Drugs List

Therapeutic Indications

Uses

Chronic pulmonary infection caused by P.aeruginosa in cystic fibrosis

Contraindications

Children under 6 years
Myasthenia gravis

Precautions and Warnings

Elderly
Severe haemoptysis
Auditory impairment
Breastfeeding
Dehydration
Muscle weakness
Neuromuscular disorder
Parkinson's disease
Pregnancy
Renal impairment
Vestibular impairment

Correct dehydration before commencing therapy
Consult national/regional policy on the use of anti-infectives
Treatment to be initiated and supervised by a specialist
Any concomitant bronchodilator should be used first
Evaluate renal function before and during treatment
Monitor auditory function in at risk patients before and during treatment
Close medical supervision during initial dosing
Monitor auditory and vestibular function
Monitor for protein in urine
Monitor periodically for overgrowth of non-susceptible organisms
Monitor plasma levels in patients with auditory impairment
Monitor plasma levels in patients with renal impairment
Monitor urea and creatinine levels every 12 months
Advise patient to report hearing loss or tinnitus
Bronchospasm(lowered FEV)in presence of bronchodilator may indicate allergy
Discontinue or interrupt therapy if ototoxicity occurs
May cause bronchospasm
Potentially ototoxic and nephrotoxic
Discontinue if allergic reaction occurs
Discontinue or interrupt therapy if nephrotoxicity occurs

Use with caution in patients with confirmed or suspected neuromuscular impairment including Parkinsonism or other disorders characterised by myasthenia. Muscle weakness may be aggravated by tobramycin due to a potential curare-like effect on neuromuscular function.

Monitoring of renal function is suggested in elderly patients who may have reduced renal function that may not be evident in the results of routine screening tests, such as blood urea or serum creatinine. A creatinine clearance determination may be more useful.

Ototoxicity, manifested as both auditory and vestibular toxicity, can occur with parenteral aminoglycosides. Vertigo, ataxia or dizziness may indicate vestibular toxicity. Auditory toxicity including hearing loss did not occur with nebulised tobramycin therapy during clinical studies. However, some patients receiving nebulised tobramycin who have a history of prolonged parenteral aminoglycoside use have experienced hearing loss.

Physicians should consider the possibility of vestibular and cochlear toxicity occurring. Appropriate auditory and vestibular function tests should be carried out during therapy.
Auditory assessments should be considered before tobramycin therapy is initiated in patients with a history of prolonged systemic aminoglycoside therapy. Patients receiving concurrent parenteral aminoglycoside therapy should be monitored as clinically appropriate taking into account the risk of cumulative toxicity.
It is suggested to obtain a serial audiogram in patients who are at risk of ototoxicity and are old enough to be tested.
Tinnitus may be an early sign of ototoxicity. If patients report tinnitus or hearing loss during therapy, they may require audiological assessment.

Patients with known or suspected auditory dysfunction should have their serum tobramycin monitored. If ototoxicity occurs, treatment should be discontinued until trough serum levels fall below 2 micrograms/ml. If serum concentrations are greater than 12 micrograms/ml, treatment should be discontinued.

Serum tobramycin concentrations should only be monitored through venipuncture and not by finger prick blood sampling. Skin contamination of the fingers with the preparation may lead to falsely elevated serum levels. Contamination cannot be avoided by washing the hands prior to testing.

Bronchospasm may occur with therapy and should be treated as medically appropriate. The first dose of tobramycin should be given under supervision. The forced expiratory volume in one second (FEV1) should be measured before and after nebulisation. If bronchospasm occurs in patients not receiving a bronchodilator, the test should be repeated at a later date with a bronchodilator given before tobramycin. If bronchospasm occurs after a bronchodilator has been administered, this may indicate and allergic reaction. Therapy should be discontinued if an allergic reaction occurs.

Pregnancy and Lactation

Pregnancy

Use tobramycin with caution during pregnancy.

The manufacturers suggest nebulised tobramycin should not be used during pregnancy unless the benefits to the mother outweigh the risks to the foetus or baby. Inform patients of the potential risks to the foetus.

Tobramycin crosses the placenta into foetal circulation and amniotic fluid. Ototoxicity has not been reported as an effect of tobramycin during therapy. However, eighth cranial nerve toxicity in the foetus is well known with other aminoglycosides and should not be ruled out with tobramycin. There are little data, at the time of writing, on the use of inhaled tobramycin during human pregnancy. Aminoglycosides can cause foetal harm when high systemic concentrations are achieved in pregnant women. There have been no reports linking tobramycin to congenital defects. One study concluded that there was no detectable teratogenic risk for structural defects for tobramycin and that the risk of deafness after in utero aminoglycoside exposure was small. Animal data has not shown evidence of teratogenicity in rats and rabbits. However, renal toxicity has been observed in pregnant rats after high doses of tobramycin.

Lactation

Use tobramycin with caution during breastfeeding.

The manufacturers suggest nebulised tobramycin should not be used in breastfeeding unless the benefits to the mother outweigh the risks to the foetus or baby. Because of the potential for ototoxicity and nephrotoxicity in infants, a decision should be made whether to terminate breastfeeding or discontinue therapy.

Tobramycin is poorly excreted in human breast milk and oral absorption in the infant is poor. Serum levels with typical dosage are considered to be below those attained when treating newborn infections and systemic effects are considered unlikely. However, serum levels with respect to inhaled tobramycin are unknown.

Side Effects

Abdominal pain
Allergic reaction
Anorexia
Antibiotic-associated colitis
Aphonia
Asthenia
Asthma
Ataxia
Blood disorders
Bronchospasm
Candidiasis (mouth or throat)
Chest discomfort
CNS effects
Convulsions
Cough
Decreased lung function
Diarrhoea
Discoloured sputum
Dizziness
Dysgeusia
Dysphonia
Dyspnoea
Ear disorder
Electrolyte disturbances
Encephalopathy
Epistaxis
Fungal infection
Glossitis
Haemoptysis
Headache
Hearing loss
Hypersalivation
Hypersensitivity reactions
Hyperventilation
Hypocalcaemia
Hypomagnesaemia
Hypoxia
Increase in serum transaminases
Increased sputum
Laryngitis
Lung disorder
Lymphadenopathy
Malaise
Mouth ulcers
Myalgia
Nausea
Nephrotoxicity
Neuromuscular block
Oropharyngeal candidiasis
Otitis media
Ototoxicity
Pain
Peripheral neuropathy
Pharyngitis
Polyps
Productive cough
Pruritus
Pulmonary function test abnormal
Pyrexia
Rales
Rash
Respiratory disorders
Respiratory tract infection
Rhinitis
Sinusitis
Somnolence
Stomatitis
Taste disturbances
Tinnitus
Urticaria
Vertigo
Vestibular and auditory damage
Vomiting
Weight loss

Presentation

Nebuliser solution containing tobramycin.

Drugs List

Therapeutic Indications

Uses

Chronic pulmonary infection caused by P.aeruginosa in cystic fibrosis

Dosage

The dose interval should be as close as possible to 12 hours and not less than 6 hours apart.

After 28 days of therapy, treatment should be discontinued for the following 28 days, and then re-started. A cycle of 28 days of therapy and 28 days of no treatment should be maintained.

Treatment should continue for as long as the patient continues to benefit clinically from the inclusion of tobramycin in their treatment regime. Additional or alternative pseudomonas therapy should be considered if pulmonary status deteriorates.

Chest physiotherapy should be continued throughout therapy with tobramycin.

For patients taking several respiratory therapies should receive their treatments in the following order: bronchodilator, chest physiotherapy, other inhaled medicinal products and finally tobramycin nebulised solution.

Adults

Elderly

Children

Patients with Renal Impairment

Contraindications

Children under 6 years
Myasthenia gravis

Precautions and Warnings

Elderly
Severe haemoptysis
Auditory impairment
Breastfeeding
Dehydration
Muscle weakness
Neuromuscular disorder
Parkinson's disease
Pregnancy
Renal impairment
Vestibular impairment

Correct dehydration before commencing therapy
Consult national/regional policy on the use of anti-infectives
Treatment to be initiated and supervised by a specialist
Any concomitant bronchodilator should be used first
Evaluate renal function before and during treatment
Monitor auditory function in at risk patients before and during treatment
Close medical supervision during initial dosing
Monitor auditory and vestibular function
Monitor for protein in urine
Monitor periodically for overgrowth of non-susceptible organisms
Monitor plasma levels in patients with auditory impairment
Monitor plasma levels in patients with renal impairment
Monitor urea and creatinine levels every 12 months
Advise patient to report hearing loss or tinnitus
Bronchospasm(lowered FEV)in presence of bronchodilator may indicate allergy
Discontinue or interrupt therapy if ototoxicity occurs
May cause bronchospasm
Potentially ototoxic and nephrotoxic
Discontinue if allergic reaction occurs
Discontinue or interrupt therapy if nephrotoxicity occurs

Use with caution in patients with confirmed or suspected neuromuscular impairment including Parkinsonism or other disorders characterised by myasthenia. Muscle weakness may be aggravated by tobramycin due to a potential curare-like effect on neuromuscular function.

Monitoring of renal function is suggested in elderly patients who may have reduced renal function that may not be evident in the results of routine screening tests, such as blood urea or serum creatinine. A creatinine clearance determination may be more useful.

Ototoxicity, manifested as both auditory and vestibular toxicity, can occur with parenteral aminoglycosides. Vertigo, ataxia or dizziness may indicate vestibular toxicity. Auditory toxicity including hearing loss did not occur with nebulised tobramycin therapy during clinical studies. However, some patients receiving nebulised tobramycin who have a history of prolonged parenteral aminoglycoside use have experienced hearing loss.

Physicians should consider the possibility of vestibular and cochlear toxicity occurring. Appropriate auditory and vestibular function tests should be carried out during therapy.
Auditory assessments should be considered before tobramycin therapy is initiated in patients with a history of prolonged systemic aminoglycoside therapy. Patients receiving concurrent parenteral aminoglycoside therapy should be monitored as clinically appropriate taking into account the risk of cumulative toxicity.
It is suggested to obtain a serial audiogram in patients who are at risk of ototoxicity and are old enough to be tested.
Tinnitus may be an early sign of ototoxicity. If patients report tinnitus or hearing loss during therapy, they may require audiological assessment.

Patients with known or suspected auditory dysfunction should have their serum tobramycin monitored. If ototoxicity occurs, treatment should be discontinued until trough serum levels fall below 2 micrograms/ml. If serum concentrations are greater than 12 micrograms/ml, treatment should be discontinued.

Serum tobramycin concentrations should only be monitored through venipuncture and not by finger prick blood sampling. Skin contamination of the fingers with the preparation may lead to falsely elevated serum levels. Contamination cannot be avoided by washing the hands prior to testing.

Bronchospasm may occur with therapy and should be treated as medically appropriate. The first dose of tobramycin should be given under supervision. The forced expiratory volume in one second (FEV1) should be measured before and after nebulisation. If bronchospasm occurs in patients not receiving a bronchodilator, the test should be repeated at a later date with a bronchodilator given before tobramycin. If bronchospasm occurs after a bronchodilator has been administered, this may indicate and allergic reaction. Therapy should be discontinued if an allergic reaction occurs.

Pregnancy and Lactation

Pregnancy

Use tobramycin with caution during pregnancy.

The manufacturers suggest nebulised tobramycin should not be used during pregnancy unless the benefits to the mother outweigh the risks to the foetus or baby. Inform patients of the potential risks to the foetus.

Tobramycin crosses the placenta into foetal circulation and amniotic fluid. Ototoxicity has not been reported as an effect of tobramycin during therapy. However, eighth cranial nerve toxicity in the foetus is well known with other aminoglycosides and should not be ruled out with tobramycin. There are little data, at the time of writing, on the use of inhaled tobramycin during human pregnancy. Aminoglycosides can cause foetal harm when high systemic concentrations are achieved in pregnant women. There have been no reports linking tobramycin to congenital defects. One study concluded that there was no detectable teratogenic risk for structural defects for tobramycin and that the risk of deafness after in utero aminoglycoside exposure was small. Animal data has not shown evidence of teratogenicity in rats and rabbits. However, renal toxicity has been observed in pregnant rats after high doses of tobramycin.

Lactation

Use tobramycin with caution during breastfeeding.

The manufacturers suggest nebulised tobramycin should not be used in breastfeeding unless the benefits to the mother outweigh the risks to the foetus or baby. Because of the potential for ototoxicity and nephrotoxicity in infants, a decision should be made whether to terminate breastfeeding or discontinue therapy.

Tobramycin is poorly excreted in human breast milk and oral absorption in the infant is poor. Serum levels with typical dosage are considered to be below those attained when treating newborn infections and systemic effects are considered unlikely. However, serum levels with respect to inhaled tobramycin are unknown.

Counselling

Advise patient to administer any bronchodilators first.

Advise patient to report hearing loss or tinnitus.

Tobramycin 170 mg/1.7 ml nebuliser solution
Advise patient if dose is missed with at least 6 hours remaining until the next dose to inhale the missed dose as soon as possible. If there are less than 6 hours until the next dose, the patient should wait until the next dose and avoid inhaling the missed dose.

Side Effects

Abdominal pain
Allergic reaction
Anorexia
Antibiotic-associated colitis
Aphonia
Asthenia
Asthma
Ataxia
Blood disorders
Bronchospasm
Candidiasis (mouth or throat)
Chest discomfort
CNS effects
Convulsions
Cough
Decreased lung function
Diarrhoea
Discoloured sputum
Dizziness
Dysgeusia
Dysphonia
Dyspnoea
Ear disorder
Electrolyte disturbances
Encephalopathy
Epistaxis
Fungal infection
Glossitis
Haemoptysis
Headache
Hearing loss
Hypersalivation
Hypersensitivity reactions
Hyperventilation
Hypocalcaemia
Hypomagnesaemia
Hypoxia
Increase in serum transaminases
Increased sputum
Laryngitis
Lung disorder
Lymphadenopathy
Malaise
Mouth ulcers
Myalgia
Nausea
Nephrotoxicity
Neuromuscular block
Oropharyngeal candidiasis
Otitis media
Ototoxicity
Pain
Peripheral neuropathy
Pharyngitis
Polyps
Productive cough
Pruritus
Pulmonary function test abnormal
Pyrexia
Rales
Rash
Respiratory disorders
Respiratory tract infection
Rhinitis
Sinusitis
Somnolence
Stomatitis
Taste disturbances
Tinnitus
Urticaria
Vertigo
Vestibular and auditory damage
Vomiting
Weight loss

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: August 2016

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, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.

Summary of Product Characteristics: Bramitob nebuliser solution. Chiesi Ltd. Revised July 2015.
Summary of Product Characteristics: Munuza 300mg/5ml nebuliser solution. Aristo Pharma Ltd. Revised April 2020.
Summary of Product Characteristics: Tobi 300 mg/5 ml nebuliser solution. Novartis Pharmaceuticals UK Ltd. Revised February 2016.
Summary of Product Characteristics: Tymbrineb 300 mg/5 ml nebuliser solution. Teva UK. Revised July 2016.
Summary of Product Characteristics: Vantobra 170 mg nebuliser solution. Pari Medical Ltd. Revised March 2015.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 15 April 2020

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://www.ncbi.nlm.nih.gov/books/NBK501922/
Tobramycin Last revised: 31 October 2018
Last accessed: 15 April 2020