Avycaz (ceftazidime/avibactam sodium)

Ceftazidime and avibactam is a fixed combination containing a 4:1 ratio of ceftazidime to avibactam.

The ceftazidime component is provided as a mixture of ceftazidime pentahydrate and sodium carbonate (dosage of this component is expressed in terms of anhydrous ceftazidime); the avibactam component is provided as avibactam sodium (dosage of this component is expressed in terms of avibactam).

Dosage of the fixed combination of ceftazidime and avibactam is expressed in terms of the total of the ceftazidime and avibactam content.

Each single-dose vial of ceftazidime and avibactam contains a total of 2.5 g (i.e., 2 g of ceftazidime and 0.5 g of avibactam).

Dosage adjustments based solely on age are not needed when ceftazidime and avibactam is used in geriatric patients. However, because geriatric patients are more likely to have decreased renal function and because dosage of ceftazidime and avibactam 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 ceftazidime and avibactam is used in adults with hepatic impairment.

Dosage of ceftazidime and avibactam 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 ceftazidime and avibactam adjusted accordingly.

Table 2. Ceftazidime and Avibactam Dosage for Adults with Renal Impairment

Estimated Creatinine Clearance Recommended Dosage (mL/minute) 31-50 1.25 g (ceftazidime 1 g and avibactam 0.25 g) every 8 hours 16-30 940 mg (ceftazidime 750 mg and avibactam 190 mg) every 12 hours 6-15 940 mg (ceftazidime 750 mg and avibactam 190 mg) every 24 hours <=5 940 mg (ceftazidime 750 mg and avibactam 190 mg) every 48 hours

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

Ceftazidime and avibactam is administered by IV infusion.

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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.

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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
• Colitis

• Disease of liver
• Hypoprothrombinemia
• Kidney disease with likely reduction in glomerular filtration rate (GFr)
• Lower seizure threshold
• Myoclonus
• Seizure disorder

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Less Frequent

• Hemolytic anemia
• Hypokalemia

Rare or Very Rare

• Abnormal hepatic function tests
• Agranulocytosis
• Anaphylaxis
• Angioedema
• Aplastic anemia
• Candidiasis
• Clostridioides difficile infection
• Colitis
• Encephalopathy
• Eosinophilia
• Erythema multiforme
• Hemorrhage
• Interstitial nephritis
• Jaundice
• Kidney disease with reduction in glomerular filtration rate (GFr)
• Kidney stone
• Kounis syndrome
• Leukopenia
• Lymphocytosis
• Neutropenic disorder
• Nonconvulsive status epilepticus
• Renal failure
• Seizure disorder
• Stevens-johnson syndrome
• Thrombocytopenic disorder
• Thrombocytosis
• Toxic epidermal necrolysis

More Frequent

• Diarrhea
• Nausea
• Vomiting

Less Frequent

• Acute abdominal pain
• Constipation
• Phlebitis after infusion
• Skin rash

Rare or Very Rare

• Dysgeusia
• Injection site sequelae
• Maculopapular rash
• Myoclonus
• Paresthesia
• Prolonged activated partial thromboplastin time
• Pruritus of skin
• Symptoms of anxiety
• Urticaria
• Vaginitis

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Reproduction studies in mice and rats using ceftazidime dosages up to 40 times the usual human dose have not revealed evidence of harm to the fetus. Avibactam was not teratogenic in rats or rabbits. In rats, there was no evidence of embryofetal toxicity at an avibactam dosage of 1 g/kg daily (approximately 9 times the human dosage based on area under the concentration-time curve (AUC)) and no effects on pup growth and viability at a dosage of 825 mg/kg daily. In rabbits, there was no evidence of embryofetal toxicity at an avibactam dosage of 100 mg/kg, but increased implantation loss, lower mean fetal weights, delayed ossification of bones, and other anomalies were observed at higher dosages.

There are no adequate and controlled studies using ceftazidime and avibactam in pregnant women, and the drug should be used during pregnancy only if clearly needed.

Ceftazidime is distributed into human milk in low concentrations. It is not known whether avibactam is distributed into human milk. (See Pharmacokinetics: Distribution.)

Ceftazidime and avibactam should be used with caution in nursing women.

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