Metronidazole and nystatin (United States: Not available): Drug information

Warnings/Precautions

Concerns related to adverse effects:

• Carcinogenic: Metronidazole is possibly carcinogenic based on animal data.

• CNS effects: Central or peripheral neuropathy may occur with metronidazole treatment. Consider discontinuation of therapy if ataxia or other CNS signs/symptoms occur; use with caution in patients with CNS disease. CNS signs/symptoms may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving).

• Dermatologic reactions: Severe cutaneous adverse reactions, including acute generalized exanthematous pustulosis, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported. If a reaction occurs, discontinue immediately and consider further evaluation.

• Local effects: Local irritation/sensitivity have been reported; if irritation occurs, discontinue therapy and institute appropriate treatment.

• Psychiatric effects: Suicidal ideation with or without depression has been reported with use. Discontinue use immediately if psychiatric symptoms occur.

• 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. Discontinue use and administer alternative therapy if superinfection occurs.

• Systemic effects: Systemic absorption of metronidazole from vaginal administration may occur. Adverse effects normally associated with systemic administration of metronidazole may occur following the vaginal administration.

• Urine discoloration: Patients should be informed that urine may become darker in color.

Disease-related concerns:

• Cockayne syndrome: [Canadian Boxed Warning]: Cases of severe hepatotoxicity/acute hepatic failure, including cases with a fatal outcome, with very rapid onset after treatment initiation, in patients with Cockayne syndrome have been reported with products containing metronidazole for systemic use. In this population, metronidazole and nystatin should, therefore, only be used after careful benefit-risk assessment and only if no alternative treatment is available.

• Hepatic impairment: Use with caution in patients with severe hepatic impairment due to potential accumulation; dosage adjustment is recommended in these patients. Use caution in patients with hepatic encephalopathy and in patients with a history of livery injury associated with metronidazole.

Special populations:

• Sexual partners: Sexual partners should receive concurrent treatment (oral metronidazole) when there is evidence of trichomonal infestation.

Dosage form specific issues:

• Vaginal products: May limit the effectiveness of diaphragms and condoms; concurrent use with treatment is not recommended.

Other warnings/precautions:

• Alcohol consumption: Disulfiram-like reactions to ethanol have been reported with systemic metronidazole and may occur with topical metronidazole; consider avoidance of alcoholic beverages during therapy with topical products and for at least 1 day after.

• Appropriate use: May not be effective in bacterial vaginal infections and should not be prescribed unless there is direct evidence of trichomonal infestation or candidiasis. Candidiasis confirmation should be followed up with identification of promoting factors so they can be offset or eliminated. It is recommended that treatment of Candida involve all associated sites concurrently (intestinal, vaginal, or other infections). Risk of developing resistant organisms is increased if prescribed without evidence or strong suspicion of a mixed vaginal infection.

• Fungal replication: Use of soaps with an acid pH, vaginal injections, and tampons may promote fungal replication and should be avoided during treatment.