aztreonam/avibactam

Therapeutic Classification: anti-infectives

Pharmacologic Classification: monobactams, beta lactamase inhibitors

Indications ⬆ ⬇

REMS

Complicated intra-abdominal infections in patients who have limited or no treatment options (in combination with metronidazole).

Action ⬆ ⬇

Aztreonam: Binds to the bacterial cell wall membrane, causing cell death. Avibactam: Inhibits beta-lactamase, an enzyme that destroys penicillins and cephalosporins.

Therapeutic effects:

Death of susceptible bacteria with resolution of infection.

Spectrum:

Active against Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Klebsiella oxytoca, Citrobacter freundii, and Serratia marcescens.

Pharmacokinetics ⬆ ⬇

Aztreonam

Absorption: IV administration results in complete bioavailability.

Distribution: Widely distributed to tissues.

Metabolism/Excretion: 60–70% excreted unchanged by the kidneys. Small amounts metabolized by the liver.

Half-Life: 2 hr.

Avibactam

Absorption: IV administration results in complete bioavailability.

Distribution: Widely distributed to tissues.

Metabolism/Excretion: Minimally metabolized; mainly excreted unchanged in urine.

Half-Life: 2 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IV	rapid	end of infusion	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity.

Use Cautiously in:

Renal impairment (CCr <50 mL/min);
Hepatic impairment;
OB: Safety not established in pregnancy;
Lactation: Safety not established in breastfeeding;
Pedi: Safety and effectiveness not established in children;
Geri: Consider age-related impairment of renal function in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypotension

Derm: flushing, rash, TOXIC EPIDERMAL NECROLYSIS (TEN)

F and E: hypokalemia

GI: ↑liver enzymes, abdominal pain, CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DIARRHEA (CDAD), constipation, diarrhea, nausea, vomiting

Hemat: anemia, eosinophilia, leukocytosis, thrombocytopenia, thrombocytosis

Local: phlebitis

Neuro: ageusia, dizziness, headache, insomnia, mental status changes

Misc: fever, hypersensitivity reactions

Interactions ⬆ ⬇

Drug-drug:

Concurrent use with probenecid not recommended.

Route/Dosage ⬆ ⬇

IV (Adults ): 2.67 g (2 g aztreonam/0.67 g avibactam) initially as loading dose, then 2 g (1.5 g aztreonam/0.5 g avibactam) every 6 hr for 5–14 days.

Renal Impairment

IV (Adults ): CCr 30–<50 mL/min: 2.67 g (2 g aztreonam/0.67 g avibactam) initially as loading dose, then 1 g (0.75 g aztreonam/0.25 g avibactam) every 6 hr for 5–14 days. CCr 15–<30 mL/min: 1.8 g (1.35 g aztreonam/0.45 g avibactam) initially as loading dose, then 0.9 g (0.675 g aztreonam/0.225 g avibactam) every 8 hr for 5–14 days. CCr <15 mL/min or Hemodialysis: 1.33 g (1 g aztreonam/0.33 g avibactam) initially as loading dose, then 0.9 g (0.675 g aztreonam/0.225 g avibactam) every 12 hr for 5–14 days.

Availability ⬆ ⬇

Powder for injection: aztreonam 1.5 g/avibactam 0.5 g/vial

Assessment ⬆ ⬇

Monitor body temperature. May cause fever.
Assess for hypersensitivity reactions (rash, flushing, and bronchospasm). If hypersensitivity reaction occurs, discontinue aztreonam/avibactam and start appropriate medications and/or supportive care.
Assess for skin reactions such as TEN (sore throat, painful erosions in the mouth, eyes, or genitalia, red/purple blistering rash). If a serious skin reaction occurs, discontinue aztreonam/avibactam.
Monitor for diarrhea, abdominal cramping, fever, and bloody stools during and up to 8 wk after cessation of therapy. If CDAD suspected or confirmed, discontinue aztreonam/avibactam and treat as clinically indicated.

Lab Test Considerations:

Obtain specimens for culture and sensitivity before initiating therapy. First dose may be given before receiving results.
May ↑ ALT and AST.
May ↓ potassium and hemoglobin.

Implementation ⬆ ⬇

Administer after hemodialysis if applicable.

IV Administration:

Y-Site Incompatibility:
- Do not administer other drugs through same IV line

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy. Emphasize on the importance of completing the full course of therapy.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
Advise patient about the hypersensitivity reactions that can occur and to notify health care professional or seek immediate medical attention.
Advise patient to notify health care professional if signs/symptoms of a severe rash, blistering or peeling skin with or without a fever or joint pain occur.
Advise patient to notify health care professional if severe watery or bloody diarrhea develops.
Rep: Advise women of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

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Pronunciation ⬇

Classifications ⬆ ⬇