Avitaz™ 2.5 gm powder for IV Infusion: Each vial contains sterile mixture of 2 gm Ceftazidime (as Ceftazidime Pentahydrate buffered with Sodium Carbonate) and 0.5 gm Avibactam (as Avibactam Sodium) and each ampoule contains 10 ml Water for Injections BP (Sterile).
Avitaz™ is an antibacterial combination product consisting of the semisynthetic Cephalosporin Ceftazidime Pentahydrate and the beta-lactamase inhibitor Avibactam Sodium for intravenous administration.
Pharmacology:
The Ceftazidime component of Avitaz™ is a cephalosporin antibacterial drug with in vitro activity against certain gram-negative and gram-positive bacteria. The bactericidal action of Ceftazidime is mediated through binding to essential penicillin-binding proteins (PBPs). The avibactam component of Avitaz™ is a non-beta-lactam beta-lactamase inhibitor that inactivates certain beta-lactamases that degrade Ceftazidime. Avibactam does not decrease the activity of Ceftazidime against Ceftazidime-susceptible organisms.
Indicated for the treatment of the following infections caused by susceptible Gram-negative microorganisms in adult and pediatric patients (which are born having completed at least 31 weeks gestational age):
Recommended dose in adult patients:
The recommended dosage of Avitaz™ is 2.5 gram (Ceftazidime 2 grams and Avibactam 0.5 gram) administered every 8 hours by intravenous (IV) infusion over 2 hours in patients 18 years of age and older with CrCl greater than 50 mL/min. For treatment of cIAI, metronidazole should be given concurrently. The guidelines for dosage of Avitaz™ in patients with creatinine clearance (CrCl) greater than 50 mL/min are listed in Table 1.
Table 1. Dosage of Avitaz™ 2.5 grams (Ceftazidime 2 grams and Avibactam 0.5 grams) by Indication in Adult Patients (18 years of age and older).
Infection.
Dose:
Frequency.
Infusion time (hours).
Duration of Treatment.
Complicated Intra-abdominal Infections (cIAI)*.
2.5 grams.
Every 8 hours.
2.
cIAI: 5 to 14 days.
cUTI: 7 to 14 days.
HABP/VABP: 7 to 14 days.
Complicated Urinary Tract Infections including Pyelonephritis (cUTI).
Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia (HABP/VABP).
Recommended Dosage in Pediatric Patients:
The recommended dosage of Avitaz™ in pediatric patients aged 2 years to less than 18 years and an estimated glomerular filtration rate (eGFR) greater than 50 mL/min/1.73 m² and in pediatric patients less than 2 years of age without renal impairment is described in Table 2. Avitaz™ is administered every 8 hours by intravenous infusion over 2 hours. For treatment of cIAI, metronidazole should be given concurrently.
Pediatric Patients.
Table 4. Dosage of Avitaz™ in Pediatric Patients Aged 2 years and older with Renal Impairment$^a$.
Estimated eGFR$^b$ (mL/min/1.73m$^2$).
Dose for Avitaz™ (Ceftazidime and avibactam)$^c$.
Frequency.
31 to 50.
Avitaz™ 31.25 mg/kg to a maximum of 1.25 gm (Ceftazidime 25 mg/kg and avibactam 6.25 mg/kg to a maximum dose of Ceftazidime 1 gm and avibactam 0.25 gm).
Every 8 hours.
16 to 30.
Avitaz™ 23.75 mg/kg to a maximum of 0.94 gm (Ceftazidime 19 mg/kg and avibactam 4.75 mg/kg to a maximum dose of Ceftazidime 0.75 gm and avibactam 0.19 gm).
Every 12 hours.
6 to 15.
Avitaz™ 23.75 mg/kg to a maximum of 0.94 gm (Ceftazidime 19 mg/kg and avibactam 4.75 mg/kg to a maximum dose of Ceftazidime 0.75 gm and avibactam 0.19 gm).
Every 24 hours.
Less than or equal to 5$^d$.
Avitaz™ 23.75 mg/kg to a maximum of 0.94 gm (Ceftazidime 19 mg/kg and avibactam 4.75 mg/kg to a maximum dose of Ceftazidime 0.75 gm and avibactam 0.19 gm).
Every 48 hours.
a. Dosing was derived based on the population PK modeling, which assumed similar proportional effects of renal impairment in adults and pediatric patients aged 2 years and older b. As calculated using the Schwartz bedside formula c. All doses of Avitaz™ are administered over 2 hours d. Both Ceftazidime and avibactam are hemodialyzable; thus, administer Avitaz™ after hemodialysis on hemodialysis days.
Method of administration:
Avitaz™ is supplied as a dry powder, which must be constituted and subsequently diluted, using aseptic technique prior to intravenous infusion.
Reconstitution Direction:
a) Constitute the powder in the Avitaz™ vial with 10 ml of one of the following solutions: ✓ Sterile water for injection, USP ✓ 0.9% of sodium chloride injection, USP (normal saline) ✓ 5% of dextrose injection, USP ✓ All combinations of dextrose injection and sodium chloride injection, USP, containing up to 2.5% dextrose, USP, and 0.45% sodium chloride, USP, or ✓ lactated Ringer’s injection, USP.
b) Mix gently and ensure that the contents are dissolved completely. The constituted Avitaz™ solution will have an approximate Ceftazidime concentration of 167 mg/ml and an approximate avibactam concentration of 42 mg/ml. The final volume is approximately 12 ml. The constituted solution is not for direct injection. The constituted solution must be diluted before intravenous infusion.
c) Prepare the required dose for intravenous infusion by withdrawing the appropriate volume determined from Table 5 from the constituted vial. To prepare doses for pediatric patients weighing less than 40 kg, follow the constitution instruction above to yield a solution with a final Avitaz™ concentration of approximately 209 mg/ml (Ceftazidime concentration of 167 mg/mL and an avibactam concentration of 42 mg/ml). Use these concentrations to calculate the volume of Avit.