Flagyl

Tell your doctor about all prescription, non-prescription, illegal, recreational, herbal, nutritional, or dietary drugs you're taking, especially:

• Antabuse (disulfiram)
• Anticoagulants (blood thinners) such as Coumadin (warfarin)
• Dilantin (phenytoin)
• Hismanal (astemizole)
• Lithobid (lithium)
• Phenobarbital (Luminal and Solfoton)
• Tagamet (cimetidine)
• Vitamins

Metronidazole and Other Interactions

Metronidazole may make your skin more sensitive to sunlight.

Avoid prolonged exposure to the sun and wear sunscreen, protective clothing, and sunglasses when outdoors.

The medicine may also make you dizzy. Don't drive or operate machinery until you know how metronidazole affects you.

Metronidazole and Alcohol

Consuming alcohol while taking metronidazole can cause unwanted symptoms, such as:

• Upset stomach
• Stomach cramps
• Vomiting
• Fast heartbeat
• Headache
• Flushing
• Sweating

Don't drink alcohol while using this medicine, and for at least three days after you stop taking it.

Be sure to check the labels of foods and other products to make sure they don't contain alcohol.

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 (see WARNINGS).

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.

Oral forms:

Metronidazole tablets and capsules are prescription medications used to treat infections of the reproductive system, gastrointestinal tract, respiratory system, skin, bones and joints, and other areas of the body.

Topical forms:

Metronidazole creams and gels are prescription medications used to treat inflammatory lesions associated with acne rosacea (adult acne).

Injectable forms:

Injectable forms of metronidazole are prescription medications used to treat infections of the reproductive system, gastrointestinal tract, respiratory system, skin, bones and joints, and other areas of the body.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Tell your doctor if you are breastfeeding or plan to breastfeed.

Metronidazole has been detected in human breast milk. Because of the possibility for adverse reactions in nursing infants from metronidazole, a choice should be made whether to stop nursing or to stop use of this medication. The importance of the drug to the mother should be considered.

Contraindications

• Hypersensitivity to metronidazole or other nitroimidazole derivatives.152 156 197 430 495 Cautious desensitization has been used in some situations when use of metronidazole was considered necessary.341 436 (See Hypersensitivity Reactions and Desensitization under Cautions.)

• First trimester of pregnancy.152 197 430

• Helidac Therapy (kit containing tetracycline, metronidazole, bismuth subsalicylate) contraindicated in pregnant or nursing women, pediatric patients, patients with hepatic or renal impairment, patients with known allergy to aspirin or salicylates, and those with known hypersensitivity to any component of the kit.455

Warnings/Precautions

Warnings

Seizures and peripheral neuropathy (characterized by numbness or paresthesia of an extremity) reported with metronidazole.152 156 197 430 495

Persistent peripheral neuropathy reported in some patients receiving prolonged therapy.430 If abnormal neurologic signs develop, promptly discontinue drug..152 156 197 430

Use with caution in those with CNS diseases.152 197 430

Sensitivity Reactions

Hypersensitivity reactions, including urticaria, pruritus, erythematous rash, flushing, nasal congestion, fever, and fleeting joint pains sometimes resembling serum sickness, have been reported with metronidazole.152 156 197 430 495

Because there are no effective alternatives to metronidazole in the US for treatment of trichomoniasis, CDC states that desensitization can be attempted in patients with metronidazole hypersensitivity.341 The possibility that desensitization may be hazardous should be considered435 and adequate procedures (e.g., established IV access, BP monitoring) and therapies (e.g., epinephrine, corticosteroids, antihistamines, oxygen) for management of an acute hypersensitivity reaction should be readily available.435 Pretreatment (e.g., with an antihistamine and/or corticosteroid) also should be considered.435

Desensitization has been performed by administering increasing doses of IV metronidazole incrementally until a therapeutic dose was achieved, at which time oral dosing was initiated.435 In this regimen, an initial 5-mcg dose of IV metronidazole was given and the dose increased at 15- to 20-minute intervals to 15, 50, 150, and 500 mcg and then to 1.5, 5, 15, 30, 60, and 125 mg.435 After the 125-mg IV dose, dosing was switched to oral metronidazole and doses of 250, 500, and 2 g were given at 1-hour intervals.435 For trichomoniasis, desensitization dosing can be stopped after the 2-g dose.435 Patient should be monitored for ≥4 hours after the last dose (24 hours if there was any evidence of a reaction).435

General Precautions

To reduce development of drug-resistant bacteria and maintain effectiveness of metronidazole and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.152 197 430 495

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.152 197 430 495 In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.152 197 430 495

Surgical procedures should be performed in conjunction with metronidazole therapy when indicated.152 156 197 430 495

In mixed aerobic and anaerobic infections, anti-infectives appropriate for treatment of aerobic bacteria should be used in conjunction with metronidazole.152 156 197 430 495

Use with caution in patients with evidence or history of blood dyscrasias.152 156 197 430 495

Mild leukopenia has been reported, but persistent hematologic abnormalities do not occur.152 156 197 430 495

Perform total and differential leukocyte counts before and after metronidazole treatment, especially when repeated courses are necessary.152 156 197 430 495

Metronidazole injection contains approximately 28 mEq of sodium per g of metronidazole.156 495 Use with caution in patients receiving corticosteroids and in those predisposed to edema.156 495

Known or previously unrecognized candidiasis may present more prominent symptoms during metronidazole therapy; treatment with an appropriate antifungal is required.152 156 197 430 495

When the kit containing tetracycline, metronidazole, and bismuth subsalicylate (Helidac Therapy) is used for the treatment of H. pylori infection and duodenal ulcer disease, the cautions, precautions, and contraindications associated with tetracycline and bismuth subsalicylate must be considered in addition to those associated with metronidazole.455

Specific Populations

Category B.152 156 197 430 495 Contraindicated during the first trimester of pregnancy.100 152 197 341 430 442

Distributed into milk;152 156 197 430 495 discontinue nursing or the drug.152 156 197 430 495

If a single 2-g dose of metronidazole is indicated in the mother, AAP states that breast-feeding should be interrupted for 12–24 hours following the dose.100

Except for oral treatment of amebiasis, safety and efficacy not established in pediatric patients.152 156 197 430 495

Metronidazole has been used and is recommended for use in pediatric patients for various indications other than amebiasis (e.g., trichomoniasis, giardiasis).100 153 Unusual adverse effects have not been reported in pediatric patients.100

Safety and efficacy of the kit containing metronidazole, tetracycline, and bismuth subsalicylate (Helidac Therapy) for treatment of H. pylori infection and duodenal ulcer disease have not been established in pediatric patients.455

Because of age-related decreases in hepatic function, monitor serum metronidazole concentrations and adjust dosage accordingly.152 197 430

Insufficient experience in those ≥65 years of age to determine whether they respond differently than younger adults to concomitant use of metronidazole, tetracycline, and bismuth subsalicylate (Helidac Therapy) for treatment of H. pylori infection and duodenal ulcer disease.455 Age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy should be considered.455

Patients with severe hepatic impairment metabolize metronidazole more slowly, and increased concentrations of the drug and metabolites may occur.152 156 197 430 495

Use with caution, monitor plasma metronidazole concentrations, and reduce dosage in patients with severe hepatic impairment.152 156 197 430 495

Common Adverse Effects

Nausea, headache, anorexia, dry mouth, unpleasant metallic taste.152 156 197 430 495

• Bactericidal, amebicidal, and trichomonacidal in action.g

• Un-ionized at physiologic pH and readily taken up by anaerobic organisms or cells.g In susceptible organisms or cells, metronidazole is reduced by low-redox-potential electron transport proteins (e.g., nitroreductases such as ferredoxin); the reduction product(s) apparently are responsible for the cytotoxic and antimicrobial effects of the drug (e.g., disruption of DNA, inhibition of nucleic acid synthesis).g

• Has direct anti-inflammatory effects137 139 148 166 167 and effects on neutrophil motility, lymphocyte transformation, and some aspects of cell-mediated immunity.148 168 169 170 171 172

• Spectrum of activity includes most obligately anaerobic bacteria and many protozoa.g Inactive against fungi and viruses and most aerobic or facultatively anaerobic bacteria.g

• Gram-positive anaerobes: Clostridium,148 152 156 164 174 176 C. difficile,175 176 C. perfringens,164 176 Eubacterium,148 152 156 164 174 175 Peptococcus,148 152 156 164 174 175 176 and Peptostreptococcus.148 152 156 164 174 176 177 275 278

• Gram-negative anaerobes: Active against Bacteroides fragilis,148 152 156 164 173 174 175 176 275 277 280 B. distasonis,152 156 175 176 275 B. ovatus,152 156 176 275 B. thetaiotaomicron,152 156 175 176 275 B. vulgatus,152 156 175 176 275 B. ureolyticus,275 277 Fusobacterium,148 152 156 164 174 176 177 Prevotella bivia,174 275 277 278 279 P. buccae,494 P. disiens,175 278 P. intermedia,177 275 P. melaninogenica,164 175 275 277 278 279 P. oralis,175 275 277 279 Porphyromonas,177 275 494 and Veillonella.175 176 177

• Active against Helicobacter pylori,164 Entamoeba histolytica, Trichomonas vaginalis, Giardia lamblia, and Balantidium coli.g Acts principally against the trophozoite forms of E. histolytica and has limited activity against the encysted form.g

• Resistance has been reported in some Bacteroides and T. vaginalis.g

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

• Tell all of your health care providers that you take Flagyl. This includes your doctors, nurses, pharmacists, and dentists.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take this medicine.
• This medicine may affect how much of some other drugs are in your body. If you are taking other drugs, talk with your doctor. You may need to have your blood work checked more closely while taking Flagyl with your other drugs.
• Avoid alcohol and products that have alcohol or propylene glycol in them while taking this medicine and for at least 72 hours after your last dose. Drinking alcohol or taking products that have alcohol or propylene glycol in them, like some cough syrups, may cause cramps, upset stomach, headaches, and flushing.
• Do not use longer than you have been told. A second infection may happen.
• If you are 65 or older, use Flagyl with care. You could have more side effects.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

Flagyl (metronidazole) tablets, 250 mg or 500 mg is an oral formulation of the synthetic nitroimidazole antimicrobial, 2-methyl-5-nitro-1H-imidazole-1-ethanol, which has the following structural formula:

Flagyl (metronidazole) tablets contain 250 mg or 500 mg of metronidazole. Inactive ingredients include cellulose, FD&C Blue No. 2 Lake, hydroxypropyl cellulose, hypromellose, polyethylene glycol, stearic acid, and titanium dioxide.

Hypersensitivity

Flagyl Tablets is contraindicated in patients with a prior history of hypersensitivity to metronidazole or other nitroimidazole derivatives.

In patients with trichomoniasis, Flagyl Tablets is contraindicated during the first trimester of pregnancy (see PRECAUTIONS).

Psychotic Reaction with Disulfiram

Use of oral metronidazole is associated with psychotic reactions in alcoholic patients who were using disulfiram concurrently. Do not administer metronidazole to patients who have taken disulfiram within the last two weeks (see PRECAUTIONS, Drug Interactions).

Interaction with Alcohol

Use of oral metronidazole is associated with a disulfiram-like reaction to alcohol, including abdominal cramps, nausea, vomiting, headaches, and flushing. Discontinue consumption of alcohol or products containing propylene glycol during and for at least three days after therapy with metronidazole (see PRECAUTIONS, Drug Interactions).

NDC 0025-1831-50

50 Tablets
Rx only

Flagyl®
metronidazole
tablets USP

250 mg

Pfizer
Distributed by
G.D. Searle LLC
Division of Pfizer Inc, NY, NY 10017

NDC 0025-1821-50

50 Tablets
Rx only

Flagyl®
metronidazole
tablets USP

500 mg

Pfizer
Distributed by
G.D. Searle LLC
Division of Pfizer Inc, NY, NY 10017

Sometimes it is not safe to use certain medications at the same time. Some drugs can affect your blood levels of other drugs you take, which may increase side effects or make the medications less effective.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• busulfan;

• lithium; or

• a blood thinner - warfarin, Coumadin, Jantoven.

This list is not complete. Other drugs may interact with metronidazole, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Applies to metronidazole: oral capsule, oral powder for suspension, oral suspension, oral tablet, oral tablet extended release

Other dosage forms:

• intravenous powder for solution, intravenous solution

Along with its needed effects, metronidazole (the active ingredient contained in Flagyl) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking metronidazole:

• Agitation
• back pain
• blindness
• blurred vision
• burning, numbness, tingling, or painful sensations in the hands or feet
• changes in speech patterns
• confusion
• convulsions
• decreased vision
• depression
• dizziness
• drowsiness
• eye pain
• fever
• hallucinations
• headache
• irritability
• lack of coordination
• nausea
• seizures
• shakiness and unsteady walk
• slurred speech
• stiff neck or back
• trouble speaking
• unsteadiness, trembling, or other problems with muscle control or coordination
• unusual tiredness or weakness
• vomiting
• weakness in the arms, hands, legs, or feet

• Black, tarry stools
• blood in the urine or stools
• body aches or pain
• chills
• clumsiness or unsteadiness
• difficulty with breathing
• ear congestion
• feeling of pelvic pressure
• frequent or painful urination
• loss of voice
• nasal congestion
• pinpoint red spots on the skin
• runny nose
• skin rash, hives, redness, or itching
• sneezing
• stomach and back pain (severe)
• unusual bleeding or bruising
• vaginal irritation, discharge, or dryness not present before taking the medicine

• Bleeding gums
• bloating
• chest pain
• constipation
• cough
• dark-colored urine
• fast heartbeat
• indigestion
• loss of appetite
• painful or difficult urination
• pains in the stomach, side, or abdomen, possibly radiating to the back
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• swollen glands
• yellow eyes or skin

• Blistering, peeling, or loosening of the skin
• bloody or cloudy urine
• burning while urinating
• continuing diarrhea
• continuing stomach pain
• diarrhea
• feeling of warmth
• increased volume of pale, dilute urine
• joint or muscle pain
• loss of bladder control
• red skin lesions, often with a purple center
• red, irritated eyes
• redness of the face, neck, arms, and occasionally, upper chest
• redness of the skin

Some side effects of metronidazole may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Abdominal or stomach cramps
• dizziness or lightheadedness
• feeling of constant movement of self or surroundings
• heartburn
• sensation of spinning
• trouble sleeping
• weight loss

• Change in taste sensation
• congestion
• dry mouth
• pain or tenderness around the eyes and cheekbones
• tender, swollen glands in the neck
• trouble with swallowing
• unpleasant or sharp metallic taste
• voice changes

• Decreased interest in sexual intercourse
• inability to have or keep an erection
• loss in sexual ability, desire, drive, or performance
• painful sexual intercourse

• Flagyl is a brand (trade) name for metronidazole.
• Metronidazole is an antibiotic that may be used in the treatment of anaerobic infections caused by bacteria or protozoa. Anaerobic means "living without air".

Substance Name

Metronidazole

CAS Registry Number

443-48-1

Drug Class

Antiinfective Agents

Antibacterial Agents

Antiprotozoal Agents

Nitroimidazoles