Drugs List

Therapeutic Indications

Uses

Treatment of the following infections caused by susceptible micro-organisms:

Central nervous system infections including meningitis, septicaemia and neonatal sepsis

Gastrointestinal infections including peritonitis

Complicated and recurrent urinary tract infections including pyelonephritis and cystitis

Lower respiratory tract infections including pneumonia, bronchopneumonia and acute bronchitis

Skin, bone and soft tissue infections including burns

Tobramycin may also be considered for severe staphylococcal infections where penicillin or other less potentially toxic drugs are contraindicated, and when bacterial susceptibility testing and clinical judgement support the administration of tobramycin.

Administration

For intramuscular injection, intravenous injection or intravenous infusion.

Intramuscular or intravenous injection
The appropriate dose may be withdrawn directly from the vial/ampoule.

For intravenous injection, tobramycin may be administered by direct intravenous injection or into the tubing of a drip set. When given in this way, serum levels may exceed 12mg/litre for a short time.

Intravenous infusion
Once diluted (see reconstitution), infuse over a period of 20 to 60 minutes. Admixture with any other drug should be avoided.

Handling

Chemical and physical in-use stability has been demonstrated in glucose 5% and sodium chloride 0.9% infusion solutions for 24 hours at 24 degrees C in the presence in light.

From a microbiological point of view the product should be used immediately. if not used immediately, storage times and conditions prior to use are the responsibility of the user and would not normally be for longer than 24 hours at 2 to 8 degrees C, unless dilution has taken place in controlled and validated aseptic conditions.

Reconstitution

For intravenous infusion, the tobramycin injection solution may be diluted with sodium chloride infusion 0.9% or glucose infusion 5%.

Dilute to volumes of 50 to 100ml for adult doses. The volume should be proportionately less for children.

Incompatibilities

Incompatibility or loss of activity has been reported between tobramycin and some cephalosporins, penicillins and heparin sodium. Solutions with clindamycin phosphate in glucose injection are reported to be unstable.

Tobramycin injection should not be mixed with other drugs and must be administered separately.

Contraindications

Myasthenia gravis

Precautions and Warnings

Patients receiving tobramycin should be under close clinical observation as aminoglycosides have the potential to cause nephrotoxicity and ototoxicity. Treatment duration should be as short as clinically possible. Care should be taken when treatment duration exceeds 7 days.

Vestibular and auditory ototoxicity can occur. Auditory changes are irreversible, usually bilateral, and may be partial or total. Eighth cranial nerve impairment may occur in patients with dehydration, renal impairment, or in those receiving tobramycin for prolonged periods or in higher than recommended dosages. Manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching and convulsions.

The risk of hearing loss increases with the level of exposure to high peak or high trough serum concentrations of tobramycin. Patients developing cochlear damage may not develop symptoms during therapy to warn of eighth cranial nerve toxicity. Partial or total irreversible bilateral deafness may therefore continue to develop after tobramycin has been discontinued.

Rarely, nephrotoxicity may not be observed until the first few days after therapy cessation. Aminoglycoside-induced nephrotoxicity is usually reversible.

Renal function should be assessed before starting and during treatment. Auditory and vestibular function should also be monitored during treatment with aminoglycosides. It is desirable to measure both peak and trough serum concentrations as high doses may be associated with a greater risk of toxicity. If impairment of renal, vestibular and/or auditory function occurs, dosage adjustment or discontinuation of therapy should be considered. Blood levels should always be determined in patients with chronic infections (such as cystic fibrosis), where prolonged treatment is required, in patients with renal impairment, and in infants, elderly and obese patients. See Therapeutic Drug Monitoring .

Dehydration should be corrected before starting therapy with aminoglycosides.

Obese patients - see Additional dosage
Renal impairment - see Dosage; Renal Impairment
Pregnancy - see Pregnancy section
Breastfeeding - see Lactation section

In elderly patients, it is important to monitor renal function where renal impairment may not be evident in the results of routine screening tests (such as blood urea or serum creatinine). Creatinine clearance determinations may be more useful. Ototoxicity and nephrotoxicity are more common in elderly patients.

Tobramycin should be used with caution and at a reduced dose in premature and full term neonates younger than 6 weeks of age. This is because of their renal immaturity and the prolonged serum half-life of tobramycin.

Tobramycin injection contains sodium metabisulfite which can cause allergic-type reactions (such as anaphylaxis, or life-threatening or less severe asthmatic episodes) in some susceptible people. Patients with asthma appear to be more susceptible to these reactions.

Urine should be tested to detect increased excretion of protein, cells and casts.

Serum creatinine or creatinine clearance should be measured periodically.

Audiograms should be obtained regularly in patients old enough to be tested, especially in those at increased risk of ototoxicity.

Serum calcium, magnesium and sodium should be monitored, especially in patients with renal impairment.

Patients with extensive burns may have reduced serum drug levels. Dosage should be based on serum levels in these patients.

Use with caution in patients with muscular disorders. Tobramycin may aggravate muscle weakness due to the potential curare-like effect on neuromuscular function.
A transient myasthenic syndrome has occurred in patients with normal neuromuscular function given large doses of aminoglycoside during surgery.

Appropriate therapy should be initiated in patients who develop overgrowth of non-susceptible organisms.

Pregnancy and Lactation

Pregnancy

If tobramycin is administered during pregnancy or if the patient becomes pregnant while receiving therapy, the potential risks to the foetus should be explained. Eighth cranial nerve toxicity in the foetus is well known following exposure to other aminoglycosides and may potentially occur with tobramycin.

If given during pregnancy, serum concentration monitoring is essential.

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 14-17 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 at https://www.toxbase.org/

Licensed in pregnancy? - Yes

Known human teratogen? - No.

Animal data - Renal toxicity in pregnant rats and foetuses after maternal administration of 30 to 60mg/kg tobramycin for 10 days during organogenesis.

Crosses placenta? - Yes

Effects on foetus - Eighth cranial nerve toxicity in the foetus is well known following exposure to streptomycin, and may potentially occur with tobramycin.

Lactation

Tobramycin is poorly excreted in to breast milk and systemic effects of tobramycin on the infant is unlikely.

If breast feeding is continued during tobramycin administration, the infant should be monitored for possible effects on gastrointestinal flora (e.g. diarrhoea, candidiasis, or blood in stools indicating possible antibiotic-associated colitis)

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

Nephrotoxicity
Renal impairment
Blood urea increased
Serum creatinine increased
Oliguria
Cylindruria
Proteinuria
Vestibular and auditory damage
Dizziness
Vertigo
Tinnitus
Hearing disturbances
Hearing loss
Increase in serum ALT/AST
Serum bilirubin increased
Decrease in plasma calcium
Hypomagnesaemia
Decreased serum sodium
Reduced plasma potassium levels
Anaemia
Granulocytopenia
Thrombocytopenia
Leucopenia
Leucocytosis
Eosinophilia
Fever
Rash
Itching
Urticaria
Nausea
Vomiting
Headache
Lethargy
Local pain (injection site)
Confusion
Disorientation
Antibiotic-associated colitis
Exfoliative dermatitis
Diarrhoea
Ototoxicity
Neuromuscular block
Peripheral neuropathy
Convulsions
Electrolyte disturbances
CNS effects

Presentation

Solution for injection containing tobramycin 40mg/1ml

Solution for injection containing tobramycin 80mg/2ml

Solution for injection containing tobramycin 240mg/6ml

Drugs List

Therapeutic Indications

Uses

Treatment of the following infections caused by susceptible micro-organisms:

Central nervous system infections including meningitis, septicaemia and neonatal sepsis

Gastrointestinal infections including peritonitis

Complicated and recurrent urinary tract infections including pyelonephritis and cystitis

Lower respiratory tract infections including pneumonia, bronchopneumonia and acute bronchitis

Skin, bone and soft tissue infections including burns

Tobramycin may also be considered for severe staphylococcal infections where penicillin or other less potentially toxic drugs are contraindicated, and when bacterial susceptibility testing and clinical judgement support the administration of tobramycin.

Dosage

The usual duration of treatment is seven to ten days. In more severe or complicated infections a longer duration of therapy may be necessary. In these cases renal, auditory and vestibular function should be monitored as neurotoxicity is more likely when treatment duration exceeds 10 days.

Peak and trough blood levels should be determined where possible to ensure that correct dosages are administered. Blood levels should always be determined in patients with chronic infections (such as in cystic fibrosis), where prolonged treatment is required, in patients with renal impairment, and in infants, elderly. See Therapeutic Drug Monitoring.

Adults

Elderly

Children

Neonates

Patients with Renal Impairment

Additional Dosage Information

Administration

For intramuscular injection, intravenous injection or intravenous infusion.

Intramuscular or intravenous injection
The appropriate dose may be withdrawn directly from the vial/ampoule.

For intravenous injection, tobramycin may be administered by direct intravenous injection or into the tubing of a drip set. When given in this way, serum levels may exceed 12mg/litre for a short time.

Intravenous infusion
Once diluted (see reconstitution), infuse over a period of 20 to 60 minutes. Admixture with any other drug should be avoided.

Handling

Chemical and physical in-use stability has been demonstrated in glucose 5% and sodium chloride 0.9% infusion solutions for 24 hours at 24 degrees C in the presence in light.

From a microbiological point of view the product should be used immediately. if not used immediately, storage times and conditions prior to use are the responsibility of the user and would not normally be for longer than 24 hours at 2 to 8 degrees C, unless dilution has taken place in controlled and validated aseptic conditions.

Reconstitution

For intravenous infusion, the tobramycin injection solution may be diluted with sodium chloride infusion 0.9% or glucose infusion 5%.

Dilute to volumes of 50 to 100ml for adult doses. The volume should be proportionately less for children.

Incompatibilities

Incompatibility or loss of activity has been reported between tobramycin and some cephalosporins, penicillins and heparin sodium. Solutions with clindamycin phosphate in glucose injection are reported to be unstable.

Tobramycin injection should not be mixed with other drugs and must be administered separately.

Therapeutic Drug Monitoring

Serum concentrations

Following intramuscular injection of 1mg/kg in adults with normal renal function, peak plasma concentrations averaging 4 to 6micrograms/ml are attained within 30 to 90 minutes. At 8 hours, plasma concentrations are 1microgram/ml or less.
One-hour ('peak') serum concentrations should not exceed 10mg/litre; pre-dose ('trough') concentration should be less than 2mg/litre.

Following intravenous infusion of 1mg/kg over 30 to 60 minutes, similar plasma concentration to those achieved after intramuscular injection are obtained.

In neonates, average peak tobramycin concentrations of about 5micrograms/ml are seen 30 to 60 minutes after a single intramuscular injection of 2mg/kg. Plasma concentrations averaged 1 to 2micrograms/ml at 12 hours.
Extended interval dose regimen in neonates: pre-dose ('trough') concentration should be less than 2mg/litre.

Once daily dose regimens in children: pre-dose ('trough') concentration should be less than 1mg/litre.

Multiple dose daily regimen in children: one-hour ('peak') serum concentration should not exceed 10mg/litre (8-12mg/litre in cystic fibrosis); pre-dose ('trough') concentration should be less than 2mg/litre.

Serum level assays should be performed after 2 or 3 doses and also at 3 or 4 day intervals during therapy.
If renal function changes during therapy, serum concentrations should be monitored more frequently.

To measure the peak level, a serum sample should be taken about 30 minutes following intravenous infusion or one hour after intramuscular injection. Trough levels are measured by obtaining serum samples at 8 hours post dose or just before the next dose is given.

Contraindications

Myasthenia gravis

Precautions and Warnings

Patients receiving tobramycin should be under close clinical observation as aminoglycosides have the potential to cause nephrotoxicity and ototoxicity. Treatment duration should be as short as clinically possible. Care should be taken when treatment duration exceeds 7 days.

Vestibular and auditory ototoxicity can occur. Auditory changes are irreversible, usually bilateral, and may be partial or total. Eighth cranial nerve impairment may occur in patients with dehydration, renal impairment, or in those receiving tobramycin for prolonged periods or in higher than recommended dosages. Manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching and convulsions.

The risk of hearing loss increases with the level of exposure to high peak or high trough serum concentrations of tobramycin. Patients developing cochlear damage may not develop symptoms during therapy to warn of eighth cranial nerve toxicity. Partial or total irreversible bilateral deafness may therefore continue to develop after tobramycin has been discontinued.

Rarely, nephrotoxicity may not be observed until the first few days after therapy cessation. Aminoglycoside-induced nephrotoxicity is usually reversible.

Renal function should be assessed before starting and during treatment. Auditory and vestibular function should also be monitored during treatment with aminoglycosides. It is desirable to measure both peak and trough serum concentrations as high doses may be associated with a greater risk of toxicity. If impairment of renal, vestibular and/or auditory function occurs, dosage adjustment or discontinuation of therapy should be considered. Blood levels should always be determined in patients with chronic infections (such as cystic fibrosis), where prolonged treatment is required, in patients with renal impairment, and in infants, elderly and obese patients. See Therapeutic Drug Monitoring .

Dehydration should be corrected before starting therapy with aminoglycosides.

Obese patients - see Additional dosage
Renal impairment - see Dosage; Renal Impairment
Pregnancy - see Pregnancy section
Breastfeeding - see Lactation section

In elderly patients, it is important to monitor renal function where renal impairment may not be evident in the results of routine screening tests (such as blood urea or serum creatinine). Creatinine clearance determinations may be more useful. Ototoxicity and nephrotoxicity are more common in elderly patients.

Tobramycin should be used with caution and at a reduced dose in premature and full term neonates younger than 6 weeks of age. This is because of their renal immaturity and the prolonged serum half-life of tobramycin.

Tobramycin injection contains sodium metabisulfite which can cause allergic-type reactions (such as anaphylaxis, or life-threatening or less severe asthmatic episodes) in some susceptible people. Patients with asthma appear to be more susceptible to these reactions.

Urine should be tested to detect increased excretion of protein, cells and casts.

Serum creatinine or creatinine clearance should be measured periodically.

Audiograms should be obtained regularly in patients old enough to be tested, especially in those at increased risk of ototoxicity.

Serum calcium, magnesium and sodium should be monitored, especially in patients with renal impairment.

Patients with extensive burns may have reduced serum drug levels. Dosage should be based on serum levels in these patients.

Use with caution in patients with muscular disorders. Tobramycin may aggravate muscle weakness due to the potential curare-like effect on neuromuscular function.
A transient myasthenic syndrome has occurred in patients with normal neuromuscular function given large doses of aminoglycoside during surgery.

Appropriate therapy should be initiated in patients who develop overgrowth of non-susceptible organisms.

Pregnancy and Lactation

Pregnancy

If tobramycin is administered during pregnancy or if the patient becomes pregnant while receiving therapy, the potential risks to the foetus should be explained. Eighth cranial nerve toxicity in the foetus is well known following exposure to other aminoglycosides and may potentially occur with tobramycin.

If given during pregnancy, serum concentration monitoring is essential.

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 14-17 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 at https://www.toxbase.org/

Licensed in pregnancy? - Yes

Known human teratogen? - No.

Animal data - Renal toxicity in pregnant rats and foetuses after maternal administration of 30 to 60mg/kg tobramycin for 10 days during organogenesis.

Crosses placenta? - Yes

Effects on foetus - Eighth cranial nerve toxicity in the foetus is well known following exposure to streptomycin, and may potentially occur with tobramycin.

Lactation

Tobramycin is poorly excreted in to breast milk and systemic effects of tobramycin on the infant is unlikely.

If breast feeding is continued during tobramycin administration, the infant should be monitored for possible effects on gastrointestinal flora (e.g. diarrhoea, candidiasis, or blood in stools indicating possible antibiotic-associated colitis)

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

Effects on Ability to Drive and Operate Machinery

Not applicable.

Counselling

If the patient becomes pregnant while receiving therapy, the potential risks to the foetus should be explained.

Side Effects

Nephrotoxicity
Renal impairment
Blood urea increased
Serum creatinine increased
Oliguria
Cylindruria
Proteinuria
Vestibular and auditory damage
Dizziness
Vertigo
Tinnitus
Hearing disturbances
Hearing loss
Increase in serum ALT/AST
Serum bilirubin increased
Decrease in plasma calcium
Hypomagnesaemia
Decreased serum sodium
Reduced plasma potassium levels
Anaemia
Granulocytopenia
Thrombocytopenia
Leucopenia
Leucocytosis
Eosinophilia
Fever
Rash
Itching
Urticaria
Nausea
Vomiting
Headache
Lethargy
Local pain (injection site)
Confusion
Disorientation
Antibiotic-associated colitis
Exfoliative dermatitis
Diarrhoea
Ototoxicity
Neuromuscular block
Peripheral neuropathy
Convulsions
Electrolyte disturbances
CNS effects

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 ).

Shelf Life and Storage

Store at or below 25 degrees C.

Keep the container in the outer carton.

Further Information

Last Full Review Date: June 2012

Reference Sources

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: Tobramycin injection 40mg/1ml . Flynn Pharmaceuticals. Revised April 2019.

Summary of Product Characteristics: Tobramycin Injection 40mg/ml. Hospira UK Ltd. Revised February 2009.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 05 September 2017

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
Tobramycin Last revised: January 4, 2011.
Last accessed: June 26, 2012.