Skip to Content

Bismuth Subcitrate, Metronidazole, and Tetracycline

Pronunciation

(BIZ muth sub CIT rate, me troe NI da zole, & tet ra SYE kleen)

Index Terms

  • Bismuth Subcitrate Potassium, Tetracycline, and Metronidazole
  • Bismuth/Metronid/Tetracycline
  • Metronidazole, Bismuth Subcitrate Potassium, and Tetracycline
  • Tetracycline, Metronidazole, and Bismuth Subcitrate Potassium

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule:

Pylera: Bismuth subcitrate potassium 140 mg, metronidazole 125 mg, and tetracycline hydrochloride 125 mg

Brand Names: U.S.

  • Pylera

Pharmacologic Category

  • Antibiotic, Miscellaneous
  • Antibiotic, Tetracycline Derivative
  • Antidiarrheal

Pharmacology

Bismuth: Has both antisecretory and antimicrobial action; may provide some anti-inflammatory action as well.

Metronidazole: After diffusing into the organism, interacts with DNA to cause a loss of helical DNA structure and strand breakage resulting in inhibition of protein synthesis and cell death in susceptible organisms.

Tetracycline: Inhibits bacterial protein synthesis by binding with the 30S and possibly the 50S ribosomal subunit(s) of susceptible bacteria; may also cause alterations in the cytoplasmic membrane.

Bismuth, metronidazole, and tetracycline individually have demonstrated in vitro activity against most susceptible strains of H. pylori isolated from patients with duodenal ulcers.

Absorption

Food reduced AUC by 6% (metronidazole), 34% (tetracycline), and 60% (bismuth)

Use: Labeled Indications

Duodenal ulcer associated with Helicobacter pylori infection: In combination with omeprazole for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or history of within the past 5 years) to eradicate H. pylori

Contraindications

Hypersensitivity to bismuth, metronidazole (or other nitroimidazole derivatives), tetracycline, or any component of the formulation; severe renal impairment; concomitant use with disulfiram (within the previous 2 weeks), methoxyflurane, or alcohol and products containing propylene glycol (during therapy and for ≥3 days after)

Dosing: Adult

Duodenal ulcer associated with H. pylori infection: Oral: Three capsules (bismuth subcitrate 420 mg, metronidazole 375 mg, and tetracycline 375 mg) 4 times daily after meals and at bedtime (plus omeprazole 20 mg twice daily) for 10 days

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.

Severe impairment: Use is contraindicated.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.

Administration

Swallow capsules whole with 240 mL (8 oz) of water after meals and at bedtime. Administer concomitant omeprazole after morning meal and evening meal.

Storage

Store at 20°C to 25°C (68°F to 77°F).

Drug Interactions

Alcohol (Ethyl): MetroNIDAZOLE (Systemic) may enhance the adverse/toxic effect of Alcohol (Ethyl). A disulfiram-like reaction may occur. Avoid combination

Aminolevulinic Acid: Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid. Monitor therapy

Antacids: May diminish the therapeutic effect of Bismuth Subcitrate. Management: Avoid administration of antacids within 30 minutes of bismuth subcitrate (tripotassium bismuth dicitrate) administration. Consider therapy modification

Atovaquone: Tetracycline may decrease the serum concentration of Atovaquone. Monitor therapy

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

Bile Acid Sequestrants: May decrease the absorption of Tetracycline Derivatives. Consider therapy modification

Bismuth Subcitrate: May decrease the serum concentration of Tetracycline Derivatives. Management: Avoid administration of oral tetracyclines within 30 minutes of bismuth subcitrate administration. This is of questionable significance for at least some regimens intended to treat H. pylori infections. Consider therapy modification

Bismuth-Containing Compounds: May enhance the neurotoxic effect of Bismuth Subcitrate. Avoid combination

Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Busulfan: MetroNIDAZOLE (Systemic) may increase the serum concentration of Busulfan. Management: The toxic effects of busulfan may be greatly increased with concomitant use of metronidazole. This combination should probably be avoided when possible. If these agents must be used together, increased monitoring for busulfan toxicity is recommended. Consider therapy modification

Calcium Salts: May decrease the serum concentration of Tetracycline Derivatives. Management: If coadministration of oral calcium with oral tetracyclines can not be avoided, consider separating administration of each agent by several hours. Consider therapy modification

Capecitabine: MetroNIDAZOLE (Systemic) may increase serum concentrations of the active metabolite(s) of Capecitabine. Monitor therapy

Carbocisteine: MetroNIDAZOLE (Systemic) may enhance the adverse/toxic effect of Carbocisteine. Specifically, metronidazole may enhance adverse effects of alcohol that is present in liquid formulations of carbocisteine-containing products. Avoid combination

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Avoid combination

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Disulfiram: May enhance the adverse/toxic effect of MetroNIDAZOLE (Systemic). Avoid combination

Dronabinol: MetroNIDAZOLE (Systemic) may enhance the adverse/toxic effect of Dronabinol. Specifically, metronidazole may produce severe intolerance to the alcohol contained in the dronabinol oral solution. Consider therapy modification

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Fluorouracil (Systemic): MetroNIDAZOLE (Systemic) may increase the serum concentration of Fluorouracil (Systemic). Monitor therapy

Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

Iron Salts: Tetracycline Derivatives may decrease the absorption of Iron Salts. Iron Salts may decrease the serum concentration of Tetracycline Derivatives. Exceptions: Ferric Carboxymaltose; Ferric Gluconate; Ferric Hydroxide Polymaltose Complex; Ferric Pyrophosphate Citrate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose. Consider therapy modification

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Lanthanum: May decrease the serum concentration of Tetracycline Derivatives. Management: Administer oral tetracycline antibiotics at least two hours before or after lanthanum. Consider therapy modification

Lopinavir: MetroNIDAZOLE (Systemic) may enhance the adverse/toxic effect of Lopinavir. Specifically, the combination of metronidazole and lopinavir/ritonavir solution, which contains 42% alcohol, may result in a disulfiram-like reaction. MetroNIDAZOLE (Systemic) may enhance the arrhythmogenic effect of Lopinavir. Management: Avoid the concomitant use of lopinavir/ritonavir and metronidazole if possible. If these agents are used concomitantly, monitor for QTc prolongation/arrhythmia and if the lopinavir/ritonavir solution is used, development of a disulfiram-like reaction. Consider therapy modification

Magnesium Dimecrotate: May interact via an unknown mechanism with Tetracycline Derivatives. Monitor therapy

Magnesium Salts: May decrease the absorption of Tetracycline Derivatives. Only applicable to oral preparations of each agent. Consider therapy modification

Mebendazole: May enhance the adverse/toxic effect of MetroNIDAZOLE (Systemic). Particularly the risk for Stevens-Johnson syndrome or toxic epidermal necrolysis may be increased. Avoid combination

Mecamylamine: Tetracycline Derivatives may enhance the neuromuscular-blocking effect of Mecamylamine. Avoid combination

MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Consider therapy modification

Mipomersen: Tetracycline Derivatives may enhance the hepatotoxic effect of Mipomersen. Monitor therapy

Mitotane: May decrease the serum concentration of CYP3A4 Substrates. Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease the serum concentration of Tetracycline Derivatives. Management: If coadministration of a polyvalent cation-containing multivitamin with oral tetracyclines can not be avoided, separate administration of each agent by several hours. Consider therapy modification

Multivitamins/Minerals (with AE, No Iron): May decrease the serum concentration of Tetracycline Derivatives. Management: If coadministration of a polyvalent cation-containing multivitamin with oral tetracyclines can not be avoided, separate administration of each agent by several hours. Consider therapy modification

Mycophenolate: MetroNIDAZOLE (Systemic) may decrease the serum concentration of Mycophenolate. Specifically, metronidazole may decrease concentrations of the active metabolite of mycophenolate. Monitor therapy

Neuromuscular-Blocking Agents: Tetracycline Derivatives may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Penicillins: Tetracycline Derivatives may diminish the therapeutic effect of Penicillins. Consider therapy modification

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Monitor therapy

Quinapril: May decrease the serum concentration of Tetracycline Derivatives. Management: Separate doses of quinapril and oral tetracycline derivatives by at least 2 hours in order to reduce the risk of interaction. Monitor for reduced efficacy of the tetracycline if these products are used concomitantly. Consider therapy modification

Retinoic Acid Derivatives: Tetracycline Derivatives may enhance the adverse/toxic effect of Retinoic Acid Derivatives. The development of pseudotumor cerebri is of particular concern. Exceptions: Adapalene; Bexarotene (Topical); Tretinoin (Topical). Avoid combination

Ritonavir: May enhance the adverse/toxic effect of MetroNIDAZOLE (Systemic). Specifically, the combination of ritonavir oral solution or ritonavir soft gelatin capsule, both of which contain alcohol, and metronidazole may result in a disulfiram-like reaction. Avoid combination

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification

St John's Wort: May decrease the serum concentration of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Strontium Ranelate: May decrease the serum concentration of Tetracycline Derivatives. Management: In order to minimize any potential impact of strontium ranelate on tetracycline antibiotic concentrations, it is recommended that strontium ranelate treatment be interrupted during tetracycline therapy. Avoid combination

Sucralfate: May decrease the absorption of Tetracycline Derivatives. Management: Administer the tetracycline derivative at least 2 hours prior to sucralfate in order to minimize the impact of this interaction. Consider therapy modification

Sucroferric Oxyhydroxide: May decrease the serum concentration of Tetracycline Derivatives. Management: Administer oral/enteral doxycycline at least 1 h before sucroferric oxyhydroxide. Specific dose separation guidelines for other tetracyclines are not presently available. No interaction is anticipated with parenteral administration of tetracyclines. Consider therapy modification

Tegafur: MetroNIDAZOLE (Systemic) may increase serum concentrations of the active metabolite(s) of Tegafur. Monitor therapy

Tetracycline Derivatives: Bismuth Subcitrate may decrease the serum concentration of Tetracycline Derivatives. Management: Avoid administration of oral tetracyclines within 30 minutes of bismuth subcitrate administration. This is of questionable significance for at least some regimens intended to treat H. pylori infections. Consider therapy modification

Tipranavir: MetroNIDAZOLE (Systemic) may enhance the adverse/toxic effect of Tipranavir. A disulfiram-like reaction may occur due to the alcohol contained in tipranavir capsules. Monitor therapy

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Monitor therapy

Vitamin K Antagonists (eg, warfarin): MetroNIDAZOLE (Systemic) may increase the serum concentration of Vitamin K Antagonists. Management: Consider alternatives to concomitant therapy with these agents. If concomitant therapy cannot be avoided, consider reducing the dose of the vitamin K antagonist and monitor for increased INR/bleeding. Consider therapy modification

Zinc Salts: May decrease the absorption of Tetracycline Derivatives. Only a concern when both products are administered orally. Management: Consider doxycycline as a noninteracting tetracycline derivative. Separate dose administration of oral tetracycline derivative and oral zinc salts by at least 2 hours to minimize interaction. Exceptions: Zinc Chloride. Consider therapy modification

Test Interactions

See individual agents.

Adverse Reactions

Also see individual agents. Adverse reactions are associated with concomitant administration of omeprazole.

>10%: Gastrointestinal: Abnormal stools (16%)

1% to 10%:

Central nervous system: Headache (5%), dizziness (3%)

Dermatologic: Maculopapular rash (1%)

Gastrointestinal: Nausea (8%), diarrhea (7%), abdominal pain (5%), dysgeusia (4%), dyspepsia (3%), constipation (1%), xerostomia (1%)

Genitourinary: Vaginitis (3%), urine abnormality (1%)

Hepatic: Increased serum ALT (1%), increased serum AST (1%)

Neuromuscular & skeletal: Weakness (3%)

Miscellaneous: Laboratory test abnormality (2%)

<1% (Limited to important or life-threatening): Abdominal distention, candidiasis, chest pain, chest discomfort, duodenal ulcer, eructation, gastritis, gastroenteritis, increased appetite, increased creatine phosphokinase, malaise, myalgia, tachycardia

Warnings/Precautions

Concerns related to adverse effects:

• CNS effects: Bismuth may be neurotoxic with excessive doses. Aseptic meningitis (symptoms may occur within hours of a dose), encephalopathy (cerebellar toxicity with ataxia, dizziness, dysarthria, and/or CNS lesions), seizures, peripheral neuropathy (including extremity numbness and paresthesia) and optic neuropathy have been reported with metronidazole, especially with increased doses and chronic treatment; monitor and consider discontinuation of therapy if signs/symptoms occur. Symptoms associated with aseptic meningitis, neurotoxicity, and encephalopathy generally resolve following therapy discontinuation. Use with caution in patients with a history of seizure disorder.

• Oral/gastrointestinal effects: Bismuth may cause temporary darkening of the tongue and/or black stools; generally reversible within several days after treatment is discontinued.

• Photosensitivity: Tetracycline may cause photosensitivity; discontinue if skin erythema occurs. Use skin protection and avoid prolonged exposure to sunlight; do not use tanning equipment.

• Pseudotumor cerebri: Has been (rarely) reported with tetracycline use; usually resolves with discontinuation.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Blood dyscrasias: Use metronidazole with caution in patients with or history of blood dyscrasias; leukopenia has occurred. Monitor CBC with differential at baseline and after treatment.

• Hepatic impairment: Use with caution in patients with hepatic impairment due to potential metronidazole accumulation.

H. pylori infection: If H. pylori is not eradicated in patients being treated with metronidazole in a regimen, it should be assumed that metronidazole-resistance has occurred and it should not be used again.

• Renal impairment: Tetracycline may be associated with increases in BUN secondary to antianabolic effects; use caution in patients with renal impairment.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Pediatric: May cause tissue hyperpigmentation, enamel hypoplasia, or permanent tooth discoloration; use of tetracyclines should be avoided during tooth development (children <8 years of age) unless other drugs are not likely to be effective or are contraindicated. Pylera is not FDA-approved for use in children.

Monitoring Parameters

Monitor CBC with differential at baseline and after treatment (due to metronidazole). H. pylori eradication confirmation, when indicated (Chey, 2007).

Pregnancy Risk Factor

D

Pregnancy Considerations

Animal reproduction studies have not been conducted with this combination. Metronidazole and tetracycline both cross the human placenta and may have adverse effects to the fetus. See individual agents.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea, diarrhea, abdominal pain, tongue discoloration, or stool discoloration. Have patient report immediately to prescriber burning or numbness feeling, vision changes, change in balance, severe dizziness, passing out, seizures, difficulty speaking; black, tarry, or bloody stools; vomiting blood; severe headache; blindness; double vision; or blurred vision (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

More about bismuth subcitrate potassium/metronidazole/tetracycline

Consumer resources

Professional resources

Related treatment guides

Hide