Drugs List

Therapeutic Indications

Uses

Chronic pulmonary infection caused by P.aeruginosa in cystic fibrosis

Administration

Aztreonam nebuliser solution is administered by inhalation over a 2 to 3 minute period, using Altera Nebuliser System (consisting of a product specific Altera Nebuliser Handset and an Altera Aerosol Head connected to an eBase Controller or an eFlow rapid control unit.)

Aztreonam nebuliser solution should not be mixed with any other medicinal products in the Altera Nebuliser Handset.

Contraindications

Children under 6 years

Precautions and Warnings

Haemoptysis
Pregnancy
Renal impairment

Superinfection may occur during therapy
Discontinue if allergic reaction occurs

Use with caution in patients with a history of allergy to beta-lactam antibiotics, such as penicillins, cephalosporins, and/or carbapenems as cross-reactivity may occur. Aztreonam is reported by the manufacturer to be only weakly immunogenic. If the patient had a hypersensitivity to another beta-lactam antibiotic initial administration should take place where immediate medical assistance can be provided.

Bronchospasm is a complication associated with nebulised therapies. Patients should use a bronchodilator before each dose of aztreonam. If a case of bronchospasm is suspected to be part of an allergic reaction appropriate measures should be taken.

Safety and efficacy of aztreonam solution for nebulisation has not been tested in patients with a forced expiratory volume in one second (FEV1) less than 25% or greater than 75% of predicted.

The development of antibiotic-resistant P. aeruginosa and superinfection with other pathogens represent potential risks associated with antibiotic treatment. During clinical studies of aztreonam nebuliser solution a decrease in P. aeruginosa sensitivity occurred in patients to both aztreonam and other beta-lactam antibiotics. Decreased P. aeruginosa sensitivity was not predictive of clinical efficacy of aztreonam during the study. Among patients with multidrug-resistant P. aeruginosa, improvements in respiratory symptoms and pulmonary function were observed following treatment with aztreonam. The development of resistance in P. aeruginosa to parenteral aztreonam or other beta-lactam antibiotics may have consequences for the treatment of acute lung infections with systemic antibiotics. Increased detection of methicillin -resistant and -sensitive staphylococcus aureus (MRSA and MSSA), aspergillus and candida species occurred in patients treated with several aztreonam treatment courses. An association between persistent isolation of MRSA and worsening of clinical outcome has been documented. When clinical studies of branded aztreonam nebuliser solution were conducted isolation of MRSA wasn't associated with worsening lung function.

Pregnancy and Lactation

Pregnancy

Use aztreonam with caution in pregnancy.

There is limited data about the use of aztreonam in pregnant women however the animal data suggests low risk. The low toxicity in animal studies and the fact that the drug is given by injection in neonates both suggest low risk. Therefore aztreonam should not be withheld in pregnancy if indicated.

The data shows that aztreonam, when 1 gram was administered by maternal intravenous injection, crosses into the foetal serum and amniotic fluid. However the systemic concentration of aztreonam following inhaled administration is approximately 1% of the concentration resulting from a standard dose of aztreonam by injection. Given the low systemic exposure of aztreonam in the mother the level of exposure to the infant is expected to be minimal. Given the relative safety of beta-lactam antibiotics generally in pregnancy, aztreonam is not expected to be harmful.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use aztreonam with caution in breastfeeding.

Aztreonam is excreted in human milk at very low concentrations. Systemic concentration of aztreonam following inhaled administration is approximately 1% of the concentration resulting from a standard dose of aztreonam by injection. Due to the low oral absorption, aztreonam exposure in breastfed infants due to mothers receiving nebulised aztreonam is likely to be extremely low. Nebulised aztreonam can be used during breastfeeding.

Aztreonam may affect the intestinal flora of the newborn infant and cause thrush or diarrhoea, this is not a reason to discontinue breastfeeding however.

The American academy of pediatrics classifies aztreonam as compatible with breastfeeding.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Allergic reaction
Arthralgia
Bronchospasm
Chest discomfort
Cough
Dyspnoea
Haemoptysis
Joint swelling
Nasal congestion
Pharyngolaryngeal pain
Pyrexia
Rash
Rhinorrhoea
Wheezing

Presentation

Powder and solvent for nebuliser solution containing 75mg aztreonam (as aztreonam lysine) per 1ml vial

Drugs List

Therapeutic Indications

Uses

Chronic pulmonary infection caused by P.aeruginosa in cystic fibrosis

Dosage

For patients receiving several respiratory therapies, the recommended order is:

1. Bronchodilator
2. Mucolytics such as dornase alfa
3. Chest physiotherapy
4. Other inhaled medicinal products
5. and then lastly Aztreonam

Adults

Children

Patients with Renal Impairment

Additional Dosage Information

Administration

Aztreonam nebuliser solution is administered by inhalation over a 2 to 3 minute period, using Altera Nebuliser System (consisting of a product specific Altera Nebuliser Handset and an Altera Aerosol Head connected to an eBase Controller or an eFlow rapid control unit.)

Aztreonam nebuliser solution should not be mixed with any other medicinal products in the Altera Nebuliser Handset.

Contraindications

Children under 6 years

Precautions and Warnings

Haemoptysis
Pregnancy
Renal impairment

Superinfection may occur during therapy
Discontinue if allergic reaction occurs

Use with caution in patients with a history of allergy to beta-lactam antibiotics, such as penicillins, cephalosporins, and/or carbapenems as cross-reactivity may occur. Aztreonam is reported by the manufacturer to be only weakly immunogenic. If the patient had a hypersensitivity to another beta-lactam antibiotic initial administration should take place where immediate medical assistance can be provided.

Bronchospasm is a complication associated with nebulised therapies. Patients should use a bronchodilator before each dose of aztreonam. If a case of bronchospasm is suspected to be part of an allergic reaction appropriate measures should be taken.

Safety and efficacy of aztreonam solution for nebulisation has not been tested in patients with a forced expiratory volume in one second (FEV1) less than 25% or greater than 75% of predicted.

The development of antibiotic-resistant P. aeruginosa and superinfection with other pathogens represent potential risks associated with antibiotic treatment. During clinical studies of aztreonam nebuliser solution a decrease in P. aeruginosa sensitivity occurred in patients to both aztreonam and other beta-lactam antibiotics. Decreased P. aeruginosa sensitivity was not predictive of clinical efficacy of aztreonam during the study. Among patients with multidrug-resistant P. aeruginosa, improvements in respiratory symptoms and pulmonary function were observed following treatment with aztreonam. The development of resistance in P. aeruginosa to parenteral aztreonam or other beta-lactam antibiotics may have consequences for the treatment of acute lung infections with systemic antibiotics. Increased detection of methicillin -resistant and -sensitive staphylococcus aureus (MRSA and MSSA), aspergillus and candida species occurred in patients treated with several aztreonam treatment courses. An association between persistent isolation of MRSA and worsening of clinical outcome has been documented. When clinical studies of branded aztreonam nebuliser solution were conducted isolation of MRSA wasn't associated with worsening lung function.

Pregnancy and Lactation

Pregnancy

Use aztreonam with caution in pregnancy.

There is limited data about the use of aztreonam in pregnant women however the animal data suggests low risk. The low toxicity in animal studies and the fact that the drug is given by injection in neonates both suggest low risk. Therefore aztreonam should not be withheld in pregnancy if indicated.

The data shows that aztreonam, when 1 gram was administered by maternal intravenous injection, crosses into the foetal serum and amniotic fluid. However the systemic concentration of aztreonam following inhaled administration is approximately 1% of the concentration resulting from a standard dose of aztreonam by injection. Given the low systemic exposure of aztreonam in the mother the level of exposure to the infant is expected to be minimal. Given the relative safety of beta-lactam antibiotics generally in pregnancy, aztreonam is not expected to be harmful.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use aztreonam with caution in breastfeeding.

Aztreonam is excreted in human milk at very low concentrations. Systemic concentration of aztreonam following inhaled administration is approximately 1% of the concentration resulting from a standard dose of aztreonam by injection. Due to the low oral absorption, aztreonam exposure in breastfed infants due to mothers receiving nebulised aztreonam is likely to be extremely low. Nebulised aztreonam can be used during breastfeeding.

Aztreonam may affect the intestinal flora of the newborn infant and cause thrush or diarrhoea, this is not a reason to discontinue breastfeeding however.

The American academy of pediatrics classifies aztreonam as compatible with breastfeeding.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Allergic reaction
Arthralgia
Bronchospasm
Chest discomfort
Cough
Dyspnoea
Haemoptysis
Joint swelling
Nasal congestion
Pharyngolaryngeal pain
Pyrexia
Rash
Rhinorrhoea
Wheezing

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: March 2014

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press https://www.medicinescomplete.com [March 21, 2014].

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Paediatric Formulary Committee. BNF for Children (online) London: BMJ Group, Pharmaceutical Press, and RCPCH Publications https://www.medicinescomplete.com [Accessed on March 21, 2014].

Summary of Product Characteristics: Cayston 75mg powder and solvent for nebuliser solution. Gilead Sciences Ltd. Revised July 2012.

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Aztreonam Last revised: September 7, 2013
Last accessed: March 21, 2014