Avycaz(ceftazidime-avibactam)是一种新型抗生素/固定剂量的复方药物，Avycaz与甲硝唑联合用于治疗复杂性腹腔内感染 (cIAI) 及复杂性尿路感染 (cUTI) 成人患者，其中包括肾脏感染（肾盂肾炎），适用于治疗选择有限或没有替代治疗选择的患者。
● 葡萄糖注射液和氯化钠注射液，USP的所有组合，含直至2.5%葡萄糖，USP，和0.45% 氯化钠，USP，或
AVYCAZ(AVIBACTAM SODIUM CEFTAZIDIME)POWDER IV (INFUSION)
Avycaz (ceftazidime-avibactam) is a combination of a cephalosporin and a beta-lactamase inhibitor.
Avycaz in combination with metronidazole, is indicated for the treatment of complicated intra-abdominal infections (cIAI) caused by the following susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Providencia stuartii, Enterobacter cloacae, Klebsiella oxytoca, and Pseudomonas aeruginosa in patients 18 years or older.
Avycaz is also indicated for the treatment of complicated urinary tract infections (cUTI) 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 in patients 18 years or older.
Avycaz is supplied as a solution for intravenous infusion. The recommended dosage of Avycaz is 2.5 grams (2 grams ceftazidime and 0.5 grams avibactam) administered every 8 hours by intravenous (IV) infusion over 2 hours. For treatment of cIAI, metronidazole should be given concurrently.
ADULT DOSAGE & INDICATIONS
2.5g (2g/0.5g) IV q8h for 5-14 days in combination w/ metronidazole
Urinary Tract Infections
Complicated Infections, Including Pyelonephritis:
2.5g (2g/0.5g) IV q8h for 7-14 days
CrCl 31-50mL/min: 1.25g (1g/0.25g) IV q8h
CrCl 16-30mL/min: 0.94g (0.75g/0.19g) IV q12h
CrCl 6-15mL/min: 0.94g (0.75g/0.19g) IV q24h
CrCl ≤5mL/min: 0.94g (0.75g/0.19g) IV q48h
Administer after hemodialysis on hemodialysis days
For patients w/ changing renal function, monitor CrCl at least daily and adjust the dose accordingly
Administer by IV infusion over 2 hrs.
Preparation of Sol for Administration
1. Constitute powder in the vial w/ 10mL of 1 of the following sol: sterile water for inj (SWFI); 0.9% NaCl inj; D5 inj; all combinations of dextrose inj and NaCl inj, containing up to 2.5% dextrose, and 0.45% NaCl; or lactated Ringer's inj.
2. Mix gently; constituted sol will have an approx ceftazidime level of 0.167g/mL and an approx avibactam level of 0.042g/mL. The constituted sol is not for direct injection; must be diluted before IV infusion.
3. Prepare the required dose for IV infusion by withdrawing the appropriate volume from the constituted vial; refer to PI for volume to withdraw.
4. Before infusion, dilute the withdrawn volume of the constituted sol further w/ the same diluent used for constitution of the powder (except SWFI), to achieve total volume between 50mL (0.04g/mL ceftazidime and 0.01g/mL avibactam) to 250mL (0.008g/mL ceftazidime and 0.002g/mL avibactam) in an infusion bag. If SWFI was used for constitution, use any of the other appropriate constitution diluents for dilution.
5. Mix gently and ensure contents are dissolved completely.
The sol for administration at the range of diluted concentrations of ceftazidime 0.008g/mL and avibactam 0.002g/mL to ceftazidime 0.04g/mL and avibactam 0.01g/mL is compatible w/ the more commonly used IV infusion fluids in infusion bags such as:
1. 0.9% NaCl inj
2. D5 inj
3. All combinations of dextrose inj and NaCl inj, containing up to 2.5% dextrose, and 0.45% NaCl
4. Lactated Ringer's inj
5. Baxter Mini-Bag Plus containing 0.9% NaCl inj or D5 inj
Upon constitution w/ appropriate diluent, the constituted sol may be held for no longer than 30 min prior to transfer and dilution in a suitable infusion bag.
Following dilution of the constituted sol w/ the appropriate diluents, sol in the infusion bags are stable for 12 hrs when stored at room temperature; may also be refrigerated at 2-8°C (36-46°F) for up to 24 hrs; and then should be used w/in 12 hrs of subsequent storage at room temperature.
Inj: (Ceftazidime/Avibactam) 2g/0.5g
Known serious hypersensitivity to the components of Avycaz (ceftazidime and avibactam), avibactam-containing products, or other members of the cephalosporin class.
Reserve use in patients who have limited or no alternative treatment options. Decreased clinical response in patients w/ baseline CrCl 30 to ≤50mL/min. Serious and occasionally fatal hypersensitivity (anaphylactic) reactions and serious skin reactions reported; d/c if an allergic reaction occurs. Cross-sensitivity among β-lactam antibacterials reported; caution in penicillin (PCN) or other β-lactam allergic patients. Clostridium difficile-associated diarrhea (CDAD) reported; may need to d/c if CDAD is suspected or confirmed. Seizures, nonconvulsive status epilepticus, encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia reported, particularly in the setting of renal impairment; adjust dosing based on CrCl. Use in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit and increases the risk of development of drug-resistant bacteria. Caution in elderly. Lab test interactions may occur.
N/V, constipation, anxiety, abdominal pain, dizziness, increased blood alkaline phosphatase, increased alanine aminotransferase.
Not recommended w/ probenecid.
PREGNANCY AND LACTATION
Pregnancy: Category B.
Lactation: Caution in nursing.
MECHANISM OF ACTION
Ceftazidime: Cephalosporin; binds to essential PCN-binding proteins. Avibactam: β-lactamase inhibitor; inactivates some β-lactamases and protects ceftazidime form degradation by certain β-lactamases.
Absorption: Administration of variable doses resulted in different parameters. Distribution: Ceftazidime: Plasma protein binding (<10%); Vd=17L; found in breast milk. Avibactam: Plasma protein binding (5.7-8.2%); Vd=22.2L. Elimination: Single Dose: T1/2=3.27 hrs (ceftazidime), 2.22 hrs (avibactam). Multiple Doses: T1/2=2.76 hrs (ceftazidime), 2.71 hrs (avibactam). Ceftazidime: Urine (Approx 80-90%, unchanged). Avibactam: Urine (97%), feces (0.20%).
Assess for hypersensitivity to drug, cephalosporins, PCNs, carbapenems, or other β-lactam antibiotics; renal impairment; pregnancy/nursing status; and possible drug interactions. Perform culture and susceptibility testing.
Monitor for signs/symptoms of hypersensitivity reactions, CDAD, seizures, nonconvulsive status epilepticus, encephalopathy, coma, asterixis, neuromuscular excitability, myoclonia, and other adverse reactions. Monitor CrCl at least daily w/ changing renal function.
Advise that allergic reactions, including serious allergic reactions, may occur and require immediate treatment. Advise that diarrhea is a common problem caused by antibacterial drugs; instruct to contact physician if severe watery or bloody diarrhea develops. Inform that neurological adverse reactions may occur; instruct to inform physician immediately if any neurological signs and symptoms develop. Inform that therapy should only be used to treat bacterial, not viral, infections. Advise to take exactly ud; inform that skipping doses or not completing full course of therapy may decrease effectiveness of therapy and increase bacterial resistance.
Single-use vial—1, 10
25°C (77°F); excursions permitted between 15-30°C (59-86°F). Protect from light.