Azactam 1 g Powder for Solution for Injection or Infusion

Ireland - English - HPRA (Health Products Regulatory Authority)

Buy It Now

Active ingredient:
Aztreonam
Available from:
Bristol-Myers Squibb Pharmaceuticals uc
ATC code:
J01DF; J01DF01
INN (International Name):
Aztreonam
Dosage:
1 gram(s)
Pharmaceutical form:
Powder for solution for injection/infusion
Prescription type:
Product subject to prescription which may not be renewed (A)
Therapeutic area:
Monobactams; aztreonam
Authorization status:
Marketed
Authorization number:
PA0002/052/002
Authorization date:
1985-03-05

6972

6972

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1303354A8

Package leaflet: Information for the patient

Azactam

TM

1g or 2g

Powder for Solution for Injection or Infusion

Aztreonam

Please read this leaflet carefully before you start taking your medicine because

it contains important information for you.

Please keep this leaflet. You may need to read it again.

-

If you have any further questions, ask your doctor.

This medicine has been prescribed for you only. Do not pass it on to others. It

may harm them, even if their signs of illness are the same as yours.

If you get any side effects, talk to your doctor or pharmacist. This includes any

possible side effects not listed in this leaflet.

What is in this leaflet:

1. What Azactam is and what it is used for

2. What you need to know before you are given your medicine

3. How you will be given your medicine

4. Possible side effects

5. How to store your medicine

6. Contents of the pack and other information

1. What Azactam is and what it is used for

The name of this medicine is Azactam. The active ingredient in Azactam is aztreonam. Azactam is available in two

strengths and each vial contains either 1g or 2g aztreonam as a powder for solution for injection or infusion. Aztreonam is

an antibiotic and a member of the family of medicines called monobactams. Azactam also contains L-arginine.

Azactam is for the treatment of serious infections caused by bacteria which require an antibiotic injection.

2. What you need to know before you are given your medicine

Do not take Azactam if:

You are allergic to aztreonam or L-arginine or any of the ingredients of this medicine (listed in Section 6)

You are pregnant or planning to become pregnant

Warnings and precautions

Talk to your doctor before taking Azactam.

Take special care with Azactam if

You have ever had an allergic reaction to any antibiotics

You have diarrhoea or usually get diarrhoea when you take antibiotics or have ever suffered from problems with your

stomach or intestines. If you develop severe or prolonged or bloody diarrhoea during or after using Azactam tell your

doctor as soon as possible since it may be necessary to interrupt the treatment.

You have any Liver problems

You have any Kidney problems or are using a certain antibiotics (aminoglycosides)

You are taking a medicine for blood clots (anticoagulants)

You have any blood disorders, e.g. severe reduction in blood cells which can cause weakness, bruising or make

infections more likely (pancytopenia)

You have skin disorders, including serious illness with blistering of the skin (toxic epidermal necrolysis)

You have fits (convulsions or seizures)

You develop any bacterial or fungal infections

You test positive in a Coombs’ test (a test for some blood problems)

You must tell your doctor if you experience unexplained confusion, altered mental function, coma, seizure, or weakness.

Other medicine and Azactam

Always tell your doctor or pharmacist about other medicines you may be taking or have recently taken including those

obtained without a prescription. Some medicines can have an effect on each other’s actions.

Pregnancy and breastfeeding

If you are pregnant or may become pregnant, you should speak to your doctor before being treated with Azactam.

Breast-feeding is not recommended while taking Azactam. Tell your doctor if you are breast-feeding.

Driving and using machinery

This medicine could affect your ability to drive or use machinery (see sections 2 and 4). Azactam has also been shown to

cause dizziness, confusion, and blurred vision (please see Section 4 below).

Azactam contains aztreonam.

3. How you will be given your medicine

Azactam will be given to you under the supervision of an experienced doctor.

How it will be given, either as an infusion (a drip) and/or into a vein (intravenously) will be determined by your doctor.

Adults:

The adult dose range is 1 to 8g daily. This dose can be split equally over the day meaning you may be given between one

to four doses a day. Maximum recommended dose is 8 g per day.

Children

The usual daily dose in children older than one week is 30 mg per kg of body weight given every 6 to 8 hours, but in

severe infections in patients two years of age or older, this will be increased to 50 mg per kg of body weight every

6 to 8 hours. The maximum daily dose in children should not exceed the maximum recommended dose for adults.

Elderly:

Kidney function is a major determinant of the dose of Azactam given to the elderly. The doctor will assess kidney

function by measuring a chemical called creatinine in the blood and also in the urine. If this level is above a certain limit

(30 mL/min), the normal recommended adult dose will be given. However, if this level is below the limit (30 mL/min),

the dose will be adjusted accordingly by the doctor.

Liver and Kidney

The dose of Azactam given will also be adjusted by the doctor for anyone with severe kidney disease, for example kidney

failure.

If you are given more Azactam than you should

It is unlikely that you will receive more Azactam than you should as it will be administered by injection into a muscle or

vein by a doctor, nurse or other suitably trained person. If this does happen you will be closely monitored.

You must tell your doctor if you experience unexplained confusion, altered mental function, coma, seizure, or weakness.

If you have any further questions on the use of this medicines, ask your doctor.

4. Possible side effects

Like all medicines, Azactam can cause unwanted side effects, although not everybody gets them.

Tell your doctor immediately if you get any of the following symptoms:

swelling of the face, lips, tongue and/or throat with difficulty in swallowing or breathing. These may be signs of

an allergic reaction.

severe, persistent or bloody diarrhoea (which may be associated with stomach pain or fever). This is rare side

effect which may occur after treatment with antibiotics and can be a sign of serious bowel inflammation.

Patients treated with Azactam have reported the following side effects:

Uncommon: may affect less than 1 in 10 people

Temporary increases in the levels of some chemicals in your blood (creatinine)

Rare: may affect up to 1 in 1000 people

Pins and needles

PLEASE DETACH BEFORE HANDING ABOVE SECTION TO PATIENT

INFORMATION FOR HEALTH PROFESSIONALS

Below is a summary of the dosage and administration for Azactam. Reference should be made to

the Summary of Product characteristics (SmPC) for full prescribing information.

ADMINISTRATION:

Intramuscular or intravenous injection, or intravenous infusion.

Adults:

The dose range of Azactam is 1 to 8g daily in equally divided doses. The usual dose is 3 to 4g

daily. The maximum recommended dose is 8g daily. The dosage and route of administration

should be determined by the susceptibility of the causative organisms, severity of infection, and

the condition of the patient.

Type of Infection

(1)

Dosage

Frequency

(hours)

Route

Urinary tract infections

500 mg or 1 g

8 or 12

IM or IV

Gonorrhoea/cystitis

single dose

Cystic Fibrosis

6 - 8

Moderately severe systemic infections

1 g or 2 g

8 or 12

IM or IV

Severe systemic or life-threatening infections

6 or 8

IM or IV

Other infections either

IM or IV

Because of the serious nature of infections due to Pseudomonas aeruginosa, a dose of 2g every 6 or

8 hours is recommended, at least for initial therapy in systemic infections caused by this organism.

The intravenous route is recommended for patients requiring single doses greater than 1g, or

those with bacterial septicaemia, localised parenchymal abscess (e.g. intra-abdominal abscess),

peritonitis, meningitis or other severe systemic or life-threatening infections.

Paediatric:

The usual dose for patients older than one week is 30mg/kg/dose every 6 or 8 hours.

For severe infections in patients 2 years of age or older, 50mg/kg/dose every 6 or 8 hours is

recommended. The recommended dose for all patients in the treatment of infections due to

P. aeruginosa

is 50 mg/kg every six to eight hours. The maximum daily paediatric dose should

not exceed the maximum recommended dose for adults. Dosage information is not yet available

for new-borns less than 1 week old.

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.

Elderly patients normally have a creatinine clearance in excess of 30mL/min and therefore would

receive the normal recommended dose. If renal function is below this level, the dosage schedule

should be adjusted (see Renal Impairment).

Renal Impairment:

Prolonged serum levels of aztreonam may occur in patients with transient or persistent renal

insufficiency. Therefore, after an initial usual dose, the dosage of aztreonam should be halved in

patients with estimated creatinine clearances between 10 and 30 mL/min/1.73 m

In patients with severe renal failure (creatinine clearance less than 10 mL/min/1.73 m

), such as

those supported by hemodialysis, the usual dose 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.

Hepatic impairment:

A dose reduction of 20-25% is recommended for long-term treatment of patients with chronic

liver disease with cirrhosis, especially in cases of alcoholic cirrhosis and when renal function is

also impaired.

Live Text:

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Production Site:

Anagni

Country:

CTM:

Emiliano Parisi

Product Name:

INS AZACTAM

Change: New BMS Logo

Printing Colours:

Black

Product Code:

1303354A8

Barcode Type:

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Format/Dimension:

130 x 480 (130 x 24) mm

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Technical Colours:

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Inflammation of the liver

Spinning sensation

Muscle pain

Changes to blood count

Positive results in a Coombs’ test (a test for some blood problems)

Difficulty sleeping

Changes in your heart beat (measured by electrocardiogram-ECG)

Feeling of being unwell

Dizziness

Ringing in the ears

Double vision

Gastrointestinal bleeding

Diarrhoea with blood or mucous or inflammation

Bad breath

Chest pain

Fever

Weakness

Yellowing of the skin

Thrush or other vaginal irritation

Fits

Headache

Wheezing

Breast tenderness

Shortness of breath

Sneezing

Nasal congestion

Fall in blood pressure

Confusion

Bleeding

Lengthening of the time it takes for a cut to stop bleeding

Decrease in blood cells

Increase or decrease in the number of infection fighting blood cells

Not known: frequency cannot be estimated from available data

Narrowing of the airways in the lungs

Inflammation of the veins

Tender or painful veins

Increase in some liver enzymes

Increase in blood alkaline phosphatise (certain substance in the blood)

Sweating

Excessive sweating

Swelling of eyes, lips and throat

Abdominal cramps

Mouth ulcers

Nausea and/or vomiting

Diarrhoea

Altered taste

Discomfort at the injection site

Weakness

Severe allergic reaction

Skin conditions including

Serious skin rashes

Swelling of the skin that resembles severe burns

Inflammation and peeling of the skin

Rash

Itching

Red or purple discolouration of the skin

Pin point bleeding under the skin

Confusion, altered mental function, coma, seizure, or weakness

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in

this leaflet. You can also report side effects directly via:

HPRA Pharmacovigilance

Earlsfort Terrace

IRL-Dublin 2

Tel: +353 1 6764971

Fax: +353 1 6762517

Website: www.hpra.ie

e-mail: medsafety@hpra.ie

By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store your medicine

Keep this medicine out of the sight and reach of children.

This medicine will be stored in the pharmacy at not more than 25°C and prepared in a special area before the doctor or

nurse gives it to you. This product is for single use only.

Do not use this medicines after the expiry date which is stated on the vial label and on the carton. The expiry date refers

to the last day of that month. .

6. Further Information

What Azactam contains

The active substance is aztreonam. Each vial contains either 1g or 2g aztreonam. The other ingredients are: L-arginine

(780mg per g of aztreonam).

What Azactam looks like and the contents of the pack

Azactam comes in clear glass vials, closed with siliconed grey butyl rubber closure, sealed with aluminium seal with a

plastic flip off button, in packs of 1 x 15 mL.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Bristol-Myers Squibb Pharmaceuticals uc

Plaza 254, Blanchardstown Corporate Park 2, Ballycoolin

Dublin 15, D15 T867

Ireland

Manufacturer:

Swords Laboratories T/A Bristol-Myers Squibb Pharmaceutical Operations,

External Manufacturing

Plaza 254

Blanchardstown Corporate Park 2

Dublin 15, D15 T867

Ireland

Date of last revision: March 2020

RECONSTITUTION:

Azactam Powder for Solution for Injection or Infusion is supplied in 15mL vials. Upon the

addition of the diluent the contents should be shaken immediately and vigorously. Vials of

reconstituted Azactam are not intended for multi-dose use, and any unused solution from a

single dose must be discarded. Depending on the type and amount of diluent, the pH ranges from

4.5 to 7.5, and the colour may vary from colourless to light straw-yellow, which may develop a

slight pink tint on standing; however this does not affect the potency.

For intramuscular injections:

For each gram of aztreonam add at least 3mL Water for

Injections Ph Eur or 0.9% Sodium Chloride BP and shake well.

Single-Dose Vial Size

Volume of Diluent to be added

0.5g

1.5mL

1.0g

3.0mL

Azactam is given by deep injection into a large muscle mass, such as the upper outer quadrant of

the gluteus maximus or the lateral part of the thigh.

For intravenous injection:

To the contents of the vial add 6 to 10mL of Water for Injections Ph

Eur, and shake well. Slowly inject directly into the vein over a period of 3 to 5 minutes.

For intravenous infusion:

For each gram of aztreonam, add at least 3mL of Water for Injections

Ph Eur and shake well. Dilute this initial solution with an appropriate infusion solution to a final

concentration less than 2% w/v (at least 50mL solution per gram of aztreonam). The infusion

should be administered over 20-60 minutes.

Appropriate infusion solutions include: 0.9% Sodium Chloride Injection BP 5% Glucose

Intravenous Infusion BP, 5% or 10% Mannitol Intravenous Infusion BP, Sodium Lactate

Intravenous Infusion BP, 0.9%, 0.45% or 0.2% Sodium Chloride & 5% Glucose I.V. Infusion BP,

Compound Sodium Chloride Injection BPC 1959 (Ringer’s Solution for Injection), Compound

Sodium Lactate Intravenous Infusion BP (Hartmann’s Solution for Injection).

A volume control administration set may be used to deliver the initial solution of Azactam into

a compatible infusion solution being administered. With use of a Y-tube administration set,

careful attention should be given to the calculated volume of Azactam solution required so that

the entire dose will be infused. With intermittent infusion of Azactam and another drug via a

common delivery tube, the tube should be flushed before and after delivery of Azactam with

any appropriate infusion solution compatible with both drug solutions. Except for the antibiotics

described below, the drugs should not be delivered simultaneously.

Reconstitution:

Intravenous infusion solution of Azactam for Injection prepared with

0.9% Sodium Chloride Injection BP or 5% Glucose Intravenous Infusion BP, in PVC or glass

containers, to which clindamycin phosphate, gentamicin sulphate, tobramycin sulphate, or

cephazolin sodium have been added at concentrations usually used clinically, are stable for up to

24 hours in a refrigerator (2-8°C). Ampicillin sodium admixtures with aztreonam in 0.9% sodium

chloride injection BP are stable for 24 hours in a refrigerator (2-8°C); stability in 5% Glucose

Intravenous Infusion BP is eight hours under refrigeration. Store the reconstituted solution at

2°C-8°C (under refrigeration) for not more than 24 hours. Discard any unused solution.

If aztreonam and metronidazole are to be used together, they should be administered separately

as a cherry red colour has been observed after storage of solutions containing combinations of

the two products.

Any unused medicinal product or waste material should be disposed of in accordance with local

requirements.

Date of last revision: January 2019

1303354A8

Live Text:

Yes /

Production Site:

Anagni

Country:

CTM:

Emiliano Parisi

Product Name:

INS AZACTAM

Change: New BMS Logo

Printing Colours:

Black

Product Code:

1303354A8

Barcode Type:

2/5 (6972)

Format/Dimension:

130 x 480 (130 x 24) mm

Font Size Text:

8 pt/9 pt

Technical Colours:

Diecut

Min. Font Size Text:

8 pt

Line Space:

8 pt/9,4 pt

(2,8 mm/3,3 mm)

Proof No.:

22.06.2020

Tornese

Pag. 2/2

Approved

Health Products Regulatory Authority

02 January 2019

CRN008N23

Page 1 of 14

Summary of Product Characteristics

1 NAME OF THE MEDICINAL PRODUCT

Azactam 1 g Powder for Solution for Injection or Infusion

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each vial contains 1g aztreonam.

Excipients with known effect

For a full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Powder for solution for injection or infusion

A sterile white to off-white, sodium free powder.

4 CLINICAL PARTICULARS

4.1 Therapeutic Indications

The treatment of the following infections caused by susceptible aerobic

Gram-negative micro-organisms:

Urinary tract infections: Including pyelonephritis and cystitis (initial and recurrent)

and asymptomatic bacteriuria, including those due to pathogens resistant to the

aminoglycosides, cephalosporins or penicillins.

Gonorrhoea: Acute uncomplicated urogenital or anorectal infections including

infections due to beta-lactamase producing or non-producing strains of N.

gonorrhoeae.

Lower respiratory tract infections: Including pneumonia, bronchitis and lung

infections in patients with cystic fibrosis.

Bacteraemia / septicaemia.

Meningitis caused by Haemophilus influenzae or Neisseria meningitidis. Since

Azactam provides only Gram negative cover, it should not be given alone as initial

blind therapy, but may be used with an antibiotic active against Gram positive

organisms until the results of sensitivity tests are known.

Bone and joint infections.

Health Products Regulatory Authority

02 January 2019

CRN008N23

Page 2 of 14

Skin and soft tissue infections: Including those associated with postoperative wounds,

ulcers and burns.

Intra-abdominal infections: Peritonitis.

Gynaecological infections: Pelvic inflammatory disease, endometritis, and pelvic

cellulitis.

Azactam is indicated for adjunctive therapy to surgery in the management of

infections caused by susceptible organisms, including abscesses, infections

complicating hollow viscus perforations, cutaneous infections and infections of

serous surfaces.

Bacteriological studies to determine the causative organism(s) and their sensitivity to

aztreonam should be performed. Therapy may be instituted prior to receiving the

results of sensitivity tests.

In patients at risk of infections due to non-susceptible pathogens, additional

antibiotic therapy should be initiated concurrently with Azactam to provide

broad-spectrum coverage before identification and susceptibility testing results of

the causative organism(s) are known. Based on these results, appropriate antibiotic

therapy should be continued.

Some patients with serious Pseudomonas infections may benefit from concurrent use

of Azactam and an aminoglycoside because of their synergistic action. If such

concurrent therapy is considered in these patients, susceptibility tests should be

performed in vitro to determine the activity in combination. The usual monitoring of

serum levels and renal function during aminoglycoside therapy applies.

4.2 Posology and method of administration

Posology

Intramuscular or intravenous injection or intravenous infusion.

Adults:

The dose range of Azactam is 1 to 8 g daily in equally divided doses. The usual dose

is 3 to 4 g daily. The maximum recommended dose is 8 g daily. The dosage and

route of administration should be determined by the susceptibility of the causative

organisms, severity of infection, and the condition of the patient.

Health Products Regulatory Authority

02 January 2019

CRN008N23

Page 3 of 14

Dosage Guide: Adults

Type of Infection ​

Dosage

Frequency (hours)

Route

Urinary tract infections ​

500 mg or 1 g

8 or 12

IM or IV

Gonorrhoea / cystitis ​

single dose

Cystic Fibrosis ​

6 - 8

Moderately severe

systemic infections ​

1 g or 2 g

8 or 12

IM or IV

Severe systemic or

life-threatening

infections ​

6 or 8

IM or IV

Other infections ​

either

IM or IV

The intravenous route is recommended for patients requiring single doses greater

than 1 g, or those with bacterial septicaemia, localised parenchymal abscess (e.g.

intra- abdominal abscess), peritonitis, meningitis or other severe systemic or

life-threatening infections. Because of the serious nature of infections due to Ps.

aeruginosa, a dosage of 2 g every 6 to 8 hours is recommended, at least for initial

therapy in systemic infections caused by this organism.

Paediatric population:

The usual dosage for patients older than one week is 30 mg/kg/dose every 6 or 8

hours. For severe infections in patients 2 years of age or older, 50 mg/kg/dose every

6 to 8 hours is recommended.

The maximum daily paediatric dose should not exceed the maximum recommended

dose for adults.

Dosage information is not yet available for new-borns less than 1 week old.

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.

Elderly patients with a creatinine clearance in excess of 30 mL/min should receive the

normal recommended dose. If renal function is below this level, the dosage schedule

should be adjusted (see Renal Impairment).

Health Products Regulatory Authority

02 January 2019

CRN008N23

Page 4 of 14

Renal Impairment:

Prolonged serum levels of aztreonam may occur in patients with transient or

persistent renal insufficiency. Therefore, after an initial usual dose, the dosage of

aztreonam should be halved in patients with estimated creatinine clearances

between 10 and 30 mL/min/1.73 m2.

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 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.

Hepatic impairment:

A dose reduction of 20-25% is recommended for long-term treatment of patients

with chronic liver disease with cirrhosis, especially in cases of alcoholic cirrhosis and

when renal function is also impaired.

For instructions on dilution of the product before administration, see section 6.6.

4.3 Contraindications

Hypersensitivity to the active substance(s) or to any of the excipients listed in section

6.1.

Aztreonam is contraindicated in pregnancy. Aztreonam crosses the placenta and

enters the foetal circulation.

4.4 Special warnings and precautions for use

Allergic reactions

Antibiotics, like other drugs, should be given with caution to any patients with a

history of allergic reaction to structurally related compounds. If an allergic reactions

occurs, discontinue the drug and institute supportive treatments as appropriate.

Serious hypersensitivity reactions may require epinephrine and other emergency

measures.

Renal/hepatic impairment

Use of beta-lactam containing therapies, including aztreonam, can cause

encephalopathy (e.g. confusion, impairment of consciousness, epilepsy, movement

disorders); particularly in patients with renal impairment and in association with beta-

lactam overdose.

Health Products Regulatory Authority

02 January 2019

CRN008N23

Page 5 of 14

The biological half-life is prolonged in patients with renal insufficiency or creatinine

clearance of less than 30 mL/min. Dosage adjustments should be based on creatinine

clearance.

In so far as the elderly may have a significant degree of renal dysfunction, dosage of

the drug should be undertaken with particular care (See section on dosage and

administration in the elderly.)

Experience in patients with impaired hepatic function is limited. Appropriate

monitoring of liver function in such patients is recommended during therapy.

Serious blood/skin disorders

Serious blood disorders (incl. pancytopenia) and skin disorders (incl. toxic epidermal

necrolysis) have been reported with the use of aztreonam. In case of serious

hemogram and skin changes, it is recommended to stop aztreonam.

Convulsions

Convulsions have rarely been reported during treatment with beta-lactams, including

aztreonam (see section 4.8).

Clostridium difficile associated diarrhoea

Clostridium difficile associated diarrhoea (CDAD) has been reported with use of

nearly all antibacterial agents, including Azactam, and may range in severity from

mild diarrhoea to fatal colitis. CDAD must be considered in all patients who present

with diarrhoea following antibiotic use. Careful medical history is necessary since

CDAD has been reported to occur over two months after the administration of

antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not

directed against C. difficile may need to be discontinued. Medication that inhibits

intestinal peristalsis should not be given.

Concurrent therapy with other antimicrobial agents and aztreonam is recommended

as initial therapy in seriously ill patients who are at risk of having an infection due to

pathogens that may not be susceptible to aztreonam.

Specific studies have not shown significant cross-reactivity between aztreonam and

either penicillins or cephalosporins. The incidence of hypersensitivity to Azactam in

clinical trials has been very low but caution should be exercised in patients with a

history of hypersensitivity until further experience is gained.

Overgrowth of non-susceptible organisms

Therapy with Azactam may result in overgrowth of non-susceptible organisms,

including gram-positive organisms and fungi. Should superinfection occur during

therapy, appropriate measures should be taken.

Health Products Regulatory Authority

02 January 2019

CRN008N23

Page 6 of 14

Prolongation of prothrombin time / increased activity of oral anticoagulants

Prolongation of prothrombin time has been reported rarely in patients receiving

aztreonam. Additionally, numerous cases of increased activity of oral anticoagulants

have been reported in patients receiving antibiotics, including beta-lactams. Severe

infection or inflammation, and the age and general condition of the patient appear

to be risk factors. Appropriate monitoring should be undertaken when

anticoagulants are prescribed concomitantly. Adjustments in the dose of oral

anticoagulants may be necessary to maintain the desired level of anticoagulation

(see section 4.5 and 4.8).

Concomitant use with aminoglycosides

If an aminoglycoside is used concurrently with aztreonam, especially if high dosages

of the former are used or if therapy is prolonged, renal function should be monitored

because of the potential nephrotoxicity and ototoxicity of aminoglycoside antibiotics.

Paediatric population

Data on safety and effectiveness in neonates younger than one week are limited; use

in this population needs to be carefully assessed.

Arginine

Aztreonam for injection contains arginine. Studies in low birth weight infants have

demonstrated that arginine administered in the aztreonam formulation may result in

increases in serum arginine, insulin, and indirect bilirubin. The consequences of

exposure to this amino acid during treatment of neonates have not been fully

ascertained.

Interference with serological testing

A positive direct or indirect Coombs test may develop during treatment with

aztreonam.

4.5 Interaction with other medicinal products and other forms of interactions

Concomitant administration of probenecid or furosemide and aztreonam cause

clinically insignificant increases in the serum levels of aztreonam.

Due to the induction of beta-lactamases, certain antibiotics (eg, cefoxitin, imipenem)

have been found to cause antagonism with many beta-lactams, including aztreonam,

for certain gram-negative aerobes, such as Enterobacter species and Pseudomonas

species.

Appropriate monitoring should be undertaken when anticoagulants are prescribed

concomitantly. Adjustments in the dose of oral anticoagulants may be necessary to

maintain the desired level of anticoagulation (see section 4.4 and 4.8).

Health Products Regulatory Authority

02 January 2019

CRN008N23

Page 7 of 14

Single-dose pharmacokinetic studies have not shown any significant interaction

between aztreonam and gentamicin, cephradine, clindamycin or metronidazole.

No disulfiram-like reactions with alcohol ingestion have been reported.

4.6 Fertility, pregnancy and lactation

Pregnancy

Aztreonam is contraindicated in pregnancy. Aztreonam crosses the placenta and

enters the foetal circulation.

There are no adequate and well-controlled studies in pregnant women. Studies in

pregnant rats and rabbits, with daily doses up to 15 and 5 times the maximum

recommended human dose respectively, revealed no evidence of embryo- or

fetotoxicity or teratogenicity. Because animal reproduction studies are not always

predictive of human response, aztreonam should be used during pregnancy only if

clearly needed.

Breastfeeding

Aztreonam is excreted in breast milk in concentrations that are less than 1% of those

in simultaneously obtained maternal serum. Lactating mothers should refrain from

breast feeding during the course of therapy.

4.7 Effects on ability to drive and use machines

This medicine can have an important impact on the ability to drive and use machines

should encephalopathy occur (see 4.4 Special warnings and special precautions for

use and 4.9 Overdose).

4.8 Undesirable effects

The list of undesirable effects shown below is presented by system organ class,

MedDRA preferred term, and frequency.

System Organ

Class

Frequency

MedDRA Term

Blood and

lymphatic

system

disorders

Rare

Pancytopenia

, thrombocytopenia,

thrombocythaemias, leukocytosis, neutropenia,

eosinophilia, anaemia, prothrombin time prolonged,

activated partial thromboplastin time prolonged,

Coombs test positive

Ear and

labyrinth

disorders

Rare

Vertigo, tinnitus

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Eye disorders

Rare

Diplopia

Gastrointestinal

disorders

Rare

Gastro intestinal haemorrhage,

pseudomembranous colitis

, breath odour

Not known

Abdominal pains, mouth ulceration, nausea,

vomiting, diarrhoea, altered taste

General

disorders and

administration

site conditions

Rare

Chest pain, pyrexia, asthenia, malaise

Not known

Injection site discomfort, weakness, sweating,

muscle aches, fever, transient increases in serum

creatinine

Hepato-biliary

disorders

Rare

Hepatitis, jaundice

Not known

Transaminases increased*, blood alkaline

phosphatase increased*

Infections and

infestations

Rare

Vaginitis, vaginal candidiasis

Immune system

disorders

Not known

Anaphylactic reaction

Investigations

Rare

Electrocardiogram change

Musculoskeletal,

connective

tissue and bone

disorders

Rare

Myalgia

Nervous system

disorders

Rare

Convulsions

, paresthesia, dizziness, headache

​Not known

Dysgeusia, ​

Encephalopathy (confusional state,

altered state of consciousness, epilepsy, movement

disorder)

Psychiatric

disorders

Rare

Confusional state, insomnia

Renal and

urinary

disorders

Uncommon

Blood creatinine increased

Reproductive

system and

breast disorders

Rare

Breast tenderness

Respiratory,

thoracic and

mediastinal

disorders

Rare

Wheezing, dyspnoea, sneezing, nasal congestion

​Not known

​Bronchospasm

Skin and

subcutaneous

tissue disorders

Not known

Toxic epidermal necrolysis

, angioedema, erythema

multiforme, dermatitis exfoliative, hyperhidrosis,

petechiae, purpura, urticaria, rash, pruritus

Vascular

disorders

Rare

Hypotension, haemorrhage

​Not known

​Phlebitis, thrombophlebitis, flushing

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*Usually reversing during therapy and without overt signs or symptoms of

hepatobiliary dysfunction.

See section 4.4.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is

important. It allows continued monitoring of the benefit/risk balance of the medicinal

product. Healthcare professionals are asked to report any suspected adverse

reactions via:

HPRA Pharmacovigilance

Earlsfort Terrace

IRL-Dublin 2

Tel: +353 1 6764971

Fax: +353 1 6762517

Website: www.hpra.ie

e-mail: medsafety@hpra.ie

4.9 Overdose

Use of beta-lactam containing therapies, including aztreonam, can cause

encephalopathy (e.g. confusion, impairment of consciousness, epilepsy, movement

disorders); particularly in patients with renal impairment and in association with

beta-lactam overdose.

There have been no reported cases of overdosage. If necessary, aztreonam can be

removed from the body by haemodialysis and/or peritoneal dialysis. Aztreonam has

been shown to be cleared from the serum by continuous arteriovenous

hemofiltration.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Anti-infectives for systemic use, ATC code: J01DF01

Aztreonam is a monocyclic beta-lactam (monobactam) anti-infective with bactericidal

activity against a spectrum of most Gram-negative aerobic pathogens, including

Pseudomonas aeruginosa.

Aztreonam is active in vitro against most strains of the following Gram-negative

micro-organisms:

Escherichia coli, Enterobacter species, Klebsiella species, (including K. pneumoniae and

K. oxytoca), Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia

species (including P. stuartii and P. rettgeri), Pseudomonas species (including Ps.

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aeruginosa), Serratia marcescens, Neisseria gonorrhoeae (including

penicillinase-producing strains), Haemophilus influenzae (including

ampicillin-resistant and other penicillinase-producing strains), Neisseria meningitidis,

Citrobacter species.

Aztreonam does not induce beta-lactamase activity and it is highly resistant to

hydrolysis by the beta-lactamases produced by most pathogens.

Certain antibiotics (e.g. cefoxitin, imipenem) may induce high levels of

beta-lactamase in vitro in some gram-negative aerobes such as Enterobacter and

Pseudomonas species, resulting in antagonism to aztreonam.

5.2 Pharmacokinetic properties

Aztreonam is the first member of a new class of antibiotics, the monobactams. It has

been synthesised as a monocyclic beta-lactam antibiotic in which the sulphonic acid

substituent in the 1-position of the nuclear ring activates the beta-lactam moiety.

While the drug may undergo some metabolism in the liver, it is excreted mostly

unchanged through bile and appears to undergo much of its biotransformation in

the gut lumen. Excretion depends principally on renal pathways.

Single 30-minute i.v. infusions of 0.5 g, 1.0 g, and 2.0 g in healthy volunteers

produced immediate serum levels of 54, 90 and 240 mg/L, and single 3-minute i.v.

injections of the same doses produced peak levels of 58, 125 and 242 mg/L. Peak

levels of aztreonam are achieved at about one hour after i.m. administration. After

identical single i.m. or i.v. doses, the serum concentrations are comparable at 1 hour

(1.5 hours from the start of i.v. infusion), with similar slopes of serum concentrations

thereafter.

The serum half-life of aztreonam averaged 1.7 hours in subjects with normal renal

function, independent of the dose and route. In healthy subjects 60-70% of a single

i.m. or i.v. dose was recovered in the urine by 8 hours, and urinary excretion was

essentially complete by 12 hours. In renal dysfunction, these times may be

considerably prolonged.

As with other antibiotics, in the treatment of acute pulmonary exacerbations in

patients with cystic fibrosis, while clinical improvement is usually noted, lasting

bacterial eradications may not be achieved.

Unlike broad spectrum antibiotics, aztreonam produces no effects on the normal

anaerobic intestinal flora.

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5.3 Preclinical safety data

Aztreonam was well tolerated in a comprehensive series of preclinical toxicity and

safety studies.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

L-arginine (780 mg per g of aztreonam)

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products except for

those mentioned in section 6.6.

6.3 Shelf life

(a) Product unopened: 3 years.

(b) Reconstituted product:

It is good practice to reconstitute immediately before use. If this is not possible,

Azactam is stable for 24 hours (8 hours for glucose intravenous infusion) if stored in a

refrigerator (2-8

C) when reconstituted with the recommended infusion solution to a

final concentration not exceeding 2% w/v.

From a microbiological point of view, the product should be used immediately. If not

used immediately, in-use storage times and conditions prior to use are the

responsibility of the user and would normally not be longer than 24 hours at 2 to 8ºC

unless reconstitution/dilution etc. has taken place in controlled and validated aseptic

conditions.

6.4 Special precautions for storage

a) Storage before reconstitution:

Do not store above 25

b) Storage after reconstitution:

See Sections 6.3. and 6.6.

6.5 Nature and contents of container

Type III Ph. Eur. clear glass vial, closed with siliconed grey butyl rubber closure, sealed

with aluminium seal and plastic flip off button: pack of 1 x 15 mL.

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6.6 Special precautions for disposal of a used medicinal product or waste

materials derived from such medicinal product and other handling of the

product

For single use only.

Any unused medicinal product or waste material should be disposed of in

accordance with local requirements.

Reconstitution:

Azactam Powder for solution for injection or infusion is supplied in 15 ml vials. Upon

the addition of the diluent the contents should be shaken immediately and

vigorously. Vials of reconstituted Azactam are not intended for multi-dose use, and

any unused solution from a single dose must be discarded. Depending on the type

and amount of diluent, the pH ranges from 4.5 to 7.5, and the colour may vary from

colourless to light straw-yellow, which may develop a slight pink tint on standing;

however this does not affect the potency.

For intramuscular injection: For each gram of aztreonam add at least 3 mL of Water

for Injections Ph Eur or 0.9% Sodium Chloride Injection BP and shake well.

Single-Dose Vial Size

Volume of Diluent to be added

0.5 g

1.5 mL

1.0 g

3.0 mL

Azactam is given by deep injection into a large muscle mass, such as the upper outer

quadrant of the gluteus maximus or the lateral part of the thigh.

For intravenous injection: To the contents of the vial add 6 to 10 mL of Water for

Injections Ph Eur, and shake well. Slowly inject directly into the vein over a period of

3 to 5 minutes.

For intravenous infusion: Each gram of drug should be reconstituted initially with at

least 3 mL of Water for Injections. This solution should then be diluted in the

appropriate infusion solution to a concentration not exceeding 1 g of drug per 50 mL

of solution. The infusion should be administered over 20-60 minutes. Appropriate

infusion solutions include:

0.9% Sodium Chloride Injection BP;

5% Glucose Intravenous Infusion BP;

5%, 10% Mannitol Intravenous Infusion BP;

Sodium Lactate Intravenous Infusion BP;

0.9%, 0.45% or 0.2% Sodium Chloride and 5% Glucose Intravenous Infusion BP;

Compound Sodium Chloride Injection BPC 1959 (Ringer's Solution for Injection);

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Compound Sodium Lactate Intravenous Infusion BP (Hartmann's Solution for

Injection).

A volume control administration set may be used to deliver the initial solution of

Azactam into a compatible infusion solution being administered. With use of a

Y-tube administration set, careful attention should be given to the calculated volume

of Azactam solution required so that the entire dose will be infused.

With intermittent infusion of Azactam and another drug via a common delivery tube,

the tube should be flushed before and after delivery of Azactam with any appropriate

infusion solution compatible with both drug solutions. Except for the antibiotics

described below, the drugs should not be delivered simultaneously.

Intravenous infusion solutions of Azactam for Injection prepared with 0.9% Sodium

Chloride Injection BP or 5% Glucose Intravenous Infusion BP, to which clindamycin

phosphate, gentamicin sulphate, tobramycin sulphate, or cephazolin sodium have

been added at concentrations usually used clinically, are stable for up to 24 hours in

a refrigerator (2-8°C). Ampicillin sodium admixtures with aztreonam in 0.9% Sodium

Chloride Injection BP are stable for 24 hours in a refrigerator (2-8°C); stability in 5%

Glucose Intravenous Infusion BP is eight hours under refrigeration.

If aztreonam and metronidazole are to be used together, they should be

administered separately as a cherry red colour has been observed after storage of

solutions containing combinations of the two products.

7 MARKETING AUTHORISATION HOLDER

Bristol-Myers Squibb Pharmaceuticals uc

Plaza 254, Blanchardstown Corporate Park 2

Ballycoolin

Dublin 15

D15 T867

Ireland

8 MARKETING AUTHORISATION NUMBER

PA0002/052/002

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 05 March 1985

Date of last renewal: 05 March 2010

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10 DATE OF REVISION OF THE TEXT

January 2019

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