Avibactam and cefTAZidime

Avibactam and ceftazidime is injected into a vein through an IV. You may be shown how to use an IV at home. Do not self-inject this medicine if you do not understand how to give the injection and properly dispose of used needles, IV tubing, and other items used to inject the medicine.

This medicine must be given slowly, and the infusion can take at least 2 hours to complete. You may need to use this medicine for up to 14 days. Follow your doctor's dosing instructions very carefully.

Avibactam and ceftazidime is a powder medicine that must be mixed with a liquid (diluent) in an IV bag before using it. If you are using the injections at home, be sure you understand how to properly mix and store the medicine.

After mixing the powder with the diluent, store the IV bag in a refrigerator for up to 24 hours. Do not freeze. After you take the IV bag out of the refrigerator, you must use it within 12 hours.

Do not use avibactam and ceftazidime if it has changed colors or has particles in it. Call your pharmacist for new medication. The mixture should appear clear to light yellow.

Use this medicine for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared. Skipping doses may also increase your risk of further infection that is resistant to antibiotics. Avibactam and ceftazidime will not treat a viral infection such as the flu or a common cold.

This medicine can cause unusual results with certain lab tests for glucose (sugar) in the urine. Tell any doctor who treats you that you are using avibactam and ceftazidime.

Store the dry unmixed powder medicine at room temperature away from moisture, heat, and light.

Other drugs may interact with avibactam and ceftazidime, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

Applies to avibactam / ceftazidime: intravenous powder for injection

General

The most common side effects reported in the phase 2 complicated intraabdominal infection (cIAI) trial were vomiting and nausea. Serious side effects were reported in 9 of 101 patients using this drug with metronidazole compared with 11 of 102 patients using meropenem. The most common side effects leading to discontinuation of this drug were skin and subcutaneous tissue disorders. In a phase 3 cIAI trial, death occurred in 13 of 529 patients using this drug with metronidazole compared with 8 of 529 patients using meropenem.

The most common side effects reported in the phase 2 complicated urinary tract infection trial were constipation and anxiety. Serious side effects were reported in 6 of 68 patients using this drug compared with 2 of 67 patients using imipenem-cilastatin. This drug was discontinued prematurely in 1 patient due to accidental overdose and 1 patient due to atrial fibrillation.[Ref]

Gastrointestinal

Very common (10% or more): Vomiting (up to 14%)
Common (1% to 10%): Nausea, constipation, abdominal pain, upper abdominal pain
Frequency not reported: Clostridium difficile-associated diarrhea[Ref]

Other

In a phase 3 cIAI trial, death occurred in 2.5% of patients using this drug with metronidazole and 1.5% of patients using meropenem. In a subgroup of patients with baseline CrCl 30 to 50 mL/min, death occurred in 8 of 31 patients using this drug with metronidazole and 3 of 35 patients using meropenem; patients using this drug received a 33% lower daily dose than is currently recommended for this patient population. In patients with baseline CrCl greater than 50 mL/min, death occurred in 5 of 498 patients using this drug with metronidazole and 5 of 494 patients using meropenem. Cause of death varied; contributing factors included progression of underlying infection, baseline pathogens isolated that were unlikely to respond to study drug, and delayed surgical intervention.[Ref]

Common (1% to 10%): Seroconversion from negative to positive direct Coombs test result, death
Frequency not reported: Decreased clinical response, accidental overdose

Ceftazidime:
-Frequency not reported: Candidiasis[Ref]

Psychiatric

Common (1% to 10%): Anxiety[Ref]

Metabolic

Common (1% to 10%): Increased blood alkaline phosphatase
Frequency not reported: Hypokalemia

Ceftazidime:
-Frequency not reported: Increased blood lactate dehydrogenase[Ref]

Hepatic

Common (1% to 10%): Increased blood ALT
Frequency not reported: Increased GGT

Ceftazidime:
-Frequency not reported: Jaundice[Ref]

Nervous system

Common (1% to 10%): Dizziness

Ceftazidime:
-Frequency not reported: Dysgeusia, paresthesia, seizures, nonconvulsive status epilepticus, encephalopathy, coma, asterixis, neuromuscular excitability, myoclonia[Ref]

Renal

Frequency not reported: Acute renal failure, renal impairment

Ceftazidime:
-Frequency not reported: Tubulointerstitial nephritis[Ref]

Dermatologic

Frequency not reported: Rash, skin and subcutaneous tissue disorders

Beta-lactam antibacterial drugs:
-Frequency not reported: Serious skin reactions

Ceftazidime:
-Frequency not reported: Angioedema, erythema multiforme, pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria[Ref]

Hematologic

Frequency not reported: Eosinophilia, thrombocytopenia, prolonged prothrombin time

Ceftazidime:
-Frequency not reported: Agranulocytosis, hemolytic anemia, leukopenia, lymphocytosis, neutropenia, thrombocytosis[Ref]

Cardiovascular

Frequency not reported: Atrial fibrillation[Ref]

Hypersensitivity

Beta-lactam antibacterial drugs:
-Frequency not reported: Serious and sometimes fatal hypersensitivity (anaphylactic) reactions[Ref]

Local

Ceftazidime:
-Frequency not reported: Infusion-site inflammation, injection-site hematoma, injections-site phlebitis, injection-site thrombosis[Ref]

Genitourinary

Ceftazidime:
-Frequency not reported: Vaginal inflammation[Ref]

Some side effects of avibactam / ceftazidime may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

2.5 g IV every 8 hours
Duration of therapy: 5 to 14 days

Comments:
-The dose is expressed as the total of ceftazidime content plus avibactam content (in a constant 4:1 ratio).
-Metronidazole should be used concomitantly.

Use: In combination with metronidazole, for the treatment of complicated intraabdominal infections due to the following susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Providencia stuartii, Enterobacter cloacae, K oxytoca, Pseudomonas aeruginosa

No adjustment recommended.

This drug should be used during pregnancy only if clearly needed. US FDA pregnancy category: B

Animal studies have failed to reveal evidence of fetal harm with ceftazidime. Animal studies have failed to reveal evidence of teratogenicity or embryofetal toxicity with avibactam at doses up to 11 and 2 times the human exposure (based on AUC) in rats and rabbits, respectively; increased post-implantation loss, reduced fetal weights, delayed ossification of several bones, and other anomalies were seen with higher doses in rabbits. There are no controlled data in human pregnancy. US FDA pregnancy category B: Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.