Version July 2025
Metronidazole has been shown to be carcinogenic in mice and rats. It is unknown whether metronidazole is associated with carcinogenicity in humans.
Dosage guidance:
Dosage form information: Commercially available formulation (eg, Pylera and generics) are supplied as a 10-day therapy pack. Prescribing of individual agents may be preferred for patients requiring a 14-day course of treatment.
Helicobacter pylori eradication: 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 14 days (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
Severe impairment: Use is contraindicated.
Mild to moderate impairment (Child-Pugh class A or B): There are no dosage adjustments provided in the manufacturer's labeling; use with caution. See individual agents.
Severe impairment (Child-Pugh class C): Use may not be appropriate in severe impairment; accumulation of metronidazole may occur. See individual agents.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. 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%, postmarketing, and/or case reports: Abdominal distention, anxiety, back pain, candidiasis, chest discomfort, chest pain, drowsiness, duodenal ulcer, eructation, fatigue, flatulence, gastritis, gastroenteritis, increased appetite, increased creatine phosphokinase, malaise, myalgia, skin rash, tachycardia, tongue discoloration (darkening), visual disturbance, vomiting, weight gain
Hypersensitivity (eg, erythema rash, flushing, fever, urticaria) to bismuth, metronidazole, other nitroimidazole derivatives, tetracycline, or any component of the formulation; severe renal impairment; pregnancy; concomitant use with disulfiram (within the previous 2 weeks); concomitant use with alcohol or other products containing propylene glycol (during therapy and for ≥3 days after); Cockayne syndrome.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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. CNS symptoms generally resolve within days to weeks following therapy discontinuation; discontinue promptly if abnormal neurologic signs develop.
• Dermatologic reactions: Severe cutaneous adverse reactions, including acute generalized exanthematous pustulosis, drug rash with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported with metronidazole; symptoms may be serious and potentially life-threatening. Fixed drug eruptions, including generalized bullous fixed drug eruption, have occurred with tetracycline; reactions may worsen with subsequent administration. If severe skin reactions occur, discontinue use and institute appropriate therapy.
• Intracranial hypertension: Intracranial hypertension (IH), including pseudotumor cerebri has been reported with use of tetracyclines; females of childbearing age who are overweight or have a history of IH are at greater risk. IH typically resolves after discontinuation of treatment but the possibility for permanent visual loss exists; prompt ophthalmic evaluation is warranted if visual disturbances occur.
• Oral/gastrointestinal effects: Bismuth may cause temporary and harmless darkening of the tongue and/or black stools; generally reversible within several days after treatment is discontinued.
• Photosensitivity: Tetracycline may cause photosensitivity; avoid exposure to the sun or sun lamps; discontinue use at first evidence of skin erythema.
• 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; mild leukopenia has occurred.
• Hepatic impairment: Use with caution in patients with mild to moderate hepatic impairment due to potential metronidazole accumulation; use in patients with severe hepatic impairment may not be appropriate.
• 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 is contraindicated in patients with severe renal impairment.
Special populations:
• Pediatric: May cause tissue hyperpigmentation, enamel hypoplasia, or permanent tooth discoloration; more common during long-term treatment, but has been observed following repeated short-term courses. Use of tetracyclines should be avoided during tooth development (children <8 years) unless other drugs are not likely to be effective or are contraindicated.
Other warnings/precautions:
• Appropriate use: Helicobacter pylori eradication: Short-term combination therapy (≤7 days) has been associated with a higher incidence of treatment failure. The American College of Gastroenterology recommends 14 days of therapy (triple or quadruple) for eradication of H. pylori (ACG [Chey 2024]).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Pylera: Bismuth subcitrate potassium 140 mg, metronidazole 125 mg, and tetracycline hydrochloride 125 mg
Generic: Bismuth subcitrate potassium 140 mg, metronidazole 125 mg, and tetracycline hydrochloride 125 mg
Yes
Capsules (Pylera Oral)
140-125-125 mg (120): $731.28
Disclaimer: The pricing data provide a representative AWP and/or AAWP price from a single manufacturer of the brand and/or generic product, respectively. The pricing data should be used for benchmarking purposes only, and as such should not be used to set or adjudicate any prices for reimbursement or purchasing functions. Pricing data is updated monthly.
Oral: Swallow capsules whole with 240 mL (8 oz) of water after meals and at bedtime. Administer concomitant omeprazole after morning meal and evening meal.
Helicobacter pylori eradication: 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.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs (contraindicated in pregnancy) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Community/Ambulatory Care Settings).
KIDs List: Tetracycline, when used in neonates, infants, and children <8 years of age, is identified on the Key Potentially Inappropriate Drugs in Pediatrics (KIDs) list. In neonates, tetracycline should be used with caution due to risk of retardation of skeletal development and bone growth in premature neonates (strong recommendation; moderate quality of evidence); in infants and children <8 years of age, it should be used with caution due to risk of tooth discoloration and enamel hypoplasia (strong recommendation; high quality of evidence) (PPA [Meyers 2020]).
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Alcohol (Ethyl): MetroNIDAZOLE (Systemic) may increase adverse/toxic effects of Alcohol (Ethyl). A disulfiram-like reaction may occur. Risk X: Avoid
Aminolevulinic Acid (Systemic): Photosensitizing Agents may increase photosensitizing effects of Aminolevulinic Acid (Systemic). Risk X: Avoid
Aminolevulinic Acid (Topical): Photosensitizing Agents may increase photosensitizing effects of Aminolevulinic Acid (Topical). Risk C: Monitor
Antacids: May decrease therapeutic effects of Bismuth Subcitrate. Management: Avoid administration of antacids within 30 minutes of bismuth subcitrate (tripotassium bismuth dicitrate) administration. Risk D: Consider Therapy Modification
Atovaquone: Tetracycline (Systemic) may decrease serum concentration of Atovaquone. Risk C: Monitor
Bacillus clausii: Antibiotics may decrease therapeutic effects of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider Therapy Modification
BCG (Intravesical): Antibiotics may decrease therapeutic effects of BCG (Intravesical). Risk X: Avoid
BCG Vaccine (Immunization): Antibiotics may decrease therapeutic effects of BCG Vaccine (Immunization). Risk C: Monitor
Bile Acid Sequestrants: May decrease absorption of Tetracyclines. Risk C: Monitor
Bismuth-Containing Compounds: May increase neurotoxic effects of Bismuth Subcitrate. Risk X: Avoid
Busulfan: MetroNIDAZOLE (Systemic) may increase serum concentration of Busulfan. Management: Avoid coadministration metronidazole and busulfan due to increased risks of busulfan toxicity. If coadministration is required, monitor busulfan concentrations closely and adjust the busulfan dose as needed. Risk D: Consider Therapy Modification
Calcium Salts: May decrease serum concentration of Tetracyclines. Management: If coadministration of oral calcium with oral tetracyclines cannot be avoided, consider separating administration of each agent by several hours. Risk D: Consider Therapy Modification
Cardiac Glycosides: Tetracycline (Systemic) may increase serum concentration of Cardiac Glycosides. Risk C: Monitor
Cholera Vaccine: Antibiotics may decrease therapeutic effects of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid
Disulfiram: May increase adverse/toxic effects of MetroNIDAZOLE (Systemic). In particular, the risk for CNS toxicities such as psychosis may be increased. Risk X: Avoid
DroNABinol: MetroNIDAZOLE (Systemic) may increase adverse/toxic effects of DroNABinol. Specifically, metronidazole may produce severe intolerance to the alcohol contained in the dronabinol oral solution. Risk X: Avoid
Fecal Microbiota (Live) (Oral): May decrease therapeutic effects of Antibiotics. Risk X: Avoid
Fecal Microbiota (Live) (Rectal): Antibiotics may decrease therapeutic effects of Fecal Microbiota (Live) (Rectal). Risk X: Avoid
Fluorouracil Products: MetroNIDAZOLE (Systemic) may increase serum concentration of Fluorouracil Products. Risk C: Monitor
Fosphenytoin: May decrease serum concentration of MetroNIDAZOLE (Systemic). MetroNIDAZOLE (Systemic) may increase serum concentration of Fosphenytoin. Risk C: Monitor
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may increase QTc-prolonging effects of Haloperidol. Risk C: Monitor
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor
Iron Preparations: Tetracyclines may decrease absorption of Iron Preparations. Iron Preparations may decrease serum concentration of Tetracyclines. Management: Avoid this combination if possible. Administer oral iron preparations at least 2 hours before, or 4 hours after, the dose of the oral tetracycline derivative. Monitor for decreased therapeutic effect of oral tetracycline derivatives. Risk D: Consider Therapy Modification
Lactobacillus and Estriol: Antibiotics may decrease therapeutic effects of Lactobacillus and Estriol. Risk C: Monitor
Lanthanum: May decrease serum concentration of Tetracyclines. Management: Administer oral tetracycline antibiotics at least 2 hours before or after lanthanum. Risk D: Consider Therapy Modification
Lithium: MetroNIDAZOLE (Systemic) may increase adverse/toxic effects of Lithium. MetroNIDAZOLE (Systemic) may increase serum concentration of Lithium. Risk C: Monitor
Magnesium Dimecrotate: And Tetracyclines may interact via an unclear mechanism. Risk C: Monitor
Magnesium Salts: May decrease absorption of Tetracyclines. Only applicable to oral preparations of each agent. Management: Avoid coadministration of oral magnesium salts and oral tetracyclines. If coadministration cannot be avoided, administer oral magnesium at least 2 hours before, or 4 hours after, oral tetracyclines. Monitor for decreased tetracycline therapeutic effects. Risk D: Consider Therapy Modification
Mebendazole: May increase adverse/toxic effects of MetroNIDAZOLE (Systemic). Particularly the risk for Stevens-Johnson syndrome or toxic epidermal necrolysis may be increased. Risk X: Avoid
Mecamylamine: Tetracyclines may increase neuromuscular-blocking effects of Mecamylamine. Risk X: Avoid
Methotrexate: Tetracyclines may increase serum concentration of Methotrexate. Risk C: Monitor
Methoxsalen (Systemic): Photosensitizing Agents may increase photosensitizing effects of Methoxsalen (Systemic). Risk C: Monitor
Methoxyflurane: Tetracyclines may increase nephrotoxic effects of Methoxyflurane. Risk X: Avoid
Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease serum concentration of Tetracyclines. Management: Avoid this combination if possible. If coadministration cannot be avoided, administer the polyvalent cation-containing multivitamin at least 2 hours before or 4 hours after the tetracycline derivative. Monitor for decreased tetracycline effects. Risk D: Consider Therapy Modification
Multivitamins/Minerals (with AE, No Iron): May decrease serum concentration of Tetracyclines. Management: If coadministration of a polyvalent cation-containing multivitamin with oral tetracyclines cannot be avoided, administer the polyvalent cation-containing multivitamin either 2 hours before or 4 hours after the tetracycline product. Risk D: Consider Therapy Modification
Mycophenolate: Antibiotics may decrease active metabolite exposure of Mycophenolate. Specifically, concentrations of mycophenolic acid (MPA) may be reduced. Risk C: Monitor
Neuromuscular-Blocking Agents: Tetracyclines may increase neuromuscular-blocking effects of Neuromuscular-Blocking Agents. Risk C: Monitor
Penicillins: Tetracyclines may decrease therapeutic effects of Penicillins. Risk C: Monitor
PHENobarbital: MetroNIDAZOLE (Systemic) may increase adverse/toxic effects of PHENobarbital. A disulfiram-like reaction may occur if combined with phenobarbital dosage forms that contain propylene glycol or alcohol. PHENobarbital may decrease serum concentration of MetroNIDAZOLE (Systemic). Risk C: Monitor
Phenytoin: MetroNIDAZOLE (Systemic) may increase adverse/toxic effects of Phenytoin. A disulfiram-like reaction may occur if combined with phenytoin dosage forms that contain propylene glycol. Phenytoin may decrease serum concentration of MetroNIDAZOLE (Systemic). MetroNIDAZOLE (Systemic) may increase serum concentration of Phenytoin. Risk C: Monitor
Polyethylene Glycol-Electrolyte Solution: May decrease absorption of Tetracyclines. Management: Give oral tetracyclines at least 2 hours before or at least 6 hours after polyethylene glycol-electrolyte solutions that contain magnesium sulfate (Suflave brand). Other products without magnesium do not require dose separation. Risk D: Consider Therapy Modification
Porfimer: Photosensitizing Agents may increase photosensitizing effects of Porfimer. Risk X: Avoid
Primidone: May decrease serum concentration of MetroNIDAZOLE (Systemic). Risk C: Monitor
Products Containing Ethanol: MetroNIDAZOLE (Systemic) may increase adverse/toxic effects of Products Containing Ethanol. A disulfiram-like reaction may occur. Risk X: Avoid
Products Containing Propylene Glycol: MetroNIDAZOLE (Systemic) may increase adverse/toxic effects of Products Containing Propylene Glycol. A disulfiram-like reaction may occur. Risk X: Avoid
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Quinapril: May decrease serum concentration of Tetracyclines. Risk C: Monitor
QuiNINE: Tetracycline (Systemic) may increase serum concentration of QuiNINE. Risk C: Monitor
Retinoic Acid Derivatives: Tetracyclines may increase adverse/toxic effects of Retinoic Acid Derivatives. The development of pseudotumor cerebri is of particular concern. Risk X: Avoid
Sodium Picosulfate: Antibiotics may decrease therapeutic effects 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. Risk D: Consider Therapy Modification
Strontium Ranelate: May decrease serum concentration of Tetracyclines. 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. Risk X: Avoid
Sucralfate: May decrease absorption of Tetracyclines. Management: Administer most tetracycline derivatives at least 2 hours prior to sucralfate in order to minimize the impact of this interaction. Administer oral omadacycline 4 hours prior to sucralfate. Risk D: Consider Therapy Modification
Sucroferric Oxyhydroxide: May decrease serum concentration of Tetracyclines. Management: Administer oral/enteral doxycycline at least 1 hour before sucroferric oxyhydroxide. Specific dose separation guidelines for other tetracyclines are not presently available. No interaction is anticipated with parenteral administration of tetracyclines. Risk D: Consider Therapy Modification
Sulfonylureas: MetroNIDAZOLE (Systemic) may increase serum concentration of Sulfonylureas. Risk C: Monitor
Tipranavir: MetroNIDAZOLE (Systemic) may increase adverse/toxic effects of Tipranavir. A disulfiram-like reaction may occur due to the alcohol contained in tipranavir capsules. Risk C: Monitor
TOLBUTamide: CYP2C9 Inhibitors (Weak) may increase serum concentration of TOLBUTamide. Risk C: Monitor
Typhoid Vaccine: Antibiotics may decrease therapeutic effects of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider Therapy Modification
Vecuronium: MetroNIDAZOLE (Systemic) may increase neuromuscular-blocking effects of Vecuronium. Risk C: Monitor
Verteporfin: Photosensitizing Agents may increase photosensitizing effects of Verteporfin. Risk C: Monitor
Vitamin K Antagonists: MetroNIDAZOLE (Systemic) may increase 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. Risk D: Consider Therapy Modification
Zinc Salts: May decrease absorption of Tetracyclines. Only a concern when both products are administered orally. Management: Separate administration of oral tetracycline derivatives and oral zinc salts by at least 2 hours to minimize this interaction. Risk D: Consider Therapy Modification
This combination is contraindicated in pregnant patients. Metronidazole and tetracycline both cross the human placenta and may have adverse effects to the fetus. See individual monographs for additional information.
Metronidazole and tetracycline are excreted in breast milk in concentrations similar to the maternal plasma; it is not known if bismuth is excreted in breast milk. Because of the potential for serious adverse reactions in the nursing infant, the manufacturer recommends that breast-feeding be interrupted during therapy and for 2 days after the last dose. See individual agents.
Monitor CBC with differential at baseline and after treatment (due to metronidazole); development of abnormal neurologic signs/symptoms; signs and symptoms of severe cutaneous adverse reactions. H. pylori eradication confirmation, when indicated (ACG [Chey 2017]).
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.
Also see individual agents.
Absorption: Food reduced AUC by 6% (metronidazole), 34% (tetracycline), and 60% (bismuth)
