Version May 2024
Metronidazole has been shown to be carcinogenic in mice and rats. It is unknown whether metronidazole is associated with carcinogenicity in humans.
H. pylori infection with duodenal ulcer: Oral: Bismuth subsalicylate 525 mg (two 262.4 mg chewable tablets), metronidazole 250 mg, and tetracycline 500 mg administered together 4 times daily, in combination with a standard dose proton pump inhibitor 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.
Severe impairment (Child-Pugh class C): Use may not be appropriate in severe impairment; accumulation of metronidazole may occur.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Also see individual agents.
>10%: Gastrointestinal: Nausea (12%)
1% to 10%:
Gastrointestinal: Abdominal pain (7%), anorectal pain (1%), anorexia (2%), constipation (2%), darkening of stools (1%), diarrhea (7%), duodenal ulcer (1%), dyspepsia (2%), flatulence (1%), gastrointestinal hemorrhage (1%), melena (3%), tongue discoloration (darkening: 2%), vomiting (2%)
Nervous system: Dizziness (2%), headache (2%), insomnia (1%), metallic taste (1%), pain (1%), paresthesia (1%)
Neuromuscular & skeletal: Asthenia (2%)
Respiratory: Sinusitis (1%), upper respiratory tract infection (2%)
<1%:
Cardiovascular: Acute myocardial infarction, cerebral ischemia, chest pain, hypertension, syncope
Dermatologic: Acne vulgaris, ecchymoses, pruritus, skin photosensitivity, skin rash
Gastrointestinal: Dysphagia, eructation, gastrointestinal candidiasis, glossitis, intestinal obstruction, stomatitis, xerostomia
Genitourinary: Urinary tract infection
Hematologic & oncologic: Neoplasm, rectal hemorrhage
Hepatic: Increased serum alanine aminotransferase, increased serum aspartate aminotransferase
Infection: Infection
Nervous system: Drowsiness, malaise, nervousness
Neuromuscular & skeletal: Arthritis, rheumatoid arthritis, tendinopathy
Ophthalmic: Conjunctivitis
Respiratory: Flu-like symptoms, rhinitis
Hypersensitivity (eg, urticaria, erythematous rash, flushing, fever) to tetracycline, aspirin or other salicylates, metronidazole or other nitroimidazole derivatives, or any component of the formulation; concurrent use with methoxyflurane; concurrent use with or within 2 weeks of disulfiram; concurrent use with alcohol or other products containing propylene glycol (during therapy and for ≥3 days after); severe renal impairment; 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; monitor patients with CNS conditions closely and discontinue promptly if abnormal neurologic signs develop.
• Cutaneous reactions: Skin and subcutaneous disorders, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia and systemic symptoms, have been reported; discontinue treatment at first sign of cutaneous reaction.
• Intracranial hypertension: Intracranial hypertension (IH), including pseudotumor cerebri, has been reported with use of tetracyclines; women 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/GI 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.
• Potential for carcinogenicity: [US Boxed Warning]: Metronidazole has been shown to be carcinogenic in mice and rates. It is unknown whether metronidazole is associated with carcinogenicity in humans.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including Clostridioides 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.
• 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:
- Tetracycline 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 of age) unless other drugs are not likely to be effective or are contraindicated.
- Children and teenagers who have or are recovering from chickenpox or flu-like symptoms should not use bismuth subsalicylate. Changes in behavior (along with nausea and vomiting) may be an early sign of Reye syndrome; patients should be instructed to contact their health care provider if these occur.
Other warnings/precautions:
• Appropriate use: H. pylori eradication: Short-term combination therapy (≤7 days) has been associated with a higher incidence of treatment failure. The American College of Gastroenterology recommends 10 to 14 days of therapy (triple or quadruple) for eradication of H. pylori (Chey 2017).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Miscellaneous, Oral:
Helidac Therapy: Tetracycline hydrochoride 500 mg (56s), bismuth subsalicylate 262.4 mg (112s), and metronidazole 250 mg (56s) (224 ea) [contains butylparaben, edetate (edta) calcium disodium, fd&c blue #1 (brilliant blue), fd&c red #40 (allura red ac dye), fd&c yellow #6 (sunset yellow), methylparaben, propylparaben, quinoline yellow (d&c yellow #10), saccharin sodium]
No
Oral: Administer each dose with meals and at bedtime. Swallow metronidazole tablets and tetracycline capsules whole with 240 mL (8 oz) of water and chew bismuth subsalicylate tablets thoroughly.
Helicobacter pylori infection: Treatment of patients with H. pylori infection and duodenal ulcer disease (active or a history of duodenal ulcer), in combination with an H2 antagonist. Note: Although combination therapy with an H2 antagonist is recommended in the product labeling, proton pump inhibitors are preferred (ACG [Chey 2017]).
KIDs List: Salicylates, when used in pediatric patients <18 years of age with suspicion of viral illness (influenza, chickenpox), are identified on the Key Potentially Inappropriate Drugs in Pediatrics (KIDs) list and should be used with caution due to risk of Reye syndrome (weak recommendation; very low quality of evidence) (PPA [Meyers 2020]).
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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Agents with Blood Glucose Lowering Effects: Salicylates may enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Ajmaline: Salicylates may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Risk C: Monitor therapy
Alcohol (Ethyl): MetroNIDAZOLE (Systemic) may enhance the adverse/toxic effect of Alcohol (Ethyl). A disulfiram-like reaction may occur. Risk X: Avoid combination
Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Risk X: Avoid combination
Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Risk C: Monitor therapy
Ammonium Chloride: May increase the serum concentration of Salicylates. Risk C: Monitor therapy
Angiotensin-Converting Enzyme Inhibitors: Salicylates may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Salicylates may diminish the therapeutic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Antacids: May decrease the absorption of Tetracyclines. Management: Separate administration of antacids and oral tetracycline derivatives by several hours when possible to minimize the extent of this potential interaction. Monitor for decreased therapeutic effects of tetracyclines. Risk D: Consider therapy modification
Anticoagulants: Salicylates may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Atovaquone: Tetracycline (Systemic) may decrease the serum concentration of Atovaquone. Risk C: Monitor therapy
Bacillus clausii: Antibiotics may diminish the therapeutic effect 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 diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Benzbromarone: Salicylates may diminish the therapeutic effect of Benzbromarone. Risk C: Monitor therapy
Bile Acid Sequestrants: May decrease the absorption of Tetracyclines. Risk C: Monitor therapy
Bismuth Subcitrate: Bismuth-Containing Compounds may enhance the neurotoxic effect of Bismuth Subcitrate. Risk X: Avoid combination
Bismuth Subsalicylate: May decrease the serum concentration of Tetracyclines. Management: Consider dosing tetracyclines 2 hours before or 6 hours after bismuth. The need to separate doses during Helicobacter pylori eradication regimens is questionable. Risk D: Consider therapy modification
Busulfan: MetroNIDAZOLE (Systemic) may increase the 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 the 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
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. Risk X: Avoid combination
Carbonic Anhydrase Inhibitors: Salicylates may enhance the adverse/toxic effect of Carbonic Anhydrase Inhibitors. Salicylate toxicity might be enhanced by this same combination. Management: Avoid these combinations when possible.Dichlorphenamide use with high-dose aspirin as contraindicated. If another combination is used, monitor patients closely for adverse effects. Tachypnea, anorexia, lethargy, and coma have been reported. Risk D: Consider therapy modification
Cholera Vaccine: Antibiotics may diminish the therapeutic effect 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 combination
Corticosteroids (Systemic): Salicylates may enhance the adverse/toxic effect of Corticosteroids (Systemic). These specifically include gastrointestinal ulceration and bleeding. Corticosteroids (Systemic) may decrease the serum concentration of Salicylates. Withdrawal of corticosteroids may result in salicylate toxicity. Risk C: Monitor therapy
Dexketoprofen: Salicylates may enhance the adverse/toxic effect of Dexketoprofen. Dexketoprofen may diminish the therapeutic effect of Salicylates. Salicylates may decrease the serum concentration of Dexketoprofen. Management: The use of high-dose salicylates (3 g/day or more in adults) together with dexketoprofen is inadvisable. Consider administering dexketoprofen 30-120 min after or at least 8 hrs before cardioprotective doses of aspirin to minimize any possible interaction. Risk X: Avoid combination
Disulfiram: May enhance the adverse/toxic effect of MetroNIDAZOLE (Systemic). In particular, the risk for CNS toxicities such as psychosis may be increased. Risk X: 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. Risk X: Avoid combination
Fecal Microbiota (Live) (Oral): May diminish the therapeutic effect of Antibiotics. Risk X: Avoid combination
Fecal Microbiota (Live) (Rectal): Antibiotics may diminish the therapeutic effect of Fecal Microbiota (Live) (Rectal). Risk X: Avoid combination
Fluorouracil Products: MetroNIDAZOLE (Systemic) may increase the serum concentration of Fluorouracil Products. Risk C: Monitor therapy
Fosphenytoin: May decrease the serum concentration of MetroNIDAZOLE (Systemic). MetroNIDAZOLE (Systemic) may increase the serum concentration of Fosphenytoin. Risk C: Monitor therapy
Ginkgo Biloba: May enhance the anticoagulant effect of Salicylates. Management: Consider alternatives to this combination of agents. Monitor for signs and symptoms of bleeding (especially intracranial bleeding) if salicylates are used in combination with ginkgo biloba. Risk D: Consider therapy modification
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy
Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Salicylates. Bleeding may occur. Risk C: Monitor therapy
Hyaluronidase: Salicylates may diminish the therapeutic effect of Hyaluronidase. Risk C: Monitor therapy
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Influenza Virus Vaccine (Live/Attenuated): May enhance the adverse/toxic effect of Salicylates. Specifically, Reye's syndrome may develop. Risk X: Avoid combination
Iron Preparations: Tetracyclines may decrease the absorption of Iron Preparations. Iron Preparations may decrease the 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 diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Lanthanum: May decrease the 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 enhance the adverse/toxic effect of Lithium. MetroNIDAZOLE (Systemic) may increase the serum concentration of Lithium. Risk C: Monitor therapy
Loop Diuretics: Salicylates may diminish the therapeutic effect of Loop Diuretics. Loop Diuretics may increase the serum concentration of Salicylates. Risk C: Monitor therapy
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. Risk D: Consider therapy modification
Magnesium Dimecrotate: May interact via an unknown mechanism with Tetracyclines. Risk C: Monitor therapy
Magnesium Salts: May decrease the 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 enhance the adverse/toxic effect of MetroNIDAZOLE (Systemic). Particularly the risk for Stevens-Johnson syndrome or toxic epidermal necrolysis may be increased. Risk X: Avoid combination
Mecamylamine: Tetracyclines may enhance the neuromuscular-blocking effect of Mecamylamine. Risk X: Avoid combination
Methotrexate: Salicylates may increase the serum concentration of Methotrexate. Salicylate doses used for prophylaxis of cardiovascular events are not likely to be of concern. Management: Consider avoiding coadministration of methotrexate and salicylates. If coadministration cannot be avoided, monitor for increased toxic effects of methotrexate. Salicylate doses used for prophylaxis of cardiovascular events are not likely to be of concern. Risk D: Consider therapy modification
Methoxsalen (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Methoxsalen (Systemic). Risk C: Monitor therapy
Methoxyflurane: Tetracyclines may enhance the nephrotoxic effect of Methoxyflurane. Risk X: Avoid combination
Mipomersen: Tetracyclines may enhance the hepatotoxic effect of Mipomersen. Risk C: Monitor therapy
Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease the 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 the 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: MetroNIDAZOLE (Systemic) may decrease the serum concentration of Mycophenolate. Specifically, metronidazole may decrease concentrations of the active metabolite of mycophenolate. Risk C: Monitor therapy
Neuromuscular-Blocking Agents: Tetracyclines may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents (Nonselective): May enhance the adverse/toxic effect of Salicylates. An increased risk of bleeding may be associated with use of this combination. Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the cardioprotective effect of Salicylates. Salicylates may decrease the serum concentration of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Management: Nonselective NSAIDs may reduce aspirin's cardioprotective effects. Administer ibuprofen 30-120 minutes after immediate-release aspirin, 2 to 4 hours after extended-release aspirin, or 8 hours before aspirin. Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the adverse/toxic effect of Salicylates. Specifically, the risk of gastrointestinal (GI) toxicity is increased. Management: Coadministration of salicylates and topical NSAIDs is not recommended. If salicylates and topical NSAIDs are coadministered, ensure the benefits outweigh the risks and monitor for increased NSAID toxicities. Risk D: Consider therapy modification
Penicillins: Tetracyclines may diminish the therapeutic effect of Penicillins. Risk C: Monitor therapy
PHENobarbital: MetroNIDAZOLE (Systemic) may enhance the adverse/toxic effect of PHENobarbital. A disulfiram-like reaction may occur if combined with phenobarbital dosage forms that contain propylene glycol or alcohol. PHENobarbital may decrease the serum concentration of MetroNIDAZOLE (Systemic). Risk C: Monitor therapy
Phenytoin: MetroNIDAZOLE (Systemic) may enhance the adverse/toxic effect of Phenytoin. A disulfiram-like reaction may occur if combined with phenytoin dosage forms that contain propylene glycol. Phenytoin may decrease the serum concentration of MetroNIDAZOLE (Systemic). MetroNIDAZOLE (Systemic) may increase the serum concentration of Phenytoin. Risk C: Monitor therapy
Polyethylene Glycol-Electrolyte Solution: May decrease the 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 enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy
Potassium Phosphate: May increase the serum concentration of Salicylates. Risk C: Monitor therapy
PRALAtrexate: Salicylates may increase the serum concentration of PRALAtrexate. Salicylate doses used for prophylaxis of cardiovascular events are unlikely to be of concern. Management: Consider avoiding concomitant use of salicylates and pralatrexate. If coadministered, monitor for increased pralatrexate adverse effects. Salicylate doses used for prophylaxis of cardiovascular events are not likely to be of concern. Risk D: Consider therapy modification
Primidone: May decrease the serum concentration of MetroNIDAZOLE (Systemic). Risk C: Monitor therapy
Probenecid: Salicylates may diminish the therapeutic effect of Probenecid. Risk X: Avoid combination
Products Containing Propylene Glycol: MetroNIDAZOLE (Systemic) may enhance the adverse/toxic effect of Products Containing Propylene Glycol. A disulfiram-like reaction may occur. Risk X: Avoid combination
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect 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 therapy
Quinapril: May decrease the serum concentration of Tetracyclines. Risk C: Monitor therapy
QuiNINE: Tetracycline (Systemic) may increase the serum concentration of QuiNINE. Risk C: Monitor therapy
Retinoic Acid Derivatives: Tetracyclines may enhance the adverse/toxic effect of Retinoic Acid Derivatives. The development of pseudotumor cerebri is of particular concern. Risk X: 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. Risk X: Avoid combination
Salicylates: May enhance the anticoagulant effect of other Salicylates. Risk C: 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. Risk D: Consider therapy modification
Strontium Ranelate: May decrease the 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 combination
Sucralfate: May decrease the 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 the 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
Sulfinpyrazone: Salicylates may decrease the serum concentration of Sulfinpyrazone. Risk X: Avoid combination
Sulfonylureas: Tetracyclines may enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy
Tetracyclines: Bismuth Subsalicylate may decrease the serum concentration of Tetracyclines. Management: Consider dosing tetracyclines 2 hours before or 6 hours after bismuth. The need to separate doses during Helicobacter pylori eradication regimens is questionable. Risk D: Consider therapy modification
Thrombolytic Agents: Salicylates may enhance the adverse/toxic effect of Thrombolytic Agents. An increased risk of bleeding may occur. Risk C: Monitor therapy
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. Risk C: Monitor therapy
TOLBUTamide: CYP2C9 Inhibitors (Weak) may increase the serum concentration of TOLBUTamide. Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect 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
Valproate Products: Salicylates may increase the serum concentration of Valproate Products. Risk C: Monitor therapy
Varicella Virus-Containing Vaccines: Salicylates may enhance the adverse/toxic effect of Varicella Virus-Containing Vaccines. Specifically, the risk for Reye's syndrome may increase. Risk X: Avoid combination
Vecuronium: MetroNIDAZOLE (Systemic) may enhance the neuromuscular-blocking effect of Vecuronium. Risk C: Monitor therapy
Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Risk C: 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. Risk D: Consider therapy modification
Zinc Salts: May decrease the 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
Tetracyclines, metronidazole, and salicylates cross the placenta. Use of this combination during pregnancy may cause adverse maternal and fetal outcomes. The combination of tetracycline, bismuth subsalicylate, and metronidazole should not be used in pregnant women; other agents are recommended for the treatment of H. pylori infection in pregnancy (Nguyen 2019).
Refer to individual monographs for additional information
Metronidazole and tetracycline are present in breast milk.
Based on the metronidazole component, the manufacturer recommends a decision be made to discontinue breastfeeding or to discontinue therapy, considering the importance of treatment to the mother. Alternatively, the mother may pump and discard breast milk during treatment and for 24 hours after taking the last metronidazole dose.
Refer to individual monographs for additional information
Monitor CBC with differential at baseline and after treatment (due to metronidazole); development of abnormal neurologic signs/symptoms. H. pylori eradication confirmation, when indicated (Chey 2007).
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.
See individual agents.
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