Metronidazole/Tetracycline/Bismuth Subsalicylate

Metronidazole shown to be carcinogenic in mice and rats; tumors affecting the liver, lungs, mammary and lymphatic tissues detected in several studies of metronidazole in rats and mice; unknown whether metronidazole is associated with carcinogenicity in humans

Reports of fatal renal toxicity with concurrent use of tetracycline and methoxyflurane

Tetracycline can cause fetal harm when administered to a pregnant woman (see Pregnancy)

Tetracycline administered during pregnancy at high doses (>2 g IV) associated with rare but serious cases of maternal hepatotoxicity (see Pregnancy)

Use of tetracyclines during tooth development (last half of pregnancy, infancy, and childhood to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown); this adverse reaction is more common during long-term use of the drug, but has been observed following repeated short-term courses

Known or previously unrecognized candidiasis may present more prominent symptoms during therapy with metronidazole that requires treatment with an antifungal agent

Photosensitivity, manifested by an exaggerated sunburn reaction, observed in patients taking tetracycline

Bismuth-containing products may cause temporary and harmless darkening of the tongue and/or black stools, generally reversible within several days after treatment is stopped

Metronidazole is a nitroimidazole, and should be used with care in patients with evidence of or history of blood dyscrasias

Skin and subcutaneous disorders including Stevens-Johnson syndrome, toxic epidermal necrolysis and DRESS syndrome (drug rash with eosinophilia and systemic symptoms) reported

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 reported with products containing metronidazole for systemic use

Prescribing therapy in absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria

Metronidazole may interfere with certain types of determinations of serum chemistry values, such as AST, SGOT, ALT, SGPT, LDH, triglycerides, and hexokinase glucose

Bismuth absorbs x-rays and may interfere with x-ray diagnostic procedures of gastrointestinal tract

Severe irreversible hepatotoxicity/acute liver failure with fatal outcomes reported after initiation of metronidazole in patients with Cockayne syndrome

Use of bismuth subsalicylate/metronidazole/tetracycline is not recommended in children and teenagers who have or who are recovering from varicella (chicken pox) or influenza due to the risk of Reye syndrome, a rare but serious illness

Severe renal impairment; tetracyclines may increase BUN; higher tetracycline serum concentrations may lead to azotemia, hyperphosphatemia, and acidosis