Azactam

Name: Azactam

Azactam Overview

Azactam is a prescription medicine used to treat certain bacterial infections. Azactam is in a class of drugs called monobactam antibacterials. It interferes with the growth of bacterial cells and causes them to die.

This medication is available in an injectable form to be given directly into a vein (IV) or muscle (IM) by a healthcare professional.

Common side effects of Azactam include nausea, vomiting, and irritation or discomfort at injection site.

 

Uses of Azactam

Azactam is a prescription medicine used to treat certain bacterial infections.

This medication may be prescribed for other uses. Ask your doctor or pharmacists for more information.

 

 

Azactam and Pregnancy

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

This medication falls into category B. There are no well-done studies that have been done in humans with Azactam. In animal studies, pregnant animals were given this medication, and the babies did not show any medical issues related to this medication.

 

Azactam and Lactation

Tell your doctor if you are breastfeeding or plan to breastfeed. The active ingredient in Azactam can pass into breast milk. Talk to your doctor about the best way to breastfeed your baby if you take Azactam. 

Azactam Dosage

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the susceptibility of the bacteria, severity and site of infection, and the condition of the patient.

 

Advice to Patients

  • Advise patients that antibacterials (including aztreonam) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).1 253 287

  • Importance of completing full course of therapy, even if feeling better after a few days.1 253 287

  • Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with aztreonam or other antibacterials in the future.1 253 287

  • Importance of discontinuing therapy and informing clinician if an allergic reaction occurs.1 253 287

  • Advise patients that diarrhea is a common problem caused by systemic anti-infectives and usually ends when the drug is discontinued.1 253 287 Importance of contacting a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as ≥2 months after the last dose.1 253 287

  • Oral inhalation via nebulization: Advise patients to reconstitute the powder for inhalation solution using only the diluent provided by the manufacturer and to administer reconstituted solution only with the Altera nebulizer system.306

  • Oral inhalation via nebulization: Advise patients to complete the full 28-day oral inhalation regimen, even if feeling better;306 if a dose is missed, advise patient to take all 3 daily doses as long as the doses are at least 4 hours apart.306

  • Oral inhalation via nebulization: Advise patients to inform their clinician if they have new or worsening symptoms and to immediately contact a clinician if possible allergic reaction occurs.306

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses.1 253 287 306

  • Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.1 253 287 306

  • Importance of advising patients of other important precautionary information.1 253 287 306 (See Cautions.)

Before Using Azactam

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Studies have been done in children and have shown that aztreonam is effective in treating certain bacterial infections and that side effects in children are similar to those experienced by adults. Elevations of liver enzymes and reductions in white blood cell counts were seen in children who were given high doses of this medicine or who had more serious infections.

Geriatric

Aztreonam has been tested in a limited number of patients 65 years of age or older and has not been shown to cause different side effects or problems in older people than it does in younger adults.

Pregnancy

Pregnancy Category Explanation
All Trimesters B Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate studies in pregnant women OR animal studies have shown an adverse effect, but adequate studies in pregnant women have failed to demonstrate a risk to the fetus.

Breast Feeding

Studies in women suggest that this medication poses minimal risk to the infant when used during breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are receiving this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Cholera Vaccine, Live

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Liver disease—Patients receiving high doses of aztreonam for a long time, who also have severe liver disease, may have an increased chance of side effects
  • Kidney disease—Patients with kidney disease may have an increased chance of side effects

What are some other side effects of Azactam?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

  • Loose stools (diarrhea).
  • Pain where the shot was given.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

How do I store and/or throw out Azactam?

  • If you need to store Azactam at home, talk with your doctor, nurse, or pharmacist about how to store it.

Azactam Dosage and Administration

Dosage in Adult Patients

Azactam may be administered intravenously or by intramuscular injection. Dosage and route of administration should be determined by susceptibility of the causative organisms, severity and site of infection, and the condition of the patient.

Table 4: Azactam Dosage Guidelines for Adults*
Type of Infection Dose Frequency
(hours)
*  Maximum recommended dose is 8 g per day.

Urinary tract infections

500 mg or 1 g

8 or 12

Moderately severe systemic infections

1 g or 2 g

8 or 12

Severe systemic or life-threatening infections

2 g

6 or 8

Because of the serious nature of infections due to Pseudomonas aeruginosa, dosage of 2 g every six or eight hours is recommended, at least upon initiation of therapy, in systemic infections caused by this organism.

The intravenous route is recommended for patients requiring single doses greater than 1 g or those with bacterial septicemia, localized parenchymal abscess (eg, intra-abdominal abscess), peritonitis, or other severe systemic or life-threatening infections.

The duration of therapy depends on the severity of infection. Generally, Azactam should be continued for at least 48 hours after the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. Persistent infections may require treatment for several weeks. Doses smaller than those indicated should not be used.

Renal Impairment in Adult Patients

Prolonged serum levels of aztreonam may occur in patients with transient or persistent renal insufficiency. Therefore, the dosage of Azactam should be halved in patients with estimated creatinine clearances between 10 and 30 mL/min/1.73 m2 after an initial loading dose of 1 or 2 g.

When only the serum creatinine concentration is available, the following formula (based on sex, weight, and age of the patient) may be used to approximate the creatinine clearance (Clcr). The serum creatinine should represent a steady state of renal function.

                                             weight (kg) × (140−age)
               Males: Clcr = 
                                          72 × serum creatinine (mg/dL)

               Females: 0.85 × above value

In patients with severe renal failure (creatinine clearance less than 10 mL/min/1.73 m2), such as those supported by hemodialysis, the usual dose of 500 mg, 1 g, or 2 g should be given initially. The maintenance dose should be one-fourth of the usual initial dose given at the usual fixed interval of 6, 8, or 12 hours. For serious or life-threatening infections, in addition to the maintenance doses, one-eighth of the initial dose should be given after each hemodialysis session.

Dosage in the Elderly

Renal status is a major determinant of dosage in the elderly; these patients in particular may have diminished renal function. Serum creatinine may not be an accurate determinant of renal status. Therefore, as with all antibiotics eliminated by the kidneys, estimates of creatinine clearance should be obtained and appropriate dosage modifications made if necessary.

Dosage in Pediatric Patients

Azactam should be administered intravenously to pediatric patients with normal renal function. There are insufficient data regarding intramuscular administration to pediatric patients or dosing in pediatric patients with renal impairment. (See PRECAUTIONS: Pediatric Use.)

Table 5: Azactam Dosage Guidelines for Pediatric Patients*
Type of Infection Dose Frequency
(hours)
*  Maximum recommended dose is 120 mg/kg/day.

Mild to moderate infections

30 mg/kg

8

Moderate to severe infections

30 mg/kg

6 or 8

CLINICAL STUDIES

A total of 612 pediatric patients aged 1 month to 12 years were enrolled in uncontrolled clinical trials of aztreonam in the treatment of serious Gram-negative infections, including urinary tract, lower respiratory tract, skin and skin-structure, and intra-abdominal infections.

Preparation of Parenteral Solutions

General

Upon the addition of the diluent to the container, contents should be shaken immediately and vigorously. Constituted solutions are not for multiple-dose use; should the entire volume in the container not be used for a single dose, the unused solution must be discarded.

Depending upon the concentration of aztreonam and diluent used, constituted Azactam yields a colorless to light straw yellow solution which may develop a slight pink tint on standing (potency is not affected). Parenteral drug products should be inspected visually for particulate matter and discoloration whenever solution and container permit.

Admixtures with Other Antibiotics

Intravenous infusion solutions of Azactam not exceeding 2% w/v prepared with Sodium Chloride Injection, USP 0.9% or Dextrose Injection, USP 5%, to which clindamycin phosphate, gentamicin sulfate, tobramycin sulfate, or cefazolin sodium have been added at concentrations usually used clinically, are stable for up to 48 hours at room temperature or 7 days under refrigeration. Ampicillin sodium admixtures with aztreonam in Sodium Chloride Injection, USP 0.9% are stable for 24 hours at room temperature and 48 hours under refrigeration; stability in Dextrose Injection, USP 5% is 2 hours at room temperature and 8 hours under refrigeration.

Aztreonam-cloxacillin sodium and aztreonam-vancomycin hydrochloride admixtures are stable in Dianeal 137 (Peritoneal Dialysis Solution) with 4.25% Dextrose for up to 24 hours at room temperature.

Aztreonam is incompatible with nafcillin sodium, cephradine, and metronidazole.

Other admixtures are not recommended since compatibility data are not available.

Intravenous Solutions

For Bolus Injection: The contents of an Azactam 15 mL capacity vial should be constituted with 6 to 10 mL Sterile Water for Injection, USP.

For Infusion: If the contents of a 15 mL capacity vial are to be transferred to an appropriate infusion solution, each gram of aztreonam should be initially constituted with at least 3 mL Sterile Water for Injection, USP. Further dilution may be obtained with one of the following intravenous infusion solutions:

  Sodium Chloride Injection, USP, 0.9%   Ringer’s Injection, USP   Lactated Ringer’s Injection, USP   Dextrose Injection, USP, 5% or 10%   Dextrose and Sodium Chloride Injection, USP, 5%:0.9%, 5%:0.45%, or 5%:0.2%   Sodium Lactate Injection, USP (M/6 Sodium Lactate)   Ionosol® B and 5% Dextrose   Isolyte® E   Isolyte® E with 5% Dextrose   Isolyte® M with 5% Dextrose   Normosol®-R   Normosol®-R and 5% Dextrose   Normosol®-M and 5% Dextrose   Mannitol Injection, USP, 5% or 10%   Lactated Ringer’s and 5% Dextrose Injection   Plasma-Lyte M and 5% Dextrose Intramuscular Solutions

The contents of an Azactam 15 mL capacity vial should be constituted with at least 3 mL of an appropriate diluent per gram aztreonam. The following diluents may be used:

  Sterile Water for Injection, USP   Sterile Bacteriostatic Water for Injection, USP (with benzyl alcohol or with methyl- and propylparabens)   Sodium Chloride Injection, USP, 0.9%   Bacteriostatic Sodium Chloride Injection, USP (with benzyl alcohol) Stability of Intravenous and Intramuscular Solutions

Azactam solutions for intravenous infusion at concentrations not exceeding 2% w/v must be used within 48 hours following constitution if kept at controlled room temperature (59°F-86°F/15°C-30°C) or within 7 days if refrigerated (36°F-46°F/2°C-8°C).

Azactam solutions at concentrations exceeding 2% w/v, except those prepared with Sterile Water for Injection, USP or Sodium Chloride Injection, USP, should be used promptly after preparation; the 2 excepted solutions must be used within 48 hours if stored at controlled room temperature or within 7 days if refrigerated.

Intravenous Administration

Bolus Injection: A bolus injection may be used to initiate therapy. The dose should be slowly injected directly into a vein, or the tubing of a suitable administration set, over a period of 3 to 5 minutes (see next paragraph regarding flushing of tubing).

Infusion: With any intermittent infusion of aztreonam and another drug with which it is not pharmaceutically compatible, the common delivery tube should be flushed before and after delivery of aztreonam with any appropriate infusion solution compatible with both drug solutions; the drugs should not be delivered simultaneously. Any Azactam infusion should be completed within a 20- to 60-minute period. With use of a Y-type administration set, careful attention should be given to the calculated volume of aztreonam solution required so that the entire dose will be infused. A volume control administration set may be used to deliver an initial dilution of Azactam (see Preparation of Parenteral Solutions: Intravenous Solutions: For Infusion) into a compatible infusion solution during administration; in this case, the final dilution of aztreonam should provide a concentration not exceeding 2% w/v.

Intramuscular Administration

The dose should be given by deep injection into a large muscle mass (such as the upper outer quadrant of the gluteus maximus or lateral part of the thigh). Aztreonam is well tolerated and should not be admixed with any local anesthetic agent.

References

1. Naber KG, Dette GA, Kees F, Knothe H, Grobecker H. Pharmacokinetics, in vitro activity, therapeutic efficacy, and clinical safety of aztreonam vs. cefotaxime in the treatment of complicated urinary tract infections. J Antimicrob Chemother 1986;17:517-527. 2. Creasey WA, Platt TB, Frantz M, Sugerman AA. Pharmacokinetics of aztreonam in elderly male volunteers. Br J Clin Pharmacol 1985;19:233-237. 3. Meyers BR, Wilkinson P, Mendelson MH, et al. Pharmacokinetics of aztreonam in healthy elderly and young adult volunteers. J Clin Pharmacol 1993;33:470-474. 4. Sattler FR, Schramm M, Swabb EA. Safety of aztreonam and SQ 26,992 in elderly patients with renal insufficiency. Rev Infect Dis 1985;7 (suppl 4):S622-S627. 5. Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard - Ninth Edition. CLSI document M07-A9, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2012. 6. National Committee for Clinical Laboratory Standards. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow AerobicallyFifth Edition. Approved Standard NCCLS Document M7-A5, Vol. 20, No. 2, NCCLS, Wayne, PA, January 2000. 7. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Disk Diffusion Susceptibility Tests; Approved Standard – Eleventh Edition CLSI document M02-A11, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2012. 8. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; Twenty-third Informational Supplement, CLSI document M100-S23. CLSI document M100-S23, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2013. 9. Deger F, Douchamps J, Freschi E, et al. Aztreonam in the treatment of serious gram-negative infections in the elderly. Int J Clin Pharmacol Ther and Toxicol 1988;26:22-26. 10. Knockaert DC, Dejaeger E, Nestor L, et al. Aztreonam-flucloxacillin double beta-lactam treatment as empirical therapy of serious infections in very elderly patients. Age and Aging 1981;20:135-139. 11. Roelandts F. Clinical use of aztreonam in a psychogeriatric population. Acta Clin Belg 1992;47:251-255. 12. Andrews R, Fasoli R, Scoggins WG, et al. Combined aztreonam and gentamicin therapy for pseudomonal lower respiratory tract infections. Clin Therap 1994;16:236-252.


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Manufactured by:
Bristol-Myers Squibb Company
Princeton, NJ 08543 USA

Made in Italy


1268779A0
Rev June 2013

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