Bismuth Subsalicylate

Bismuth subsalicylate is a poorly absorbed bismuth salt of salicylic acid used for acute diarrhoea, dyspepsia and Helicobacter pylori eradication. Bismuth acts locally while the salicylate is absorbed almost completely, so salicylate precautions apply.

Classification. Antidiarrhoeal; gastric mucosal protectant; antimicrobial adjunct.

Mechanism. In the gut it dissociates into bismuth salts and salicylic acid. Salicylate reduces intestinal prostaglandin-mediated secretion. Bismuth coats the mucosa, binds bacterial toxins and has direct bactericidal activity, including against H. pylori.

Pharmacodynamics. Antisecretory and antidiarrhoeal effects begin within 1 to 2 hours. Bismuth forms bismuth sulphide in the gut, which blackens stool and sometimes the tongue.

Pharmacokinetics. Less than 1% of bismuth is absorbed, whereas more than 80% of the salicylate is absorbed. Each 262 mg of bismuth subsalicylate gives about 100 mg of salicylate. Bismuth is excreted in urine and bile and may accumulate in kidney impairment.

Adult oral doses unless stated. Doses by milligrams of bismuth subsalicylate; check product strength, which varies between products.

Acute diarrhoea, including travellers' diarrhoea, and indigestion.

• 524 mg every 30 to 60 minutes as needed.

• Maximum 8 doses (4.2 g) in 24 hours.

• Use for no more than 2 days; review if diarrhoea persists, or if fever, blood in stool or severe abdominal pain develops.

• Oral rehydration solution is the priority for fluid loss; bismuth does not replace it.

Prevention of travellers' diarrhoea. 524 mg four times daily with meals and at bedtime for up to 3 weeks. It reduces incidence by about half; use is limited by salicylate load and blackened stool.

Helicobacter pylori eradication (bismuth quadruple therapy). Bismuth subsalicylate 524 mg four times daily for 14 days with tetracycline 500 mg four times daily, metronidazole 400 to 500 mg three times daily and a PPI twice daily (for example omeprazole 20 mg twice daily). It is preferred where clarithromycin resistance is high or after a failed first attempt. Clarithromycin resistance is reported to be high in several East African settings.

Children. Avoid under 12 years because of the salicylate load and risk of Reye syndrome. Do not give to adolescents recovering from influenza or varicella.

Contraindications.

• Salicylate or aspirin hypersensitivity, including asthma triggered by NSAIDs.

• Active gastrointestinal bleeding or ulcer bleeding; bleeding disorders.

• Children and adolescents with viral illness (Reye syndrome).

• Third trimester of pregnancy; avoid in the whole of pregnancy where possible.

• Moderate to severe kidney impairment.

Common adverse effects. Black stool and tongue (harmless, but can mimic melaena), nausea and constipation. Tinnitus is an early sign of salicylate excess.

Serious adverse effects.

• Salicylate toxicity with high doses, prolonged use, kidney impairment or coadministration with aspirin: tinnitus, hyperventilation, metabolic acidosis, confusion.

• Bismuth encephalopathy (myoclonus, ataxia, confusion) after prolonged high-dose use or with kidney impairment.

• Gastrointestinal bleeding in those with ulcers or on anticoagulants.

• Reye syndrome in children with influenza or varicella.

Major interactions.

• Warfarin and other anticoagulants: salicylate raises bleeding risk and may raise INR; avoid or monitor INR closely.

• Aspirin and other salicylates: additive toxicity; avoid.

• Methotrexate: reduced clearance; avoid.

• Probenecid and sulfinpyrazone: effect antagonised.

• Valproic acid: displacement from protein binding; monitor.

• Fluoroquinolones: reduced absorption; separate dosing by at least 2 hours. Tetracycline is given together with bismuth in the eradication regimen by design.

• Antidiabetic drugs: salicylate may enhance hypoglycaemia.

• Bismuth is radiopaque and can interfere with abdominal radiography.

Special groups.

• Pregnancy: avoid; salicylate in the third trimester risks premature ductus arteriosus closure and bleeding.

• Breastfeeding: salicylate enters milk; avoid.

• Children: avoid under 12 years, and in older children use only after exclusion of viral illness.

• Older adults: increased bleeding and salicylate toxicity risk; use lowest dose for the shortest time.

• Kidney impairment: avoid; bismuth and salicylate accumulate.

• Liver impairment: use with caution; salicylate increases bleeding risk.

Formulations. Chewable tablets and caplets 262 mg; oral liquid 262 mg in 15 mL or 525 mg in 15 mL. Availability and strength vary by market.

Administration. Chew tablets thoroughly or swallow caplets with water. Shake liquids. For eradication regimens take with meals and at bedtime.

Baseline. Kidney function and bleeding risk before any use over 2 days. Review all salicylate, NSAID and anticoagulant use.

Monitoring.

• Hydration status, stool frequency and temperature during diarrhoea treatment.

• INR in anticoagulated patients if used.

• Tinnitus, confusion or hyperventilation as early features of salicylate or bismuth toxicity.

• Warn that black stool is expected; melaena also produces black stool, so assess for dizziness, haematemesis and haemodynamic change.

Therapeutic drug monitoring. Not routinely used. Check serum salicylate and blood gas if toxicity is suspected.

Stopping. Stop after 2 days for diarrhoea, or at the end of the 14 day eradication course. Stop immediately for tinnitus, confusion, bleeding or salicylate toxicity.

Referral and escalation. Urgent review for bloody diarrhoea, fever, severe dehydration, suspected cholera or dysentery, or diarrhoea lasting over 2 days. Salicylate toxicity needs hospital management with correction of acidosis and consideration of urinary alkalinisation and haemodialysis.