Dosing & Uses
Dosage Forms & Strengths
ceftolozane/tazobactam
powder for reconstitution, IV
- 1.5g/vial (ie, 1.5g = 1g ceftolozone plus 0.5g tazobactam)
- Dose is based on the sum of the ingredients
Complicated Intra-abdominal Infections
Indicated for use in combination with metronidazole for complicated intra-abdominal infections cause by Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Bacteroides fragilis, Streptococcus anginosus, Streptococcus constellatus, and Streptococcus salivarius
1.5 g IV q8hr x4-14 days
Complicated Urinary Tract Infections
Indicated for complicated urinary tract infections, including pyelonephritis, caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa
1.5 g IV q8hr x7 days
Dosage Modifications
Hepatic impairment: No dosage adjustment required
Renal impairment
- CrCl 30-50 mL/min: 750 mg (500 mg/250 mg) IV q8hr
- CrCl 15-29 mL/min: 375 mg (250 mg/125 mg) IV q8hr
- ESRD on hemodialysis: Administer a single loading dose of 750 mg (500 mg/250 mg) followed by a 150-mg (100 mg/50 mg) maintenance dose administered q8hr for the remainder of the treatment period (on hemodialysis days, administer the dose at the earliest possible time following completion of dialysis)
Safety and efficacy not established
Adverse Effects
1-10%
Nausea (2.8-7.9%)
Headache (2.5-5.8%)
Diarrhea (1.9-6.2%)
Pyrexia (1.7-5.6%)
Constipation (1.9-3.9%)
Insomnia (1.3-3.5%)
Vomiting (1.1-3.3%)
Hypokalemia (0.8-3.3%)
ALT increased (1.7-1.5%)
AST increased (1-1.7%)
Anemia (0.4-1.5%)
Thrombocytosis (0.4-1.9%)
Abdominal pain (0.8-1.2%)
Anxiety (0.2-1.9%)
Dizziness (0.8-1.1%)
Hypotension (0.4-1.7%)
Atrial fibrillation (0.2-1.2%)
Rash (0.9-1.7%)
<1%
Cardiac disorders: Tachycardia, angina pectoris
Gastrointestinal disorders: Ileus, gastritis, abdominal distension, dyspepsia, flatulence, paralytic ileus
General disorders and administration site conditions: Infusion site reactions
Infections and infestations: Candidiasis candidiasis (including oropharyngeal and vulvovaginal), fungal urinary tract infection
Investigations: Increased serum gamma-glutamyl transpeptidase (GGT), increased serum alkaline phosphatase, positive Coombs test
Metabolism and nutrition disorders: Hyperglycemia, hypomagnesemia, hypophosphatemia
Nervous system disorders: Ischemic stroke
Renal and urinary system: Renal impairment, renal failure
Respiratory, thoracic, and mediastinal disorders: Dyspnea
Skin and subcutaneous tissue disorders: Urticaria
Vascular disorders: Venous thrombosis
Warnings
Contraindications
Hypersensitivity to any of the components
Cautions
Clinical cure rates lower in patients with baseline CrCl of 30 to ≤50 mL/min when compared with other antibiotics in clinical trials
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions reported with beta-lactam antibacterial agents
As with all antibiotics, Clostridium difficile-associated diarrhea (CDAD) has been reported; if suspected, discontinue and initiate prompt treatment for CDAD
Prescribing antibiotics in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and risks the development of drug-resistant bacteria
Pregnancy & Lactation
Pregnancy Category: B
Lactation: Unknown if distributed in human breast milk
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
Ceftolozane: Cephalosporin that has demonstrated potent in vitro activity against Pseudomonas aeruginosa
Tazobactam: Beta-lactamase inhibitor
Absorption
Day 1 measurements
Peak plasma time: 1.02 hr
Peak plasma concentration: 69.1/18.4 mcg/mL
AUC: 172/24.4 mcg•h/mL
Distribution
Protein bound: 16-21/30%
Vd: 13.5/18.2 L
Metabolism
Ceftolozane: Not metabolized to any appreciable extent
Tazobactam: The beta-lactam ring is hydrolyzed to form the pharmacologically inactive tazobactam metabolite M1
Elimination
Half-life: 2.77/0.91 hr
Renal clearance (ceftolozane): 3.41-5.59 L/hr
Excretion
- Ceftolozane: >95% excreted unchanged in urine
- Tazobactam: >80% excreted as the parent compound with the remainder excreted as the M1 metabolite
Administration
IV Compatibilities
Not established
IV Preparation
Reconstitute vial with 10 mL of sterile water for injection or 10 mL 0.9% NaCl and gently shake to dissolve
Final volume is ~11.4 mL
Must be further diluted; reconstituted solution is NOT for direct injection
Withdraw appropriate volume for dose (see list below) and add to 100 mL of 0.9% NaCl or D5W
Inspect for particulate matter and discoloration; color ranges from clear, colorless solutions to solutions that are clear and slightly yellow
Dose volume
- 1.5 g (1 g/0.5 g): 11.4 mL (entire vial contents)
- 750 mg (500 mg/250 mg): 5.7 mL
- 375 mg (250 mg/125 mg): 2.9 mL
- 150 mg (100 mg/50 mg): 1.2 mL
IV Administration
Infuse IV over 1 hr
Storage
Unreconstituted vials: Store refrigerated 2-8°C (36-46°F); protect from light
Reconstituted vials: May keep at room temperature for 1 hr before transfer and dilution in infusion bag
Diluted solution (IV bag): Stable for 24 hr when stored at room temperature or 7 days when refrigerated at 2-8°C (36-46°F)
Do not freeze
Images
Patient Handout
Formulary
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