Prescribing Details
Description
Zitum AV is a combination of Ceftazidime and Avibactam. Ceftazidime is a cephalosporin antibacterial drug with activity against certain gram-negative and gram-positive bacteria. The bactericidal action of ceftazidime is mediated through binding to essential penicillin-binding proteins (PBPs). Avibactam 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.
Uses
No Data
Indications
Zitum AV is indicated for the treatment of-
. Complicated intra-abdominal infections (clAI) in adult and pediatric patients (at least 31 weeks gestational age) in combination with metronidazole
. Complicated urinary tract infections (cUTI) including pyelonephritis in adult and pediatric patients (at least 31 weeks gestational age)
. Hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/ VABP)
Dosage and administration
Route of administration: Zitum AV should be administered as IV infusion over 2 hours.
Adults with creatinine clearance (CrCl) greater than 50 ml/min
| Indication | Dose | Duration of treatment |
|---|---|---|
| Complicated intra-abdominal infections (used in combination with metronidazole) (cIAI) | Zitum AV 2.5 g (ceftazidime 2 g and avibactam 0.5 g) every 8 hours | cIAI: 5-14 days cUTI: 7-14 days HABP/VABP: 7-14 days |
| Complicated urinary tract infections including pyelonephritis (cUTI) | ||
| Hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) |
Pediatric patients aged 2 years to less than 18 years with eGFR greater than 50 mL/min/1.73 m2 and in pediatric patients less than 2 years of age without renal impairment
| Indication | Age | Dose | Frequency | Duration of treatment |
|---|---|---|---|---|
| cIAI (in combination with metronidazole), cUTI including pyelonephritis and HABP/ VABP | 2 years to less than 18 yearsa | Zitum AV 62.5 mg/kg to a maximum of 2.5 g (ceftazidime 50 mg/kg and avibactam 12.5 mg/kg to a maximum dose of ceftazidime 2 g and avibactam 0.5 g) | Every 8 hours | cIAI: 5-14 days cUTI: 7-14 days HABP/ VABP: 7-14 days |
| 6 months to less than 2 years | Zitum AV 62.5 mg/kg (ceftazidime 50 mg/kg and avibactam 12.5 mg/kg) | |||
| 3 months to less than 6 months | Zitum AV 50 mg/kg (ceftazidime 40 mg/kg and avibactam 10 mg/kg) | |||
| Greater than 28 daysb to less than 3 months | Zitum AV 37.5 mg/kg (ceftazidime 30 mg/kg and avibactam 7.5 mg/kg) | |||
| Less than or equal to 28 daysc with GA 31 weeks and older | Zitum AV 25 mg/kg (ceftazidime 20 mg/kg and avibactam 5 mg/kg) | |||
|
a For pediatric patients (2 years or older) with eGFR less than or equal to 50 mL/min/1.73m2, dosage adjustments are recommended. |
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Renal impairment
Adult Patients
| CrCl (ml/minute) | Recommended dose | Frequency |
|---|---|---|
| 31 to 50 | Zitum AV 1.25 g (ceftazidime 1 g and avibactam 0.25 g) | Every 8 hours |
| 16 to 30 | Zitum AV 0.94 g (ceftazidime 0.75 g and avibactam 0.19 g) | Every 12 hours |
| 6 to 15 | Zitum AV 0.94 g (ceftazidime 0.75 g and avibactam 0.19 g) | Every 24 hours |
| Less than or equal to 5 | Zitum AV 0.94 g (ceftazidime 0.75 g and avibactam 0.19 g) | Every 48 hours |
Pediatric patients 2 years and older
| Estimated eGFR (mL/min/1.73m2) |
Recommended dose | Frequency |
|---|---|---|
| 31 to 50 | Zitum AV 31.25 mg/kg to a maximum of 1.25 g (ceftazidime 25 mg/kg and avibactam 6.25 mg/kg to a maximum dose of ceftazidime 1 g and avibactam 0.25 g) | Every 8 hours |
| 16 to 30 | Zitum AV 23.75 mg/kg to a maximum of 0.94 g (ceftazidime 19 mg/kg and avibactam 4.75 mg/kg to a maximum dose of ceftazidime 0.75 g and avibactam 0.19 g) | Every 12 hours |
| 6 to 15 | Zitum AV 23.75 mg/kg to a maximum of 0.94 g (ceftazidime 19 mg/kg and avibactam 4.75 mg/kg to a maximum dose of ceftazidime 0.75 g and avibactam 0.19 g) | Every 24 hours |
| Less than or equal to 5 | Zitum AV 23.75 mg/kg to a maximum of 0.94 g (ceftazidime 19 mg/kg and avibactam 4.75 mg/kg to a maximum dose of ceftazidime 0.75 g and avibactam 0.19 g) | Every 48 hours |
Both ceftazidime and avibactam are hemodialyzable; thus, administer Zitum AV after hemodialysis on hemodialysis days. All doses of Zitum AV are administered over 2 hours.
Administration instructions
. Constitute the powder in the Zitum AV vial with 10 ml of one of the following solutions- sterile water for injection, 0.9% of sodium chloride injection (normal saline), 5% of dextrose injection, all combinations of dextrose injection and sodium chloride injection (containing up to 2.5% dextrose and 0.45% sodium chloride) or lactated ringer's injection.
. Mix gently until it dissolves completely. The constituted Zitum AV solution will have an approximate concentration of ceftazidime 167 mg/ml and avibactam 42 mg/ml. The final volume is approximately 12 ml. The constituted solution is not for direct injection and must be diluted before IV infusion. Use these concentrations to calculate the volume of Zitum AV required to prepare the prescribed dose.
. Prepare the required dose for intravenous infusion by withdrawing the appropriate volume determined from below table from the constituted vial.
Preparation of Zitum AV doses for adult and pediatric patients (weighing 40 kg or more)
| Zitum AV (ceftazidime and avibactam) dose | Volume to withdraw from constituted vial for further dilution to 50 to 250 ml |
|---|---|
| 2.5 g (2 g and 0.5 g) | 12 ml (entire contents) |
| 1.25 g (1 g and 0.25 g) | 6 ml |
| 0.94 g (0.75 g and 0.19 g) | 4.5 ml |
| Dilution to 250 ml should only be used for the 2.5 g dose | |
. Before infusion, dilute the withdrawn volume of the constituted Zitum AV solution further with the same diluent used for constitution of the powder (except sterile water for injection), to achieve a ceftazidime concentration of 8 to 40 mg/ml and an avibactam concentration of 2 to 10 mg/ml in an infusion bag. If sterile water for injection was used for constitution, use any of the other appropriate constitution diluents for dilution.
. Mix gently and ensure that the contents are dissolved completely. Visually inspect the diluted Zitum AV solution (for administration) for particulate matter and discoloration prior to administration (the color of the Zitum AV infusion solution for administration ranges from clear to light yellow or yellow green).
. Diluted Zitum AV solution in the infusion bag can be stored up to 12 hours when stored at room temperature and up to 24 hours at 2°C to 8°C.
Use in pregnancy & lactation
Pregnancy: There are no adequate and well-controlled studies of this combination in pregnant women.
Lactation: There are no information available on the effects of this combination on the breast-fed child or on milk production.
Use in children and adolescents
The safety and effectiveness in children and adolescents have been described in dose and administration section.
Geriatric use
Precautions
Monitor CrCl at least daily in adult and pediatric patients with changing renal function and adjust the dosage accordingly. Discontinue the drug if an allergic or fatal hypersensitivity reaction occurs. Clostridioides difficile-associated diarrhea (CDAD) has been reported for nearly all systemic antibacterial drugs, including ceftazidime & avibactam powder, and may range in severity from mild diarrhea to fatal colitis. If CDAD is suspected or confirmed, antibacterial drugs not directed against C. difficile may need to be discontinued. Seizures, nonconvulsive status epilepticus, encephalopathy, coma, asterixis, neuromuscular excitability and myoclonia can occur in patients treated with ceftazidime, particularly in patients with renal impairment. There's increased risk of the development of drug-resistant bacteria following administration of this combination without proven or strongly suspected bacterial infection.
Side effects
The most common side effects are vomiting, diarrhea, rash, headache, dizziness, nausea, increased transaminases and infusion site phlebitis.
Contraindications
It is contraindicated in patients with known hypersensitivity to ceftazidime or avibactam or any other members of the cephalosporin class or any other components of this product.
Drug interactions
Drug interaction with medication: Avibactam is a substrate of OAT1 and OAT3 transporters. Probenecid inhibits OAT uptake of avibactam when co-administered. It is recommended that glucose tests based on enzymatic glucose oxidase reactions be used during treatment.
Drug interaction with food and others: Not applicable.
Overdose
In case of overdose, general supportive measures and proper monitoring should be initiated. Ceftazidime and avibactam both are hemodialyzable.
Preparation
No Data
Pharmaceutical precautions
No Data
Presentation
Zitum AV 2.5 g Injection for IV Infusion: Each vial contains Ceftazidime 2 g as Ceftazidime Pentahydrate USP and Avibactam 0.5 g as Avibactam Sodium INN.
Package quantities
Storage
Store below 25°C in a dry place, protected from light. Keep away from the reach of children.
Packing
Zitum AV 2.5 g Injection for IV Infusion: Each box contains 1 vial of Zitum AV sterile powder and 1 ampoule of 10 ml water for injection BP.
