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Pronunciation

(AZ tree oh nam)

Generic Available (U.S.)

Yes: Injection (powder for reconstitution)

Index Terms

• Azthreonam

Prescribing and Access Restrictions

Cayston® (aztreonam inhalation solution) is only available through a select group of specialty pharmacies and cannot be obtained through a retail pharmacy. Because Cayston® may only be used with the Altera® Nebulizer System, it can only be obtained from the following specialty pharmacies: Cystic Fibrosis Services, Inc; IV Solutions; Foundation Care; and Pharmaceutical Specialties, Inc. This network of specialty pharmacies ensures proper access to both the drug and device. To obtain the medication and proper nebulizer, contact the Cayston Access Program at 1-877-7CAYSTON (1-877-722-9786) or at www.cayston.com.

U.S. Brand Names

• Azactam®
• Cayston®

Canadian Brand Names

• Azactam®

Pharmacologic Category

• Antibiotic, Miscellaneous

Use: Labeled Indications

Injection: Treatment of patients with urinary tract infections, lower respiratory tract infections, septicemia, skin/skin structure infections, intra-abdominal infections, and gynecological infections caused by susceptible gram-negative bacilli

Inhalation: Improve respiratory symptoms in cystic fibrosis (CF) patients with Pseudomonas aeruginosa

Pregnancy Risk Factor

B

Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies; therefore, the manufacturer classifies aztreonam as pregnancy category B. Aztreonam crosses the placenta and enters cord blood during middle and late pregnancy. Distribution to the fetus is minimal in early pregnancy. The amount of aztreonam available systemically following inhalation is significantly less in comparison to doses given by injection.

Lactation

Enters breast milk/not recommended (AAP rates “compatible”; AAP 2001 update pending)

Breast-Feeding Considerations

Very small amounts of aztreonam are excreted in breast milk. The poor oral absorption of aztreonam (<1%) may limit adverse effects to the infant. Nondose-related effects could include modification of bowel flora. Maternal use of aztreonam inhalation is not likely to pose a risk to breast-feeding infants.

Contraindications

Hypersensitivity to aztreonam or any component of the formulation

Warnings/Precautions

Concerns related to adverse effects:

•Bronchospasm: Inhalation: May occur occur following nebulization; administer a bronchodilator prior to treatment.

• Cephalosporin/penicillin allergy: Rare cross-allergenicity to penicillins and cephalosporins has been reported.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Renal impairment: Use the injectable formulation with caution in patients with renal impairment; dosing adjustment required. Dosage adjustment is not required in patients receiving aztreonam via inhalation.

Dosage form specific issues:

• Inhalation: Appropriate use: Safety and efficacy has not been established in patients with FEV₁ <25% or >75% predicted. To reduce the development of resistant bacteria and maintain efficacy reserve use for CF patients with known Pseudomonas aeruginosa. Patients colonized with Burkholderia cepacia have not been studied.

Adverse Reactions

Injection: Adults:

1% to 10%:

Dermatologic: Rash

Gastrointestinal: Diarrhea, nausea, vomiting

Local: Thrombophlebitis, pain at injection site

<1%: Abdominal cramps, abnormal taste, anaphylaxis, anemia, angioedema, aphthous ulcer, breast tenderness, bronchospasm, C. difficile-associated diarrhea, chest pain, confusion, diaphoresis, diplopia, dizziness, dyspnea, eosinophilia, erythema multiforme, exfoliative dermatitis, fever, flushing, halitosis, headache, hepatitis, hypotension, insomnia, jaundice, leukopenia, liver enzymes increased, muscular aches myalgia, neutropenia, numb tongue, pancytopenia, paresthesia, petechiae, pruritus, pseudomembranous colitis, purpura, seizure, sneezing, thrombocytopenia, tinnitus, toxic epidermal necrolysis, urticaria, vaginitis, vertigo, weakness, wheezing

Inhalation:

>10%:

Central nervous system: Pyrexia (13%; more often observed in children)

Respiratory: Cough (54%), nasal congestion (16%), pharyngeal pain (12%), wheezing (16%)

1% to 10%:

Cardiovascular: Chest discomfort (8%)

Dermatologic: Rash (2%)

Gastrointestinal: Abdominal pain (7%), vomiting (6%)

Respiratory: Bronchospasm (3%)

<1%, postmarketing, and/or case reports: Facial edema, hypersensitivity reaction, throat tightness

Drug Interactions

BCG: Antibiotics may diminish the therapeutic effect of BCG. Risk X: Avoid combination

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 24 hours after cessation of antibacterial agents. Risk D: Consider therapy modification

Storage

Inhalation: Prior to reconstitution, store at 2°C to 8°C (36°F to 46°F). Once removed from refrigeration, aztreonam and the diluent may be stored at room temperature (up to 25°C [77°F]) for ≤28 days. Protect from light. Use immediately after reconstitution.

Injection: Prior to reconstitution, store at room temperature; avoid excessive heat. Reconstituted solutions are colorless to light yellow straw and may turn pink upon standing without affecting potency. Use reconstituted solutions and I.V. solutions (in NS and D₅W) within 48 hours if kept at room temperature (25°C) or 7 days under refrigeration (4°C).

Infusion: Solution for infusion may be frozen at less than -2°C (less than -4°F) for up to 3 months. Thawed solution should be used within 24 hours if thawed at room temperature or within 72 hours if thawed under refrigeration. Do not refreeze.

Reconstitution

Inhalation: Reconstitute immediately prior to use. Squeeze diluent into opened glass vial. Replace rubber stopper and gently swirl vial until contents have completely dissolved.

I.M.: Reconstitute with at least 3 mL SWFI, sterile bacteriostatic water for injection, NS, or bacteriostatic sodium chloride.

I.V.:

Bolus injection: Reconstitute with 6-10 mL SWFI.

Infusion: Reconstitute to a final concentration ≤2%; the final concentration should not exceed 20 mg/mL.

Compatibility

Solution for infusion: Stable in D₅LR, D₅1/4NS, D₅1/2NS, D₅NS, D₅W, D₁₀W, mannitol 5%, mannitol 10%, LR, NS; variable stability (consult detailed reference) in peritoneal dialysis solution.

Y-site administration: Compatible: Allopurinol, amifostine, amikacin, aminophylline, ampicillin, ampicillin/sulbactam, bivalirudin, bleomycin, bumetanide, buprenorphine, butorphanol, calcium gluconate, carboplatin, carmustine, cefazolin, cefepime, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, cimetidine, ciprofloxacin, cisatracurium, cisplatin, clindamycin, co-trimoxazole, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daptomycin, dexamethasone sodium phosphate, dexmedetomidine, diltiazem, diphenhydramine, dobutamine, docetaxel, dopamine, doxorubicin HCl, doxorubicin liposome, doxycycline, droperidol, enalaprilat, etoposide, etoposide phosphate, famotidine, fenoldopam, filgrastim, floxuridine, fluconazole, fludarabine, fluorouracil, foscarnet, furosemide, gallium nitrate, gemcitabine, gentamicin, granisetron, haloperidol lactate, heparin, hetastarch in lactated electrolyte, hydrocortisone sodium succinate, hydromorphone, hydroxyzine HCl, idarubicin, ifosfamide, imipenem/cilastatin, insulin (regular), leucovorin calcium, linezolid, magnesium sulfate, mannitol, mechlorethamine, melphalan, meperidine, mesna, methotrexate, methylprednisolone sodium succinate, metoclopramide, minocycline, morphine, nalbuphine, nicardipine, ondansetron, pemetrexed, piperacillin, piperacillin/tazobactam, potassium chloride, promethazine, propofol, quinupristin-dalfopristin, ranitidine, remifentanil, sargramostim, sodium bicarbonate, teniposide, theophylline, thiotepa, ticarcillin/clavulanate, tobramycin, vinblastine, vincristine, vinorelbine, zidovudine. Incompatible: Acyclovir, amphotericin B, amphotericin B cholesteryl sulfate complex, amsacrine, azithromycin, chlorpromazine, daunorubicin HCl, ganciclovir, lorazepam, metronidazole, mitomycin, mitoxantrone, prochlorperazine edisylate, streptozocin. Variable (consult detailed reference): Anakinra, vancomycin.

Compatibility in syringe: Compatible: Clindamycin.

Compatibility when admixed: Compatible: Ampicillin/sulbactam, cefazolin, ciprofloxacin, clindamycin, gentamicin, linezolid, tobramycin. Incompatible: Metronidazole, nafcillin. Variable (consult detailed reference): Ampicillin, cefoxitin, vancomycin.

Mechanism of Action

Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested. Monobactam structure makes cross-allergenicity with beta-lactams unlikely.

Pharmacodynamics/Kinetics

Absorption: I.M.: Well absorbed; I.M. and I.V. doses produce comparable serum concentrations; Inhalation: Low systemic absorption

Distribution: Injection: Widely to most body fluids and tissues

V_d: Children: 0.2-0.29 L/kg; Adults: 0.2 L/kg

Relative diffusion of antimicrobial agents from blood into CSF: Good only with inflammation (exceeds usual MICs)

CSF:blood level ratio: Meninges: Inflamed: 8% to 40%; Normal: ~1%

Protein binding: 56%

Metabolism: Injection: Hepatic (minor %)

Half-life elimination: Injection:

Children 2 months to 12 years: 1.7 hours

Adults: Normal renal function: 1.7-2.9 hours

End-stage renal disease: 6-8 hours

Time to peak: I.M., I.V. push: Within 60 minutes; I.V. infusion: 1.5 hours

Excretion: Injection: Urine (60% to 70% as unchanged drug); feces (~13% to 15%)

Dosage

Children >1 month: I.M., I.V.:

Mild-to-moderate infections: I.M., I.V.: 30 mg/kg every 8 hours

Moderate-to-severe infections: I.M., I.V.: 30 mg/kg every 6-8 hours; maximum: 120 mg/kg/day (8 g/day)

Cystic fibrosis: I.V.: 50 mg/kg/dose every 6-8 hours (ie, up to 200 mg/kg/day); maximum: 8 g/day

Children ≥7 years and Adults: Inhalation (nebulizer):Cystic fibrosis: 75 mg 3 times daily (at least 4 hours apart) for 28 days; do not repeat for 28 days after completion

Adults:

Urinary tract infection: I.M., I.V.: 500 mg to 1 g every 8-12 hours

Moderately-severe systemic infections: 1 g I.V. or I.M. or 2 g I.V. every 8-12 hours

Severe systemic or life-threatening infections (especially caused by Pseudomonas aeruginosa): I.V.: 2 g every 6-8 hours; maximum: 8 g/day

Meningitis (gram-negative): I.V.: 2 g every 6-8 hours

Dosing adjustment in renal impairment:

Oral inhalation: Dosage adjustment not required for mild, moderate, or severe renal impairment

I.M., I.V.: Adults: Following initial dose, maintenance doses should be given as follows:

Cl_cr 10-30 mL/minute: 50% of usual dose at the usual interval

Cl_cr <10 mL/minute: 25% of usual dosage at the usual interval

Intermittent hemodialysis (IHD): Dialyzable (20% to 50%): Loading dose of 500 mg, 1 g, or 2 g, followed by 25% of initial dose at usual interval; for serious/life-threatening infections, administer one-eighth (1/8) of initial dose after each hemodialysis session (given in addition to the maintenance doses). Alternatively, may administer 500 mg every 12 hours (Heintz, 2009). Note: Dosing dependent on the assumption of 3 times/week, complete IHD sessions.

Peritoneal dialysis (PD): Administer as for Cl_cr <10 mL/minute

Continuous renal replacement therapy (CRRT) (Heintz, 2009; Trotman, 2005): Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug concentrations in relation to target trough (if appropriate). The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1-2 L/hour and minimal residual renal function) and should not supersede clinical judgment:

CVVH: Loading dose of 2 g followed by 1-2 g every 12 hours

CVVHD/CVVHDF: Loading dose of 2 g followed by either 1 g every 8 hours or 2 g every 12 hours (Heintz, 2009)

Administration: I.M.

Administer by deep injection into large muscle mass, such as upper outer quadrant of gluteus maximus or the lateral part of the thigh. Doses >1 g should be administered I.V.

Administration: I.V.

I.V. route is preferred for doses >1 g or in patients with severe life-threatening infections. Administer by slow I.V. push over 3-5 minutes or by intermittent infusion over 20-60 minutes.

Administration: Inhalation

Administer using only an Altera® nebulizer system; administer alone; do not mix with other nebulizer medications. Administer a bronchodilator before administration of aztreonam (short-acting: 15 minutes to 4 hours before; long-acting: 30 minutes to 12 hours before). For patients on multiple inhaled therapies, administer bronchodilator first, then mucolytic, and lastly, aztreonam.

To administer Cayston®, pour reconstituted solution into the handset of the nebulizer system, turn unit on. Place the mouthpiece in the patient's mouth and encourage to breath normally through the mouth. Administration time is usually 2-3 minutes. Administer doses ≥4 hours apart.

Administration: I.V. Detail

Monitor infusion/injection sites carefully. Administer around-the-clock to promote less variation in peak and trough serum levels.

pH: 4.5-7.5 (aqueous solution)

Monitoring Parameters

Injection: Periodic liver function test; monitor for signs of anaphylaxis during first dose

Inhalation: Consider measuring FEV₁ prior to initiation of therapy

Test Interactions

May interfere with urine glucose tests containing cupric sulfate (Benedict's solution, Clinitest®); positive Coombs' test

Patient Education

Report immediately any burning, pain, swelling, or redness at infusion or injection site; swelling of mouth or tongue; or chest pain or acute onset of difficulty breathing. May cause nausea or GI distress. Report any respiratory difficulty, coughing, wheezing, persistent diarrhea or vomiting, pain at injection site, unresolved fever, unhealed or new sores in mouth or vagina, or vaginal discharge.

Geriatric Considerations

Injection: Adjust dose relative to renal function.

Additional Information

Although marketed as an agent similar to aminoglycosides, aztreonam is a monobactam antimicrobial with almost pure gram-negative aerobic activity. It cannot be used for gram-positive infections.

Anesthesia and Critical Care Concerns/Other Considerations

Clinical Pearls/Comments: Although marketed as an agent similar to aminoglycosides, aztreonam is a monobactam antimicrobial with almost pure gram-negative aerobic activity. It cannot be used for gram-positive infections, whereas aminoglycosides are often used for synergy in gram-positive infections.

Dental Health: Effects on Dental Treatment

No significant effects or complications reported

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

May rarely produce confusion

Mental Health: Effects on Psychiatric Treatment

Rarely produces leukopenia and neutropenia; use caution with clozapine and carbamazepine

Nursing: Physical Assessment/Monitoring

Assess results of culture and sensitivity tests and patient's allergy history before initiating therapy. I.V.: Infusion site should be monitored closely. Patient should be monitored closely during first dose for anaphylaxis. Bronchospasm may occur following inhalation administration; administer a bronchodilator prior to treatment.

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Infusion, premixed iso-osmotic solution:

Azactam®: 1 g (50 mL); 2 g (50 mL)

Injection, powder for reconstitution: 1 g, 2 g

Azactam®: 1 g, 2 g

Powder for reconstitution, for oral inhalation [preservative free]:

Cayston®: 75 mg [supplied with diluent]

References

American Academy of Pediatrics Committee on Drugs, "Transfer of Drugs and Other Chemicals Into Human Milk," Pediatrics, 2001, 108(3):776-89.

Bosso JA and Black PG, “The Use of Aztreonam in Pediatric Patients: A Review,” Pharmacotherapy, 1991, 11(1):20-5.

Brogden RN and Heel RC, “Aztreonam. A Review of Its Antibacterial Activity, Pharmacokinetic Properties and Therapeutic Use,” Drugs, 1986, 31(2):96-130.

Creasey WA, Platt TB, Frantz M, et al, “Pharmacokinetics of Aztreonam in Elderly Male Volunteers,” Br J Clin Pharmacol, 1985, 19:233-7.

Retsch-Bogart GZ, Quittner Al, Gibson RL, et al, “Efficacy and Safety of Inhaled Aztreonam Lysine for Airway Pseudomonas in Cystic Fibrosis,” Chest, 2009, 135 (5):1223-32.

Settler FR, Schramm M, and Swabb EA, “Safety of Aztreonam and SQ 26,992 in Elderly Patients With Renal Insufficiency,” Rev Infect Dis, 1985, (Suppl 4):5622.

Stutman HR, Chartrand SA, Tolentino T, et al, “Aztreonam Therapy for Serious Gram-Negative Infections in Children,” Am J Dis Child, 1986, 140(11):1147-51.

Trotman RL, Williamson JC, Shoemaker DM, et al, "Antibiotic Dosing in Critically Ill Adult Patients Receiving Continuous Renal Replacement Therapy," Clin Infect Dis, 2005, 41(8):1159-66.

Tunkel AR, Hartman BJ, Kaplan SL, et al, “Practice Guidelines for the Management of Bacterial Meningitis,” Clin Infect Dis, 2004, 39(9):1267-84.

International Brand Names

• Azactam (AR, AT, AU, BB, BE, BF, BG, BJ, BM, BR, BS, BZ, CH, CI, CL, CN, CO, CZ, DE, DK, EG, ES, ET, FI, FR, GB, GH, GM, GN, GR, GY, HN, IE, IT, JM, JP, KE, LR, MA, ML, MR, MU, MW, NE, NG, NL, NO, PE, PH, PK, PL, PT, RU, SC, SD, SE, SG, SL, SN, SR, TN, TR, TT, TW, TZ, UG, VE, ZA, ZM, ZW)
• Azenam (IN)
• Aztram (PH)
• Mezactam (KP)
• Vebac (ID)

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Last full review/revision May 2011

Content last modified May 2011