Bismuth Salts

Name: Bismuth Salts

Introduction

Antidiarrhea agent; antidyspepsia agent; internal deodorant.3 5 6 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 32 37

Antiulcer agent (as part of multiple-drug regimens for Helicobacter pylori infection).1 2 4 35 42 45

Bismuth Salts Dosage and Administration

Administration

Oral Administration

Capsules

Bismuth subgallate: Administer orally up to 4 times daily with meals.3 43 Swallow capsule whole.43

Bismuth subcitrate potassium in fixed combination with metronidazole and tetracycline hydrochloride (Pylera): Administer orally 4 times daily after meals and at bedtime;2 39 give omeprazole concomitantly as part of regimen.2 39 (See Fixed Combination Containing Bismuth Subcitrate Potassium, Metronidazole, and Tetracycline Hydrochloride [Pylera] under Dosage.) Swallow capsule whole.2 Administer with full glass (240 mL) of water, particularly with bedtime doses, to reduce risk of esophageal irritation and ulceration by tetracycline hydrochloride component.2 If a dose of Pylera is missed, take next dose at regularly scheduled time; do not double the dose.2 Contact clinician if >4 doses are missed.2

Suspension

Bismuth subsalicylate: Shake suspension well prior to administration.13 14 15 16 19 21 23 24 Use dose cup provided by manufacturer for accurate dosing.13 16 21 23 For Diotame, twist off lid and dispense appropriate dose by squeezing tube.24

Chewable Tablets

Bismuth subgallate: Administer orally up to 4 times daily with meals.3 43 Chew or swallow whole.43

Bismuth subsalicylate: Chew or dissolve in mouth and swallow.1 13 17 20 24

Bismuth subsalicylate (with metronidazole and tetracycline hydrochloride in Helidac Therapy kit): Administer each component orally 4 times daily with meals and at bedtime.1 Chew and swallow bismuth subsalicylate tablets.1 Administer tetracycline hydrochloride and metronidazole components with full glass (240 mL) of water, particularly with bedtime doses, to reduce risk of esophageal irritation and ulceration by tetracycline hydrochloride component.1 If a dose of Helidac Therapy is missed, take next dose at regularly scheduled time; do not double the dose.1 If >4 doses are missed, contact clinician. 1

Conventional Tablets

Bismuth subsalicylate (e.g., Pepto-Bismol Easy-to-Swallow Caplets): Swallow with water; do not chew.13 18

Dosage

Available as bismuth subgallate, bismuth subcitrate potassium, and bismuth subsalicylate; dosages expressed in terms of the salts.1 3 13 14 15 16 17 18 19 20 21 22 23 24

Bismuth subcitrate potassium available in fixed combination with metronidazole and tetracycline hydrochloride (Pylera); dosage of Pylera expressed as number of capsules.2

Pediatric Patients

Acute Nonspecific Diarrhea and Travelers’ Diarrhea Bismuth Subsalicylate Oral

Children ≥12 years of age: 525 mg every 30–60 minutes or 1.05 g every hour as needed, not to exceed 4.2 g in a 24-hour period.10 13 14 16 17 18 20 21 22 23 24 Use until diarrhea stops, but not >2 days.10 13 14 16 17 18 21 23

Children ≥12 years of age: Alternatively, administer 1.05 g every 30 minutes† to every hour as needed, not to exceed 4.2 g in a 24-hour period.14 15 19 20 46

Flatulence or Stool Odor Bismuth Subgallate Oral

Children ≥12 years of age: 200–400 mg up to 4 times daily.3 5

Dyspepsia (Upset Stomach) Bismuth Subsalicylate Oral

Children ≥12 years of age: 525 mg every 30–60 minutes as needed, not to exceed 4.2 g in a 24-hour period.13 16 17 18 20 21 22 23 24 25 Do not use for >2 days.13 17 18 21 23

Children ≥12 years of age: Alternatively, administer 1.05 g every 30–60 minutes† as needed, not to exceed 4.2 g in a 24-hour period.13 14 15 16 19 20 21 46

Adults

Acute Nonspecific Diarrhea and Travelers’ Diarrhea Bismuth Subsalicylate Oral

525 mg every 30–60 minutes or 1.05 g every hour as needed, not to exceed 4.2 g in a 24-hour period.10 13 14 16 17 18 20 21 22 23 24 Use until diarrhea stops, but not >2 days.10 13 14 16 17 18 21 23

Alternatively, administer 1.05 g every 30 minutes† to every hour as needed, not to exceed 4.2 g in a 24-hour period.14 15 19 20 46

Prevention of Travelers’ Diarrhea† Bismuth Subsalicylate Oral

525 mg 4 times daily has been recommended.32 33 34 40

Helicobacter pylori Infection and Duodenal Ulcer Disease Bismuth Subsalicylate, Metronidazole, and Tetracycline Hydrochloride Regimen Oral

525 mg of bismuth subsalicylate in conjunction with metronidazole (250 mg) and tetracycline hydrochloride (500 mg) 4 times daily for 10–14 days; give concomitantly with ranitidine (150 mg) twice daily or usual dosage of a proton-pump inhibitor once or twice daily.35

Salvage therapy for persistent H. pylori infection: Administer for 7–14 days.35

Bismuth Subsalicylate (with Metronidazole and Tetracycline Hydrochloride) in Helidac Therapy Kit Oral

525 mg of bismuth subsalicylate in conjunction with metronidazole (250 mg) and tetracycline hydrochloride (500 mg) 4 times daily (at meals and at bedtime) for 14 days; give concomitantly with usual dosage of H2-receptor antagonist.1

Fixed Combination Containing Bismuth Subcitrate Potassium, Metronidazole, and Tetracycline Hydrochloride (Pylera) Oral

3 capsules 4 times daily (after meals and at bedtime) for 10 days; give concomitantly with omeprazole 20 mg twice daily (after morning and evening meal) for 10 days.2 39

Flatulence or Stool Odor Bismuth Subgallate Oral

200–400 mg up to 4 times daily.3 5

Dyspepsia (Upset Stomach) Bismuth Subsalicylate Oral

525 mg every 30–60 minutes as needed, not to exceed 4.2 g in a 24-hour period.13 16 17 18 20 21 22 23 24 25 Do not use for >2 days.13 17 18 21 23

Alternatively, administer 1.05 g every 30–60 minutes† as needed, not to exceed 4.2 g in a 24-hour period.13 14 15 16 19 20 21 46

Prescribing Limits

Pediatric Patients

Acute Nonspecific Diarrhea and Travelers’ Diarrhea Bismuth Subsalicylate Oral

Children ≥12 years of age: Maximum 4.2 g in a 24-hour period.10 13 14 16 17 18 20 21 22 23 24 46 Self-medication should not exceed 2 days.10 13 14 16 17 18 21 23

Dyspepsia (Upset Stomach) Bismuth Subsalicylate Oral

Children ≥12 years of age: Maximum 4.2 g in a 24-hour period.10 13 14 16 17 18 20 21 22 23 24 46 Self-medication should not exceed 2 days.10 13 14 16 17 18 21 23

Adults

Acute Nonspecific Diarrhea and Travelers’ Diarrhea Bismuth Subsalicylate Oral

Maximum 4.2 g in a 24-hour period.10 13 14 16 17 18 20 21 22 23 24 46 Self-medication should not exceed 2 days.10 13 14 16 17 18 21 23

Dyspepsia (Upset Stomach) Bismuth Subsalicylate Oral

Maximum 4.2 g in a 24-hour period.10 13 14 16 17 18 20 21 22 23 24 46 Self-medication should not exceed 2 days.10 13 14 16 17 18 21 23

Special Populations

No special population dosage recommendations at this time.1 2 3 13 14 15 16 17 18 19 20 21 22 23 24 39 41 43 (See Geriatric Use and also see Renal Impairment, under Cautions.)

Cautions for Bismuth Salts

Contraindications

  • Helidac Therapy (kit containing bismuth subsalicylate, metronidazole, tetracycline hydrochloride) contraindicated in pregnant or nursing women, pediatric patients, patients with hepatic or renal impairment, patients with known allergy to aspirin or salicylates, and those with known hypersensitivity to any component of the kit.1

  • Pylera (fixed-combination capsule containing bismuth subcitrate potassium, metronidazole, tetracycline hydrochloride) contraindicated in pregnant or nursing women, pediatric patients, patients with hepatic or renal impairment, and those with known hypersensitivity to any ingredient in the capsule.2

Warnings/Precautions

Warnings

GI Disorders

Do not use bismuth subsalicylate (e.g., Maalox Total relief) for self-medication in patients with an ulcer, bleeding disorder, or bloody or black stools.10 13 14 16 17 18 19 21 23 48 49

Reye’s Syndrome

Risk of Reye’s syndrome with bismuth subsalicylate in children or adolescents who have or are recovering from varicella or influenza-like symptoms.1 7 13 14 15 16 17 18 19 21 23 24 (See Pediatric Use under Cautions.)

Neurotoxicity

Neurotoxicity associated with excessive doses of bismuth salts reported rarely; reversible following discontinuance of drug.1 2

Discoloration of Tongue and/or Stool

Possible transient and harmless darkening of tongue and/or black stool; do not confuse stool darkening with melena.1 2 10 13 14 15 16 17 18 19 21 23 24 34

Lead Content

Bismuth mined from the ground, and commercially available Pepto-Bismol preparations, may contain small amounts of naturally occurring lead.13 44 Amounts of lead in Pepto-Bismol preparations are low compared with average daily lead exposure.13 44 Pepto-Bismol preparations not intended for chronic use.13 44

Sensitivity Reactions

Hypersensitivity

Bismuth subsalicylate contains salicylate; do not use in patients allergic to salicylates (including aspirin).10 13 15 16 17 18 19 21 23 24 34

General Precautions

Selection and Use of Anti-infectives in H. pylori Regimens

To reduce development of drug-resistant bacteria and maintain effectiveness of Helidac Therapy, Pylera, and other anti-infective agents, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.1 2

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.1 2 In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.1 2

Phenylketonuria

Diotame chewable tablets contain aspartame (NutraSweet), which is metabolized in the GI tract to phenylalanine following oral administration.24 26 27 28 29 30

Use of Fixed Combinations or Multiple-Drug Kits

When the fixed-combination preparation containing bismuth subcitrate potassium, metronidazole, and tetracycline hydrochloride (Pylera) or the kit containing bismuth subsalicylate, metronidazole, and tetracycline hydrochloride (Helidac Therapy) is used for the treatment of H. pylori infection and duodenal ulcer disease, the cautions, precautions, and contraindications associated with metronidazole and tetracycline hydrochloride must be considered in addition to those associated with bismuth subcitrate potassium or bismuth subsalicylate.1 2

Medication Errors

Serious medication errors have been reported to FDA in which consumers used Maalox Total Relief (bismuth subsalicylate) when they intended to use traditional Maalox liquid antacid products containing aluminum hydroxide, magnesium hydroxide, and simethicone (e.g., Maalox Advanced Regular Strength, Maalox Advanced Maximum Strength).48 49 50 Because of the potential for serious adverse effects associated with accidental use of bismuth subsalicylate (which is chemically related to aspirin), the manufacturer of Maalox Total Relief initially agreed to change the trade name of the product to one that did not include “Maalox”; however, the manufacturer instead discontinued the bismuth subsalicylate preparation in the summer of 2010.49 51

Specific Populations

Pregnancy

Bismuth subsalicylate: Category C (Category D in 3rd trimester).36 37

Helidac Therapy, Pylera: Category D.1 2

Helidac Therapy, Pylera: Effect on labor and delivery unknown.1 2

Lactation

Bismuth subsalicylate: Use with caution.36

Helidac Therapy, Pylera: Discontinue nursing or the drug.1 2

Pediatric Use

Do not use bismuth subsalicylate in children or adolescents who have or are recovering from varicella or influenza-like symptoms.1 7 13 14 15 16 17 18 19 21 23 24 Changes in behavior accompanied by nausea and vomiting in children or adolescents taking the drug may be an early sign of Reye’s syndrome.1 7 13 14 15 16 17 18 19 21 23 24

Safety and efficacy of the commercially available Helidac Therapy kit or the fixed-combination preparation Pylera in pediatric patients infected with H. pylori not established.1 2 39 47 Pylera or the Helidac Therapy kit should not be used in children <8 years of age.1 2 39 (See Contraindications under Cautions.)

Geriatric Use

Insufficient experience in those ≥65 years of age to determine whether they respond differently than younger adults to the commercially available Helidac Therapy kit or the fixed-combination preparation or Pylera for treatment of H. pylori infection and duodenal ulcer disease.1 2

Consider age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.1 2

Hepatic Impairment

Accumulation of bismuth salts may occur in patients with severe hepatic disease.45 39 The commercially available Helidac Therapy kit and the fixed-combination preparation Pylera are contraindicated in patients with hepatic impairment.1 2 (See Contraindications under Cautions and also see Special Populations under Pharmacokinetics.)

Renal Impairment

Use bismuth subsalicylate with caution, if at all, in patients with renal impairment.37 39 The commercially available Helidac Therapy kit and the fixed-combination preparation Pylera are contraindicated in patients with renal impairment.1 2 (See Contraindications under Cautions.)

Common Adverse Effects

Bismuth: Transient and harmless darkening of the tongue and/or black stools,1 2 3 6 13 14 15 16 17 18 19 21 23 24 32 33 decreased peristalsis (with bismuth subgallate).6

Helidac Therapy: Nausea,1 diarrhea,1 abdominal pain,1 melena,1 upper respiratory infection.1

Pylera: Stool abnormality,2 diarrhea,2 dyspepsia,2 abdominal pain,2 nausea,2 headache,2 flu syndrome,2 taste perversion,2 asthenia,2 vaginitis,2 dizziness.2

Interactions for Bismuth Salts

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Anticoagulants

Salicylate salts (e.g., bismuth subsalicylate) may increase risk of bleeding with concomitant anticoagulant therapy1

Monitor anticoagulant therapy; adjust anticoagulant dosage as needed1

Antidiabetic agents

Possibly enhanced hypoglycemic effects with concomitant salicylate salt therapy1

Use with caution1

Aspirin

Use with caution1

Ciprofloxacin

Bismuth subsalicylate slightly decreases peak plasma concentrations and AUC of ciprofloxacin9

Not considered clinically important9

Doxycycline

Bismuth subsalicylate may decrease absorption of doxycycline8 33

Avoid using bismuth subsalicylate for self-medication in travelers taking doxycycline for malaria prophylaxis34

Methotrexate

Avoid using bismuth subsalicylate for self-medication concomitantly with methotrexate34

Omeprazole

Omeprazole increases extent of absorption of bismuth from Pylera capsules following concomitant administration2

Probenecid

Use concomitantly with caution, if at all1 34

Radiographic imaging (radiographs)

Bismuth absorbs x-rays; may interfere with radiographic diagnostic procedures of GI tract1 2 39

Salicylates

Do not use bismuth subsalicylate for self-medication concomitantly with other salicylate drugs10 13 14 16 17 18 19 21 23

Sulfinpyrazone

Use concomitantly with caution1

Tests for occult blood

Darkening of stool from bismuth salts does not interfere with tests for occult blood1 2

Tetracycline

Bismuth and/or calcium carbonate (excipient of bismuth subsalicylate tablets) reduces systemic absorption of tetracycline; clinical importance unknown since relative contribution of systemic versus local antimicrobial activity against H. pylori not determined1 2

Advice to Patients

  • Importance of advising patients of the cautions, precautions, and contraindications associated with metronidazole and tetracycline hydrochloride when using Helidac Therapy or Pylera.1 2

  • Importance of informing patient that temporary and harmless darkening of the tongue and/or black stool may occur with bismuth salts, and that stool darkening should not be confused with blood in the stool.1 2 3 13 14 15 16 17 18 19 21 23 24 34

  • Do not use bismuth subsalicylate for self-medication in presence of peptic ulcers, bleeding disorders, bloody or black stool, known allergy to salicylates (including aspirin), or if taking other salicylates; consult clinician before use if diarrhea is accompanied by fever, mucus in stools, or if patient is on a sodium-restricted diet or currently taking drugs for anticoagulation, diabetes, gout, or arthritis.10 13 14 15 16 17 18 19 21 23 24

  • Importance of instructing patients to discontinue bismuth subsalicylate for self-medication and inform clinician if symptoms worsen, ringing in the ears or loss of hearing occurs, or if diarrhea or other symptoms do not improve after 2 days of therapy.10 13 14 15 16 17 18 19 21 23 24 34

  • Importance of advising patients not to use bismuth subsalicylate in children or adolescents who have or are recovering from chickenpox or flu-like symptoms.1 7 13 14 15 16 17 18 19 21 23 24 Importance of informing clinician if changes in behavior accompanied by nausea and vomiting occur while using bismuth subsalicylate, because these symptoms may be an early sign of Reye’s syndrome.1 7 13 14 15 16 17 18 19 21 23 24

  • Importance of adequate hydration (with clear fluids) to help prevent dehydration caused by diarrhea.10 13 16 17 18 21 23 24

  • Importance of informing patients with phenylketonuria that Diotame chewable tablets contain aspartame.24

  • Importance of instructing patients about correct administration of Helidac Therapy or Pylera capsules, including administration of each dose after meals and at bedtime and with a full glass of water (particularly at bedtime to reduce risk of esophageal irritation and ulceration), swallowing Pylera capsules whole, chewing and swallowing bismuth subsalicylate tablets, and about duration of therapy.1 2 39

  • Importance of informing patients that Helidac Therapy contains salicylates, and to contact a clinician if ringing in the ears occurs with concomitant aspirin therapy.1

  • Importance of advising patient that if a dose of Helidac Therapy or Pylera is missed, the next dose should be taken at the regularly scheduled time; the dose should not be doubled.1 2 Importance of informing clinicians if >4 doses of Helidac Therapy or Pylera are missed.1 2

  • Importance of advising patients that antibacterials (including Helidac Therapy and Pylera) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).1

  • Importance of completing full course of therapy, even if feeling better after a few days.1

  • Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with Helidac Therapy or other anti-infective agents in the future.1

  • Advise patients that Helidac Therapy or the Pylera fixed combination may reduce the effectiveness of oral contraceptives and that alternative nonhormonal contraceptive measures should be used.1 2 39

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products, as well as any concomitant illnesses.1 2

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 2 13 14 15 16 17 18 19 21 23

  • Importance of advising patients of other important precautionary information.1 2 (See Cautions.)

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