Ceftazidime/avibactam

What is Ceftazidime/avibactam?

• Ceftazidime/avibactam (Avycaz) is a combination of ceftazidime, a cephalosporin, and avibactam, a beta-lactamase inhibitor used with metronidazole to treat abdominal infections.
• It is also used to treat pneumonia that developed in people who are on ventilators or who were in a hospital, and kidney and urinary tract infections.

Ceftazidime and avibactam

What are the uses of this medicine?

Ceftazidime/avibactam (Avycaz) is used in the treatment of: Complicated Intra-abdominal Infections (cIAI):

• Avycaz (ceftazidime and avibactam) in combination with metronidazole, is indicated for the treatment of complicated intra-abdominal infections (cIAI) in adult and pediatric patients aged 3 months and older.

Complicated Urinary Tract Infections (cUTI), including Pyelonephritis:

• Avycaz (ceftazidime and avibactam) is indicated for the treatment of complicated urinary tract infections (cUTI) including pyelonephritis in adult and pediatric patients aged 3 months and older.

Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia (HABP/VABP):

• VYCAZ (ceftazidime and avibactam) is indicated for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in adult and pediatric patients aged 3 months and older.

How does this medicine work?

• A combination preparation containing the third-generation cephalosporin ceftazidime and the sodium salt form of avibactam, a non-beta-lactam beta-lactamase inhibitor, with antibiotic and beta-lactamase inhibiting activity, respectively.
• Upon administration, ceftazidime binds to essential penicillin-binding proteins (PBPs) and inhibits cell wall synthesis in certain bacteria. Avibactam binds to and inactivates beta-lactamases, thereby protecting ceftazidime from degradation and increasing ceftazidime’s efficacy.

Avycaz has been shown to be active against most isolates of the following bacteria:

In Complicated Intra-abdominal Infections (cIAI):

Gram-negative Bacteria

• Citrobacter freundii complex
• Enterobacter cloacae
• Escherichia coli
• Klebsiella oxytoca
• Klebsiella pneumoniae
• Proteus mirabilis
• Pseudomonas aeruginosa

In Complicated Urinary Tract Infections (cUTI), including Pyelonephritis Gram-negative Bacteria:

• Citrobacter freundii complex
• Enterobacter cloacae
• Escherichia coli
• Klebsiella pneumoniae
• Proteus mirabilis
• Pseudomonas aeruginosa

In Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia (HABP/VABP): Gram-negative Bacteria:

• Enterobacter cloacae
• Escherichia coli
• Haemophilus influenzae
• Klebsiella pneumoniae
• Proteus mirabilis
• Pseudomonas aeruginosa
• Serratia marcescens

Who Should Not Use this medicine ?

This medicine cannot be used in patients who:

• with known serious hypersensitivity to the components of Avycaz (ceftazidime and avibactam), avibactam-containing products, or other members of the cephalosporin class.

What drug interactions can this medicine cause?

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Be sure to mention any of the following:

• probenecid (Probalan, in Col-Probenecid)

Is this medicine FDA approved?

• The combination was approved for medical use in the United States and the European Union in 2015.

How should this medicine be used?

Recommended dosage:

Recommended Dosage in Adult Patients:

• The recommended dosage of Avycaz is 2.5 grams (ceftazidime 2 grams and avibactam 0.5 grams) 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.

Recommended Dosage in Pediatric Patients:

• The recommended dosage of Avycaz 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.

In pediatric patients aged 6 months to less than 2 years:

• Avycaz 62.5 mg/kg (Ceftazidime 50 mg/kg and avibactam 12.5 mg/kg).

In pediatric patients aged 3 months to less than 6 months:

• Avycaz 50 mg/kg (Ceftazidime 40 mg/kg and avibactam 10 mg/kg).

• Monitor CrCl at least daily in adult and pediatric patients with changing renal function and adjust the dosage of Avycaz accordingly.

Administration:

• The combination of ceftazidime and avibactam injection comes as a powder to be added to fluid and injected intravenously.
• It is usually infused intravenously over a period of 2 hours every 8 hours.
• The length of your treatment depends on your general health, the type of infection you have and how well you respond to the medication.
• Your doctor will tell you how long to use ceftazidime and avibactam injection.
• You may receive ceftazidime and avibactam injection in a hospital or you may administer the medication at home.
• If you will be receiving ceftazidime and avibactam injection at home, your healthcare provider will show you how to use the medication.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As 2.5g (ceftazidime and avibactam) for injection is supplied as a sterile powder for constitution in single-dose vials containing ceftazidime 2 grams (equivalent to 2.635 grams of ceftazidime pentahydrate/sodium carbonate powder) and avibactam 0.5 grams (equivalent to 0.551 grams of avibactam sodium).

This medicine is available in fallowing brand namesː

• Avycaz

What side effects can this medication cause?

The most common side effects of this medicine include: In Adult Patients:

• diarrhea, nausea and vomiting.

The most common adverse reactions in cUTI patients are diarrhea and nausea. The most common adverse reactions in HABP/VABP patients were diarrhea and vomiting.

In Pediatric Patients:

• vomiting, diarrhea, rash, and infusion site phlebitis.

Less common side effects may in clude:

• Hypersensitivity Reactions
• Clostridium difficile-Associated Diarrhea
• Central Nervous System Reactions

What special precautions should I follow?

• Decreased clinical response in adult cIAI patients with baseline CrCl of 30 to less than or equal to 50 mL/ min. Monitor CrCl at least daily in adult and pediatric patients with changing renal function and adjust the dosage of Avycaz accordingly.
• Advise patients, their families, or caregivers that allergic reactions, including serious allergic reactions, could occur that require immediate treatment. Ask them about any previous hypersensitivity reactions to Avycaz, other beta-lactams (including cephalosporins), or other allergens.
• Clostridium difficile-associated diarrhea (CDAD) has been reported for nearly all systemic antibacterial drugs, including Avycaz, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial drugs alters the normal flora of the colon and may permit overgrowth of C. difficile.
• If CDAD is suspected or confirmed, antibacterial drugs not directed against C. difficile may need to be discontinued. Manage fluid and electrolyte levels as appropriate, supplement protein intake, monitor antibacterial treatment of C. difficile, and institute surgical evaluation as clinically indicated.
• Seizures, nonconvulsive status epilepticus (NCSE), encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia have been reported in patients treated with ceftazidime, particularly in the setting of renal impairment. Adjust dosing based on creatinine clearance.
• Prescribing Avycaz in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

What to do in case of emergency/overdose?

• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.
• In the event of overdose, discontinue Avycaz and institute general supportive treatment.
• Ceftazidime and avibactam can be removed by hemodialysis.

Can this medicine be used in pregnancy?

• There are no adequate and well-controlled studies of Avycaz, ceftazidime, or avibactam in pregnant women.
• Because animal reproduction studies are not always predictive of human response, this drug should be used in pregnancy only if clearly needed.

Can this medicine be used in children?

• The safety and effectiveness of Avycaz in the treatment of cUTI, cIAI, and HABP/VABP have been established in pediatric patients aged 3 months to less than 18 years.
• Safety and effectiveness of Avycaz in pediatric patients below the age of 3 months have not been established.

What are the active and inactive ingredients in this medicine?

Active ingredients:

• CEFTAZIDIME
• AVIBACTAM SODIUM

Inactive ingredients:

• SODIUM CARBONATE

Who manufactures and distributes this medicine?

Distributed by:

• Allergan USA, Inc.
• Madison, NJ

Manufactured by:

• ACS Dobfar SpA
• Via Alessandro Fleming, 2
• Verona, Italy

• Avycaz is a registered trademark of Allergan Sales, LLC.

What should I know about storage and disposal of this medication?

• Avycaz vials should be stored at 25°C (77°F); excursions permitted between 15°C and 30°C (59°F and 86°F).

• Dailymed label info on Ceftazidime/avibactam
• FDA Ceftazidime/avibactam