Drugs List

Therapeutic Indications

Uses

Ps.aeruginosa lung infections in cystic fibrosis
Severe G-ve infections where other antibiotics contraindicated/ineffective

Treatment of severe systemic infections caused by sensitive Gram-negative organisms where alternative antibiotics are contra-indicated or ineffective because of resistance. Types of infection include lower respiratory tract infection, urinary tract infection and hospital acquired pneumonia (HAP).

Treatment of pseudomonas aeruginosa lung infection in patients with cystic fibrosis by nebulisation.

Administration

Intravenous
Administered by intravenous injection or infusion (over 30 to 60 minutes)

Patients with a totally implantable venous access device (TIVAD) in place may tolerate a bolus injection of up to 2 million units in 10 ml given over a minimum of 5 minutes.

Inhalation
Administered by nebulisation.
Nebulisation should take place in a well ventilated room.

Contraindications

Myasthenia gravis
Pregnancy

Precautions and Warnings

Children under 1 year
Severe haemoptysis
Breastfeeding
Haemodialysis
Hepatic impairment
Porphyria
Renal impairment

Advise ability to drive/operate machinery may be affected by side effects
Consult national/regional policy on the use of anti-infectives
Not all available brands are licensed for all indications
Not all available brands are licensed for all routes of administration
Not all routes are licensed for all indications
Any concomitant bronchodilator should be used first
Use in well ventilated area if administered by inhalation
Monitor renal function before treatment and regularly during treatment
Close medical supervision during initial dosing
Monitor for signs of neurological toxicity
Monitor lung function if administered by inhalation
Monitor plasma levels and adapt dose in patients with renal impairment
Bronchospasm(lowered FEV)in presence of bronchodilator may indicate allergy
Consider colitis if patient presents with chronic diarrhoea
Nephrotoxicity or neurotoxicity may occur if recommended dose is exceeded
Discontinue if drug-related rash or other hypersensitivity reactions occur
Discontinue if severe and persistent diarrhoea develops
Bronchodilator therapy may be used to reduce bronchospasm
Advise patient to rinse mouth with water after each inhaled dose

Use with caution in patients receiving curariform muscle relaxants or antibiotics with similar nephrotoxic or neurotoxic effects, such as aminoglycosides.

Bronchospasm may occur on inhalation of antibiotics. This may be prevented or treated with appropriate use of beta 2 agonists. If troublesome, treatment should be withdrawn.

Pregnancy and Lactation

Pregnancy

Colistimethate is contraindicated during pregnancy.

While some sources suggest that the inhalation of nebulised colistimethate sodium is probably safe to use during pregnancy, the manufacturers suggest colistimethate sodium should only be used during pregnancy if the benefit to the mother outweighs the potential risk to the foetus.

There is no adequate data on the use of colistimethate during human pregnancy. Single dose studies in human pregnancy show that colistimethate crosses the placental barrier and there is a risk of foetal toxicity if repeated doses are given to pregnant patients.

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 colistimethate with caution in breastfeeding.

The Drugs and Lactation Database (LactMed) suggests inhaled colistimethate sodium is acceptable for use in breastfeeding. The manufacturers suggest colistimethate sodium should only be used in breastfeeding if the benefit to the mother outweighs the potential risk to the foetus.

Colistimethate is secreted in breast milk. Colistin is poorly absorbed orally, it is unlikely to be absorbed in appreciable amounts by the infant. However, modification of bowel flora, direct effects on the infant and interference with culture results cannot be excluded.

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

Alteration of autonomic nervous system
Angioedema
Apnoea
Ataxia
Blood urea increased
Bronchospasm (on inhalation)
Candida albicans infection
Confusion
Cough
Decrease in creatinine clearance
Dizziness
Drug fever
Dysarthria
Facial paraesthesia
Forced expiratory volume decreased
Headache
Hypersensitivity reactions
Local reaction at injection site
Myasthenia
Nephrotoxicity
Neurotoxicity
Pain
Paraesthesia
Perioral paraesthesia
Pruritus
Psychosis
Rash
Renal failure
Renal impairment
Serum creatinine increased
Shortness of breath
Slurred speech
Sore mouth
Sore throat
Vasomotor instability
Vertigo
Visual disturbances
Wheezing

Presentation

Colistimethate sodium parenteral and solution for nebulisation

Drugs List

Therapeutic Indications

Uses

Ps.aeruginosa lung infections in cystic fibrosis
Severe G-ve infections where other antibiotics contraindicated/ineffective

Treatment of severe systemic infections caused by sensitive Gram-negative organisms where alternative antibiotics are contra-indicated or ineffective because of resistance. Types of infection include lower respiratory tract infection, urinary tract infection and hospital acquired pneumonia (HAP).

Treatment of pseudomonas aeruginosa lung infection in patients with cystic fibrosis by nebulisation.

Dosage

The dosage is determined by the severity and type of infection, the sensitivity of the causative bacteria and the age, weight and renal function of the patient.

Adults

Children

Patients with Renal Impairment

Administration

Intravenous
Administered by intravenous injection or infusion (over 30 to 60 minutes)

Patients with a totally implantable venous access device (TIVAD) in place may tolerate a bolus injection of up to 2 million units in 10 ml given over a minimum of 5 minutes.

Inhalation
Administered by nebulisation.
Nebulisation should take place in a well ventilated room.

Therapeutic Drug Monitoring

Serum level estimations are recommended, especially in renal impairment, neonates and patients with cystic fibrosis.
Peak plasma-colistimethate concentration (approximately 1 hour after the intravenous administration) 5 to 15 mg/litre. Trough 2 to 6 mg/litre

Contraindications

Myasthenia gravis
Pregnancy

Precautions and Warnings

Children under 1 year
Severe haemoptysis
Breastfeeding
Haemodialysis
Hepatic impairment
Porphyria
Renal impairment

Advise ability to drive/operate machinery may be affected by side effects
Consult national/regional policy on the use of anti-infectives
Not all available brands are licensed for all indications
Not all available brands are licensed for all routes of administration
Not all routes are licensed for all indications
Any concomitant bronchodilator should be used first
Use in well ventilated area if administered by inhalation
Monitor renal function before treatment and regularly during treatment
Close medical supervision during initial dosing
Monitor for signs of neurological toxicity
Monitor lung function if administered by inhalation
Monitor plasma levels and adapt dose in patients with renal impairment
Bronchospasm(lowered FEV)in presence of bronchodilator may indicate allergy
Consider colitis if patient presents with chronic diarrhoea
Nephrotoxicity or neurotoxicity may occur if recommended dose is exceeded
Discontinue if drug-related rash or other hypersensitivity reactions occur
Discontinue if severe and persistent diarrhoea develops
Bronchodilator therapy may be used to reduce bronchospasm
Advise patient to rinse mouth with water after each inhaled dose

Use with caution in patients receiving curariform muscle relaxants or antibiotics with similar nephrotoxic or neurotoxic effects, such as aminoglycosides.

Bronchospasm may occur on inhalation of antibiotics. This may be prevented or treated with appropriate use of beta 2 agonists. If troublesome, treatment should be withdrawn.

Pregnancy and Lactation

Pregnancy

Colistimethate is contraindicated during pregnancy.

While some sources suggest that the inhalation of nebulised colistimethate sodium is probably safe to use during pregnancy, the manufacturers suggest colistimethate sodium should only be used during pregnancy if the benefit to the mother outweighs the potential risk to the foetus.

There is no adequate data on the use of colistimethate during human pregnancy. Single dose studies in human pregnancy show that colistimethate crosses the placental barrier and there is a risk of foetal toxicity if repeated doses are given to pregnant patients.

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 colistimethate with caution in breastfeeding.

The Drugs and Lactation Database (LactMed) suggests inhaled colistimethate sodium is acceptable for use in breastfeeding. The manufacturers suggest colistimethate sodium should only be used in breastfeeding if the benefit to the mother outweighs the potential risk to the foetus.

Colistimethate is secreted in breast milk. Colistin is poorly absorbed orally, it is unlikely to be absorbed in appreciable amounts by the infant. However, modification of bowel flora, direct effects on the infant and interference with culture results cannot be excluded.

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

Alteration of autonomic nervous system
Angioedema
Apnoea
Ataxia
Blood urea increased
Bronchospasm (on inhalation)
Candida albicans infection
Confusion
Cough
Decrease in creatinine clearance
Dizziness
Drug fever
Dysarthria
Facial paraesthesia
Forced expiratory volume decreased
Headache
Hypersensitivity reactions
Local reaction at injection site
Myasthenia
Nephrotoxicity
Neurotoxicity
Pain
Paraesthesia
Perioral paraesthesia
Pruritus
Psychosis
Rash
Renal failure
Renal impairment
Serum creatinine increased
Shortness of breath
Slurred speech
Sore mouth
Sore throat
Vasomotor instability
Vertigo
Visual disturbances
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: November 2015

Reference Sources

Martindale: The Complete Drug Reference (online) London: Brayfield A (ed). Pharmaceutical Press. Accessed on 6 November 2015.

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.

Summary of Product Characteristics: ColiFin 1 and 2 million international units. Pari Medical Ltd. Revised February 2010.
Summary of Product Characteristics: Colomycin Injection. Forest Laboratories UK Ltd. Revised June 2015.
Summary of Product Characteristics: Promixin 1 million international units powder for solution for infusion. Profile Pharma Ltd. Revised January 2016.
Summary of Product Characteristics: Promixin 1 million international units powder for solution for nebuliser solution. Profile Pharma Ltd. Revised November 2017.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 14 June 2019

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
Colistimethate. Last revised: 1 April 2016
Last accessed: 4 August 2016