Schedule H

Intravenous (IV), Intramuscular (IM)

• Injection: 100 mg/2 mL vial

• Injection: 250 mg/2 mL vial

• Injection: 500 mg/2 mL vial

Note: No marketed nebulisable formulation available in India. Inhalational use requires dilution of injectable formulation (specialist/off-label use only).

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India):

1. Severe Gram-Negative Infections (Hospital-acquired infections, septicaemia, respiratory tract infections, complicated urinary tract infections, intra-abdominal infections)

Route: Intravenous (preferred) or Intramuscular

Once-Daily Dosing (Extended Interval — Preferred):

Parameter Dose Clinical Notes

Starting dose 15 mg/kg IV once daily Based on actual body weight; infuse over 30–60 minutes

Titration Adjust based on renal function and TDM Target peak: 56–64 μg/mL; trough: <1 μg/mL

Usual maintenance dose 15 mg/kg once daily

Maximum dose 1.5 g/day; total cumulative dose ≤15 g per treatment course

Duration 7–10 days Step-down to oral agents as soon as clinically appropriate

Traditional Dosing (Divided Doses):

Parameter Dose Clinical Notes

Starting dose 7.5 mg/kg IV/IM every 12 hours Alternative regimen

Titration Based on renal function and serum levels Target peak: 20–35 μg/mL; trough: <10 μg/mL

Usual maintenance dose 15 mg/kg/day in 2 divided doses

Maximum dose 1.5 g/day

Clinical Note: Once-daily (extended interval) dosing is preferred for most infections due to concentration-dependent killing, enhanced post-antibiotic effect, and reduced nephrotoxicity risk.

1. Drug-Resistant Tuberculosis (MDR-TB / XDR-TB — as part of NTEP regimen)

Route: Intramuscular or Intravenous

Parameter Dose Clinical Notes

Starting dose 15 mg/kg IM/IV once daily Maximum 1 g/day

Titration Not applicable Fixed dose as per NTEP protocol

Usual maintenance dose 15 mg/kg once daily (max 1 g)

Maximum dose 1 g/day

Duration As per NTEP/PMDT regimen — typically 4–6 months in intensive phase Specialist supervision mandatory

Note: Part of Group B second-line anti-TB drugs per NTEP. Requires baseline and monthly audiometry and renal function monitoring. Consider bedaquiline-based regimens to avoid injectable toxicity where feasible.

1. Febrile Neutropenia (Empirical therapy — in combination with anti-pseudomonal beta-lactam)

Parameter Dose Clinical Notes

Starting dose 15 mg/kg IV once daily Combined with piperacillin-tazobactam or cefepime or carbapenem

Titration Based on renal function

Usual maintenance dose 15 mg/kg once daily

Maximum dose 1.5 g/day

Duration Until neutropenia resolves or source controlled Typically 7–10 days

1. Infective Endocarditis (Enterococcal — in combination with ampicillin or vancomycin)

Parameter Dose Clinical Notes

Starting dose 7.5 mg/kg IV every 12 hours Synergistic therapy

Titration Based on TDM and renal function Target peak: 20–25 μg/mL

Usual maintenance dose 15 mg/kg/day in 2 divided doses

Maximum dose 1.5 g/day

Duration 4–6 weeks (as per endocarditis guidelines) TDM and renal monitoring essential

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

1. Nebulised Amikacin for Ventilator-Associated Pneumonia (VAP) due to MDR Gram-Negatives — OFF-LABEL

Parameter Details

Indication Adjunctive therapy for VAP caused by MDR Pseudomonas, Acinetobacter, or other resistant Gram-negatives

Dose 400 mg nebulised every 8–12 hours (using IV formulation diluted appropriately)

Duration 7–14 days as adjunct to systemic therapy

Specialist only Yes — Critical Care/Pulmonology

Evidence basis Supportive RCTs (INAHALE trial); used in Indian tertiary ICUs for MDR pathogens; no India-specific guideline

Note: No marketed nebulisable formulation in India; requires dilution of IV preparation under specialist supervision.

1. Peritoneal Dialysis-Related Peritonitis — OFF-LABEL

Parameter Details

Indication Gram-negative CAPD peritonitis

Dose 25 mg/L in each exchange (continuous dosing) OR 2 mg/kg IP loading then 0.6 mg/kg per exchange

Duration 14–21 days

Specialist only Yes — Nephrology

Evidence basis ISPD guidelines; Indian nephrology practice

PAEDIATRIC DOSING (Specialist Only)

Primary Indications:

1. Neonatal Sepsis / Serious Gram-Negative Infections

Route: Intravenous (preferred) or Intramuscular

Age / Weight Category Starting Dose Frequency Maximum Daily Dose Clinical Notes

Preterm (<32 weeks GA), ≤7 days 15 mg/kg Every 36–48 hours 15 mg/kg Extended interval due to immature renal function

Preterm (32–36 weeks GA), ≤7 days 15 mg/kg Every 24–36 hours 15 mg/kg

Term neonates (≥37 weeks), ≤7 days 15 mg/kg Every 24 hours 15 mg/kg

Neonates >7 days, any weight 15 mg/kg Every 24 hours 15 mg/kg

Monitoring: Serum creatinine before each dose in first week; auditory screening recommended before discharge if therapy >5 days.

1. Infants and Children (1 month–12 years) — Severe Gram-Negative Infections

Parameter Dose Comments

Starting dose 15–20 mg/kg IV once daily OR 7.5 mg/kg every 12 hours

Titration Based on renal function and TDM

Usual maintenance dose 15–20 mg/kg/day

Maximum dose 1.5 g/day

Duration 7–10 days

1. Adolescents (>12 years)

Parameter Dose Comments

Starting dose 15 mg/kg IV once daily Use adult dosing principles

Titration Based on renal function and TDM

Usual maintenance dose 15 mg/kg once daily

Maximum dose 1.5 g/day

1. MDR-TB in Children (NTEP/PMDT Protocol)

Parameter Dose Comments

Starting dose 15–20 mg/kg IM/IV once daily Maximum 1 g/day

Titration Not applicable

Usual maintenance dose 15–20 mg/kg once daily

Maximum dose 1 g/day

Duration Per NTEP intensive phase regimen Specialist supervision; baseline and monthly audiometry mandatory

Secondary Indications — Paediatrics (Off-label, if any)

Not applicable. No established off-label paediatric indications beyond MDR-TB (covered under primary indications per NTEP).

Not recommended below gestational age of 28 weeks except under neonatology specialist supervision with extended dosing intervals and mandatory TDM.

60 No adjustment; standard dosing Routine monitoring

40–60 15 mg/kg every 24–36 hours TDM recommended

20–40 15 mg/kg every 36–48 hours TDM mandatory

<20 7.5 mg/kg; redose based on trough level (<5 μg/mL) TDM mandatory; individualised dosing

Haemodialysis 5–7.5 mg/kg post-dialysis (amikacin is dialyzable) Check post-dialysis level before next dose

CAPD 25 mg/L in each exchange OR systemic dose adjusted per residual renal function TDM recommended

CRRT 7.5–10 mg/kg every 24–48 hours based on effluent rate Highly variable; TDM essential

Key Point: Aminoglycosides exhibit concentration-dependent killing; maintaining adequate peak levels is important even when intervals are extended for renal impairment.

• Known hypersensitivity to amikacin or any aminoglycoside antibiotic

• Myasthenia gravis (risk of neuromuscular blockade and respiratory failure)

• Concurrent use with other aminoglycosides (streptomycin, gentamicin, tobramycin, kanamycin)

• History of aminoglycoside-induced ototoxicity or vestibular toxicity

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

• Pre-existing auditory or vestibular impairment — increased ototoxicity risk

• Elderly patients — reduced renal reserve; higher toxicity risk

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

• Dehydration or hypovolaemia — increases nephrotoxicity risk

• Concurrent nephrotoxic or ototoxic medications

• Neuromuscular disorders (other than myasthenia gravis) — monitor closely

• Obesity — dose based on adjusted body weight: IBW + 0.4 × (TBW – IBW)

• Burns patients — may require higher doses due to increased clearance

Aspect Recommendation

Risk category Potential fetal harm — crosses placenta; documented risk of irreversible bilateral sensorineural hearing loss in fetus

Use in pregnancy Avoid unless no safer alternative and benefit clearly outweighs risk

Preferred alternatives Beta-lactams (ceftriaxone, piperacillin-tazobactam, carbapenems) for Gram-negative infections

When to use Life-threatening infections unresponsive to safer alternatives; MDR-TB requiring injectable therapy per NTEP (specialist decision)

Monitoring Maternal renal function; therapeutic drug monitoring; neonatal audiometry after birth

Aspect Recommendation

Compatibility Compatible with breastfeeding

Drug levels in milk Low; poorly absorbed from infant GI tract

Preferred alternatives None required if clinically indicated

Recommendations Continue breastfeeding; no timing adjustments needed

Infant monitoring Observe for diarrhoea, oral thrush (rare; due to GI flora alteration)

Aspect Recommendation

Starting dose 15 mg/kg once daily (same as adults) but calculate dose using adjusted body weight if obese

Titration Extend dosing interval based on creatinine clearance; calculate using Cockcroft-Gault (not eGFR alone)

Special considerations Age-related decline in renal function is often underestimated by serum creatinine; use creatinine clearance for dosing

Extra risks Increased nephrotoxicity, vestibular toxicity (vertigo, imbalance), and ototoxicity; falls risk due to vestibular dysfunction

Monitoring Baseline and periodic audiometry; renal function before each dose or at least every 2–3 days; TDM recommended for therapy >5 days

Drug Interaction Management

Loop diuretics (furosemide, torsemide, bumetanide) Additive ototoxicity; may be irreversible Avoid concurrent use if possible; if essential, monitor auditory function closely

Other aminoglycosides (gentamicin, streptomycin, tobramycin) Additive nephrotoxicity and ototoxicity Avoid concurrent use; sequential use requires washout period

Amphotericin B (conventional) Synergistic nephrotoxicity Avoid combination if possible; use liposomal amphotericin if antifungal required

Cisplatin Additive nephrotoxicity and ototoxicity Avoid if possible; if essential, extensive monitoring required

Neuromuscular blocking agents (vecuronium, rocuronium, atracurium) Potentiation of neuromuscular blockade; prolonged paralysis, respiratory depression Use with extreme caution; monitor closely during and after anaesthesia

Botulinum toxin Enhanced neuromuscular blockade Avoid concurrent use

Drug Interaction Management

Vancomycin Increased nephrotoxicity risk Monitor renal function every 2–3 days; consider TDM for both drugs

Colistin / Polymyxin B Additive nephrotoxicity Avoid if possible; if combined, monitor renal function daily

Cyclosporine / Tacrolimus Additive nephrotoxicity Monitor renal function and calcineurin inhibitor levels closely

NSAIDs Potential additive nephrotoxicity with prolonged use Monitor renal function; avoid prolonged concurrent use

Cephalosporins (especially cephaloridine) Potential additive nephrotoxicity Monitor renal function

Carbapenems Antimicrobial synergy (often used intentionally); no significant toxicity interaction Standard monitoring

Contrast media (IV) Additive nephrotoxicity Ensure adequate hydration; space administration; monitor renal function

• Nephrotoxicity (dose and duration dependent; usually reversible) — elevated creatinine, reduced urine output

• Ototoxicity — tinnitus, hearing impairment (may be irreversible)

• Vestibular toxicity — vertigo, dizziness, nystagmus, imbalance

• Injection site pain and inflammation (IM use)

• Nausea and vomiting

• Rash

• Fever

Adverse Effect Clinical Notes

Irreversible sensorineural hearing loss Bilateral, high-frequency loss initially; risk increases with cumulative dose, duration, renal impairment, concurrent ototoxins; may progress after drug discontinuation

Vestibular damage Vertigo, ataxia, nystagmus; may be permanent

Acute kidney injury Usually reversible if detected early; risk factors: prolonged therapy, dehydration, concurrent nephrotoxins

Neuromuscular blockade Rare; respiratory paralysis possible in susceptible patients (myasthenia, post-anaesthesia, high doses); reverse with calcium gluconate

Anaphylaxis Rare; discontinue immediately; manage as anaphylactic emergency

Action: Discontinue amikacin immediately if ototoxicity symptoms (tinnitus, hearing loss, vertigo), significant rise in serum creatinine (>50% from baseline), or allergic reaction occurs.

Therapeutic Drug Monitoring Once-daily dosing: Peak (1 hour post-infusion): target 56–64 μg/mL; Trough (before next dose): <1 μg/mL. Divided dosing: Peak: 20–35 μg/mL; Trough: <10 μg/mL

During therapy Serum creatinine every 2–3 days; daily in unstable/ICU patients; urine output monitoring

Prolonged therapy (>7 days) Audiometry weekly or if symptoms develop; vestibular assessment

Neonates Serum creatinine before each dose (first 7 days); weight daily; auditory screening before discharge if therapy >5 days

MDR-TB patients Monthly audiometry (high-frequency audiometry preferred); monthly serum creatinine

TDM Indications: Prolonged therapy (>5 days), renal impairment, extremes of weight (obesity, underweight), critically ill patients, neonates, elderly, concurrent nephrotoxic/ototoxic drugs.

• Amikin (Pfizer) — originator brand

• Amikacin (Cipla)

• Amikacin (Sun Pharma)

• Amikacin (Lupin)

• Amikacin (Alkem)

• Amikacin (Intas)

• Amikacin (Zydus)

• Amikacin (Mankind)

• Mikacin (Aristo)

• Amigoz (Glenmark)

• Multiple other generic manufacturers

Note: No significant FDCs available.

• Listed in NLEM 2022

• Under DPCO/NPPA price control

• Available through government supply for TB (NTEP) and public health facilities at no cost

1. Prefer once-daily dosing — extended interval (once-daily) dosing is preferred for most systemic infections due to concentration-dependent bactericidal activity, enhanced post-antibiotic effect, and reduced nephrotoxicity risk compared to divided dosing.

1. Limit duration to 7–10 days — aminoglycoside toxicity is cumulative and duration-dependent; step-down to appropriate oral or IV agents as soon as clinically feasible to minimise ototoxicity and nephrotoxicity.

1. Calculate dose carefully — use actual body weight for normal/underweight patients; for obese patients (>20% above IBW), use adjusted body weight: IBW + 0.4 × (TBW – IBW) to avoid overdosing.

1. Renal function assessment before every dose — in unstable patients or those with renal impairment, check serum creatinine before each dose; rising creatinine is an early warning of nephrotoxicity.

1. Ototoxicity may be irreversible — counsel patients about risk of permanent hearing loss, especially with prolonged therapy; ask about tinnitus and hearing changes at each visit; consider audiometry for therapy >7 days.

1. Synergy with beta-lactams — amikacin is commonly used in combination with anti-pseudomonal beta-lactams (piperacillin-tazobactam, cefepime, carbapenems) for serious Gram-negative infections; avoid using as monotherapy for serious infections.

1. MDR-TB monitoring — when used in MDR-TB regimens, mandatory baseline and monthly audiometry is essential per NTEP guidelines; consider transitioning to all-oral regimens where feasible to avoid injectable toxicity.

amikacin; aminoglycoside; Gram-negative; nephrotoxicity; ototoxicity; MDR-TB; neonatal sepsis; TDM; once-daily dosing; NLEM India; Schedule H

RxIndia v1.0 — 08 May 2025

• CDSCO approved prescribing information

• Indian Pharmacopoeia

• NLEM 2022

• API Textbook of Medicine

• ICMR Guidelines for Antimicrobial Use 2019

• NTEP/PMDT Guidelines for Drug-Resistant TB

• AIIMS Antimicrobial Policy 2022

• IAP Neonatal Sepsis and Antibiotic Guidelines

• ISPD Peritonitis Guidelines (for CAPD dosing)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics (supportive)

• INAHALE trial data (for nebulised amikacin off-label use)