Schedule H

Oral

• Tablets: 120 mg (limited standalone availability)

• Fixed-dose combination packs for H. pylori eradication (containing bismuth subcitrate 120 mg with tetracycline, metronidazole, and PPI)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

✅ Helicobacter pylori Eradication (Bismuth-based Quadruple Therapy)

Parameter Recommendation

Starting dose 120 mg orally four times daily (before each meal and at bedtime)

Titration Not applicable

Usual maintenance dose 120 mg QID (480 mg/day total)

Maximum dose 480 mg/day

Duration 10–14 days

Combination regimen components:

• Bismuth subcitrate 120 mg QID

• Tetracycline 500 mg QID

• Metronidazole 400–500 mg TID–QID

• PPI (omeprazole 20 mg or pantoprazole 40 mg) BD

Clinical notes:

• Recommended for clarithromycin-resistant H. pylori or after first-line triple therapy failure

• All four drugs must be taken for the full duration for optimal eradication

• Counsel patients regarding multiple daily dosing schedule

✅ Peptic Ulcer Disease (Adjunctive mucosal protection)

Parameter Recommendation

Starting dose 120 mg orally four times daily, 30 minutes before meals and at bedtime

Titration Not applicable

Usual maintenance dose 120 mg QID

Maximum dose 480 mg/day

Duration 4–8 weeks

Clinical note Used as adjunct to acid suppression therapy; not first-line monotherapy

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

Indication Dose Duration Notes Evidence

Functional dyspepsia – refractory cases (OFF-LABEL) 120 mg TID–QID before meals 4–6 weeks Specialist only; after PPI/H2 blocker failure Indian GI specialist practice; limited RCT data

Chronic gastritis with erosions (OFF-LABEL) 120 mg TID–QID before meals 2–4 weeks Specialist only Indian GI practice for symptomatic relief

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

✅ Helicobacter pylori Eradication (as part of combination therapy)

Age/Weight Dose Maximum Duration Notes

<12 years Not recommended — — Use only under paediatric gastroenterologist supervision

≥12 years 120 mg QID (adult dosing) 480 mg/day 10–14 days As part of bismuth-based quadruple therapy

Weight-based dosing (if used in younger children under specialist care):

• Approximate dose: 8 mg/kg/day in 4 divided doses

• Maximum: Do not exceed 480 mg/day

Safety Monitoring:

• Monitor for neurological symptoms (rare bismuth neurotoxicity)

• Watch for salicylate-like symptoms

• Ensure adequate hydration

Secondary Indications – Paediatric (Off-label, if any)

Not applicable. No evidence-based paediatric use beyond H. pylori eradication.

Age restriction statement: Not recommended in children below 12 years except under paediatric gastroenterologist supervision due to lack of safety data and risk of bismuth accumulation.

Moderate impairment (eGFR 30–59) Use with caution; limit duration to ≤10 days; monitor for toxicity signs

Severe impairment (eGFR <30) Avoid use due to risk of bismuth accumulation and neurotoxicity

Haemodialysis Avoid use; bismuth is not effectively dialysed

Peritoneal dialysis Avoid use

• Known hypersensitivity to bismuth compounds

• Severe renal impairment (eGFR <30 mL/min/1.73 m²)

• History of bismuth encephalopathy

• Concurrent use with other bismuth-containing products (risk of toxicity)

• Active upper gastrointestinal bleeding (until bleeding controlled and aetiology established)

• Elderly patients: increased susceptibility to bismuth neurotoxicity

• Prolonged use beyond 8 weeks: risk of CNS accumulation

• Moderate renal impairment: limit duration and monitor closely

• Concurrent anticoagulant therapy: monitor for GI bleeding

• Patients with pre-existing neurological disorders

• Not for monotherapy in H. pylori infection

Parameter Details

Risk category Not formally classified; no adequate human studies

Overall safety Not recommended; theoretical risk of fetal bismuth accumulation

Preferred alternatives PPI-based triple therapy (amoxicillin + clarithromycin + PPI) if H. pylori treatment essential

When to use Only if benefit clearly outweighs risk and no safer alternatives; specialist decision

Monitoring Not defined due to lack of data; general fetal wellbeing assessment

Parameter Details

Compatibility Avoid during breastfeeding

Drug levels in milk Low but uncertain; bismuth may accumulate

Preferred alternatives PPI or H2-receptor blockers for acid suppression; defer H. pylori treatment if possible

Infant monitoring If exposed: observe for vomiting, irritability, feeding difficulties

Parameter Recommendation

Starting dose Standard adult dose (120 mg QID) may be used if renal function normal

Titration Not applicable

Duration Limit to shortest effective duration (≤14 days for H. pylori)

Special risks Higher risk of bismuth neurotoxicity (confusion, ataxia, tremor); reduced renal reserve

Monitoring Assess renal function before initiating; monitor for neurological symptoms throughout therapy

Interacting Drug Effect/Mechanism Action

Other bismuth-containing products (e.g., bismuth subsalicylate) Additive bismuth toxicity risk Avoid concurrent use

Tetracycline Bismuth may reduce tetracycline absorption via chelation Separate doses by at least 2 hours when not part of fixed regimen

Quinolones (ciprofloxacin, levofloxacin) May reduce absorption of quinolones Avoid concurrent use or separate by 2–4 hours

Interacting Drug Effect/Mechanism Action

Iron supplements Mutual chelation reducing absorption of both Separate administration by 2 hours

Zinc supplements Chelation may reduce absorption Separate doses by 2 hours

Antacids (aluminium/magnesium-containing) May reduce bismuth binding to gastric mucosa Avoid simultaneous administration

Proton pump inhibitors No pharmacokinetic interaction; commonly co-prescribed May be given together

Warfarin No direct interaction; theoretical increased GI bleeding risk Monitor INR; watch for bleeding signs

• Black discolouration of tongue (benign; due to bismuth sulfide)

• Black stools (benign; do not confuse with melaena)

• Nausea

• Metallic taste

• Abdominal discomfort or cramping

• Mild constipation

• Headache

Adverse Effect Notes

Bismuth neurotoxicity (encephalopathy) Rare; presents with confusion, ataxia, tremor, myoclonus; occurs with prolonged use or renal impairment; requires immediate discontinuation

Nephrotoxicity Risk in pre-existing CKD or prolonged high-dose use

Severe allergic reactions Rare; rash, urticaria, angioedema

Pseudomembranous colitis When used as part of quadruple therapy with antibiotics; requires discontinuation and specific treatment

Timing Parameter

Baseline Renal function (serum creatinine, eGFR); symptom assessment; neurological status in elderly

During therapy Monitor for GI tolerability; neurological symptoms (confusion, tremor, ataxia, incoordination)

Long-term Not recommended beyond 8 weeks; if prolonged use unavoidable, monitor renal function and neurological status periodically

Standalone bismuth subcitrate formulations:

• Limited standalone availability in Indian market

Fixed-dose combination packs (H. pylori eradication kits):

• PyloKit® (similar combination formulation)

Note: Pylera® is NOT AVAILABLE in India. Verify current availability of specific brands before prescribing.

NLEM/NPPA status: Not listed under NLEM 2022; not under NPPA price control. Private market availability.

• Always use bismuth subcitrate as part of combination regimen for H. pylori; never as monotherapy for eradication

• Black stools and tongue discolouration are benign and expected; counsel patients to prevent confusion with upper GI bleeding

• Limit treatment duration to ≤14 days for H. pylori and ≤8 weeks for other indications to minimise neurotoxicity risk

• Four-times-daily dosing requires careful patient counselling; adherence is critical for eradication success

• Reserve bismuth-based quadruple therapy for clarithromycin-resistant cases or after first-line triple therapy failure

• Check renal function in elderly patients before initiating therapy; avoid in severe renal impairment

bismuth subcitrate; H. pylori; quadruple therapy; peptic ulcer; cytoprotective; mucosal protection; neurotoxicity risk; renal caution; gastroenterology; Schedule H; India

RxIndia v1.0 — 14 Jan 2025

• CDSCO (Approved formulations)

• Indian Pharmacopoeia / National Formulary of India (NFI)

• API Textbook of Medicine (H. pylori management)

• Indian Society of Gastroenterology H. pylori Management Consensus

• AIIMS Antimicrobial Guidelines (Gastroenterology section)

• AIIMS Departmental Protocols (Gastroenterology)

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

• Harrison's Principles of Internal Medicine (Peptic ulcer disease)