Schedule H

Intramuscular (IM)

• Powder for injection: 750 mg vial, 1 g vial (with sterile water for injection as diluent)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Drug-Resistant Tuberculosis (MDR-TB/XDR-TB) — Second-line Agent

Used as part of combination regimen for multidrug-resistant tuberculosis under NTEP (DOTS-Plus) when other injectable agents are not available or contraindicated. No longer used for drug-sensitive TB in India.

Adult Dosing:

Parameter Recommendation

Starting dose 15 mg/kg IM once daily (round to nearest 250 mg)

Titration Not applicable

Usual maintenance dose 12–15 mg/kg IM once daily, 5–7 days/week

Maximum dose 1000 mg/day (1 g/day)

Weight-band Based Dosing (per NTEP):

Body Weight Daily Dose

30–39 kg 500 mg IM once daily

40–54 kg 750 mg IM once daily

55–70 kg 1000 mg IM once daily

70 kg 1000 mg IM once daily

Duration: 4–6 months in intensive phase (as per individualised MDR-TB regimen); maximum cumulative dose typically limited to 60 g to reduce toxicity risk

Clinical Notes:

• Always use as part of multi-drug combination therapy (never as monotherapy)

• Administered by deep IM injection (preferably upper outer quadrant of gluteus maximus)

• Rotate injection sites to prevent injection site reactions

• Not included in standard first-line TB regimens

• Being replaced by newer agents (bedaquiline, delamanid) in many MDR-TB regimens

1. Plague (Yersinia pestis)

Used for bubonic, septicaemic, and pneumonic plague — a notifiable disease and potential bioterrorism agent.

Parameter Recommendation

Starting dose 15 mg/kg IM (or 1 g)

Titration Not applicable

Usual maintenance dose 15 mg/kg IM every 12 hours (or 1 g twice daily)

Maximum dose 2 g/day (in divided doses)

Duration: 10–14 days

Clinical Notes:

• Drug of choice for plague per WHO and NCDC guidelines

• Continue treatment for at least 3 days after fever resolution

• Alternative: gentamicin, doxycycline (for less severe cases)

• Notify public health authorities immediately

1. Tularaemia (Francisella tularensis)

Rare zoonotic infection; may occur in endemic areas.

Parameter Recommendation

Starting dose 7.5–10 mg/kg IM

Titration Not applicable

Usual maintenance dose 7.5–10 mg/kg IM every 12 hours

Maximum dose 2 g/day

Duration: 10–14 days

Clinical Notes:

• Drug of choice for severe tularaemia

• Alternative: gentamicin

• Notify public health authorities

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes

Brucellosis 1 g IM once daily for first 14–21 days (with doxycycline 100 mg BD × 6 weeks) 2–3 weeks of streptomycin OFF-LABEL — Specialist only (Infectious Diseases). WHO-recommended regimen. Indian endemic regions (Rajasthan, Gujarat, Maharashtra). Gentamicin may be used as alternative.

Infective Endocarditis (Enterococcal — synergy with penicillin) 7.5 mg/kg IM every 12 hours (with ampicillin or penicillin G) 4–6 weeks OFF-LABEL — Specialist only (Cardiology/ID). For high-level gentamicin-resistant enterococci. Based on international guidelines and Indian cardiology practice.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Drug-Resistant Tuberculosis (MDR-TB) — Under NTEP

Use under paediatric pulmonologist/infectious disease specialist supervision only.

Weight-band Based Dosing:

Body Weight Daily Dose Maximum Dose

<5 kg 20 mg/kg IM once daily 150 mg

5–9 kg 20 mg/kg IM once daily 200 mg

10–14 kg 20 mg/kg IM once daily 300 mg

15–24 kg 15–20 mg/kg IM once daily 500 mg

25–34 kg 15 mg/kg IM once daily 600 mg

35–44 kg 15 mg/kg IM once daily 750 mg

≥45 kg Use adult dosing 1000 mg

Alternative mg/kg Dosing:

Parameter Recommendation

Starting dose 15–20 mg/kg IM once daily (children <15 kg: 20–30 mg/kg)

Titration Not applicable

Usual maintenance dose 15–20 mg/kg IM once daily

Maximum dose 1000 mg/day

Duration: As per individualised MDR-TB regimen (typically 4–6 months intensive phase)

Clinical Notes:

• Higher mg/kg dosing in young children reflects different pharmacokinetics

• Rotate injection sites (thigh preferred in infants/young children)

• Painful injections — consider topical anaesthetic cream (EMLA) before injection

Minimum Age Statement: May be used from birth for life-threatening indications (plague, severe MDR-TB) under specialist supervision. Generally avoided in infants <3 months unless no safer alternative exists.

Safety Monitoring:

• Baseline audiometry (age-appropriate method) before initiating treatment

• Audiometry every 2–4 weeks during treatment (or more frequently if cumulative dose increasing)

• Baseline and weekly serum creatinine

• Watch for vestibular symptoms (balance problems, vomiting)

• Monitor injection sites for pain, induration, abscess formation

• Parental education about early signs of hearing loss

Secondary Indications — Paediatrics (Off-label)

Indication Age Dose Notes

Plague All ages 15–20 mg/kg/day IM in 2 divided doses (max 2 g/day); Duration: 10–14 days OFF-LABEL in neonates — Specialist only. Public health emergency context. Based on WHO/NCDC guidelines.

Tularaemia All ages 15 mg/kg/day IM in 2 divided doses (max 2 g/day); Duration: 10 days OFF-LABEL — Specialist only. Based on WHO guidelines.

Brucellosis >8 years 15 mg/kg/day IM once daily (max 1 g) for 14–21 days with doxycycline OFF-LABEL — Specialist only. Doxycycline contraindicated <8 years; use alternative regimen in younger children.

60 No dose adjustment; standard dosing

30–59 12–15 mg/kg every 24–36 hours; OR standard dose every 48–72 hours

10–29 12–15 mg/kg every 48–72 hours; OR 7.5 mg/kg every 24 hours

<10 (not on dialysis) 12–15 mg/kg twice or thrice weekly only

Haemodialysis 12–15 mg/kg (max 500–750 mg) after each dialysis session (typically 3 times weekly); do NOT dose on non-dialysis days

CAPD/Peritoneal dialysis 15 mg/kg every 48–72 hours

Notes:

• Streptomycin is removed by haemodialysis (approximately 50%)

• Therapeutic drug monitoring (TDM) strongly recommended if available:

• Target peak (1 hour post-dose): 25–40 µg/mL

• Target trough (pre-dose): <5 µg/mL (ideally <2 µg/mL to reduce toxicity)

• More frequent audiometry and renal function monitoring required in renal impairment

• Consider alternative agents (levofloxacin, linezolid) for MDR-TB if renal impairment is severe

• Known hypersensitivity to streptomycin or other aminoglycosides

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

• Pre-existing bilateral severe sensorineural hearing loss

• Pregnancy (especially first trimester) — documented risk of fetal ototoxicity

• Concurrent use with other aminoglycosides (additive toxicity)

• Renal impairment — dose reduction required; increased risk of nephrotoxicity and ototoxicity

• Elderly patients — age-related decline in renal function; increased susceptibility to ototoxicity

• Pre-existing vestibular or cochlear dysfunction — enhanced risk of irreversible damage

• Dehydration — increases risk of nephrotoxicity; ensure adequate hydration

• Concurrent use of other ototoxic or nephrotoxic drugs (see drug interactions)

• Neuromuscular disorders (other than myasthenia gravis) — increased risk of weakness

• Prolonged treatment duration or high cumulative dose (>60 g) — significantly increased toxicity risk

• Conditions requiring neuromuscular blocking agents (surgery, ICU) — potentiation of blockade

• Hypokalaemia, hypocalcaemia, hypomagnesaemia — may potentiate aminoglycoside toxicity

Parameter Recommendation

Safety Category Contraindicated — well-documented risk of fetal ototoxicity (irreversible bilateral deafness reported); crosses placenta freely

Preferred Alternatives For MDR-TB: Bedaquiline, delamanid, fluoroquinolones (moxifloxacin, levofloxacin), linezolid — per NTEP pregnancy-specific regimens; For plague: Gentamicin (if essential), doxycycline (after first trimester if aminoglycoside contraindicated)

When to Use ONLY in life-threatening situations (severe plague, extensively drug-resistant TB) where no alternative exists AND maternal survival depends on treatment; requires informed consent and specialist input

Monitoring Serial fetal monitoring; newborn hearing screening mandatory if exposed

Parameter Recommendation

Breastfeeding Compatibility Compatible with breastfeeding; minimal infant exposure expected

Drug Levels in Milk Low (small amounts excreted; poor oral bioavailability in infant gut)

Preferred Alternatives Not required; may continue breastfeeding during streptomycin therapy

Infant Monitoring Monitor for loose stools, diarrhoea, oral candidiasis; observe for any signs of hearing problems (unlikely at milk concentrations)

Parameter Recommendation

Starting dose Lower end of dosing range: 10–12 mg/kg/day

Titration Not applicable

Maximum dose Consider limiting to 750 mg/day unless clearly indicated

Additional Risks Age-related renal decline (even with normal serum creatinine); significantly increased risk of ototoxicity (both vestibular and cochlear); pre-existing hearing loss common; falls risk if vestibular toxicity develops

Monitoring Calculate eGFR using CKD-EPI formula (not serum creatinine alone); baseline audiometry mandatory; more frequent monitoring (weekly renal function, audiometry every 2 weeks); consider therapeutic drug monitoring if available

Note: Avoid streptomycin in elderly if safer alternatives are available (e.g., bedaquiline-based MDR-TB regimens).

Interacting Drug Mechanism/Effect Management

Other aminoglycosides (gentamicin, amikacin, kanamycin) Additive ototoxicity and nephrotoxicity Contraindicated — never use two aminoglycosides concurrently

Loop diuretics (furosemide, bumetanide, ethacrynic acid) Synergistic ototoxicity; ethacrynic acid most ototoxic Avoid concurrent use if possible; if essential, use lowest effective diuretic dose; enhanced audiometry monitoring

Amphotericin B Additive nephrotoxicity Avoid if possible; if essential, monitor renal function daily; ensure adequate hydration

Neuromuscular blocking agents (vecuronium, rocuronium, pancuronium, succinylcholine) Potentiation of neuromuscular blockade; risk of prolonged paralysis and respiratory failure Avoid streptomycin close to surgery if possible; if used, inform anaesthetist; may need reduced doses of NMB agents; monitor closely for prolonged paralysis post-operatively

Botulinum toxin Additive neuromuscular blockade Avoid concurrent use

Capreomycin Additive ototoxicity and nephrotoxicity (both are injectable anti-TB drugs) Avoid concurrent use unless no alternative; if used together, requires specialist MDR-TB regimen planning; enhanced monitoring

Interacting Drug Effect Management

Vancomycin Additive nephrotoxicity Monitor serum creatinine at least twice weekly; ensure adequate hydration; consider therapeutic drug monitoring

Cyclosporine, tacrolimus Additive nephrotoxicity Monitor renal function closely; check calcineurin inhibitor levels

Cisplatin Additive ototoxicity and nephrotoxicity Avoid if possible; if used sequentially, allow washout period; enhanced audiometry monitoring

NSAIDs May reduce renal blood flow; increased nephrotoxicity risk Monitor renal function; ensure adequate hydration; use lowest NSAID dose for shortest duration

Oral anticoagulants (warfarin) Possible reduction in vitamin K-producing gut flora; enhanced anticoagulation Monitor INR more frequently during streptomycin therapy

Digoxin Aminoglycosides may reduce digoxin absorption (minor effect) Monitor clinically; usually not significant

Colistin (polymyxins) Additive nephrotoxicity and neurotoxicity Avoid if possible; if both required for MDR infections, close monitoring essential

• Injection site pain, induration, sterile abscess

• Vestibular toxicity (vertigo, dizziness, nystagmus, ataxia, nausea)

• Auditory toxicity (tinnitus, hearing loss — initially high-frequency)

• Nephrotoxicity (elevated creatinine, reduced GFR — usually reversible)

• Paraesthesias (circumoral numbness, tingling of extremities)

• Nausea, vomiting

• Fever

• Rash, urticaria

• Eosinophilia

Adverse Effect Clinical Significance

Irreversible ototoxicity Bilateral sensorineural hearing loss (high-frequency first, then progressing); vestibular damage causing permanent imbalance; risk increases with cumulative dose >60 g, prolonged duration, renal impairment, concurrent ototoxic drugs; discontinue immediately if tinnitus, vertigo, or hearing changes occur

Acute kidney injury (nephrotoxicity) Acute tubular necrosis; usually reversible if drug stopped promptly; risk increases with dehydration, concurrent nephrotoxins, renal impairment; monitor creatinine closely

Neuromuscular blockade Rare but serious; may cause respiratory paralysis; risk increased in myasthenia gravis, concurrent NMB agents, hypocalcaemia/hypomagnesaemia; requires ventilatory support; may respond to calcium gluconate

Anaphylaxis/severe hypersensitivity Rare; presents with bronchospasm, angioedema, hypotension; discontinue immediately; treat as anaphylaxis

Aplastic anaemia Very rare; discontinue if haematological abnormalities develop

Neurotoxicity Encephalopathy, seizures (rare, usually with very high doses or severe renal impairment)

Baseline:

• Audiometry (pure tone audiometry with speech discrimination; include high frequencies 4000–8000 Hz)

• Vestibular function assessment (if possible)

• Serum creatinine and calculated eGFR

• Serum potassium, calcium, magnesium (correct any deficiencies before starting)

• Full blood count

• Body weight (for dose calculation)

• Document any pre-existing hearing loss or renal impairment

After Initiation/During Treatment:

• Audiometry: Every 2–4 weeks during treatment; more frequently if symptoms develop or renal impairment present

• Serum creatinine: Weekly for first month, then every 2 weeks if stable

• Clinical assessment for vestibular symptoms (ask about dizziness, imbalance, nausea) at each visit

• Injection site inspection at each visit

• Monitor for symptoms of nephrotoxicity (reduced urine output, oedema)

• Therapeutic drug monitoring (if available): Peak and trough levels

Long-term:

• Cumulative dose tracking (risk increases significantly >60 g total)

• Audiometry at end of treatment

• Follow-up audiometry 3–6 months after treatment completion (delayed ototoxicity possible)

• Renal function assessment at treatment completion

When to Discontinue:

• Any confirmed hearing loss (even high-frequency only)

• Tinnitus that persists or worsens

• Vestibular symptoms (persistent vertigo, ataxia)

• Significant rise in serum creatinine (>50% from baseline or above reference range)

• Neuromuscular weakness

• Streptomycin Sulphate Injection IP (multiple manufacturers)

• Ambistryn-S® (Sarabhai/Piramal)

• Streptolin® (Alkem)

• Streptomycin (Cadila, Lupin, Macleods, Sun Pharma — generic)

• Government supply through NTEP for MDR-TB treatment

Note: Streptomycin is primarily available through government TB control programme (NTEP) supply chain for MDR-TB treatment. Limited private market availability.

• Included in NLEM 2022

• NPPA price-controlled

• Provided FREE under National Tuberculosis Elimination Programme (NTEP) for MDR-TB treatment through government health facilities

• Limited availability in private market

• Reserved for specific indications: Streptomycin is no longer used for drug-sensitive TB in India; reserved for MDR-TB regimens (when other injectables unavailable) and specific infections (plague, tularaemia, brucellosis)

• Ototoxicity is dose-limiting: Risk of irreversible hearing loss increases dramatically with cumulative doses >60 g and treatment duration >2–3 months; track cumulative dose carefully

• Baseline audiometry is mandatory: Document hearing status before starting; any patient complaint of tinnitus, hearing change, or vertigo warrants immediate audiometry and drug discontinuation

• IM injection technique matters: Use deep IM injection with Z-track technique; rotate sites (alternate buttocks or thighs); painful injections reduce compliance

• Renal function determines safety: Accumulation in renal impairment leads to toxicity; dose adjust based on eGFR; consider therapeutic drug monitoring in at-risk patients

• Pregnancy is contraindicated: Well-documented fetal ototoxicity (irreversible deafness) — use alternative MDR-TB drugs per NTEP pregnancy regimens

streptomycin; aminoglycoside; MDR-TB; drug-resistant tuberculosis; ototoxicity; nephrotoxicity; injectable antibiotic; NTEP; NLEM; plague; brucellosis; pregnancy-contraindicated

RxIndia v1.0 — 10 Jan 2025

• CDSCO approved prescribing information

• Indian Pharmacopoeia (IP)

• National Formulary of India (NFI)

• National List of Essential Medicines (NLEM 2022)

• NTEP Guidelines for Programmatic Management of Drug-Resistant TB in India

• ICMR Guidelines on MDR/XDR-TB

• NCDC Guidelines for Plague Management

• API Textbook of Medicine

• AIIMS Antimicrobial Guidelines

• IAP Guidelines on Paediatric Tuberculosis

• WHO Consolidated Guidelines on Tuberculosis

• Goodman & Gilman's The Pharmacological Basis of Therapeutics