Bristol-Myers Squibb Pharmaceutical Limited

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

10.       DATE OF REVISION OF THE TEXT

June 2015

4.2       Posology and method of administration - the below text have been added

Hepatic impairment:

SPC Sections 4.2, 4.4, 4.5, 4.6, 4.7, 4.8 and 4.9 of the SPC are updated in line with agreed Core Safety Profile (CSP) following the EU PSUR WS-Final Assessment Report

4.2 Posology and method of admnistration

Dosage Guide - simplified and following added

Elderly:  Following text added:

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.

Renal Impairment:   Table replaced by the following text:

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.

Paediatrics: Following sentence added:

The maximum daily paediatric dose should not exceed the maximum recommended dose for adults.

4.4. Special warnings and precautions of use

Allergic reactions:  Following sentence added:

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 approprite.  Serious hypersensitivity reactions may require epinephrine and other emergency measures.

Following sections added:

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: Following sentence added:

Medication that inhibits intestinal peristalsis should not be given.

Overgrowth of non-susceptible organisms:  Updated as below:

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. 

Following sections added:

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: 

Following added

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).

4.6        Use during pregnancy and lactation

Following added:

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.

4.7        Effects on ability to drive and use machines

Updated as follows:

No studies on the effects on the ability to drive and use machines have been performed.

4.8        Undesirable effects

A Table of list of undesirable effects presented by system organ class, MedDRA preferred term, and frequency replaces the text.

4.9        Overdose symptoms, emergency procedures, antidotes

Following added:

Aztreonam has been shown to be cleared from the serum by continuous arteriovenous hemofiltration.