Dosing and uses of Azactam (aztreonam)
Adult dosage forms and strengths
solution, inhalation
- 75mg
powder for injection
- 1g
- 2g
Systemic Infections
Moderately severe: 1-2 g IV/IM q8-12hr; not to exceed 8 g/day
Severe or life-threatening: 2 g IV/IM q6-8hr; not to exceed 8 g/day
Pseudomonal Infections
2 g IV/IM q6-8hr; not to exceed 8 g/day
Urinary Tract Infections
0.5-1 g IV/IM q8-12hr; not to exceed 8 g/day
Graft-Versus-Host Disease (Orphan)
Treatment of oral manifestations of graft-versus-host disease (GVHD)
Orphan indication sponsors
- Oral Solutions, Inc, 787 Seventh Ave, 48th Floor, New York, NY 10019
Dosing Modifications
Renal impairment
- CrCl 10-30 mL/min: 1-2 g loading dose, then 50% of usual dosage
- CrCl <10 mL/min: 1-2 g loading dose, then 25% of usual dosage
Dosing Considerations
Susceptible organisms
- Gram-negative: Citrobacter spp, Enterobacter spp, Escherichia coli, Haemophilus influenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens
Pediatric dosage forms and strengths
solution, inhalation
- 75mg
powder for injection
- 1g
- 2g
Mild-to-Moderate Infections
<9 month: Safety and efficacy not established
>9 month: 30 mg/kg IV q8hr; not to exceed 120 mg/kg/day
Moderate-to-Severe Infections
<9 month: Safety and efficacy not established
>9 month: 30 mg/kg IV q6-8hr; not to exceed 120 mg/kg/day
Cystic Fibrosis
<9 month: Safety and efficacy not established
>9 month: 50 mg/kg IV q6-8hr; not to exceed 200 mg/kg/day; not to exceed 8 g/day
>7 years: 75 mg via nebulizer three times daily, at least 4 hr apart, for 28days; not to be repeated for another 28 days
Azactam (aztreonam) adverse (side) effects
>10%
Inhalation
- Cough (54%)
- Sore throat (12%)
- Wheezing (16%)
- Fever (13%)
Injection
- Pain at injection site (12%; children); (2%; adults)
- Increase in serum transaminases (4-6%)
- Neutropenia (3-11%, children); (<1%, adults)
1-10%
Inhalation
- Chest discomfort (8%)
- Abdominal pain (7%)
- Vomiting (6%)
- Bronchospasm (3%)
- Skin rash (2%)
Injection
- Rash (4%)
- Thrombocytopenia (4%, children); (<1% adults)
- Diarrhea (1%)
- Nausea (1%)
- Vomiting (1%)
- Fever (<1%)
< 1%
Inhalation
Facial edema
Joint swelling
Tightness in chest and throat
Bronchospasm
Skin rash
Injection
Abnormal taste
Anaphylaxis
Anemia
Angioedema
Aphthous ulcer
Breast tenderness
Bronchospasm
Clostridium difficile-associated diarrhea (CDAD)
Confusion
Diplopia
Dizziness
Dsypnea
Electrocardiographic changes (transient)
Erythema multiforme
Eosinophilia
Fever
Flushing
Halitosis
Headache
Hepatitis
Hypotension
Insomnia
Jaundice
Leukocytosis
Neutropenia
Pancytopenia
Seizures
Thrombocytopenia
Tinnitus
Tongue numbness
Toxic epidermal necrolysis
Urticaria
Vaginitis
Vertigo
Weakness
Wheezing
Warnings
Contraindications
Hypersensitivity
Cautions
CDAD has been reported with use of nearly all antibacterial agents, including aztreonam
Dose reduction required with renal impairment
Coadministration with nephrotoxic drugs increases risk of renal impairment
Prolonged use may result in superinfection
Use caution in toxic epidermal necrolysis and renal impairment
Pregnancy and lactation
Pregnancy category: B
Lactation: Drug is excreted in milk in low concentrations; use not recommended (American Academy of Pediatrics committee states that drug is compatible with nursing)
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Azactam (aztreonam)
Mechanism of action
Monobactam; inhibits cell wall synthesis by binding to penicillin binding proteins
Absorption
IM form well absorbed; IM/IV forms yield comparable serum concentrations
Peak plasma time: IM/IV push, ≤60 min; IV infusion, 1.5 hr
Distribution
Distributed widely to most body fluids and tissues; crosses placenta; enters breast milk
Relative diffusion of antimicrobial agents from blood into CSF: Good only with inflammation (exceeds usual MICs); CSF level ~1% of blood level with normal meninges, 8-40% with inflamed meninges
Protein bound: 58%
Vd: Neonates, 0.26-0.36 L/kg; children, 0.2-0.29 L/kg; adults, 0.2 L/kg
Metabolism
Metabolized in liver
Elimination
Half-life: Adults with normal renal function, 1.7-2.9 hr; adults with end-stage renal disease, 6-8 hr
Excretion: Urine (60-70% as unchanged drug), feces (13-15%)
Administration
IV Incompatibilities
Additive: Metronidazole, nafcillin
Y-site: Acyclovir, alatrofloxacin, amphotericin B, amphotericin B cholesteryl sulfate, amsacrine, azithromycin, chlorpromazine, daunorubicin, ganciclovir, lorazepam, metronidazole, mitomycin, mitoxantrone, prochlorperazine, streptozocin, vancomycin(?; may depend on concentration)
IV Compatibilities
Additive (partial list): Ampicillin(?), cefazolin, cefoxitin(?), ciprofloxacin, linezolid, tobramycin, vancomycin (may be incompatible at high concentrations of both drugs)
Syringe: Clindamyin
Y-site (partial list): Allopurinol, amikacin, cephalosporins (most), cimetidine, ciprofloxacin, cisatracurium, diltiazem, diphenhydramine, dopamine, famotidine, fluconazole, furosemide, heparin, hydroxyzine, linezolid, magnesium sulfate, metoclopramide, morphine sulfate, ondansetron, propofol, sodium bicarbonate, trimethoprim-sulfamethoxazole, zidovudine
IV Preparation
Reconstituted solutions are colorless to light straw-yellow; may turn pink upon standing, without affecting potency
Use reconstituted solutions and IV solutions (in NS or D5W) within 48 hours if kept at room temperature or within 7 days if kept in refrigerator
IV/IM Administration
IM: Inject deep into large muscle mass
IV: Preferred for doses >1 g or in patients with severe life-threatening infections; administer drug by IV push over 3-5 minutes or by intermittent infusion over 20-60 minutes at final concentration not to exceed 20 mg/mL
Monitor infusion/injection sites carefully; administer around-the-clock to minimize variations in peak and trough serum levels
