Zerbaxa (ceftolozane sulfate/tazobactam sodium)

Ceftolozane and tazobactam is a fixed combination containing a 2:1 ratio of ceftolozane to tazobactam.

The ceftolozane component is provided as ceftolozane sulfate (dosage of this component is expressed in terms of ceftolozane); the tazobactam component is provided as tazobactam sodium (dosage of this component is expressed in terms of tazobactam).

Dosage of the fixed combination of ceftolozane and tazobactam is expressed in terms of the total of the ceftolozane and tazobactam content.

Each single-dose vial of ceftolozane and tazobactam contains a total of 1.5 g (i.e., 1 g of ceftolozane and 0.5 g of tazobactam).

Dosage adjustments based solely on age are not needed when ceftolozane and tazobactam is used in geriatric patients. However, because geriatric patients are more likely to have decreased renal function and because dosage of ceftolozane and tazobactam needs to be adjusted based on renal impairment, dosage should be selected with caution and it may be useful to monitor renal function.

Dosage adjustments are not needed when ceftolozane and tazobactam is used in adults with hepatic impairment.

Dosage of ceftolozane and tazobactam must be adjusted in adults with creatinine clearances of 50 mL/minute or less, including those undergoing hemodialysis. (See Table 2.)

Creatinine clearance should be monitored at least once daily in patients with changing renal function and dosage of ceftolozane and tazobactam adjusted accordingly.

Table 2. Ceftolozane and Tazobactam Dosage for Adults with Renal Impairment

Estimated Creatinine Clearance Recommended Dosage (mL/minute) 30-50 750 mg (ceftolozane 500 mg and tazobactam 250 mg) every 8 hours 15-29 375 mg (ceftolozane 250 mg and tazobactam 125 mg) every 8 hours End-stage renal disease on Single loading dose of 750 mg hemodialysis (ceftolozane 500 mg and tazobactam 250 mg) followed by maintenance dosage of 150 mg (ceftolozane 100 mg and tazobactam 50 mg) every 8 hours

On hemodialysis days, the dose should be administered as soon as possible after dialysis.

Ceftolozane and tazobactam is administered by IV infusion.

No dosing information is available for this tab.

The following drug interactions are based on studies using the fixed combination containing ceftolozane and tazobactam, ceftolozane alone, or tazobactam alone. When ceftolozane and tazobactam is used, interactions associated with both drugs in the fixed combination should be considered.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Antibiotics/Fecal Microbiota

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Fecal microbiota is a suspension of live bacteria, which may be compromised by concurrent use of antibiotics.(1)

CLINICAL EFFECTS: Antibiotics may decrease the effectiveness of fecal microbiota.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Antibiotics should not be used concurrently with fecal microbiota. Antibacterial treatment should be completed for 24 to 72 hours before initiating treatment with fecal microbiota. Do not use antibiotics for up to 8 weeks after fecal microbiota.(1)

DISCUSSION: Antibiotics may compromise the effectiveness of fecal microbiota.

Antibiotics/Fecal Microbiota Spores

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Fecal microbiota spores is a suspension of live bacterial spores, which may be compromised by concurrent use of antibiotics.(1)

CLINICAL EFFECTS: Antibiotics may decrease the effectiveness of fecal microbiota spores.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Antibiotics should not be used concurrently with fecal microbiota spores. Antibacterial treatment should be completed for 2 to 4 days before initiating treatment with fecal microbiota spores.(1)

DISCUSSION: Antibiotics may compromise the effectiveness of fecal microbiota spores.

Antimicrobials/Live Typhoid Vaccine

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: The antimicrobial may be active against the organism in the live-vaccine. Antimicrobial therapy may prevent the vaccine organism from replicating enough to trigger an immune response.(1)

CLINICAL EFFECTS: Vaccination may be ineffective.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Do not give oral typhoid vaccine until 72 hours after the last dose of antimicrobial. If possible, to optimize vaccine effectiveness, do not start antibacterial drugs for 72 hours after the last dose of oral typhoid vaccine. A longer interval should be considered for long-acting antimicrobials, such as azithromycin.(3)

DISCUSSION: Because antimicrobial therapy may prevent sufficient vaccine-organism replication to generate an immune response, the manufacturer of live-attenuated typhoid vaccine and the Centers for Disease Control (CDC) state that the vaccine should not be administered to patients receiving antimicrobial therapy.(1-3)

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

There is no enhanced messaging for this drug.

There are no contraindication contraindications for this drug.

• Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
• Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
• Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
• Chronic kidney disease stage 5 (failure) GFr<15 ml/min
• Clostridioides difficile infection

There are no moderate contraindications for this drug.

There is no enhanced messaging for this drug.

More Frequent

• Fever

Less Frequent

• Anaphylaxis
• Anemia
• Atrial fibrillation
• Dyspnea
• Hypotension
• Increased alanine transaminase
• Increased aspartate transaminase
• Leukopenia
• Thrombocytosis

Rare or Very Rare

• Acute generalized exanthematous pustulosis
• Cerebrovascular accident
• Clostridioides difficile infection
• DRESS syndrome
• Hypersensitivity drug reaction
• Ileus
• Increased alkaline phosphatase
• Kidney disease with reduction in glomerular filtration rate (GFr)
• Paralytic ileus
• Seizure disorder
• Stevens-johnson syndrome
• Toxic epidermal necrolysis
• Urticaria
• Venous thrombosis
• Vulvovaginal candidiasis

More Frequent

• Diarrhea
• Headache disorder
• Nausea
• Oral candidiasis

Less Frequent

• Acute abdominal pain
• Constipation
• Hypokalemia
• Insomnia
• Skin rash
• Symptoms of anxiety
• Vomiting

Rare or Very Rare

• Abdominal distension
• Acute renal failure
• Angina
• Candidiasis
• Dizziness
• Dyspepsia
• Flatulence
• Fungal urinary tract infection
• Gastritis
• Hyperglycemia
• Hypomagnesemia
• Hypophosphatemia
• Injection site sequelae
• Tachycardia

No enhanced messaging available.

No enhanced messaging available.

Embryofetal development studies in mice and rats using ceftolozane dosages associated with exposures approximately 7 and 4 times, respectively, the exposure expected in humans receiving a ceftolozane dosage of 1 g three times daily did not reveal evidence of fetal toxicity. In a study in rats, ceftolozane administered during pregnancy and lactation was associated with decreased auditory startle response in male pups at postnatal day 60.

Embryofetal development studies in rats using tazobactam dosages approximately 19 times the recommended human dosage revealed evidence of maternal toxicity (decreased food consumption and body weight gain), but no evidence of fetal toxicity. In a study in rats, tazobactam administered during pregnancy and lactation in dosages approximately 8 times the recommended human dosage produced decreased maternal food consumption and body weight gain at the end of gestation and an increased incidence of stillbirths. Although pups of dams receiving tazobactam in dosages of 320-1280 mg/kg daily had substantially reduced postnatal body weight at 21 days after delivery, there was no evidence of effects on development, function, learning, or fertility of the pups.

There are no adequate and controlled studies using ceftolozane and tazobactam in pregnant women, and the drug should be used during pregnancy only if potential benefits to the woman justify potential risks to the fetus.

Because it is not known whether ceftolozane or tazobactam is distributed into human milk, the fixed combination of ceftolozane and tazobactam should be used with caution in nursing women.

No enhanced messaging available.