Flagyl ER

Pregnancy category: B

Lactation

Excreted in human milk; not recommended

Following PO administration, concentrations in human milk are similar to concentrations in plasma

Potential for tumorigenicity shown in animal studies; a decision should be made whether to discontinue nursing or to discontinue metronidazole; breastfeeding women may choose to pump and discard milk for the duration of therapy and for 24 hours after therapy ends and to feed her infant stored human milk or formula

Study Data

There are published data from case-control studies, cohort studies, and 2 meta-analyses that included more than 5000 pregnant women who used metronidazole systemically during pregnancy

Many studies included first trimester exposures

One study showed an increased risk of cleft lip, with or without cleft palate, in infants exposed to metronidazole in utero; however, these findings were not confirmed

In addition, more than 10 randomized, placebo-controlled clinical trials that together enrolled over 5000 pregnant women assessed the possible effect of systemic antibiotic treatment (including with metronidazole) for bacterial vaginosis on the incidence of preterm delivery; most studies did not show an increased risk of congenital anomalies or other adverse fetal outcomes following metronidazole exposure during pregnancy

Three studies conducted to assess the risk of infant cancer following systemic metronidazole exposure during pregnancy did not show an increased risk; however, the ability of these studies to detect such a signal was limited

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

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.

Serious side effects have been reported with oral, topical, and injectable forms of metronidazole including the following:

• Rash
• Itching
• Stuffy nose
• Fever
• Joint pain

Metronidazole can cause dizziness. Do not drive or operate heavy machinery until you know how metronidazole affects you.

Do not drink alcohol during therapy or after therapy with metronidazole.  If you drink alcohol, you can experience stomach cramps, severe nausea and vomiting, headaches, and flushing.

Do not take metronidazole if you:

• are allergic to metronidazole or to any of its ingredients
• have trichomaniasis and are in the first trimester of pregnancy
• have taken disulfuram (Antabuse) within the last 2 weeks

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your weight
• your height
• your age

Oral forms:

The recommended dose of metronidazole for the treatment of trichomoniasis is 375 mg two times a day.

The recommended dose of metronidazole for the treatment of amebiasis in adults is 750 mg three times a day.

Topical forms:

The recommended dose of metronidazole for the treatment of rosacea is two applications daily, usually in the morning and evening.

Injectable forms:

The recommended dose range of metronidazole for the treatment of amebiasis in children is 35 to 50 mg/kg every day, divided into three doses.

The recommended dose of metronidazole for the treatment of anaerobic bacterial infections is 7.5 mg/kg every 6 hours. A maximum of 4 grams should not be exceeded within a 24-hour period.

If you take too much metronidazole, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If metronidazole is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

• Tell all of your health care providers that you take Flagyl ER. 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 ER 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 ER 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.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take Flagyl ER (metronidazole extended-release tablets) or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Flagyl ER. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Hypersensitivity

Flagyl ER 750 mg tablets are contraindicated in patients with a prior history of hypersensitivity to metronidazole or other nitroimidazole derivatives.

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).

In two multicenter clinical trials, a total of 270 patients received 750 mg Flagyl ER tablets orally once daily for 7 days, and 287 were treated with a comparator agent administered intravaginally once daily for 7 days (See CLINICAL STUDIES).5,6

Most adverse events were described as being of mild or moderate severity. Among patients taking Flagyl ER who reported headaches, 10% considered them severe, and less than 2% of reported episodes of nausea were considered severe. Metallic taste was reported by 9% of patients taking Flagyl ER.

Adverse events reported at ≥2% incidence for either treatment group, irrespective of treatment causality, are summarized in the table below.

Vulvovaginal candidiasis is a recognized consequence of treatment with many anti-infective agents. In these multicenter clinical trials, there were no statistically significant differences in the incidence rates of yeast vaginitis for groups of patients treated with Flagyl ER or the vaginal comparator.

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; 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 ER 750 mg tablets.