Flagyl (metronidazole) Side Effects, Warnings, and Interactions

Serious side effects of Flagyl and Flagyl ER include brain disease, fevers, mouth sores, painful urination, nerve damage resulting in prickling or tingling sensations that may become permanent, cystitis, pelvic pain or pressure, decreased sex drive, inflammation of the lining of the rectum, inflammation of the mouth and lips, inflammation of the tongue, seizures, numbness and tingling of extremities, encephalopathy, aseptic meningitis, and colon cancer in people with Crohn’s disease.

Drug interactions with Flagyl and Flagyl ER include alcohol, warfarin, cimetidine, cholestyramine, amprenavir, propylene glycol, carbamazepine, lithium, and cyclosporine. Flagyl and Flagyl ER should not be used in early pregnancy because of potential adverse effects on the fetus. Flagyl and Flagyl ER are excreted in breast milk. Because of potential adverse effects on the newborn, females who are nursing should not use metronidazole.

What are the important side effects of Flagyl (metronidazole)?

Flagyl is a useful antibiotic and is generally well tolerated with appropriate use.

The most common and minor side effects include:

• Nausea
• Headaches
• Loss of appetite
• A metallic taste
• Rarely a rash
• Abdominal cramps
• Vomiting
• Diarrhea
• Dry mouth
• Dark-colored urine
• Metallic taste in mouth
• Weight loss (anorexia)
• Dizziness
• Constipation
• Furry tongue
• Rash
• Nasal congestion
• Flushing
• Vaginal dryness

Side effects that are uncomfortable, but may become serious include:

• Brain disease
• Fevers
• Mouth sores
• Pain with urination
• Prickling or tingling sensations that may become permanent
• Cystitis
• Pelvic pain or pressure
• Decrease of libido
• Proctitis
• Stomitis
• Glossitis

Serious side effects of Flagyl are rare and the drug should be stopped if these symptoms appear:

• Seizures
• Damage of nerves resulting in numbness and tingling of extremities
• Peripheral neuropathy
• Encephalopathy
• Aseptic meningitis
• Asceptic meningitis
• Colon cancer in people with Crohn’s disease

Flagyl (metronidazole) side effects list for healthcare professionals

The following reactions have been reported during treatment with metronidazole:

Central Nervous System

The most serious adverse reactions reported in patients treated with metronidazole have been convulsive seizures, encephalopathy, aseptic meningitis, optic and peripheral neuropathy, the latter characterized mainly by numbness or paresthesia of an extremity. Since persistent peripheral neuropathy has been reported in some patients receiving prolonged administration of metronidazole, patients should be specifically warned about these reactions and should be told to stop the drug and report immediately to their physicians if any neurologic symptoms occur. In addition, patients have reported headache, syncope, dizziness, vertigo, incoordination, ataxia, confusion, dysarthria, irritability, depression, weakness, and insomnia.

Gastrointestinal

The most common adverse reactions reported have been referable to the gastrointestinal tract, particularly nausea, sometimes accompanied by headache, anorexia, and occasionally vomiting; diarrhea; epigastric distress; and abdominal cramping and constipation.

Mouth

A sharp, unpleasant metallic taste is not unusual. Furry tongue, glossitis, and stomatitis have occurred; these may be associated with a sudden overgrowth of Candida which may occur during therapy.

Dermatologic

Erythematous rash and pruritus.

Hematopoietic

Reversible neutropenia (leukopenia); rarely, reversible thrombocytopenia.

Cardiovascular

Flattening of the T-wave may be seen in electrocardiographic tracings.

Hypersensitivity

Urticaria, erythematous rash, Stevens-Johnson Syndrome, toxic epidermal necrolysis, flushing, nasal congestion, dryness of the mouth (or vagina or vulva), and fever.

Renal

Dysuria, cystitis, polyuria, incontinence, and a sense of pelvic pressure. Instances of darkened urine have been reported by approximately one patient in 100,000. Although the pigment which is probably responsible for this phenomenon has not been positively identified, it is almost certainly a metabolite of metronidazole and seems to have no clinical significance.

Other

Proliferation of Candida in the vagina, dyspareunia, decrease of libido, proctitis, and fleeting joint pains sometimes resembling “serum sickness.” Rare cases of pancreatitis, which generally abated on withdrawal of the drug, have been reported.

Patients with Crohn’s disease are known to have an increased incidence of gastrointestinal and certain extraintestinal cancers. There have been some reports in the medical literature of breast and colon cancer in Crohn’s disease patients who have been treated with metronidazole at high doses for extended periods of time. A cause and effect relationship has not been established. Crohn’s disease is not an approved indication for Flagyl tablets.

What drugs interact with Flagyl (metronidazole)?

Disulfiram

Psychotic reactions have been reported in alcoholic patients who are using metronidazole and disulfiram concurrently. Metronidazole should not be given to patients who have taken disulfiram within the last two weeks.

Alcoholic Beverages

Abdominal cramps, nausea, vomiting, headaches, and flushing may occur if alcoholic beverages or products containing propylene glycol are consumed during or following metronidazole therapy.

Warfarin And other Oral Anticoagulants

Metronidazole has been reported to potentiate the anticoagulant effect of warfarin and other oral coumarin anticoagulants, resulting in a prolongation of prothrombin time. When Flagyl is prescribed for patients on this type of anticoagulant therapy, prothrombin time and INR should be carefully monitored.

Lithium

In patients stabilized on relatively high doses of lithium, short-term metronidazole therapy has been associated with elevation of serum lithium and, in a few cases, signs of lithium toxicity. Serum lithium and serum creatinine levels should be obtained several days after beginning metronidazole to detect any increase that may precede clinical symptoms of lithium intoxication.

Busulfan

Metronidazole has been reported to increase plasma concentrations of busulfan, which can result in an increased risk for serious busulfan toxicity. Metronidazole should not be administered concomitantly with busulfan unless the benefit outweighs the risk. If no therapeutic alternatives to metronidazole are available, and concomitant administration with busulfan is medically needed, frequent monitoring of busulfan plasma concentration should be performed and the busulfan dose should be adjusted accordingly.

Drugs That Inhibit CYP450 Enzymes

The simultaneous administration of drugs that decrease microsomal liver enzyme activity, such as cimetidine, may prolong the half-life and decrease plasma clearance of metronidazole.

Drugs That Induce CYP450 Enzymes

The simultaneous administration of drugs that induce microsomal liver enzymes, such as phenytoin or phenobarbital, may accelerate the elimination of metronidazole, resulting in reduced plasma levels; impaired clearance of phenytoin has also been reported.

Drug/Laboratory Test Interactions

Metronidazole may interfere with certain types of determinations of serum chemistry values, such as aspartate aminotransferase (AST, SGOT), alanine aminotransferase (ALT, SGPT), lactate dehydrogenase (LDH), triglycerides, and glucose hexokinase. Values of zero may be observed. All of the assays in which interference has been reported involve enzymatic coupling of the assay to oxidation-reduction of nicotinamide adenine dinucleotide (NAD+ NADH). Interference is due to the similarity in absorbance peaks of NADH (340 nm) and metronidazole (322 nm) at pH 7.

Summary

Common side effects of the antibiotic Flagyl (metronidazole) include nausea, headaches, loss of appetite, vomiting, diarrhea, dry mouth, dark-colored urine, metallic taste in mouth, weight loss, constipation, and vaginal dryness. Serious side effects include brain disease, fevers, mouth sores, painful urination, nerve damage resulting in prickling or tingling sensations that may become permanent, encephalopathy, aseptic meningitis, and colon cancer in people with Crohn’s disease, among others.