Applies to ceftolozane / tazobactam: intravenous powder for solution, powder iv (infusion).

Serious side effects

Along with its needed effects, ceftolozane / tazobactam may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking ceftolozane / tazobactam:

More common

• Bloody urine
• blurred vision
• decreased frequency or amount of urine
• diarrhea
• dizziness
• fever
• headache
• increased thirst
• loss of appetite
• lower back or side pain
• nausea
• nervousness
• pounding in the ears
• slow or fast heartbeat
• swelling of the face, fingers, or lower legs
• trouble breathing
• unusual tiredness or weakness
• vomiting
• weight gain

Less common

• Confusion
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• dry mouth
• fainting
• headache, sudden and severe
• irregular heartbeat
• mood changes
• muscle pain or cramps
• numbness or tingling in the hands, feet, or lips
• pale skin
• seizures
• skin rash
• stomach cramps
• sweating
• tenderness in the stomach area
• unusual bleeding or bruising
• watery or bloody diarrhea

Rare

• Anxiety
• bone pain
• burning feeling in the chest or stomach
• chest pain or tightness
• drowsiness
• dry mouth
• dry, red, hot, or irritated skin
• fast, pounding, or irregular heartbeat or pulse
• flushed, dry skin
• fruit-like breath odor
• increased hunger
• increased urination
• indigestion
• muscle spasms (tetany) or twitching
• seizures
• severe constipation
• severe vomiting
• stomach pain or upset
• tenderness, pain, swelling, warmth, skin discoloration, and prominent superficial veins over the affected area
• thick, white, or curd-like vaginal discharge
• trembling
• trouble thinking, speaking, or walking
• unexplained weight loss
• white patches in the mouth or throat or on the tongue

Other side effects

Some side effects of ceftolozane / tazobactam may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common

• Constipation
• trouble sleeping

Rare

• Belching
• bloated or full feeling
• excess air or gas in the stomach or bowels
• heartburn
• passing gas

For Healthcare Professionals

Applies to ceftolozane / tazobactam: intravenous powder for injection.

General

In clinical studies of complicated intraabdominal infections (cIAI) and complicated urinary tract infections (cUTI), the most common side effects were nausea, diarrhea, headache, constipation, and pyrexia.

In a clinical study for hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia (HABP/VABP), side effects reported in at least 2% of patients included increased hepatic transaminase, renal impairment/renal failure, diarrhea, intracranial hemorrhage, vomiting, and Clostridioides difficile colitis; the most common side effects were diarrhea, increased ALT, and increased AST.^[Ref]

Cardiovascular

Common (1% to 10%): Hypotension, atrial fibrillation

Uncommon (0.1% to 1%): Tachycardia, angina pectoris, venous thrombosis, phlebitis (included superficial phlebitis)

Frequency not reported: Hypertension^[Ref]

Dermatologic

Common (1% to 10%): Rash

Uncommon (0.1% to 1%): Urticaria

Beta-lactam antibiotics:

-Frequency not reported: Severe cutaneous adverse reactions (including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms [DRESS], acute generalized exanthematous pustulosis)^[Ref]

Gastrointestinal

Common (1% to 10%): Nausea, diarrhea, constipation, vomiting, abdominal pain (included upper abdominal pain), C difficile colitis (included C difficile colitis, C difficile infection, Clostridioides test positive)

Uncommon (0.1% to 1%): Paralytic ileus, gastritis, abdominal distension, dyspepsia, flatulence, oropharyngeal candidiasis

Frequency not reported: C difficile-associated diarrhea^[Ref]

Genitourinary

Uncommon (0.1% to 1%): Vulvovaginal candidiasis, fungal urinary tract infection

Hematologic

Very common (10% or more): Positive direct Coombs test (up to 31.2%)

Common (1% to 10%): Anemia, thrombocytosis (included increased platelet count)

Frequency not reported: Leukopenia (included neutropenia, decreased neutrophil count)^[Ref]

In the adult cIAI and cUTI clinical studies, seroconversion to positive direct Coombs test was reported in 0.2% of patients using this drug (0% in patients using the comparator). In the adult HABP/VABP clinical study, seroconversion to positive direct Coombs test was reported in 31.2% of patients using this drug (3.6% in patients using meropenem). In the pediatric cIAI clinical study, seroconversion to positive direct Coombs test was reported in 45.3% of patients using this drug (33.3% in patients using meropenem); in the pediatric cUTI clinical study, seroconversion to positive direct Coombs test was reported in 29.7% of patients using this drug (8.7% in patients using meropenem). In clinical studies, hemolysis was not reported in patients who developed a positive direct Coombs test (in any treatment group).^[Ref]

Hepatic

Very common (10% or more): Increased hepatic transaminase (up to 11.9%; included increased ALT, increased AST, increased hepatic enzyme, hypertransaminasemia, abnormal liver function test)

Common (1% to 10%): Increased ALT, increased AST, increased transaminases, abnormal liver function test, increased serum GGT^[Ref]

Hypersensitivity

Frequency not reported: Hypersensitivity reactions^[Ref]

Local

Common (1% to 10%): Infusion site reactions^[Ref]

Metabolic

Common (1% to 10%): Hypokalemia (included decreased blood potassium)

Uncommon (0.1% to 1%): Hyperglycemia, hypomagnesemia, hypophosphatemia^[Ref]

Nervous system

Common (1% to 10%): Headache, dizziness, intracranial hemorrhage (included cerebellar hemorrhage, cerebral hematoma, cerebral hemorrhage, intracranial hemorrhage, hemorrhagic stroke, hemorrhagic transformation stroke intraventricular hemorrhage, subarachnoid hemorrhage, subdural hematoma)

Uncommon (0.1% to 1%): Ischemic stroke^[Ref]

Other

In phase 2 and 3 cIAI trials, death occurred in 14 of 564 patients using this drug and 8 of 536 patients using meropenem; causes of death varied and included worsening and/or complications of infection, surgery, and underlying conditions.^[Ref]

Common (1% to 10%): Pyrexia (included hyperthermia), increased mortality, increased serum alkaline phosphatase

Uncommon (0.1% to 1%): Candidiasis, C difficile infection, Clostridioides test positive^[Ref]

Psychiatric

Common (1 to 10%): Insomnia, anxiety^[Ref]

Renal

Common (1% to 10%): Renal impairment/renal failure (included acute renal failure, anuria, azotemia, oliguria, prerenal failure, renal failure, renal impairment)^[Ref]

Respiratory

Uncommon (0.1% to 1%): Dyspnea

Frequency not reported: Bradypnea (included decreased respiratory rate)^[Ref]