Tobramycin


Generic Medicine Info
Indications and Dosage
Inhalation/Respiratory
Cystic fibrosis
Adult: For management of chronic pulmonary infection due to Pseudomonas aeruginosa in patients with cystic fibrosis: As nebuliser solution: 300 mg 12 hourly or 170 mg 12 hourly via suitable nebuliser for 28 days, then stop treatment for the next 28 days. As inhalation powder cap: 112 mg 12 hourly via suitable inhaler device for 28 days, then stop treatment for the next 28 days. Repeat in cycles of 28 days on treatment, followed by 28 days off treatment.
Child: ≥6 years As nebuliser solution/inhalation powder cap: Same as adult dose.

Intramuscular
Mild to moderate urinary tract infections
Adult: 2-3 mg/kg as a single dose.

Ophthalmic
Ocular infections
Adult: As 0.3% eye drop solution: Mild to moderate infection: Instil 1-2 drop(s) into the affected eye(s) 4 hourly. Severe infection: Instil 2 drops into the affected eye(s) hourly until improvement, then treatment should be reduced prior to discontinuation. As 0.3% ointment: Mild to moderate infection: Apply a half-inch ribbon into the affected eye(s) 2 or 3 times daily. Severe infection: Apply half-inch ribbon into the affected eye(s) 3-4 hourly until improvement, then treatment should be reduced prior to discontinuation.
Child: >1 year As 0.3% eye drop solution/ointment: Same as adult dose.

Parenteral
Bone and joint infections, Central nervous system infections, Gastrointestinal infections, Lower respiratory tract infections, Skin and soft tissue infections
Adult: Usual dose: Serious infections: 3 mg/kg daily in 3 equally divided doses 8 hourly via IM inj or IV infusion over 20-60 minutes. Life-threatening infections: Increased up to 5 mg/kg daily in 3 or 4 divided doses, then reduce back to 3 mg/kg daily as clinically indicated. Max: 5 mg/kg daily. Usual treatment duration: 7-10 days.
Child: ≤1 week Premature or full-term neonates: Up to 4 mg/kg daily in 2 equal doses 12 hourly. >1 week 6-7.5 mg/kg daily in 3 or 4 equally divided doses. Usual treatment duration: 7-10 days.

Parenteral
Cystic fibrosis
Adult: Recommended dose: Up to 8-10 mg/kg daily in equally divided doses. Monitor serum tobramycin levels during treatment due to wide interpatient variability.
Special Patient Group
Based on some studies, individuals with mitochondrial deoxyribonucleic acid (DNA) mutations in the 12S ribosomal ribonucleic acid (RNA), particularly the m.1555A>G mutation, are at an increased risk of aminoglycoside-associated ototoxicity including those who had aminoglycoside serum levels within the recommended range. The m.1555A>G mutation is the most common mutation and occurs in families with maternally transmitted deafness. Although mitochondrial mutations are rare and penetrance is uncertain, genetic testing may be considered before starting recurrent or long-term treatment with aminoglycoside antibiotics but testing must not delay urgently needed treatment.

Additionally, according to research, patients who carry the 1555G allele may have a greater risk of aminoglycoside-induced hearing loss as compared to those with 1555A allele. Other genetic and clinical factors may also influence the risk of aminoglycoside-induced hearing loss.
Renal Impairment
Parenteral/Intramuscular:
Dosage adjustment needed.
Reconstitution
IV infusion: Add the calculated dose in 50-100 mL of NaCl 0.9% or dextrose inj 5%.
Contraindications
Hypersensitivity to tobramycin and other aminoglycosides.
Special Precautions
Patient with hearing impairment, hypocalcaemia, neuromuscular disorder (e.g. myasthenia gravis, Parkinson’s disease), dehydration; severe and active haemoptysis (inhalation); family history of ototoxicity. Patient with known m.1555A>G mitochondrial mutations. Renal impairment. Children. Pregnancy and lactation.
Adverse Reactions
Significant: Nephrotoxicity, ototoxicity (e.g. tinnitus, hearing loss, vertigo), neurotoxicity, bronchospasm (inhalation), neuromuscular blockade, respiratory failure, prolonged respiratory paralysis.
Cardiac disorders: Dyspnoea.
Eye disorders: Lid itching, swelling and conjunctival erythema (ophthalmic).
Gastrointestinal disorders: Nausea, oropharyngeal pain, vomiting, diarrhoea, dysgeusia.
General disorders and administration site conditions: Malaise, pyrexia.
Investigations: Decreased pulmonary function test.
Musculoskeletal and connective tissue disorders: Myalgia.
Nervous system disorders: Dizziness, headache.
Respiratory, thoracic and mediastinal disorders: Laryngitis (inhalation), rhinitis, dysphonia, discoloured sputum, respiratory disorder, cough, wheezing, rales, nasal congestion, epistaxis.
Skin and subcutaneous tissue disorders: Pruritus, urticaria, rash.
Vascular disorders: Haemoptysis (inhalation).
Potentially Fatal: Superinfection, including C. difficile-associated diarrhoea and pseudomembranous colitis (prolonged use). Rarely, anaphylaxis, dermatologic reactions (e.g. exfoliative dermatitis, toxic epidermal necrolysis, erythema multiforme, Stevens-Johnson syndrome).
IM/Inhalation/Respiratory/IV/Parenteral: D; Ophth: B
Patient Counseling Information
Ophthalmic: This drug may cause temporary blurred vision, if affected, do not drive or operate machinery. Wearing of contact lens is not recommended during treatment.
Monitoring Parameters
Monitor serum Ca, Mg and Na; BUN, serum creatinine, urinalysis, urine output, peak and trough plasma tobramycin levels. Assess hearing level prior to, during, and following treatment. Perform culture and sensitivity tests; consult local recommendations before treatment initiation due to antibiotic resistance risks.
Overdosage
Symptoms: Parenteral: Dizziness, tinnitus, vertigo, loss of high tone hearing acuity, respiratory failure, neuromuscular blockade, renal impairment. Management: Parenteral: Establish airway and ensure oxygenation and ventilation. Initiate resuscitative measures immediately if respiratory paralysis occurs. Monitor fluid balance, creatinine clearance and tobramycin plasma levels. Ca salts may be given to reverse neuromuscular blockade. Haemodialysis or peritoneal dialysis may help remove drug serum levels.
Drug Interactions
Enhanced of neurotoxic or nephrotoxic effects with other aminoglycosides (e.g. amikacin, streptomycin, gentamicin), amphotericin B, viomycin, polymyxin B, cisplatin, vancomycin. May increase risk of nephrotoxicity with other antibacterials (e.g. cephalosporins), ciclosporin, mannitol. Enhanced blockade of respiratory paralysis with skeletal muscle relaxants. May increase risk of nephrotoxicity and ototoxicity with platinum compounds, potent diuretics (e.g. ethacrynic acid, furosemide). Antagonistic effect with neostigmine and pyridostigmine. May potentiate the effects of warfarin and phenindione.
Action
Description: Tobramycin is an aminoglycoside antibiotic that interferes with bacterial protein synthesis by binding to 30S and 50S ribosomal subunits, resulting in a defective bacterial cell membrane.
Pharmacokinetics:
Absorption: Poorly absorbed from the gastrointestinal tract. Rapidly and completely absorbed (IM). Time to peak plasma concentration: 30-60 minutes (IM); approx 30 minutes (IV); 60 minutes (powder for inhalation).
Distribution: Distributed into most body tissues and fluids. Crosses the placenta and enters breast milk. Volume of distribution: 0.2-0.3 L/kg (systemic); 85.1 L (powder for inhalation). Plasma protein binding: <30%.
Excretion: Via urine (approx 90-95%). Elimination half-life: 2-3 hours (IV); approx 3 hours (powder for inhalation); approx 3-4.4 hours (solution for inhalation).
Chemical Structure

Chemical Structure Image
Tobramycin

Source: National Center for Biotechnology Information. PubChem Database. Tobramycin, CID=36294, https://pubchem.ncbi.nlm.nih.gov/compound/Tobramycin (accessed on Jan. 23, 2020)

Storage
Parenteral: Store between 20-25°C. Reconstituted solution: Store at room temperature (stable for 24 hours) or between 2-8°C (stable for 96 hours). Powder for inhalation: Store at 25°C. Protect from moisture. Solution for inhalation: Store between 2-8°C or at 25°C (intact or opened foil pouch) for up to 28 days. Protect from light. Ophthalmic solution/ointment: Store between 2-25°C.
ATC Classification
J01GB01 - tobramycin ; Belongs to the class of other aminoglycosides. Used in the systemic treatment of infections.
S01AA12 - tobramycin ; Belongs to the class of antibiotics. Used in the treatment of eye infections.
References
Estivill X, Govea N, Barceló A et al. Familial Progressive Sensorineural Deafness Is Mainly Due to the mtDNA A1555G Mutation and Is Enhanced by Treatment with Aminoglycosides. The American Journal of Human Genetics. 1998;62(1):27-35. doi: 10.1086/301676. Accessed 02/02/2021

Gao Z, Chen Y, Guan MX. Mitochondrial DNA mutations associated with aminoglycoside induced ototoxicity. Journal of Otology. 2017;12(1):1-8. doi: 10.1016/j.joto.2017.02.001. Accessed 02/02/2021

Göpel W, Berkowski S, Preuss M et al. Mitochondrial mutation m.1555A>G as a risk factor for failed newborn hearing screening in a large cohort of preterm infants. BMC Pediatrics. 2014;14(1):210. doi: 10.1186/1471-2431-14-210. Accessed 02/02/2021

Aminoglycosides (Gentamicin, Amikacin, Tobramycin, and Neomycin): Increased Risk of Deafness in Patients with Mitochondrial Mutations. Medicines & Healthcare products Regulatory Agency. https://www.gov.uk/government/organisations/medicines-and-healthcare-products-regulatory-agency. Accessed 02/02/2021.

Anon. Tobramycin (Ophthalmic). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 07/11/2019.

Anon. Tobramycin (Oral Inhalation). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 07/11/2019.

Anon. Tobramycin (Systemic). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 07/11/2019.

Buckingham R (ed). Tobramycin. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 07/11/2019.

Clinical Annotation for rs267606617 (MT-RNR1); Amikacin, Aminoglycoside Antibacterials, Gentamicin, Kanamycin, Neomycin, Streptomycin or Tobramycin; Ototoxicity. Pharmacogenomics Knowledgebase (PharmGKB). https://www.pharmgkb.org. Accessed 02/02/2021.

Joint Formulary Committee. Tobramycin. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 07/11/2019.

Novartis New Zealand Limited. Tobrex Eye Drops and Eye Ointment 0.3% data sheet May 2019. Medsafe. http://www.medsafe.govt.nz. Accessed 07/11/2019.

Tobramycin Inhalation Solution Inhalant (Dr. Reddy’s Laboratories Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 07/11/2019.

Tobramycin Ophthalmic Solution/Drops (Alembic Pharmaceuticals Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 07/11/2019.

Tobramycin Sulfate Injection, Powder, For Solution (Fresenius Kabi USA, LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 07/11/2019.

Disclaimer: This information is independently developed by MIMS based on Tobramycin from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
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