Zerbaxa

What Is Zerbaxa?

Zerbaxa (ceftolozane/tazobactam) is a combination antibiotic and beta-lactamase inhibitor used to treat complicated intra-abdominal infections (cIAI), and complicated urinary tract infections (cUTI), including pyelonephritis, caused by susceptible microorganisms.

What Are Side Effects of Zerbaxa?

Common side effects of Zerbaxa include:

• nausea,
• diarrhea,
• headache,
• fever,
• constipation,
• insomnia,
• vomiting,
• low blood potassium,
• anemia,
• abdominal pain,
• anxiety,
• dizziness,
• low blood pressure, and
• rash.

Dosage for Zerbaxa

The recommended dosage regimen of Zerbaxa for Injection is 1.5 g (1 g/0.5 g) administered every 8 hours by intravenous infusion over 1 hour in patients 18 years or older and with normal renal function or mild renal impairment.

What Drugs, Substances, or Supplements Interact with Zerbaxa?

Zerbaxa may interact with other drugs. Tell your doctor all medications and supplements you use.

Zerbaxa During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Zerbaxa. It is unknown if either of the drugs in Zerbaxa pass into breast milk. Consult your doctor before breastfeeding.

Additional Information

Our Zerbaxa (ceftolozane/tazobactam) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

 

Zerbaxa Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• severe stomach pain;
• diarrhea that is watery or bloody (even if it occurs months after your last dose);
• kidney problems--little or no urination, swelling in your feet or ankles, feeling tired or short of breath; or
• symptoms of bleeding in the brain--sudden numbness or weakness, problems with vision or speech.

Side effects may be more likely in older adults.

Common side effects may include:

• nausea, diarrhea;
• headache;
• fever;
• kidney problems; or
• abnormal liver function tests.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Zerbaxa (Ceftolozane and Tazobactam for Injection)

 

Zerbaxa Professional Information

SIDE EFFECTS

The following serious reactions are described in greater detail in the Warnings and Precautions section:

• Hypersensitivity reactions [see WARNINGS AND PRECAUTIONS]
• Clostridioides difficile-associated diarrhea [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and also may not reflect rates observed in practice.

Complicated Intra-Abdominal Infections And Complicated Urinary Tract Infections, Including Pyelonephritis

ZERBAXA was evaluated in Phase 3 comparator-controlled clinical trials of cIAI and cUTI, which included a total of 1015 patients treated with ZERBAXA (1.5 g every 8 hours, adjusted based on renal function where appropriate) and 1032 patients treated with comparator (levofloxacin 750 mg daily in cUTI or meropenem 1 g every 8 hours in cIAI) for up to 14 days. The mean age of treated patients was 48 to 50 years (range 18 to 92 years), across treatment arms and indications. In both indications, about 25% of the subjects were 65 years of age or older. Most patients (75%) enrolled in the cUTI trial were female, and most patients (58%) enrolled in the cIAI trial were male. Most patients (>70%) in both trials were enrolled in Eastern Europe and were White.

The most common adverse reactions (5% or greater in either indication) occurring in patients receiving ZERBAXA were nausea, diarrhea, headache, and pyrexia. Table 5 lists adverse reactions occurring in 1% or greater of patients receiving ZERBAXA in Phase 3 cIAI and cUTI clinical trials.

Table 5: Adverse Reactions Occurring in 1% or Greater of Patients Receiving ZERBAXA in Phase 3 cIAI and cUTI Clinical Trials

Preferred Term	Complicated Intra-abdominal Infections		Complicated Urinary Tract Infections, Including Pyelonephritis
	ZERBAXA* (N=482) n (%)	Meropenem (N=497) n (%)	ZERBAXA* (N=533) n (%)	Levofloxacin (N=535) n (%)
Nausea	38 (7.9)	29 (5.8)	15 (2.8)	9 (1.7)
Headache	12 (2.5)	9 (1.8)	31 (5.8)	26 (4.9)
Diarrhea	30 (6.2)	25 (5)	10 (1.9)	23 (4.3)
Pyrexia	27 (5.6)	20 (4)	9 (1.7)	5 (0.9)
Constipation	9 (1.9)	6 (1.2)	21 (3.9)	17 (3.2)
Insomnia	17 (3.5)	11 (2.2)	7 (1.3)	14 (2.6)
Vomiting	16 (3.3)	20 (4)	6 (1.1)	6 (1.1)
Hypokalemia	16 (3.3)	10 (2)	4 (0.8)	2 (0.4)
ALT increased	7 (1.5)	5 (1)	9 (1.7)	5 (0.9)
AST increased	5 (1)	3 (0.6)	9 (1.7)	5 (0.9)
Anemia	7 (1.5)	5 (1)	2 (0.4)	5 (0.9)
Thrombocytosis	9 (1.9)	5 (1)	2 (0.4)	2 (0.4)
Abdominal pain	6 (1.2)	2 (0.4)	4 (0.8)	2 (0.4)
Anxiety	9 (1.9)	7 (1.4)	1 (0.2)	4 (0.7)
Dizziness	4 (0.8)	5 (1)	6 (1.1)	1 (0.2)
Hypotension	8 (1.7)	4 (0.8)	2 (0.4)	1 (0.2)
Atrial fibrillation	6 (1.2)	3 (0.6)	1 (0.2)	0
Rash	8 (1.7)	7 (1.4)	5 (0.9)	2 (0.4)
*The ZERBAXA for injection dose was 1.5 g intravenously every 8 hours, adjusted to match renal function where appropriate. In the cIAI trials, ZERBAXA was given in conjunction with metronidazole.

Treatment discontinuation due to adverse events occurred in 2.0% (20/1015) of patients receiving ZERBAXA and 1.9% (20/1032) of patients receiving comparator drugs. Renal impairment (including the terms renal impairment, renal failure, and renal failure acute) led to discontinuation of treatment in 5/1015 (0.5%) subjects receiving ZERBAXA and none in the comparator arms.

Increased Mortality

In the cIAI trials (Phase 2 and 3), death occurred in 2.5% (14/564) of patients receiving ZERBAXA and in 1.5% (8/536) of patients receiving meropenem. The causes of death varied and included worsening and/or complications of infection, surgery and underlying conditions.

Less Common Adverse Reactions in Phase 3 cIAI and cUTI Clinical Trials

The following selected adverse reactions were reported in ZERBAXA-treated subjects at a rate of less than 1%:

Cardiac disorders: tachycardia, angina pectoris
Gastrointestinal disorders: gastritis, abdominal distension, dyspepsia, flatulence, ileus paralytic
General disorders and administration site conditions: infusion site reactions
Infections and infestations: 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

Hospital-Acquired Bacterial Pneumonia And Ventilator-Associated Bacterial Pneumonia (HABP/VABP)

ZERBAXA was evaluated in a Phase 3 comparator-controlled clinical trial for HABP/VABP, which included a total of 361 patients treated with ZERBAXA (3 g every 8 hours, adjusted based on renal function where appropriate) and 359 patients treated with comparator (meropenem 1 g every 8 hours) for up to 14 days. The mean age of treated patients was 60 years (range 18 to 98 years), across treatment arms. About 44% of the subjects were 65 years of age or older. Most patients (71%) enrolled in the trial were male. All subjects were mechanically ventilated at randomization and 92% were in an intensive care unit (ICU) at randomization. The median APACHE II score was 17, and 33% of subjects had a baseline APACHE II score of ≥20, indicating a high severity of illness for many patients enrolled in this trial.

Table 6 lists adverse reactions occurring in 2% or greater of patients receiving ZERBAXA in a Phase 3 HABP/VABP clinical trial.

Table 6: Adverse Reactions Occurring in 2% or Greater of Patients Receiving ZERBAXA in a Phase 3 HABP/VABP Clinical Trial

Adverse Reactions	ZERBAXA* N=361 n (%)	Meropenem N=359 n (%)
Hepatic transaminase increased†	43 (11.9)	26 (7.2)
Renal impairment/renal failure‡	32 (8.9)	22 (6.1)
Diarrhea	23 (6.4)	25 (7.0)
Intracranial hemorrhage§	16 (4.4)	5 (1.4)
Vomiting	12 (3.3)	10 (2.8)
Clostridioides difficile colitis¶	10 (2.8)	2 (0.6)
* The ZERBAXA for injection dose was 3 g intravenously every 8 hours, adjusted to match renal function where appropriate. † Includes alanine aminotransferase increased, aspartate aminotransferase increased, hepatic enzyme increased, hypertransaminasaemia, liver function test abnormal. ‡ Includes acute renal failure, anuria, azotemia, oliguria, prerenal failure, renal failure, renal impairment. § Includes cerebellar hemorrhage, cerebral hematoma, cerebral hemorrhage, hemorrhage intracranial, hemorrhagic stroke, hemorrhagic transformation stroke, intraventricular hemorrhage, subarachnoid hemorrhage, subdural hematoma. ¶ Includes Clostridioides difficile colitis, Clostridioides difficile infection, Clostridioides test positive.

Treatment discontinuation due to adverse reactions occurred in 1.1% (4/361) of patients receiving ZERBAXA and 1.4% (5/359) of patients receiving meropenem.

Less Common Adverse Reactions in a Phase 3 HABP/VABP Clinical Trial

The following selected adverse reactions were reported in ZERBAXA-treated subjects at a rate of less than 2%:

Investigations: blood alkaline phosphatase increased, gamma-glutamyltransferase increased, Coombs direct test positive

Laboratory Values

The development of a positive direct Coombs test may occur during treatment with ZERBAXA. The incidence of seroconversion to a positive direct Coombs test was 0.2% in patients receiving ZERBAXA and 0% in patients receiving the comparator in the cUTI and cIAI clinical trials. The incidence of seroconversion to a positive direct Coombs test was 31.2% in patients receiving ZERBAXA and 3.6% in patients receiving meropenem in the HABP/VABP clinical trial. In clinical trials, there was no evidence of hemolysis in patients who developed a positive direct Coombs test in any treatment group.

DRUG INTERACTIONS

No Information Provided

Read the entire FDA prescribing information for Zerbaxa (Ceftolozane and Tazobactam for Injection)