Bismuth subcitrate, metronidazole, and tetracycline

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• A burning, numbness, or tingling feeling that is not normal.
• Change in eyesight.
• Change in balance.
• Very bad dizziness or passing out.
• Seizures.
• Trouble speaking.
• Black, tarry, or bloody stools.
• Throwing up blood or throw up that looks like coffee grounds.
• This medicine may raise the chance of a very bad brain problem called aseptic meningitis. Call your doctor right away if you have a headache, fever, chills, very upset stomach or throwing up, stiff neck, rash, bright lights bother your eyes, feeling sleepy, or feeling confused.
• Raised pressure in the brain has happened with this medicine. Most of the time, this will go back to normal after bismuth subcitrate, metronidazole, and tetracycline is stopped. Sometimes, loss of eyesight may happen and may not go away even after this medicine is stopped. Call your doctor right away if you have a headache or eyesight problems like blurred eyesight, seeing double, or loss of eyesight.
• It is common to have diarrhea when taking bismuth subcitrate, metronidazole, and tetracycline. Rarely, a very bad form of diarrhea called Clostridium difficile (C diff)–associated diarrhea (CDAD) may occur. Sometimes, this has led to a deadly bowel problem (colitis). CDAD may happen while you are taking this medicine or within a few months after you stop taking it. Call your doctor right away if you have stomach pain or cramps, very loose or watery stools, or bloody stools. Do not try to treat loose stools without first checking with your doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Upset stomach.
• Loose stools (diarrhea).
• Headache.
• Belly pain.
• Dark tongue and stool.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

• Antibiotic, Miscellaneous
• Antibiotic, Tetracycline Derivative
• Antidiarrheal

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 (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 methoxyflurane; concomitant use with alcohol or other products containing propylene glycol (during therapy and for ≥3 days after).

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

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

Severe impairment: Use is contraindicated.

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, toxic epidermal necrolysis and drug rash with eosinophilia and systemic symptoms (DRESS) 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/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.

• 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 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. Monitor CBC with differential at baseline and after treatment.

• 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.

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; 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.

• 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.