Schedule H

Intramuscular (IM), Intravenous (IV)

Formulation Strength

Injection (IV/IM) 50 mg/2 mL vial

Injection (IV/IM) 100 mg/2 mL vial

Note: Preservative-free formulations available for neonatal use

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Serious Gram-negative Infections

(Bacteraemia, septicaemia, hospital-acquired pneumonia, intra-abdominal infections — often as combination therapy with β-lactams)

Adults with Normal Renal Function:

Parameter Recommendation

Starting dose 4–6 mg/kg/day IV or IM in 2–3 divided doses (every 8–12 hours)

Titration Adjust based on clinical response, renal function, and TDM if available

Usual maintenance dose 5–6 mg/kg/day divided every 8–12 hours

Maximum dose 7.5 mg/kg/day (not exceeding 300 mg/day in most patients)

Clinical Notes:

• Duration: Typically 7–10 days; avoid prolonged courses >10 days

• Use ideally guided by culture and sensitivity

• Combination with β-lactam (e.g., piperacillin-tazobactam, ceftazidime) recommended for Pseudomonas or serious nosocomial infections

• Once-daily dosing (5–7 mg/kg IV once daily) may be considered in selected patients with normal renal function

1. Complicated Urinary Tract Infections (including Pyelonephritis)

Parameter Recommendation

Starting dose 4–5 mg/kg/day IV or IM in divided doses

Titration Adjust per clinical response and renal function

Usual maintenance dose 4–6 mg/kg/day divided every 8–12 hours

Maximum dose 7.5 mg/kg/day

Clinical Notes:

• Duration: 7–10 days

• May be used as monotherapy for documented susceptible organisms

• Step-down to oral agents when clinically appropriate

Secondary Indications — Adults Only (Off-label, if any)

Indication Dose Duration Notes Evidence

Neutropenic fever (empirical combination regimen) 5–6 mg/kg/day IV in divided doses Until culture results/clinical response OFF-LABEL; Specialist only (haemato-oncology/ID); Part of combination therapy with anti-pseudomonal β-lactam Indian tertiary hospital protocols

Bacterial endocarditis (synergy regimen) 3 mg/kg/day IV in 2–3 divided doses 2–6 weeks per organism OFF-LABEL; Specialist only; Must be in combination with cell-wall active agent Limited Indian data; extrapolated from aminoglycoside class

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

1. Neonatal Sepsis

(IAP/NNF/AIIMS Protocols)

Age/Weight Category Dose (IV/IM) Frequency

Preterm (<34 weeks GA), ≤7 days 4–5 mg/kg Every 18–24 hours

Preterm (<34 weeks GA), >7 days 4–5 mg/kg Every 12–18 hours

Term (≥34 weeks GA), ≤7 days 4–5 mg/kg Every 12 hours

Term (≥34 weeks GA), >7 days 5–6 mg/kg Every 12 hours

Clinical Notes:

• Duration: 7–10 days for sepsis; 14–21 days for meningitis

• Monitor serum creatinine and urine output

• TDM recommended if therapy >5–7 days

• Consider audiometry/OAE before discharge if prolonged therapy

1. Serious Infections in Infants and Children (>1 month)

(Bacteraemia, complicated UTI, hospital-acquired pneumonia)

Parameter Recommendation

Starting dose 6–7.5 mg/kg/day IV/IM

Titration Adjust based on clinical response and renal function

Usual maintenance dose 6–7.5 mg/kg/day divided every 8 hours

Maximum dose 7.5 mg/kg/day

Clinical Notes:

• Duration: 7–10 days typical; minimise duration to reduce toxicity

• TDM recommended if therapy exceeds 5–7 days

• Combination therapy preferred for serious nosocomial infections

Secondary Indications — Paediatric Doses (Off-label, if any)

Indication Dose Duration Notes Evidence

Intra-abdominal infections (combination therapy) 6–7.5 mg/kg/day IV in divided doses 7–14 days OFF-LABEL; Specialist only; Combine with anti-anaerobic agent Indian tertiary paediatric hospital protocols

Safety Statement:

• Not recommended below 1 week of postnatal age except under neonatal specialist supervision in NICU setting

• Preterm neonates require extended dosing intervals and close monitoring

• Monitor renal function and auditory function in all paediatric patients receiving systemic therapy

Critical importance — aminoglycoside toxicity directly correlates with drug accumulation

Creatinine Clearance (CrCl) Dosing Adjustment

80 mL/min No adjustment; standard dosing

60–80 mL/min Standard dose; extend interval to every 12 hours

40–60 mL/min Extend interval to every 12–18 hours

20–40 mL/min Reduce dose by 30–50% OR extend interval to every 24 hours

10–20 mL/min Give 50% of dose every 24–48 hours; TDM essential

<10 mL/min Individualise per TDM; specialist supervision mandatory

Haemodialysis 2–3 mg/kg after each dialysis session (25–50% removed)

CAPD Loading dose 2 mg/kg, then per TDM

CRRT 2–3 mg/kg every 24–48 hours; adjust per TDM

Notes:

• Therapeutic drug monitoring (TDM) strongly recommended in renal impairment

• Target trough level: <2 mcg/mL (to minimise nephrotoxicity)

• Target peak level: 6–10 mcg/mL (for efficacy)

• Known hypersensitivity to netilmicin or any aminoglycoside antibiotic (cross-sensitivity exists across class)

• History of aminoglycoside-induced ototoxicity or nephrotoxicity

• Myasthenia gravis — risk of severe neuromuscular blockade and respiratory failure

• Concurrent use with other aminoglycosides (additive toxicity)

• Pre-existing renal impairment — dose adjustment and frequent monitoring essential

• Elderly patients — age-related decline in renal function; increased toxicity risk

• Pre-existing vestibular or cochlear dysfunction

• Concurrent nephrotoxic or ototoxic agents (loop diuretics, vancomycin, amphotericin B, cisplatin)

• Dehydration or hypovolaemia — correct before initiating therapy

• Neuromuscular disorders — monitor closely

• Prolonged therapy (>7–10 days) — significantly increased toxicity risk

• Obesity — use ideal body weight for dosing calculations

• Conditions requiring neuromuscular blocking agents

Parameter Recommendation

Risk category Generally avoid — potential for fetal ototoxicity and nephrotoxicity (aminoglycoside class effect)

Preferred alternatives Cephalosporins (ceftriaxone, cefotaxime) or penicillins (ampicillin, piperacillin) if organism susceptible

When to use Only in life-threatening infections where no safer alternative exists; specialist input mandatory; use lowest effective dose for shortest duration

Monitoring Fetal growth (serial ultrasound); amniotic fluid volume; neonatal audiometry after delivery if exposed in utero

Parameter Recommendation

Compatibility Compatible with breastfeeding — aminoglycosides poorly absorbed orally by infant

Preferred alternatives Cephalosporins, penicillins (if suitable for infection)

Drug levels in milk Very low (minimal oral bioavailability)

Infant monitoring Loose stools, oral thrush (theoretical effect on gut flora); feeding adequacy

Parameter Recommendation

Starting dose Lower end of dosing range (4–5 mg/kg/day)

Titration Based on renal function (calculate CrCl using Cockcroft-Gault formula) and TDM

Special risks Age-related decline in renal function (often not reflected in serum creatinine); vestibular toxicity; pre-existing hearing impairment; falls risk due to vestibular effects

Monitoring Renal function every 2–3 days; TDM if therapy >5 days; baseline and periodic audiometry if prolonged therapy; vestibular symptom assessment

Interacting Drug/Class Effect Mechanism Management

Loop diuretics (furosemide, bumetanide) Increased ototoxicity and nephrotoxicity Additive toxicity; diuretics may enhance aminoglycoside entry into inner ear Avoid concurrent use if possible; if essential, avoid rapid IV bolus of diuretic; monitor hearing

Amphotericin B Synergistic nephrotoxicity Additive renal tubular toxicity Avoid if possible; aggressive hydration; daily renal monitoring

Vancomycin Increased nephrotoxicity Additive renal toxicity Monitor renal function daily; TDM for both drugs

Cisplatin Potentiation of ototoxicity and nephrotoxicity Additive damage to cochlea and renal tubules Avoid combination

Cyclosporine, tacrolimus Synergistic nephrotoxicity Additive renal vasoconstriction Monitor renal function closely; consider alternative antibiotic

Neuromuscular blocking agents (vecuronium, rocuronium, succinylcholine) Prolonged neuromuscular blockade; respiratory failure Aminoglycosides have intrinsic neuromuscular blocking properties Use with extreme caution; monitor respiratory function; may need prolonged ventilatory support

Other aminoglycosides (gentamicin, amikacin) Additive oto- and nephrotoxicity Same class toxicity Avoid concurrent use

Interacting Drug/Class Effect Management

Cephalosporins (especially cefepime, cefotaxime) Potential additive nephrotoxicity Monitor renal function; synergistic antibacterial effect is therapeutic advantage

β-lactam antibiotics (penicillins) Synergistic antibacterial effect Preferred combination for serious Gram-negative infections

NSAIDs Reduced renal perfusion; increased aminoglycoside accumulation Monitor renal function; avoid prolonged concurrent use

Acyclovir Additive nephrotoxicity Monitor renal function; ensure adequate hydration

IV contrast agents Additive nephrotoxicity Space administration if possible; pre-hydration

Colistin Additive nephro- and neurotoxicity Monitor renal function and for neurotoxicity

Methotrexate Reduced methotrexate clearance Monitor methotrexate levels; watch for toxicity

• Nephrotoxicity (dose- and duration-dependent; typically reversible)

• Injection site pain (IM) or phlebitis (IV)

• Transient elevation in serum creatinine

• Ototoxicity — tinnitus, dizziness (early signs)

• Vestibular disturbance (vertigo, nystagmus)

• Nausea, vomiting

• Rash

• Fever

Adverse Effect Action Required

Nephrotoxicity (acute tubular necrosis) Discontinue or reduce dose; supportive care; usually reversible if detected early

Ototoxicity — Cochlear (hearing loss, especially high-frequency) May be irreversible; discontinue immediately if detected; audiometry follow-up

Ototoxicity — Vestibular (severe vertigo, ataxia) Discontinue; often irreversible; vestibular rehabilitation may be needed

Neuromuscular blockade (respiratory paralysis) Rare; discontinue; supportive ventilation; calcium gluconate may help

Anaphylaxis Discontinue immediately; emergency management

Phase Parameters

Baseline Serum creatinine; BUN; eGFR calculation; urinalysis; baseline audiometry (if prolonged therapy anticipated or high-risk patient); clinical assessment; weight for dose calculation

During treatment Renal function (creatinine, urine output) every 2–3 days; daily in critically ill or renal impairment; clinical assessment for vestibular symptoms (dizziness, nystagmus, tinnitus)

Therapeutic drug monitoring (TDM) Recommended if therapy >5–7 days, renal impairment, or neonatal/paediatric patients; Peak: 6–10 mcg/mL (30 min post-infusion); Trough: <2 mcg/mL (pre-dose)

Long-term / Repeated exposure Audiometry before and after therapy; vestibular function assessment; cumulative dose tracking

Brand Name Manufacturer Formulations

Netromycin Schering-Plough Injection 50 mg, 100 mg, 150 mg

Netilin Various Injection 50 mg, 100 mg

Netilmicin Generic Injection 50 mg, 100 mg

Netrim Various Injection 50 mg, 100 mg

Note: Preservative-free formulations preferred for neonatal use

Notes:

• Not included in NLEM 2022

• Not under NPPA price control

• Available in government hospitals under state drug procurement schemes

• Generally more expensive than gentamicin but less than amikacin

1. Lower ototoxic potential than gentamicin: Netilmicin may be preferred in neonates and patients at high risk of ototoxicity; consider when prolonged aminoglycoside therapy is anticipated

1. Less cross-resistance: Effective against some gentamicin-resistant Gram-negative strains due to resistance to certain aminoglycoside-modifying enzymes; useful alternative in documented gentamicin resistance

1. TDM improves outcomes: Therapeutic drug monitoring is underutilised but significantly reduces toxicity — advocate for TDM availability, especially in NICU and ICU settings

1. Limit duration strictly: Every day beyond 7 days significantly increases ototoxicity and nephrotoxicity risk; transition to alternative agents or step-down oral therapy as soon as clinically feasible

1. Calculate dose carefully: Use ideal body weight for obese patients; in neonates, dosing interval is as important as dose per kg — extended intervals in preterm neonates are critical

1. Combination therapy is standard: Rarely used as monotherapy except for uncomplicated UTI with documented susceptibility; combine with β-lactam for serious infections

netilmicin; aminoglycoside; antibacterial; nephrotoxic; ototoxic; neonatal sepsis; gram-negative infections; renal-adjusted; TDM required; injection; Schedule H; infectious diseases

RxIndia v1.0 — 10 Jun 2025

• CDSCO (Central Drugs Standard Control Organisation)

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

• API Textbook of Medicine

• IAP Neonatology Drug Doses (NNF)

• AIIMS Neonatology and Paediatric Antibiotic Guidelines

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine

• Indian tertiary hospital protocols (neonatal sepsis, ICU)

• Product Inserts: Netromycin, Netilin