ceftazidime/avibactam (Rx)

Brand and Other Names:Avycaz
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

ceftazidime/avibactam

powder for reconstitution for IV administration

  • (2g/0.5g)/vial
  • Powder must be reconstituted and further diluted before IV infusion
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Intra-abdominal Infections

Indicated in combination with metronidazole for complicated intra-abdominal infections (cIAIs) caused by the following susceptible gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae, Klebsiella oxytoca, Citrobacter freundii complex, and Pseudomonas aeruginosa

2.5 g (2 g/0.5 g) IV q8hr infused over 2 hr for 5-14 days

Urinary Tract Infections

Indicated for complicated urinary tract infections (cUTIs) including pyelonephritis caused by the following susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, Citrobacter koseri, Enterobacter aerogenes, Enterobacter cloacae, Citrobacter freundii, Proteus spp., and Pseudomonas aeruginosa

2.5 g (2 g/0.5 g) IV q8hr infused over 2 hr for 7-14 days

Dosage Modifications

Renal impairment

  • CrCl estimated with Cockcroft-Gault formula
  • CrCl >50 mL/min: No dose adjustment required
  • CrCl 31-50 mL/min: 1.25 g (1 g/0.25 g) IV q8hr
  • CrCl 16-30 mL/min: 0.94 g (0.75 g/0.19 g) IV q12hr
  • CrCl 6-15 mL/min: 0.94 g (0.75 g/0.19 g) IV q24hr
  • CrCl <5 mL/min: 0.94 g (0.75 g/0.19 g) IV q48hr

Hemodialysis

  • Both ceftazidime and avibactam are removed by dialysis
  • Administer ceftazidime/avibactam following hemodialysis on hemodialysis days
  • 55% of the ceftazidime dose is removed by hemodialysis
  • 55% of the avibactam dose is removed by hemodialysis
  • Monitor CrCl daily and adjust ceftazidime/avibactam dose accordingly

Dosing Considerations

To reduce the development of drug-resistant bacteria and maintain the effectiveness, use only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria

<18 years: Safety and efficacy not established

Carefully monitor renal function in patients aged >65 yr

See adult dosing section for dose adjustment based on CrCl

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Interactions

Interaction Checker

and ceftazidime/avibactam

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            1-10% (in cIAI plus metronidazole)

            Diarrhea (8%)

            Nausea (7%)

            Vomiting (5%)

            Headache (3%)

            Dizziness (2%)

            Abdominal pain (1%)

            1-10% (in cUTI)

            Constipation (10%)

            Anxiety (10%)

            Abdominal pain (7%)

            Upper abdominal pain (7%)

            Dizziness (6%)

            <1% in cIAI

            Blood and lymphatic disorders -Eosinophilia, thrombocytopenia

            General disorders and administration site conditions -Injection site phlebitis

            Infections and infestations -Candidiasis

            Investigations -Increased aspartate aminotransferase, increased alanine aminotransferase, increased gamma-glutamyltransferase, prolonged prothrombin time

            Metabolism and nutrition disorders -Hypokalemia

            Nervous system disorders -Dysgeusia

            Renal and urinary disorders -Acute renal failure, renal impairment, nephrolithiasis

            Skin and subcutaneous tissue disorders -Rash, rash maculo-papular, urticaria, pruritus

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            Warnings

            Contraindications

            Known serious hypersensitivity to avibactam, ceftazidime, or other cephalosporins

            Cautions

            In clinical trials, cure rates were lower in patients with baseline moderate renal impairment (CrCl 30-50 mL/min) who were treated for cIAI with ceftazidime/avibactam plus metronidazole (45% cure rate) compared with meropenem (74% cure rate); during the clinical trial, the ceftazidime/avibactam dose was 33% lower than what is currently recommended for patients with moderate renal impairment (see Dosage Modifications); follow current dosage adjustment recommendations for renal impairment

            Serious and occasionally fatal anaphylactic reactions and serious skin reactions have been reported with beta-lactam antibacterials; caution in patients with history of allergy to cephalosporins, penicillins, or carbapenems

            Clostridium difficile associated diarrhea (CDAD) has been associated with nearly all systemic antibacterials; severity may range from mild diarrhea to fatal colitis; may occur >2 months following antibacterial use; if CDAD suspected, manage fluid and electrolytes levels and monitor antibacterial treatment for CDAD

            Seizures, nonconvulsive status epilepticus, encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia have been reported with ceftazidime, especially in the setting of renal impairment; adjust dose according to CrCl (see Dosage Modifications)

            Confirm suspected bacterial infection when prescribing ceftazidime/avibactam to avoid the risk of developing drug-resistant bacteria

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            Pregnancy & Lactation

            Pregnancy Category: B

            Animal reproductive toxicity studies in rats and rabbits using doses approximately 9 times the human dose have not shown teratogenic effects

            Lactation: Ceftazidime is excreted in human milk in low concentrations; unknown if avibactam distributed in human breast milk; caution advised if breast feeding

            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.

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            Pharmacology

            Mechanism of Action

            Ceftazidime: Third-generation cephalosporin with broad-spectrum gram-negative activity, including Pseudomonas; arrests bacterial growth by binding to 1 or more penicillin-binding proteins, and thereby inhibiting final transpeptidation step of peptidoglycan synthesis in bacterial cell-wall synthesis and inhibiting cell-wall biosynthesis

            Avibactam: Diazabicyclooctanone, non-β-lactam, β-lactamase inhibitor; alone has no antibacterial activity at clinically relevant doses; when combined with ceftazidime, avibactam protects ceftazidime from degradation by β-lactamase enzymes and effectively extends the antibiotic spectrum of ceftazidime to include many gram-negative bacteria normally not susceptible to ceftazidime

            Absorption

            Bioavailability: 100%

            Peak plasma time: 2 hr after initiating the infusion

            Peak plasma concentration: ceftazidime 90.4 mg/L; avibactam 14.6 mg/L

            AUC: ceftazidime 291 mg•hr/L; avibactam 38.2 mg•hr/L

            Distribution

            Protein bound: ceftazidime <10%; avibactam 5.7-8.2%

            Vd: ceftazidime 17 L; avibactam 22.2 L

            Metabolism

            80-90% of ceftazidime IV dose is eliminated unchanged via the urine

            Nearly 100% of avibactam IV dose is eliminated unchanged via the urine

            Elimination

            Half-life: ceftazidime 2.76 hr; avibactam 2.71 hr

            Plasma clearance: ceftazidime 6.86 L/hr; avibactam 13.1 L/hr

            Excretion: Nearly 100% in urine for both ceftazidime and avibactam

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            Administration

            IV Compatibilities

            0.9% NaCl

            5% dextrose

            All combinations of dextrose and sodium chloride injection containing up to 2.5% dextrose and 0.45% NaCl

            Lactated Ringer injection

            IV Preparation

            Reconstitute powder with 10 mL of one of the following solutions

            • Sterile water for injection
            • 0.9% NaCl
            • 5% dextrose
            • All combinations of dextrose and sodium chloride injection containing up to 2.5% dextrose and 0.45% NaCl
            • Lactated Ringer injection

            Additional dilution required

            • Mix vial gently with 10 mL of a solution listed above
            • Reconstituted solution results in ~0.167 g/mL of ceftazidime and ~0.042 g/mL avibactam
            • Further dilute with the same diluent used for reconstitution (except sterile water for injection), to achieve a total volume of 50-250 mL before infusion
            • Mix gently and ensure contents are dissolved completely
            • Visually inspect for particulate matter and discoloration (color ranges from clear to light yellow)

            IV Administration

            Infuse IV over 2 hr

            Storage

            Unreconstituted vial

            • Store at 25°C (77°F); excursion permitted between 15-30°C (59-86°F)
            • Protect from light

            Diluted solution

            • Diluted solution (ie, final dilution of 50-250 mL) should be used within 12 hr if stored at room temperature
            • May store refrigerated (2-8°C [36-46°F]) for up to 24 hr and use within 12 hr of subsequent storage at room temperature
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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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