Drugs List

Therapeutic Indications

Uses

Bacterial infections of the central nervous system
Cerebral ventriculitis
Supplement to systemic therapy in bacterial meningitis

Gentamicin is a broad spectrum antibiotic and is usually effective against most strains of Escherichia coli, Klebsiella spp., Proteus spp., Pseudomonas aeruginosa, Staphylococci, Enterobacter spp., Citrobacter spp. and Providencia spp.

Gentamicin intrathecal injection is indicated as a supplement to systemic therapy in bacterial meningitis, ventriculitis and other bacterial infections of the central nervous system.

Administration

For intrathecal or intraventricular administration.

Contraindications

Myasthenia gravis

Precautions and Warnings

Elderly
Auditory impairment
Breastfeeding
Neuromuscular disorder
Pregnancy
Renal impairment
Vestibular impairment

Consult national/regional policy on the use of anti-infectives
Evaluate renal function before and during treatment
Monitor auditory and vestibular function
Monitor peak and trough serum levels
Potentially ototoxic and nephrotoxic

Ototoxicity has been reported following gentamicin administration. Patients at increased risk of developing ototoxicity include patients with renal impairment and possibly the elderly.
Renal function should be assessed before starting and during treatment. Auditory and vestibular function should also be monitored during treatment with aminoglycosides. Serum levels should be determined to avoid peak concentrations above 10mg/l and trough concentrations above 2mg/l.

Both ototoxicity and nephrotoxicity are related to the total exposure to gentamicin, therefore treatment duration should be as short as clinically possible.

In some patients with renal impairment a transient rise in blood urea nitrogen may occur, although this usually resolves after cessation of therapy.

Periodic serum and cerebrospinal fluid gentamicin assays should be carried out to ensure that adequate antibiotic levels are maintained and that serum and cerebrospinal fluid levels do not exceed 10mg/l.

Higher than expected levels of histamine have been identified in some batches of Gentamicin Sulphate Active Pharmaceutical Ingredient (API) used in the manufacture of gentamicin injection. At the time of writing, no products have been recalled. The MHRA advises to monitor patients for signs of histamine-related reactions. Particular caution is advised when gentamicin is used concomitantly with other drugs known to cause histamine release, in children and in patients with severe renal impairment. API batches produced between the second half of 2014 and 2017 are potentially affected which may have been used in the manufacturer of the following product:

Zentiva Gentamicin Intrathecal 5mg/ml Solution for Injection. PL number 17780/0506.

Pregnancy and Lactation

Pregnancy

Use intrathecal gentamicin with caution during pregnancy.

There are few reports of intrauterine damage caused by gentamicin. However usage in pregnancy should only be considered in life threatening situations where expected benefits outweigh potential risks.

Gentamicin rapidly crosses the placenta into the amniotic fluid and foetal circulation. Ototoxicity, a known side effect of gentamicin, has not been reported following in utero exposure. However, eighth-cranial-nerve toxicity in the foetus is well known following exposure to kanamycin and streptomycin, and may potentially occur with gentamicin.

Schaefer (2015) suggests that aminoglycosides should only be used parenterally in life threatening circumstances. Serum levels should be monitored regularly. If therapy has been prolonged, consider monitoring renal function in the neonate, as well as performing an auditory test.

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 intrathecal gentamicin with caution during breastfeeding.

Gentamicin is excreted into the breast milk in small quantities and is absorbed by the nursing infant. The American Academy of Paediatrics suggests that gentamicin is compatible with breastfeeding (Briggs, 2015).

Schaefer (2015) suggests that aminoglycosides can be given parenterally for urgent indications whilst the mother is breastfeeding. The use of the antibiotic should be critically reviewed as a risk of ototoxicity to the nursing infant cannot be ruled out.

Monitor the infant for possible effects on the gastrointestinal flora, including diarrhoea, candidiasis or blood in the stool indicating possible antibiotic-associated colitis (LactMed).

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

Abnormal liver function
Acute renal failure
Anaemia
Antibiotic-associated colitis
Confusion
Convulsions
Depression
Encephalopathy
Hallucinations
Hypersensitivity reactions
Hypomagnesaemia
Increase in blood urea nitrogen
Lethargy
Nausea
Nephrotoxicity
Neurotoxicity
Ototoxicity
Peripheral neuropathy
Purpura
Rash
Stomatitis
Vestibular and auditory damage
Vomiting

Presentation

Solution for injection containing gentamicin sulfate.

Drugs List

Therapeutic Indications

Uses

Bacterial infections of the central nervous system
Cerebral ventriculitis
Supplement to systemic therapy in bacterial meningitis

Gentamicin is a broad spectrum antibiotic and is usually effective against most strains of Escherichia coli, Klebsiella spp., Proteus spp., Pseudomonas aeruginosa, Staphylococci, Enterobacter spp., Citrobacter spp. and Providencia spp.

Gentamicin intrathecal injection is indicated as a supplement to systemic therapy in bacterial meningitis, ventriculitis and other bacterial infections of the central nervous system.

Dosage

The starting dose of gentamicin intrathecal injection is 1mg daily, intrathecally or intraventricularly, together with 1mg/kg every eight hours intramuscularly. The minimum inhibitory concentration of the infecting organism in the cerebrospinal fluid should be assessed and, if necessary, the intrathecal/intraventricular dose increased to 5mg daily, whilst keeping the intramuscular dose at 1mg/kg eight-hourly.

Patients with Renal Impairment

Additional Dosage Information

Administration

For intrathecal or intraventricular administration.

Contraindications

Myasthenia gravis

Precautions and Warnings

Elderly
Auditory impairment
Breastfeeding
Neuromuscular disorder
Pregnancy
Renal impairment
Vestibular impairment

Consult national/regional policy on the use of anti-infectives
Evaluate renal function before and during treatment
Monitor auditory and vestibular function
Monitor peak and trough serum levels
Potentially ototoxic and nephrotoxic

Ototoxicity has been reported following gentamicin administration. Patients at increased risk of developing ototoxicity include patients with renal impairment and possibly the elderly.
Renal function should be assessed before starting and during treatment. Auditory and vestibular function should also be monitored during treatment with aminoglycosides. Serum levels should be determined to avoid peak concentrations above 10mg/l and trough concentrations above 2mg/l.

Both ototoxicity and nephrotoxicity are related to the total exposure to gentamicin, therefore treatment duration should be as short as clinically possible.

In some patients with renal impairment a transient rise in blood urea nitrogen may occur, although this usually resolves after cessation of therapy.

Periodic serum and cerebrospinal fluid gentamicin assays should be carried out to ensure that adequate antibiotic levels are maintained and that serum and cerebrospinal fluid levels do not exceed 10mg/l.

Higher than expected levels of histamine have been identified in some batches of Gentamicin Sulphate Active Pharmaceutical Ingredient (API) used in the manufacture of gentamicin injection. At the time of writing, no products have been recalled. The MHRA advises to monitor patients for signs of histamine-related reactions. Particular caution is advised when gentamicin is used concomitantly with other drugs known to cause histamine release, in children and in patients with severe renal impairment. API batches produced between the second half of 2014 and 2017 are potentially affected which may have been used in the manufacturer of the following product:

Zentiva Gentamicin Intrathecal 5mg/ml Solution for Injection. PL number 17780/0506.

Pregnancy and Lactation

Pregnancy

Use intrathecal gentamicin with caution during pregnancy.

There are few reports of intrauterine damage caused by gentamicin. However usage in pregnancy should only be considered in life threatening situations where expected benefits outweigh potential risks.

Gentamicin rapidly crosses the placenta into the amniotic fluid and foetal circulation. Ototoxicity, a known side effect of gentamicin, has not been reported following in utero exposure. However, eighth-cranial-nerve toxicity in the foetus is well known following exposure to kanamycin and streptomycin, and may potentially occur with gentamicin.

Schaefer (2015) suggests that aminoglycosides should only be used parenterally in life threatening circumstances. Serum levels should be monitored regularly. If therapy has been prolonged, consider monitoring renal function in the neonate, as well as performing an auditory test.

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 intrathecal gentamicin with caution during breastfeeding.

Gentamicin is excreted into the breast milk in small quantities and is absorbed by the nursing infant. The American Academy of Paediatrics suggests that gentamicin is compatible with breastfeeding (Briggs, 2015).

Schaefer (2015) suggests that aminoglycosides can be given parenterally for urgent indications whilst the mother is breastfeeding. The use of the antibiotic should be critically reviewed as a risk of ototoxicity to the nursing infant cannot be ruled out.

Monitor the infant for possible effects on the gastrointestinal flora, including diarrhoea, candidiasis or blood in the stool indicating possible antibiotic-associated colitis (LactMed).

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

Abnormal liver function
Acute renal failure
Anaemia
Antibiotic-associated colitis
Confusion
Convulsions
Depression
Encephalopathy
Hallucinations
Hypersensitivity reactions
Hypomagnesaemia
Increase in blood urea nitrogen
Lethargy
Nausea
Nephrotoxicity
Neurotoxicity
Ototoxicity
Peripheral neuropathy
Purpura
Rash
Stomatitis
Vestibular and auditory damage
Vomiting

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: May 2017

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Summary of Product Characteristics: Gentamicin Intrathecal 5mg/ml. Zentiva. Revised June 2015.

MHRA Drug Safety Update October 2017
Available at: https://www.mhra.gov.uk
Last accessed: 25 January 2018

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
Gentamicin Last revised: 10 March 2015
Last accessed: 25 April 2017