hr
IM: 2-3 g/dose q6-12hr; not to exceed 24 g/24 hr
Urinary Tract, Uncomplicated
6-8 g/day IV/IM (100 to 125 mg/kg/day) divided q6-12 hr
Community-Acquired Pneumonia
6-8 g/day IV/IM (100 to 125 mg/kg/day) divided q6-12 hr
Acute Cholangitis
4 g IV q6hr
Moderate Infections
2-3 g/dose IV/IM q6-12hr; not to exceed 2 g IM/site
Severe Infections
3-4 g IV/IM q4-6hr; not to exceed 24 g/24 hr
Uncomplicated Gonorrhea
2 g once with 1 g probenecid 30 min before injection
Pseudomonas Infections
4 g IV/IM q4hr
Renal Impairment
CrCl 20-40 mL/min: 3-4 g q8hr
CrCl <20 mL/min: 3-4 g q12hr
Other Indications & Uses
Extended spectrum: Acinetobacter spp., Alcaligenes xylosoxidans, Bacteroides spp., Citrobacter diversus, Citrobacter freundii, E. coli, Fusobacteriae, H. influenzae, Klebsiella spp., N. gonorrhoeae, Peptococcus spp., Peptostreptococcus spp., indole-pos. Proteus spp., Providencia spp., Pseudomonas spp., Serratia spp., Streptococcus faecalis, Yersinia enterolitica
Dosage Forms & Strengths
powder for injection
- 2g
- 3g
- 4g
- 40g
Usual Dosage Range
Neonates: 100 mg/kg IV/IM q12hr
Infants and Children: 200-300 mg/kg/day IV/IM divided q4-6hr
Cystic Fibrosis
Adjust dose for renal impairment
Usual dosage range
IV: 2-4 g q6-8hr
IM: 1-2 g q8-12hr
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (12)
- antithrombin alfa
piperacillin increases effects of antithrombin alfa by pharmacodynamic synergism. Avoid or Use Alternate Drug.
- antithrombin III
piperacillin increases effects of antithrombin III by pharmacodynamic synergism. Avoid or Use Alternate Drug.
- argatroban
piperacillin will increase the level or effect of argatroban by anticoagulation. Avoid or Use Alternate Drug. cephalosporins may decrease prothrombin activity
- BCG vaccine live
piperacillin decreases effects of BCG vaccine live by pharmacodynamic antagonism. Contraindicated. Wait until antibiotic treatment complete to administer live bacterial vaccine; antibiotics may diminish therapeutic effects of BCG.
- bivalirudin
piperacillin will increase the level or effect of bivalirudin by anticoagulation. Avoid or Use Alternate Drug. cephalosporins may decrease prothrombin activity
- cholera vaccine
piperacillin, cholera vaccine. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid coadministration of cholera vaccine with systemic antibiotics since these agents may be active against the vaccine strain. Do not administer cholera vaccine to patients who have received oral or parenteral antibiotics within 14 days prior to vaccination.
- dalteparin
piperacillin increases effects of dalteparin by anticoagulation. Avoid or Use Alternate Drug. Piperacillin can inhibit platelet aggregation.
- enoxaparin
piperacillin increases effects of enoxaparin by anticoagulation. Avoid or Use Alternate Drug. Piperacillin can inhibit platelet aggregation.
- heparin
piperacillin will increase the level or effect of heparin by anticoagulation. Avoid or Use Alternate Drug. piperacillin can inhibit platelet aggregation
- microbiota oral
piperacillin decreases effects of microbiota oral by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Microbiota oral contains bacterial spores. Antibacterial agents may decrease efficacy if coadministered. Complete antibiotic regimens 2-4 days before initiating microbiota oral. .
- omadacycline
omadacycline decreases effects of piperacillin by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Tetracyclines may interfere with the bactericidal action of penicillins. Monitor for decreased therapeutic effects of penicillins if concomitantly used with a tetracycline.
- sarecycline
sarecycline decreases effects of piperacillin by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Tetracyclines may interfere with the bactericidal action of penicillins. Monitor for decreased therapeutic effects of penicillins if concomitantly used with a tetracycline.
Monitor Closely (18)
- azithromycin
azithromycin decreases effects of piperacillin by pharmacodynamic antagonism. Use Caution/Monitor. bacteriostatic agents may inhibit the effects of bactericidal agents.
- bazedoxifene/conjugated estrogens
piperacillin will decrease the level or effect of bazedoxifene/conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- chloramphenicol
chloramphenicol decreases effects of piperacillin by pharmacodynamic antagonism. Use Caution/Monitor. bacteriostatic agents may inhibit the effects of bactericidal agents.
- clarithromycin
clarithromycin decreases effects of piperacillin by pharmacodynamic antagonism. Use Caution/Monitor. bacteriostatic agents may inhibit the effects of bactericidal agents.
- demeclocycline
demeclocycline decreases effects of piperacillin by pharmacodynamic antagonism. Use Caution/Monitor. bacteriostatic agents may inhibit the effects of bactericidal agents.
- dichlorphenamide
dichlorphenamide and piperacillin both decrease serum potassium. Use Caution/Monitor.
- doxycycline
doxycycline decreases effects of piperacillin by pharmacodynamic antagonism. Use Caution/Monitor. bacteriostatic agents may inhibit the effects of bactericidal agents.
- erythromycin base
erythromycin base decreases effects of piperacillin by pharmacodynamic antagonism. Use Caution/Monitor. bacteriostatic agents may inhibit the effects of bactericidal agents.
- erythromycin ethylsuccinate
erythromycin ethylsuccinate decreases effects of piperacillin by pharmacodynamic antagonism. Use Caution/Monitor. bacteriostatic agents may inhibit the effects of bactericidal agents.
- erythromycin lactobionate
erythromycin lactobionate decreases effects of piperacillin by pharmacodynamic antagonism. Use Caution/Monitor. bacteriostatic agents may inhibit the effects of bactericidal agents.
- erythromycin stearate
erythromycin stearate decreases effects of piperacillin by pharmacodynamic antagonism. Use Caution/Monitor. bacteriostatic agents may inhibit the effects of bactericidal agents.
- minocycline
minocycline decreases effects of piperacillin by pharmacodynamic antagonism. Use Caution/Monitor. bacteriostatic agents may inhibit the effects of bactericidal agents.
- probenecid
probenecid will increase the level or effect of piperacillin by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.
- sodium picosulfate/magnesium oxide/anhydrous citric acid
piperacillin decreases effects of sodium picosulfate/magnesium oxide/anhydrous citric acid by altering metabolism. Use Caution/Monitor. Coadministration with antibiotics decreases efficacy by altering colonic bacterial flora needed to convert sodium picosulfate to active drug.
- tetracycline
tetracycline decreases effects of piperacillin by pharmacodynamic antagonism. Use Caution/Monitor. bacteriostatic agents may inhibit the effects of bactericidal agents.
- vancomycin
piperacillin increases toxicity of vancomycin by unspecified interaction mechanism. Use Caution/Monitor. Monitor kidney function in patients concomitantly administered with piperacillin and vancomycin.
- vecuronium
piperacillin increases toxicity of vecuronium by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Neuromuscular blockade may be prolonged.
- warfarin
piperacillin, warfarin. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Platelet dysfunction occurs with extended-spectrum penicillins in varying degrees. Monitor INR and adjust warfarin dose if needed.
Minor (15)
- amikacin
piperacillin increases effects of amikacin by pharmacodynamic synergism. Minor/Significance Unknown.
- aspirin
piperacillin, aspirin. Either increases effects of the other by receptor binding competition. Minor/Significance Unknown. Salicylic acid could be displaced from protein binding sites or it could itself displace other protein-bound drugs and result in an enhanced effect of the displaced drug.
- aspirin rectal
piperacillin will increase the level or effect of aspirin rectal by plasma protein binding competition. Minor/Significance Unknown. Salicylic acid could be displaced from protein binding sites or it could itself displace other protein-bound drugs and result in an enhanced effect of the displaced drug
- aspirin/citric acid/sodium bicarbonate
piperacillin will increase the level or effect of aspirin/citric acid/sodium bicarbonate by plasma protein binding competition. Minor/Significance Unknown. Salicylic acid could be displaced from protein binding sites or it could itself displace other protein-bound drugs and result in an enhanced effect of the displaced drug
- chlorothiazide
chlorothiazide increases levels of piperacillin by decreasing renal clearance. Minor/Significance Unknown.
- choline magnesium trisalicylate
piperacillin will increase the level or effect of choline magnesium trisalicylate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown. Salicylate saltscould be displaced from binding sites or could displace other highly protein-bound drugs such as penicillins
- gentamicin
piperacillin increases effects of gentamicin by pharmacodynamic synergism. Minor/Significance Unknown.
- hydrochlorothiazide
hydrochlorothiazide increases levels of piperacillin by decreasing renal clearance. Minor/Significance Unknown.
- ibuprofen IV
piperacillin will increase the level or effect of ibuprofen IV by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.
- meclofenamate
piperacillin will increase the level or effect of meclofenamate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.
- neomycin PO
piperacillin increases effects of neomycin PO by pharmacodynamic synergism. Minor/Significance Unknown.
- rose hips
rose hips will increase the level or effect of piperacillin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.
- streptomycin
piperacillin increases effects of streptomycin by pharmacodynamic synergism. Minor/Significance Unknown.
- tobramycin
piperacillin increases effects of tobramycin by pharmacodynamic synergism. Minor/Significance Unknown.
- willow bark
piperacillin will increase the level or effect of willow bark by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.
Adverse Effects
<1%
Seizure
Rash
Hemolytic anemia
Postive Coombs reaction
Prolonged prothrombin time
Interstitial nephritis
Hypersensitivity
Anaphylaxis
Thrombophlebitis
Injection site pain
Headache
Fever
Intestinal infection due to pseudomonas
Warnings
Contraindications
Hypersensitivity to penicillins, cephalosporins, imipenem
Cautions
Bleeding manifestations have occurred in some patients receiving piperacillin; these reactions have sometimes been associated with abnormalities of coagulation tests such as clotting time, platelet aggregation, and prothrombin time and are more likely to occur in patients with renal failure; if bleeding manifestations occur, the antibiotic should be discontinued and appropriate therapy instituted
Monitor renal, hepatic & especially hematopoietic functions during prolonged treatment
Hypersensitivity reactions reported; discontinue therapy and institute appropriate therapy if allergic reaction occurs; serious anaphylactic reactions require immediate emergency treatment with epinephrine, oxygen, intravenous steroids, and airway management, including intubation should also be administered as indicated
Patients may experience neuromuscular excitability or convulsions if higher than recommended doses given intravenously; use with caution in patients with history of seizure disorder; high levels, which may result from renal impairment, may increase risk of seizures
Piperacillin is a monosodium salt containing 1.85 mEq of Na+ per g (42.5 mg of Na+ per g); this should be considered when treating patients requiring restricted salt intake; periodic electrolyte determinations should be made in patients with low potassium reserves, and the possibility of hypokalemia should be kept in mind with patients who have potentially low potassium reserves and who are receiving cytotoxic therapy or diuretics
Found to be an independent risk factor for renal failure and was associated with delayed recovery of renal function as compared to other beta-lactam antibacterial drugs; if alternative treatment options are inadequate or unavailable, monitor renal function during treatment
Combined use of piperacillin and vancomycin may be associated with an increased incidence of acute kidney injury
Serious skin reactions, including toxic epidermal necrolysis and Stevens-Johnson syndrome, acute exanthematous pustulosis, and drug reaction with eosinophilia and systemic symptoms (DRESS) reported; monitor closely if rash develops; discontinue if lesions progress
Leukopenia and neutropenia may occur during prolonged therapy; monitor hematologic tests during prolonged therapy
Use may result in fungal or bacterial superinfection; prescribing therapy in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to patient and increases risk of development of drug-resistant bacteria
Dosage adjustment recommended in patients with renal impairment or receiving hemodialysis
Therapy has been associated with an increased incidence of fever and rash in cystic fibrosis patient
Clostridium difficile-associated diarrhea
- C. difficile produces toxins A and B which contribute to development of Clostridium difficile-associated diarrhea (CDAD); hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy, CDAD must be considered in all patients who present with diarrhea following antibiotic use
- Careful medical history is necessary since CDAD has been reported to occur over two months after administration of antibacterial agents; if CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued; appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated
Pregnancy & Lactation
Pregnancy
Piperacillin and tazobactam cross the placenta in humans; however, there are insufficient data in pregnant women to inform a drug-associated risk for major birth defects and miscarriage; no fetal structural abnormalities observed in rats or mice when piperacillin/tazobactam was administered intravenously during organogenesis at doses 1 to 2 times and 2 to 3 times human dose, respectively, based on body-surface area’ however, fetotoxicity in presence of maternal toxicity was observed in developmental toxicity and peri/postnatal studies conducted in rats (intraperitoneal administration prior to mating and throughout gestation or from gestation day 17 through lactation day 21) at doses less than the maximum recommended human daily dose based on body-surface area
Lactation
Piperacillin is excreted in human milk; tazobactam concentrations in human milk not studied; no information available on effects of piperacillin and tazobactam on breastfed child or on milk production; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from therapy or from underlying maternal condition.
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Inhibits biosynthesis of cell wall mucopeptides and stage of active multiplication; has antipseudomonal activity
Pharmacokinetics
Half-Life: 36-80 min, dose dependent, higher in renal insufficiency
Protein Bound: 16%
Absorption: 70-80% (IM)
Peak Plasma Time: 30-50 min (IM)
Absorption: 70-80% (IM)
Distribution: Crosses placenta
Metabolism: Liver
Excretion: Urine (primarily); feces (partially)
Administration
IV Compatibilities
Solution: compatible with common solvents
Additive: clindamycin, flucloxacillin, fluconazole, hydrocortisone, linezolid, ofloxacin, KCl, verapamil
Syringe: heparin
Y-site (partial list): allopurinol, bivalirudin, ciprofloxacin, diltiazem, esmolol, famotidine, heparin, hydromorphone, linezolid, lorazepam, magnesium sulfate, meperidine, midazolam, morphine, ranitidine, verapamil, zidovudine
IV Incompatibilities
Solution: aminoglycosides
Additive: aminoglycosides, ciprofloxacin
Y-site: aminoglycosides, amiodarone, amphotericin B cholesteryl SO4, cisatracurium(?), filgrastim, fluconazole, gatifloxacin, gemcitabine, ondansetron, sargramostim, vinorelbine
IV/IM Preparation
IV: reconstitute each gram w/ 5 mL SWI, BWI, NS, D5W or other compatible diluents
Slight darkening does not indicate potency loss
IV/IM Administration
Slow direct inj over 3-5 min, OR
Intermittent infusion in at least 50 mL over 20-30 min
IM: upper outer quadrant of buttock
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