(BIZ muth, me troe NI da zole, & tet ra SYE kleen)
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
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)
Duodenal ulcer associated with H. pylori infection: Oral: 3 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
Refer to adult dosing.
Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer 's labeling; use with caution.
Severe impairment: Use is contraindicated.
There are no dosage adjustments provided in the manufacturer 's labeling; use with caution.
Swallow capsules whole with 240 mL (8 oz) of water after meals and at bedtime. Administer concomitant omeprazole after morning meal and evening meal.
Store at 20 ‚ °C to 25 ‚ °C (68 ‚ °F to 77 ‚ °F).
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
Combination package:
Helidac ‚ ® [each package contains 14 blister cards (2-week supply); each card contains the following]:
Tablet, chewable: Bismuth subsalicylate: 262.4 mg (8s)
Tablet: Metronidazole: 250 mg (4s)
Capsule: Tetracycline hydrochloride: 500 mg (4s)
Alcohol (Ethyl): MetroNIDAZOLE (Systemic) may enhance the adverse/toxic effect of Alcohol (Ethyl). A disulfiram-like reaction may occur. Avoid combination
Antacids: May decrease the absorption of Tetracycline Derivatives. Consider therapy modification
ARIPiprazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy
ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy
Atovaquone: Tetracycline may decrease the serum concentration of Atovaquone. Monitor therapy
Avanafil: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Avanafil. Management: The maximum avanafil adult dose is 50 mg per 24-hour period when used together with a moderate CYP3A4 inhibitor. Patients receiving such a combination should also be monitored more closely for evidence of adverse effects. Consider therapy modification
BCG: Antibiotics may diminish the therapeutic effect of BCG. Avoid combination
Bile Acid Sequestrants: May decrease the absorption of Tetracycline Derivatives. Consider therapy modification
Bismuth Subsalicylate: May decrease the serum concentration of Tetracycline Derivatives. Management: Consider dosing tetracyclines 2 hours before or 6 hours after bismuth. The need to separate doses during Helicobacter pylori eradication regimens is questionable. Consider therapy modification
Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Bosentan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosentan. Management: Concomitant use of both a CYP2C9 inhibitor and a CYP3A inhibitor or a single agent that inhibits both enzymes with bosentan is likely to cause a large increase in serum concentrations of bosentan and is not recommended. See monograph for details. Monitor therapy
Bosutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosutinib. Avoid combination
Budesonide (Systemic, Oral Inhalation): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Systemic, Oral Inhalation). Management: Consider reducing the oral budesonide dose when used together with a CYP3A4 inhibitor. This interaction is likely less severe with orally inhaled budesonide. Monitor patients closely for signs/symptoms of corticosteroid excess. Consider therapy modification
Budesonide (Topical): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Topical). Management: Per US prescribing information, avoid this combination. Canadian product labeling does not recommend strict avoidance. If combined, monitor for excessive glucocorticoid effects as budesonide exposure may be increased. Consider therapy modification
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
Cannabis: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. Monitor therapy
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
Cilostazol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in patients who are also receiving moderate inhibitors of CYP3A4. Consider therapy modification
Colchicine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Colchicine. Management: Reduce colchicine dose as directed when using with a moderate CYP3A4 inhibitor, and increase monitoring for colchicine-related toxicity. Use extra caution in patients with impaired renal and/or hepatic function. Consider therapy modification
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
CYP3A4 Substrates: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of CYP3A4 Substrates. Monitor therapy
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
Dapoxetine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dapoxetine. Management: The dose of dapoxetine should be limited to 30 mg/day when used together with a moderate inhibitor of CYP3A4. 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
Domperidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Domperidone. Avoid combination
DOXOrubicin (Conventional): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to moderate CYP3A4 inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification
Dronabinol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dronabinol. Monitor therapy
Eliglustat: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eliglustat. Management: Use should be avoided under some circumstances. See full drug interaction monograph for details. Consider therapy modification
Eplerenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eplerenone. Management: When used concomitantly with moderate inhibitors of CYP3A4, eplerenone dosing recommendations may vary depending on international labeling. Consult appropriate labeling for specific recommendations. Consider therapy modification
Everolimus: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for patients being treated for subependymal giant cell astrocytoma or renal cell carcinoma. See prescribing information for specific dose adjustment and monitoring recommendations. Consider therapy modification
FentaNYL: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of FentaNYL. Management: Monitor patients closely for several days following initiation of this combination, and adjust fentanyl dose as necessary. Consider therapy modification
Fluorouracil (Systemic): MetroNIDAZOLE (Systemic) may increase the serum concentration of Fluorouracil (Systemic). Monitor therapy
Halofantrine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Halofantrine. Consider therapy modification
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
Hydrocodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Hydrocodone. Monitor therapy
Hydrocodone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Hydrocodone. Monitor therapy
Ibrutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ibrutinib. Management: If a moderate CYP3A inhibitor must be used, consider reducing the dose of ibrutinib to 140mg daily and monitor closely for signs of toxicity. Avoid combination
Ifosfamide: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. Monitor therapy
Imatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Imatinib. Monitor therapy
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 Pyrophosphate Citrate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose. Consider therapy modification
Ivabradine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivabradine. Avoid combination
Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivacaftor. Management: Ivacaftor dose reductions are required; consult prescribing information for specific age- and weight-based recommendations. Consider therapy modification
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
Lomitapide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lomitapide. Avoid combination
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
Lurasidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurasidone. Management: U.S. labeling: start at 20 mg/day and limit to max of 80 mg/day with moderate CYP3A4 inhibitor. Canadian labeling: limit to max of 40 mg/day with moderate CYP3A4 inhibitor; avoid concomitant use of grapefruit products. 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
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
Naloxegol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naloxegol. Avoid combination
Neuromuscular-Blocking Agents: Tetracycline Derivatives may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy
Olaparib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Olaparib. Management: Avoid use of moderate CYP3A4 inhibitors in patients being treated with olaparib. If such concurrent use cannot be avoided, the dose of olaparib should be reduced to 200 mg twice daily. Avoid combination
OxyCODONE: CYP3A4 Inhibitors (Moderate) may enhance the adverse/toxic effect of OxyCODONE. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite Oxymorphone may also be increased. Consider therapy modification
Penicillins: Tetracycline Derivatives may diminish the therapeutic effect of Penicillins. Consider therapy modification
Pimecrolimus: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of Pimecrolimus. Monitor therapy
Pimozide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pimozide. Avoid combination
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Avoid combination
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Monitor therapy
Propafenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Propafenone. 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
Ranolazine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ranolazine. Management: Limit the ranolazine adult dose to a maximum of 500 mg twice daily in patients concurrently receiving moderate CYP3A4 inhibitors (e.g., diltiazem, verapamil, erythromycin, etc.). 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, which contains 43% alcohol, and metronidazole may result in a disulfiram-like reaction. Avoid combination
Rivaroxaban: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Rivaroxaban. This warning is more specifically for drugs that are inhibitors of both CYP3A4 and P-glycoprotein. For erythromycin, refer to more specific erythromycin-rivaroxaban monograph recommendations. Management: In patients with impaired renal function (i.e., CrCl 15-80 mL/min) the U.S. prescribing information warns that moderate inhibitors of P-glycoprotein and CYP3A4 should not be used unless the potential benefits outweigh the potential risks. Consider therapy modification
Salmeterol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Salmeterol. Monitor therapy
Saxagliptin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Saxagliptin. Monitor therapy
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Simeprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir. Avoid combination
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 Johns 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
Suvorexant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Suvorexant. Consider therapy modification
Tegafur: MetroNIDAZOLE (Systemic) may increase serum concentrations of the active metabolite(s) of Tegafur. Monitor therapy
Tetrahydrocannabinol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol. 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. Monitor therapy
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Tolvaptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolvaptan. Avoid combination
Trabectedin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Trabectedin. Avoid combination
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
Ulipristal: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ulipristal. Management: This is specific for when ulipristal is being used for signs/symptoms of uterine fibroids (Canadian indication). When ulipristal is used as an emergency contraceptive, patients receiving this combination should be monitored for ulipristal toxicity. Avoid combination
Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Monitor therapy
Vilazodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vilazodone. 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. Exceptions: Zinc Chloride. Consider therapy modification
Zopiclone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zopiclone. Management: The initial starting dose of zopiclone should not exceed 3.75 mg if combined with a moderate CYP3A4 inhibitor. Monitor patients for signs and symptoms of zopiclone toxicity if these agents are combined. Consider therapy modification
Monitor CBC with differential at baseline and after treatment (due to metronidazole). H. pylori eradication confirmation, when indicated (Chey, 2007).
See individual agents.
Also see individual agents.
Helidac ‚ ® (includes studies with/without concomitant acid-suppression therapy):
>10%: Gastrointestinal: Nausea (12%)
1% to 10%:
Central nervous system: Dizziness (2%), headache (2%), insomnia (1%), pain (1%)
Gastrointestinal: Abdominal pain (7%), diarrhea (7%), melena (3%), anorexia (2%), constipation (2%), dyspepsia (2%), tongue discoloration (2%), vomiting (2%), abnormal stools (1%), anal discomfort (1%), duodenal ulcer (1%), flatulence (1%), GI hemorrhage (1%), taste perversion (1%)
Neuromuscular & skeletal: Weakness (2%), paresthesia (1%)
Respiratory: Upper respiratory infection (2%), sinusitis (1%)
<1% (Limited to important or life-threatening): Acne, ALT increased, AST increased, arthritis, bruising, cerebral ischemia, chest pain, conjunctivitis, dysphagia, eructation, flu-like syndrome, gastrointestinal moniliasis, glossitis, hypertension, infection, intestinal obstruction, malaise, MI, neoplasm, nervousness, photosensitivity reaction, pruritus, rash, rectal hemorrhage, rheumatoid arthritis, rhinitis, somnolence, stomatitis, syncope, tendonitis, tooth discoloration and enamel hypoplasia, urinary tract infection, xerostomia
Pylera ¢ „ ¢ (with concomitant omeprazole):
>10%: Gastrointestinal: Abnormal stools (16%)
1% to 10%:
Cardiovascular: Chest pain (1%), palpitation (1%)
Central nervous system: Headache (8%), dizziness (3%), pain (2%), anxiety (1%)
Dermatologic: Maculopapular rash (1%)
Gastrointestinal: Abdominal pain (9%), diarrhea (9%), dyspepsia (9%), nausea (8%), taste perversion (5%), gastritis (1%), gastroenteritis (1%), vomiting (1%), xerostomia (1%)
Genitourinary: Vaginitis (4%), urine abnormality (2%)
Hepatic: ALT increased (2%), AST increased (1%)
Neuromuscular & skeletal: Weakness (4%), back pain (2%)
Respiratory: Pharyngitis (2%), rhinitis (1%)
Miscellaneous: Flu-like syndrome (5%), infection (1% to 2%)
<1% (Limited to important or life-threatening): Cough, flatulence, rash, sinusitis
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.
D
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.
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.
Food reduced AUC by 6% (metronidazole), 34% (tetracycline), and 60% (bismuth)
- 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 dyspepsia, diarrhea, tongue discoloration, or stool discoloration. Have patient report immediately to prescriber paresthesia, vision changes, change in balance, severe dizziness, syncope, difficulty speaking, melena, hematemesis, considerable headache, 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 healthcare 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.