Tobramycin

Parenteral
Septicaemia
Adult: For serious infections: 3 mg/kg daily in 3 equally divided doses 8 hourly. Life-threatening infections: Up to 5 mg/kg daily in 3 or 4 equally divided doses, then reduce back to 3 mg/kg daily as soon as clinically indicated. All doses are given via IM inj, slow IV inj, or IV infusion over 20-60 minutes. Usual treatment duration: 7-10 days; may be longer in difficult and complicated cases.
Child: 6-7.5 mg/kg daily in 3 or 4 equally divided doses (2-2.5 mg/kg 8 hourly or 1.5-1.89 mg/kg 6 hourly) via IM inj, slow IV inj, or IV infusion over 20-60 minutes. Usual treatment duration: 7-10 days; may be longer in difficult and complicated cases.
Renal impairment: Loading dose: 1 mg/kg. Adjust the subsequent dosages either with reduced doses administered at 8-hour intervals or normal doses given at prolonged intervals. Dosage recommendations may vary depending on the serum tobramycin concentrations and degree of renal impairment (refer to specific product guidelines).
Reconstitution: IV infusion: Adult: Dilute the calculated dose with 50-100 mL NaCl 0.9% or dextrose 5% inj. Neonates and children: Volume of diluent must be proportionately less than that of the adults.
Incompatibility: IM/IV inj: Incompatible with certain cephalosporins and penicillins.

Parenteral
Lower respiratory tract infections
Adult: For serious infections: 3 mg/kg daily in 3 equally divided doses 8 hourly. Life-threatening infections: Up to 5 mg/kg daily in 3 or 4 equally divided doses, then reduce back to 3 mg/kg daily as soon as clinically indicated. All doses are given via IM inj, slow IV inj, or IV infusion over 20-60 minutes. Usual treatment duration: 7-10 days; may be longer in difficult and complicated cases.
Child: 6-7.5 mg/kg daily in 3 or 4 equally divided doses (2-2.5 mg/kg 8 hourly or 1.5-1.89 mg/kg 6 hourly) via IM inj, slow IV inj, or IV infusion over 20-60 minutes. Usual treatment duration: 7-10 days; may be longer in difficult and complicated cases.
Renal impairment: Loading dose: 1 mg/kg. Adjust the subsequent dosages either with reduced doses administered at 8-hour intervals or normal doses given at prolonged intervals. Dosage recommendations may vary depending on the serum tobramycin concentrations and degree of renal impairment (refer to specific product guidelines).
Reconstitution: IV infusion: Adult: Dilute the calculated dose with 50-100 mL NaCl 0.9% or dextrose 5% inj. Neonates and children: Volume of diluent must be proportionately less than that of the adults.
Incompatibility: IM/IV inj: Incompatible with certain cephalosporins and penicillins.

Parenteral
Gastrointestinal infections
Adult: For serious infections: 3 mg/kg daily in 3 equally divided doses 8 hourly. Life-threatening infections: Up to 5 mg/kg daily in 3 or 4 equally divided doses, then reduce back to 3 mg/kg daily as soon as clinically indicated. All doses are given via IM inj, slow IV inj, or IV infusion over 20-60 minutes. Usual treatment duration: 7-10 days; may be longer in difficult and complicated cases.
Child: 6-7.5 mg/kg daily in 3 or 4 equally divided doses (2-2.5 mg/kg 8 hourly or 1.5-1.89 mg/kg 6 hourly) via IM inj, slow IV inj, or IV infusion over 20-60 minutes. Usual treatment duration: 7-10 days; may be longer in difficult and complicated cases.
Renal impairment: Loading dose: 1 mg/kg. Adjust the subsequent dosages either with reduced doses administered at 8-hour intervals or normal doses given at prolonged intervals. Dosage recommendations may vary depending on the serum tobramycin concentrations and degree of renal impairment (refer to specific product guidelines).
Reconstitution: IV infusion: Adult: Dilute the calculated dose with 50-100 mL NaCl 0.9% or dextrose 5% inj. Neonates and children: Volume of diluent must be proportionately less than that of the adults.
Incompatibility: IM/IV inj: Incompatible with certain cephalosporins and penicillins.

Parenteral
Complicated urinary tract infections
Adult: For serious infections: 3 mg/kg daily in 3 equally divided doses 8 hourly. Life-threatening infections: Up to 5 mg/kg daily in 3 or 4 equally divided doses, then reduce back to 3 mg/kg daily as soon as clinically indicated. All doses are given via IM inj, slow IV inj, or IV infusion over 20-60 minutes. Usual treatment duration: 7-10 days; may be longer in difficult and complicated cases.
Child: 6-7.5 mg/kg daily in 3 or 4 equally divided doses (2-2.5 mg/kg 8 hourly or 1.5-1.89 mg/kg 6 hourly) via IM inj, slow IV inj, or IV infusion over 20-60 minutes. Usual treatment duration: 7-10 days; may be longer in difficult and complicated cases.
Renal impairment: Loading dose: 1 mg/kg. Adjust the subsequent dosages either with reduced doses administered at 8-hour intervals or normal doses given at prolonged intervals. Dosage recommendations may vary depending on the serum tobramycin concentrations and degree of renal impairment (refer to specific product guidelines).
Reconstitution: IV infusion: Adult: Dilute the calculated dose with 50-100 mL NaCl 0.9% or dextrose 5% inj. Neonates and children: Volume of diluent must be proportionately less than that of the adults.
Incompatibility: IM/IV inj: Incompatible with certain cephalosporins and penicillins.

Parenteral
Bone and joint infections
Adult: For serious infections: 3 mg/kg daily in 3 equally divided doses 8 hourly. Life-threatening infections: Up to 5 mg/kg daily in 3 or 4 equally divided doses, then reduce back to 3 mg/kg daily as soon as clinically indicated. All doses are given via IM inj, slow IV inj, or IV infusion over 20-60 minutes. Usual treatment duration: 7-10 days; may be longer in difficult and complicated cases.
Child: 6-7.5 mg/kg daily in 3 or 4 equally divided doses (2-2.5 mg/kg 8 hourly or 1.5-1.89 mg/kg 6 hourly) via IM inj, slow IV inj, or IV infusion over 20-60 minutes. Usual treatment duration: 7-10 days; may be longer in difficult and complicated cases.
Renal impairment: Loading dose: 1 mg/kg. Adjust the subsequent dosages either with reduced doses administered at 8-hour intervals or normal doses given at prolonged intervals. Dosage recommendations may vary depending on the serum tobramycin concentrations and degree of renal impairment (refer to specific product guidelines).
Reconstitution: IV infusion: Adult: Dilute the calculated dose with 50-100 mL NaCl 0.9% or dextrose 5% inj. Neonates and children: Volume of diluent must be proportionately less than that of the adults.
Incompatibility: IM/IV inj: Incompatible with certain cephalosporins and penicillins.

Parenteral
Skin and skin structure infections
Adult: For serious infections: 3 mg/kg daily in 3 equally divided doses 8 hourly. Life-threatening infections: Up to 5 mg/kg daily in 3 or 4 equally divided doses, then reduce back to 3 mg/kg daily as soon as clinically indicated. All doses are given via IM inj, slow IV inj, or IV infusion over 20-60 minutes. Usual treatment duration: 7-10 days; may be longer in difficult and complicated cases.
Child: 6-7.5 mg/kg daily in 3 or 4 equally divided doses (2-2.5 mg/kg 8 hourly or 1.5-1.89 mg/kg 6 hourly) via IM inj, slow IV inj, or IV infusion over 20-60 minutes. Usual treatment duration: 7-10 days; may be longer in difficult and complicated cases.
Renal impairment: Loading dose: 1 mg/kg. Adjust the subsequent dosages either with reduced doses administered at 8-hour intervals or normal doses given at prolonged intervals. Dosage recommendations may vary depending on the serum tobramycin concentrations and degree of renal impairment (refer to specific product guidelines).
Reconstitution: IV infusion: Adult: Dilute the calculated dose with 50-100 mL NaCl 0.9% or dextrose 5% inj. Neonates and children: Volume of diluent must be proportionately less than that of the adults.
Incompatibility: IM/IV inj: Incompatible with certain cephalosporins and penicillins.

Parenteral
Central nervous system infections
Adult: For serious infections: 3 mg/kg daily in 3 equally divided doses 8 hourly. Life-threatening infections: Up to 5 mg/kg daily in 3 or 4 equally divided doses, then reduce back to 3 mg/kg daily as soon as clinically indicated. All doses are given via IM inj, slow IV inj, or IV infusion over 20-60 minutes. Usual treatment duration: 7-10 days; may be longer in difficult and complicated cases.
Child: 6-7.5 mg/kg daily in 3 or 4 equally divided doses (2-2.5 mg/kg 8 hourly or 1.5-1.89 mg/kg 6 hourly) via IM inj, slow IV inj, or IV infusion over 20-60 minutes. Usual treatment duration: 7-10 days; may be longer in difficult and complicated cases.
Renal impairment: Loading dose: 1 mg/kg. Adjust the subsequent dosages either with reduced doses administered at 8-hour intervals or normal doses given at prolonged intervals. Dosage recommendations may vary depending on the serum tobramycin concentrations and degree of renal impairment (refer to specific product guidelines).
Reconstitution: IV infusion: Adult: Dilute the calculated dose with 50-100 mL NaCl 0.9% or dextrose 5% inj. Neonates and children: Volume of diluent must be proportionately less than that of the adults.
Incompatibility: IM/IV inj: Incompatible with certain cephalosporins and penicillins.

Parenteral
Cystic fibrosis
Adult: Up to 8-10 mg/kg daily in equally divided doses via IM inj, slow IV inj, or IV infusion over 20-60 minutes. Dosage and treatment recommendations may vary among countries and individual products (refer to specific product guidelines).
Renal impairment: Loading dose: 1 mg/kg. Adjust the subsequent dosages either with reduced doses administered at 8-hour intervals or normal doses given at prolonged intervals. Dosage recommendations may vary depending on the serum tobramycin concentrations and degree of renal impairment (refer to specific product guidelines).
Reconstitution: IV infusion: Adult: Dilute the calculated dose with 50-100 mL NaCl 0.9% or dextrose 5% inj. Neonates and children: Volume of diluent must be proportionately less than that of the adults.
Incompatibility: IM/IV inj: Incompatible with certain cephalosporins and penicillins.

Intramuscular
Mild to moderate urinary tract infections
Adult: 2-3 mg/kg as a single dose.
Incompatibility: Incompatible with certain cephalosporins and penicillins.

Inhalation
Cystic fibrosis
Adult: For long-term management in patients with chronic pulmonary infection due to Pseudomonas aeruginosa: As 300 mg/5 mL nebuliser solution: 300 mg 12 hourly for 28 days, then stop treatment for the next 28 days. As 170 mg/1.7 mL nebuliser solution: 170 mg 12 hourly for 28 days, then stop treatment for the next 28 days. As powder for inhalation: 112 mg 12 hourly 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 or powder for inhalation: Same as adult dose.

Ophthalmic
Ocular infections
Adult: As 0.3% eye drop solution: Mild to moderate infection: Instil 1-2 drops into the affected eye(s) 4 hourly. Severe infection: Instil 2 drops into the affected eye(s) hourly until improvement, then reduce treatment prior to discontinuation. As 0.3% eye ointment: Mild to moderate infection: Apply a half-inch ribbon into the affected eye(s) 2 or 3 times daily. Severe infection: Apply a half-inch ribbon into the affected eye(s) 3-4 hourly until improvement, then reduce treatment prior to discontinuation. Usual treatment duration: 7-10 days.
Child: ≥2 months As 0.3% eye drop solution or ointment: Same as adult dose. Treatment recommendations may vary among countries or individual products (refer to specific product guidelines).

Special Populations: IV/IM: Obese patients: Dosage adjustments may be required (refer to specific product guidelines). Pharmacogenomics: Tobramycin, an aminoglycoside antibiotic, exerts its effect through the inhibition of protein synthesis by binding to the bacterial 30S ribosome, which is responsible for mRNA translation within the prokaryotic cell. MT-RNR1 is a gene that codes for human mitochondrial ribosomal RNA. Certain variations in this gene may increase the risk of aminoglycoside-induced ototoxicity even when serum levels are within the normal range. It is believed that these variations cause the human mitochondrial ribosomes to resemble the bacterial ribosomes more closely, thus allowing the aminoglycosides to bind more readily. Although mitochondrial mutations are rare and penetrance is uncertain, genetic testing may be considered. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline as of May 2021: MT-RNR1 increased risk of aminoglycoside-induced hearing loss Patients with MT-RNR1 variant associated with increased risk of aminoglycoside-induced hearing loss e.g. m.1095T>C, m.1494C>T, m.1555A>G. These patients have a very high risk of developing hearing loss if tobramycin is administered. Avoid the use of tobramycin unless the increased risk of permanent hearing loss is outweighed by the severity of the infection and the lack of alternative therapies. If no effective alternative is available, frequently evaluate patients for hearing loss during treatment and ensure all appropriate precautions are utilised (e.g. shortest possible treatment duration, lowest dose, renal function monitoring, therapeutic drug monitoring, hydration). MT-RNR1 normal risk of aminoglycoside-induced hearing loss Patients with no detectable MT-RNR1 increased risk variant or a variant associated with normal risk of aminoglycoside-induced hearing loss e.g. m.827A>G. These patients have a normal risk of developing hearing loss if tobramycin is administered. Use tobramycin at standard doses for the shortest possible time course with therapeutic dose monitoring. Regularly evaluate for hearing loss in accordance with local guidelines. MT-RNR1 uncertain risk of aminoglycoside-induced hearing loss Patients with MT-RNR1 variant associated with uncertain risk of aminoglycoside-induced hearing loss e.g. m.663A>G, m.669T>C, m.747A>G, m.786G>A, m.807A>G, m.807A>C, m.839A>G, m.896A>G, m.930A>G, m.951G>A, m.960C>del, m.961T>G, m.961T>del, m.961T>del+Cn, m.988G>A, m.1189T>C, m.1243T>C, m.1520T>C, m.1537C>T, m.1556C>T. These patients have weak or no evidence of increased risk of MT-RNR1-associated hearing loss if tobramycin is administered. Use tobramycin at standard doses for the shortest possible time course with therapeutic dose monitoring. Regularly evaluate for hearing loss in accordance with local guidelines.

Hypersensitivity to tobramycin or other aminoglycosides.

Patient with pre-existing vertigo, tinnitus, hearing loss, family history of aminoglycoside-induced deafness, hypocalcaemia, neuromuscular disorder (e.g. myasthenia gravis, parkinsonism), volume depletion, excessive burns, cystic fibrosis; active, severe haemoptysis (inhalation). Avoid concurrent and sequential use of other nephrotoxic, neurotoxic or ototoxic drugs. Obese patient. Patient with certain variants in the MT-RNR1 gene (e.g. m.1555A>G). Renal impairment. Neonates, children, and elderly. Pregnancy and lactation. Patient Counselling Ophthalmic: This drug may cause temporary blurred vision or other visual disturbances, if affected, do not drive or operate machinery. Wearing contact lenses is not recommended during treatment of eye infections. If wearing contact lenses is continued during treatment, remove the lenses before instilling the drops and wait for 15 minutes before reinserting them. Monitoring Parameters Perform culture and susceptibility tests; consult local institutional recommendations before treatment initiation due to antibiotic resistance risks. Monitor serum creatinine, CrCl, BUN, urinalysis, urine output, peak and trough plasma tobramycin levels (periodically); serum Ca, Mg and Na. Assess hearing function before, during, and after treatment. Obtain FEV₁ prior to and after nebulisation.

Significant: Vestibular and auditory ototoxicity (particularly during prolonged therapy or high doses), nephrotoxicity (including acute renal failure); bronchospasm (inhalation); may delay corneal wound healing (ophthalmic). Blood and lymphatic system disorders: Anaemia, eosinophilia, granulocytopenia, leucopenia, leucocytosis, thrombocytopenia. Eye disorders: Eyelid oedema or pruritus, conjunctival erythema, ocular discomfort or hyperaemia. Gastrointestinal disorders: Nausea, vomiting, diarrhoea; oropharyngeal pain, throat irritation, dysgeusia (inhalation). General disorders and administration site conditions: Fever, pain at the inj site, lethargy; malaise (inhalation). Investigations: Increased blood bilirubin, AST, ALT, LDH; decreased blood Ca, Mg, Na, K; decreased pulmonary function test (inhalation). Musculoskeletal and connective tissue disorders: Myalgia, musculoskeletal chest pain. Nervous system disorders: Headache, dizziness. Psychiatric disorders: Disorientation, mental confusion. Respiratory, thoracic and mediastinal disorders: Laryngitis, cough, lung disorder, rhinitis, sputum discolouration, dysphonia, dyspnoea, rales, nasal congestion, aphonia, chest discomfort, epistaxis. Skin and subcutaneous tissue disorders: Rash, urticaria, itching.
Potentially Fatal: Bacterial or fungal superinfection including Clostridioides difficile-associated diarrhoea and pseudomembranous colitis (prolonged use). Rarely, severe allergic reactions (including anaphylaxis), dermatologic reactions (e.g. exfoliative dermatitis, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis).

Symptoms: Dizziness, vertigo, tinnitus, loss of high tone hearing acuity, neuromuscular blockade or respiratory failure, and renal impairment. Management: Establish airway and ensure oxygenation and ventilation. Initiate resuscitative measures immediately if respiratory paralysis occurs. Consider haemodialysis or peritoneal dialysis to help remove tobramycin from the blood. Carefully monitor fluid balance, CrCl, and plasma tobramycin levels until the tobramycin level falls below 2 mg/L. Ca salts may be given to reverse neuromuscular blockade.

Increased risk of ototoxicity with potent diuretics (e.g. etacrynic acid, furosemide). Increased risk of neurotoxic and/or nephrotoxic effects with other aminoglycosides (e.g. amikacin, streptomycin, gentamicin), cephalosporins (particularly cefalotin), vancomycin, viomycin, amphotericin B, polymyxin B, cisplatin, ciclosporin. May enhance neuromuscular blockade and increase the risk of respiratory paralysis with neuromuscular blocking agents (e.g. suxamethonium, tubocurarine). Antagonistic effect with neostigmine and pyridostigmine. May potentiate the effects of warfarin and phenindione.

Tobramycin is an aminoglycoside antibiotic that inhibits bacterial protein synthesis by binding to 30S ribosomal subunits, resulting in a defective bacterial cell membrane.
Absorption: Rapid and completely absorbed (IM). Time to peak plasma concentration: 30-90 minutes (IM); approx 30 minutes (IV); 60 minutes (powder for inhalation).
Distribution: Rapidly distributed into most body fluids and tissues (IM/IV); concentrates mainly in the airways (inhalation). Crosses the placenta and enters breast milk. Volume of distribution: 0.2-0.3 L/kg (IM/IV); 85.1 L (powder for inhalation). Plasma protein binding: <10%.
Excretion: Via urine (approx 90-95%). Elimination half-life: 2-3 hours (IM/IV); approx 3 hours (inhalation).

Inhalation: Solution for inhalation: Store between 2-8°C, or up to 25°C (intact or opened foil pouch) for up to 28 days. Do not freeze. Protect from light. Powder for inhalation: Store between 15-30°C. Protect from moisture. Intramuscular: Store intact vials between 20-25°C. Protect from light. Ophthalmic: Ophthalmic solution/ointment: Store between 2-25°C. Protect the eye drop solution from excessive heat. Parenteral: Store intact vials between 20-25°C. Protect from light. Reconstituted solution: Store at room temperature (stable for 24 hours) or between 2-8°C (stable for 96 hours).

Aminoglycosides / Eye Anti-Infectives & Antiseptics

S01AA12 - tobramycin ; Belongs to the class of antibiotics. Used in the treatment of eye infections.
J01GB01 - tobramycin ; Belongs to the class of other aminoglycosides. Used in the systemic treatment of infections.