Bismuth Subcitrate

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.

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 (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.

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

Tetracycline may cause photosensitivity; avoid exposure to the sun or sun lamps; discontinue use at first evidence of skin erythema.

Metronidazole has been shown to be carcinogenic in mice and rates. It is unknown whether metronidazole is associated with carcinogenicity in humans.

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:

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.

Severe hepatotoxicity/acute hepatic failure (has been fatal) has been reported with systemic metronidazole in patients with Cockayne syndrome; onset is rapid after initiation of treatment. Use metronidazole only after risk vs benefit assessment and if there are no appropriate alternatives in patients with Cockayne syndrome. Obtain LFTs prior to treatment initiation, within the first 2 to 3 days of initiation, frequently during therapy, and after treatment is complete. Discontinue treatment if elevated LFTs occur and monitor until LFTs return to baseline.

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.

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.

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:

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:

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 Other warnings/precautions:

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 10 to 14 days of therapy (triple or quadruple) for eradication of H. pylori (Chey 2017).