Schedule H

Intravenous, Intramuscular, Ophthalmic

• Injection: 80 mg/2 mL vial (IV/IM)

• Ophthalmic Solution: 0.3% w/v eye drops (5 mL)

• Ophthalmic Ointment: 0.3% w/w eye ointment

• Inhalation Solution/Nebuliser Formulations: NOT AVAILABLE in India (import on case-by-case basis only)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Severe Gram-Negative Infections (including Pseudomonas aeruginosa) — Systemic Use

Traditional Multiple Daily Dosing:

Parameter Details

Starting dose 1–2 mg/kg IV/IM loading dose

Titration Adjust based on serum drug levels and renal function

Usual maintenance dose 3–5 mg/kg/day IV/IM in 3 divided doses (every 8 hours)

Maximum dose 5–7 mg/kg/day (in divided doses); up to 8 mg/kg/day in severe infections

Duration 7–10 days

Extended-Interval (Once-Daily) Dosing:

Parameter Details

Starting dose 5–7 mg/kg IV once daily

Titration Adjust based on serum levels and renal function

Usual maintenance dose 5–7 mg/kg IV once daily

Maximum dose 7 mg/kg/day

Duration 7–10 days

Clinical notes:

• Typically used in combination with anti-pseudomonal beta-lactam (e.g., piperacillin-tazobactam, ceftazidime) for synergy

• Therapeutic drug monitoring (TDM) mandatory if duration >5 days or renal impairment present

• Traditional dosing: Target peak 4–10 µg/mL, trough <2 µg/mL

• Extended-interval dosing preferred in patients with normal renal function

1. Bacterial Conjunctivitis and External Eye Infections — Ophthalmic Use

Eye Drops (0.3%):

Parameter Details

Starting dose 1–2 drops into affected eye(s) every 4–6 hours

Titration In severe infection: 1–2 drops every 1 hour for initial 24–48 hours, then taper

Usual maintenance dose 1–2 drops every 4–6 hours

Maximum dose 2 drops every hour (severe cases only)

Duration 5–7 days; reassess if no improvement by day 3

Eye Ointment (0.3%):

Parameter Details

Starting dose Apply 1 cm ribbon to affected eye(s) 2–3 times daily

Titration Not applicable

Usual maintenance dose 1 cm ribbon 2–3 times daily

Maximum dose 1 cm ribbon every 3–4 hours in severe cases

Duration 5–7 days

Clinical notes: Combine drops (daytime) with ointment (night-time) for optimal coverage in moderate-severe cases.

1. Bacterial Keratitis — Ophthalmic Use

Parameter Details

Starting dose Fortified tobramycin drops (1.3%) or standard 0.3% drops hourly

Titration Reduce frequency as clinical response observed

Usual maintenance dose Taper to every 2–4 hours based on response

Maximum dose Hourly application initially

Duration 2–3 weeks; ophthalmologist supervision essential

Clinical notes: Often combined with fortified cefazolin for broad-spectrum coverage. Specialist supervision required.

Secondary Indications — Adults Only (Off-label)

Indication Dose Duration Evidence Basis Notes

Chronic Pseudomonas colonisation in cystic fibrosis/bronchiectasis (Inhalation) 300 mg nebulised twice daily 28 days on / 28 days off cycles International RCTs; tertiary care Indian specialist practice OFF-LABEL. Inhalation formulation NOT routinely available in India. Specialist only. Import on case basis.

Infective endocarditis (Enterococcal — as part of combination therapy) 1 mg/kg IV every 8 hours (with ampicillin/penicillin) 4–6 weeks ICMR AMR guidelines; Indian specialist practice OFF-LABEL. TDM mandatory. Specialist only.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

1. Severe Gram-Negative Infections — Systemic Use (IV/IM)

Neonates:

Age/Weight Starting Dose Maintenance Dose Dosing Interval Maximum Dose

Preterm <1 week 2.5 mg/kg 2.5 mg/kg Every 18–24 hours 2.5 mg/kg/dose

Term <7 days 2.5 mg/kg 2.5 mg/kg Every 12–18 hours 2.5 mg/kg/dose

Term ≥7 days 2.5 mg/kg 2.5 mg/kg Every 8–12 hours 2.5 mg/kg/dose

Infants and Children (>1 month to 12 years):

Parameter Details

Starting dose 2–2.5 mg/kg IV/IM

Titration Adjust based on serum drug levels

Usual maintenance dose 6–7.5 mg/kg/day in 3 divided doses (every 8 hours)

Maximum dose 7.5 mg/kg/day

Duration 7–10 days

Children >12 years: Use adult dosing

Safety monitoring:

• Serum drug levels (peak/trough) after 3rd dose

• Renal function (creatinine, urea) at baseline and every 2–3 days

• Audiometry if treatment >5 days

• Signs of vestibular toxicity (balance, nystagmus)

1. Bacterial Conjunctivitis — Ophthalmic Use

Age Dose Frequency Duration Clinical Notes

2 months 1 drop (0.3%) Every 4–6 hours 5–7 days Reduce frequency as response observed

Severe cases (>2 months) 1 drop Every 1–2 hours initially, then taper 5–7 days Specialist supervision

Age restriction: Not recommended in infants <1 month without ophthalmologist supervision.

Secondary Indications — Paediatric Doses (Off-label)

Indication Age Dose Duration Evidence Basis Notes

Cystic fibrosis with chronic Pseudomonas colonisation (Inhalation) ≥6 years 300 mg nebulised twice daily 28 days on / 28 days off International RCTs; limited Indian tertiary care use OFF-LABEL. Inhalation formulation NOT available in India. Specialist only.

Age restriction: Systemic use not recommended in neonates/infants without paediatric infectious disease specialist supervision due to ototoxicity and nephrotoxicity risks. Inhalational use not recommended <6 years.

Systemic (IV/IM) use requires mandatory dose adjustment:

CAPD 0.6 mg/kg loading, then based on levels; add to dialysate for peritonitis

Key points:

• Therapeutic drug monitoring (TDM) essential in all patients with renal impairment

• Avoid in rapidly worsening renal function unless no alternative

• Extended-interval dosing may not be appropriate in severe renal impairment

Ophthalmic use: No adjustment required.

Ophthalmic use: No adjustment required.

• Known hypersensitivity to tobramycin or any aminoglycoside antibiotic

• Myasthenia gravis (risk of neuromuscular blockade exacerbation)

• Pre-existing severe bilateral sensorineural hearing loss (systemic use)

• Concurrent use with other systemic aminoglycosides

• Pre-existing renal impairment — increased risk of nephrotoxicity; dose adjustment and TDM mandatory

• Pre-existing hearing impairment or vestibular dysfunction — increased ototoxicity risk

• Elderly patients — age-related renal decline increases toxicity risk

• Prolonged therapy (>7–10 days) — significantly increases nephrotoxicity and ototoxicity risk

• Dehydration or hypovolaemia — correct before initiating therapy

• Concurrent use with other nephrotoxic or ototoxic agents

• Neuromuscular disorders other than myasthenia gravis

• Obesity — use ideal body weight for dosing calculations

• Never mix aminoglycosides with beta-lactam antibiotics in same IV line (chemical inactivation)

Parameter Details

Risk category Category D (systemic use) — evidence of fetal ototoxicity

Overall safety Aminoglycosides cross placenta; documented cases of irreversible bilateral deafness in infants exposed in utero

Preferred alternatives Beta-lactams (penicillins, cephalosporins) are preferred for most gram-negative infections in pregnancy

When permissible Only for life-threatening gram-negative infections when no safer alternative exists; specialist input mandatory

Monitoring Fetal auditory assessment if exposure beyond first trimester; maternal renal function

Ophthalmic use: Minimal systemic absorption; likely safe.

Parameter Details

Compatibility Compatible — minimal oral absorption by infant

Expected milk levels Low

Preferred alternatives Gentamicin has similar profile; for systemic therapy, short course preferred

Infant monitoring Loose stools, oral thrush, feeding difficulties

Ophthalmic use: Safe in lactating mothers.

Parameter Details

Starting dose 2 mg/kg IV/IM; consider extended-interval dosing with lower doses (4–5 mg/kg once daily)

Titration Slower — based on renal function and serum drug levels

Special considerations Always calculate creatinine clearance (Cockcroft-Gault) — serum creatinine may underestimate renal impairment in elderly

Increased risks Nephrotoxicity (age-related renal decline), ototoxicity (pre-existing presbycusis), vestibular toxicity (falls risk)

Monitoring Baseline audiometry; renal function every 2–3 days; TDM after 2nd or 3rd dose

Loop diuretics (furosemide, bumetanide, torsemide) Additive ototoxicity via cochlear damage Avoid concurrent use if possible; if unavoidable, close audiometric monitoring

Other aminoglycosides (gentamicin, amikacin) Additive nephrotoxicity and ototoxicity Avoid concurrent systemic use

Amphotericin B Additive nephrotoxicity Avoid combination if possible; if essential, monitor renal function daily

Vancomycin Additive nephrotoxicity Use with caution; monitor renal function and drug levels closely

Neuromuscular blocking agents (vecuronium, rocuronium, atracurium) Enhanced neuromuscular blockade Caution in ICU/anaesthetic settings; may require dose adjustment of muscle relaxant

Cisplatin Additive nephrotoxicity and ototoxicity Avoid combination; if essential, monitor closely

Cyclosporin/Tacrolimus Additive nephrotoxicity Avoid if possible; monitor renal function and drug levels

Interacting Drug Mechanism Clinical Recommendation

Penicillins/Cephalosporins (IV admixture) Chemical inactivation if mixed in same solution Administer separately; do not mix in same IV line or syringe

NSAIDs Reduced renal blood flow potentiating nephrotoxicity Monitor renal function; use shortest duration of NSAID

Aciclovir/Ganciclovir Additive nephrotoxicity Monitor renal function closely

Colistin Additive nephrotoxicity and neurotoxicity Use combination cautiously; monitor renal and neurological function

Capreomycin/Streptomycin (TB regimens) Cross-resistance and additive toxicity Avoid combination in anti-TB regimens

Botulinum toxin Enhanced neuromuscular blockade effect Use with caution in patients receiving botulinum therapy

Systemic use:

• Nephrotoxicity (usually reversible if detected early)

• Ototoxicity — cochlear (tinnitus, hearing impairment) and vestibular (dizziness, vertigo, ataxia)

• Injection site pain (IM administration)

• Nausea

• Fever

Ophthalmic use:

• Local burning/stinging on instillation

• Transient blurred vision

• Lid itching and swelling

• Conjunctival erythema

Adverse Effect Action Required

Irreversible ototoxicity (deafness, permanent vestibular damage) Discontinue immediately; audiological evaluation; may be permanent

Acute tubular necrosis / Acute kidney injury Discontinue; supportive care; may require renal replacement therapy

Neuromuscular blockade (respiratory depression, especially with anaesthesia) Discontinue; supportive ventilation; calcium gluconate may help

Anaphylaxis (rare) Discontinue immediately; emergency treatment

Superinfection / Fungal overgrowth (prolonged ophthalmic use) Discontinue; initiate appropriate antifungal therapy

During treatment Serum drug levels (peak/trough) — mandatory if duration >5 days, renal impairment, or high-dose therapy. Traditional dosing: Peak 4–10 µg/mL, Trough <2 µg/mL. Renal function every 2–3 days. Daily assessment for tinnitus, hearing changes, dizziness, balance problems

After treatment Repeat audiometry if symptoms; renal function until normalised

Long-term Not typically used chronically; if inhaled therapy in cystic fibrosis (off-label): regular audiometry, renal function, pulmonary function

Ophthalmic use Monitor for hypersensitivity, secondary infection, or lack of response by day 3

Injection:

• Tobacin® (Alkem)

• Tobra® (Cipla)

• Negabact® (Abbott)

• Tobramycin Injection (Various generic manufacturers)

Ophthalmic:

• Toba® (Sun Pharma) — Eye drops, Ointment

• Tobrex® (Novartis) — Eye drops, Ointment

• Tobacin Eye Drops® (Alkem)

• Tobrasol® (Indoco)

Fixed-Dose Combinations (Ophthalmic):

Note: Inhalation formulations are NOT routinely available in India.

• Tobramycin injection is included in NLEM 2022; NPPA price ceiling applicable

• Government supply available through public health facilities

1. Therapeutic drug monitoring (TDM) is essential — Always monitor peak and trough levels for systemic use exceeding 5 days or in patients with renal impairment to prevent toxicity.

1. Never mix with beta-lactams in same IV line — Chemical inactivation occurs; administer through separate IV access or flush line adequately between infusions.

1. Extended-interval (once-daily) dosing is preferred — For patients with normal renal function, once-daily dosing provides equivalent efficacy with potentially reduced nephrotoxicity; not suitable for severe renal impairment.

1. Use ideal body weight for dosing in obese patients — Aminoglycosides distribute poorly into adipose tissue; using total body weight leads to overdosing.

1. Ototoxicity may be irreversible — Monitor for early symptoms (tinnitus, dizziness, hearing changes); stop immediately if suspected. Vestibular toxicity often precedes cochlear damage.

1. Ophthalmic tip: Drops for day, ointment for night — Combining formulations provides optimal coverage for moderate-severe external eye infections while maintaining daytime visual clarity.

Tobramycin; aminoglycoside; gram-negative; Pseudomonas; nephrotoxic; ototoxic; TDM-required; ophthalmic-antibiotic; NLEM-India; renal-adjustment; Schedule-H

RxIndia v1.0 — 20 May 2025

• CDSCO approved product information

• Indian Pharmacopoeia / National Formulary of India (IP/NFI)

• NLEM 2022

• AIIMS Antimicrobial Policy 2023

• API Textbook of Medicine

• IAP Guidelines for Paediatric Antibiotic Use

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine

• ICMR AMR Guidelines (for endocarditis combination therapy)

• International RCTs (for off-label inhalation use in cystic fibrosis)