Metronidazole

Boxed warning

Metronidazole has a boxed warning, indicating serious and severe side effects may occur.¹ Boxed warnings (formerly “black box warnings”) are the strongest safety-related warnings the US Food and Drug Administration (FDA) issues.

Metronidazole was found to cause certain cancers in animal studies. Therefore, this drug should only be used for the specific conditions it is indicated for, exactly as indicated, and only when necessary.

What is metronidazole?

Metronidazole is a synthetic derivative of nitroimidazole, a class of drugs that has antiprotozoal and antibacterial effects.

The drug is used in the treatment of many anaerobic bacterial, protozoan, and parasitic infections.

It works by causing cells to die in the existing organisms and halting them from reproducing, which eventually causes the infection to clear.²

As with all antibiotics, taking metronidazole unnecessarily can cause the bacteria in the body to develop resistance against the drug when prescribed in the future.

What is metronidazole used to treat?

Metronidazole is an antibiotic used to treat anaerobic and microaerophilic bacteria and certain protozoa or parasites. Doctors commonly prescribe it to treat a wide range of bacterial infections in different parts of the body, including the stomach, brain, heart, lungs, liver, bloodstream, skin, joints, and spinal cord.

The medication is most commonly used to treat:

• Trichomoniasis vaginalis

• Liver and intestinal amebiasis

• Skin and bone infections

• Gastrointestinal infections

• Meningitis and brain abscess

• Dental abscess

• Respiratory or cardiac infections caused by certain bacteria

• Gynecological infections (endometritis, bacterial vaginosis, ovarian abscess)

You can’t take metronidazole to treat viral infections like the common cold, flu, or viral pneumonia.

In some cases, doctors prescribe metronidazole along with other drugs to treat other conditions such as stomach ulcers.³

Metronidazole dosage forms and strengths

Metronidazole can be administered via three routes: orally, intravenously, and topically.

The medication is available in the following forms and strengths:

• Capsule: 375mg

• Tablet: 250mg and 500mg

• Extended-release tablet: 750mg

• Injection: concentration 5mg/mL

• Gel: 0.75 and 1%

• Cream: 0.75%

• Lotion:  0.75%

Metronidazole is a generic medication. The intravenous formulation and some oral formulations, including the oral tablets, are available under the brand name Flagyl. Brand-name products for the topical formulations include Metrogel, Metrolotion, and Noritate. 

The dosage you need to take will depend on the condition being treated. If you need to take the drug intravenously, your dosage will also depend on your age and weight.⁴

The tablets or suspension forms are approved for use in children for treating some conditions, such as amebiasis. Your child’s doctor will determine their dosage, which will also depend on their age and weight.

It’s important to only take metronidazole as directed by your doctor. Misusing the drug can cause drug resistance, making it difficult to treat future infections.

How to take metronidazole

Below, you’ll find guidance on how to take metronidazole depending on the formulation you are taking and why you are taking it.

Tablets

Metronidazole tablets dissolve very quickly in the stomach and are best taken after meals and with lots of water to avoid an upset stomach.

Capsules

Metronidazole capsules can be taken with or without food because the shell takes longer to dissolve. This prevents the drug from immediately reacting with the fluids in your stomach. However, if you experience an upset stomach when taking the capsules, you might find that taking the medication with a meal or immediately after a meal can help.

Extended-release tablets

Extended-release metronidazole tablets are designed to stay in the body longer than regular tablets. This means you only need to take them once daily.

Don’t take the tablet with food. Take it at least an hour before your meal or two hours after.

Take extended-release tablets whole — there’s no need to split, crush, or chew them.

Topical metronidazole

Topical metronidazole is often prescribed for use once or twice a day. It is only used externally.

When applying topical metronidazole to the skin in the form of cream or lotion, make sure the treatment area is clean. Apply a thin layer of the medication, rub gently, and wait for it to dry for at least five minutes.⁵

Metronidazole gel can only be applied intravaginally — not to the skin. Use the applicator to apply it once or twice a day.

Do not use metronidazole gel, cream, or lotion in or near your eyes or mouth. If these areas are exposed to topical metronidazole, rinse the area with lots of water and contact your doctor.

Intravenous metronidazole

If you need to take the intravenous form of metronidazole, it will be administered in a healthcare setting.

How long does it take for metronidazole to work?

Metronidazole takes around 1–2 hours to take effect in the body. Depending on the condition being treated, the dosage, and the prescription duration, metronidazole may alleviate your symptoms in 3–14 days.

Speak to your doctor if your symptoms persist after you have taken all of the prescribed medication.

Who should not take metronidazole?

Metronidazole is generally safe for most people, but it is contraindicated in the following cases:⁶

• Pregnant women with trichomoniasis during the first trimester. Metronidazole may potentially harm your baby if you take it during the first trimester.

• History of hypersensitivity to metronidazole or other nitroimidazole drugs. Metronidazole is unsuitable for you if you are allergic to the drug or previously had an allergic reaction to nitroimidazole drugs.

• Alcohol use and abuse. Studies show metronidazole reacts with alcohol, causing adverse side effects referred to as disulfiram-like reactions.⁷ Do not consume any alcohol during your treatment and for three days after completing your course of medication.

• Those who are currently taking disulfiram. Disulfiram is a drug used to treat alcoholism. It can cause a psychotic reaction when taken alongside metronidazole. You should not take metronidazole if you have taken disulfiram within the last 14 days.

• People with Cockayne syndrome. Metronidazole can cause severe, irreversible, and potentially fatal acute liver failure in people with Cockayne syndrome.

Your doctor will carefully consider whether metronidazole is a suitable medication for you if you have any of the following conditions:

• Kidney problems

• Liver issues

• Fungal superinfections

• Drug-resistant bacteria and parasites

• Blood dyscrasia

Metronidazole may worsen symptoms of these conditions or cause an adverse reaction.

Potential side effects of metronidazole

Patients report different side effects after taking metronidazole, ranging from mild to severe.

Common side effects

The common side effects of metronidazole can last from a few minutes to hours. They include the following:

• Stomach cramps

• Nausea

• Vomiting

• Constipation

• Diarrhea

• Loss of appetite

• Dry mouth

• Headache

• Mouth or tongue irritation

• Metallic taste

Call your doctor if any of these symptoms persist.

Severe side effects

Metronidazole can also cause severe side effects, such as:

• Central nervous system problems, including encephalopathy, aseptic meningitis, convulsive seizures, depression, insomnia, and optic and peripheral neuropathy (may appear as numbness or a prickling feeling in the hands or feet)

• Dizziness

• Vision problems

• Numbness

• Hot flashes

• Yellowing eyes

• Hives

• Rash or itchy skin

• Confusion

• Agitation

• Joint pain

• Difficulty with coordination

Call 911 immediately if you experience any of these severe side effects.

Long-term use of metronidazole

Doctors typically prescribe oral metronidazole for 5–10 days. You can use topical metronidazole for up to two months to treat rosacea.

Only use the medication as prescribed by your doctor. Do not use it for longer than recommended, as this can greatly increase your risk of adverse effects.

Allergy information

If you’re allergic to metronidazole, you may experience the following symptoms:

• Difficulty breathing

• Swelling of the tongue, face, lips, or throat (difficulty speaking)

• Hives

• Blisters and peeling skin

• Stuffy nose, chills, or sore throat

Call 911 immediately if you experience an allergic reaction to metronidazole.

Overdoses

Only take metronidazole as prescribed by your doctor. Signs of overdose may include the following:

• Nerve problems, i.e., a tingling sensation in your hands and feet

• Extreme nausea

• Vomiting

• Seizures

• Difficulty with muscle movement

Missed doses

If you miss a dose of metronidazole, take one as soon as you remember. Wait eight hours before taking the next dose. Never take two doses at the same time or close in time to each other, as it may cause an overdose or an adverse reaction to the medication.

Metronidazole and pregnancy

Metronidazole is a pregnancy category B drug, meaning no adequate and well-controlled human studies prove it is safe.⁸

Don’t use metronidazole for trichomoniasis during the first trimester of pregnancy as it is unclear how it affects a developing fetus. Its use during the second and third trimesters of pregnancy should be carefully evaluated as metronidazole crosses the placental barrier and enters fetal circulation rapidly.

Animal studies at doses similar to the maximum recommended human dose showed no evidence of harm to the fetus. However, metronidazole was found to cause cancer in rodents.

Despite this, animal studies don’t always reflect how a human would respond to a drug. In any case, you should only use this drug during pregnancy if clearly needed. Your doctor will consider other alternative treatments.

It’s important to tell your doctor or pharmacist if you are pregnant before getting a metronidazole prescription so they can check if it’s safe for you to use.

Metronidazole and breastfeeding

Breastfeeding mothers can pass small quantities of metronidazole to their babies. Since metronidazole was found to have carcinogenic effects in mice, experts can’t rule out the risk of the drug affecting the baby through breast milk.

A decision should be made about whether to discontinue breastfeeding or stop using the drug. Your doctor will consider how important the drug is to you.

Alternatively, you might decide to feed your infant stored human milk or formula during the duration of treatment and for 24 hours afterward.

What to discuss with your doctor before taking metronidazole

Your doctor will check your medical history to determine if it’s safe to prescribe metronidazole.

To ensure maximum safety, here’s what you should discuss with your doctor before getting a metronidazole prescription:

• History of liver disease/liver problems

• Kidney issues or if you’re undergoing dialysis

• Any other medical condition you have

• Any allergies you have

• If you are pregnant, planning on becoming pregnant, or breastfeeding

• All medications or supplements you are currently taking, including herbs

• Present fungal infection (if being treated for bacterial infection)

Stopping metronidazole

Never pause or discontinue metronidazole until you complete the prescribed dose, even when you start feeling better. Stopping your dose prematurely may cause drug resistance or reinfection.

Drug interactions

Metronidazole may interact with the following drugs to cause adverse effects:

• Warfarin — may cause excessive bleeding

• Busulfan — increases plasma concentration of busulfan, which may cause dangerous toxic levels

• Lithium — slows down the excretion of lithium, which may cause lithium toxicity

• Disulfiram — may cause psychotic reactions or confusion

• Cimetidine — increases levels of metronidazole in the blood

• Phenytoin or phenobarbital — these drugs reduce plasma levels of metronidazole

This is not an exhaustive list of all drug interactions. Please tell your doctor all the medications you are currently taking.

Drug approval history

Metronidazole was first approved to treat vaginal trichomoniasis in the 1950s. The drug’s effectiveness in treating anaerobic bacteria was an accidental discovery. Researchers discovered it cured a patient diagnosed with both bacterial gingivitis and trichomonad vaginitis in 1962.⁹ The FDA approved metronidazole in 1963 as an immediate-release tablet.

Here are some key dates in the drug’s history:

1963: Metronidazole was first approved as an oral tablet to be sold under the brand name Flagyl.¹⁰

1981: Metronidazole was approved for intravenous administration.¹¹

1988: A topical formulation of metronidazole was first approved by the FDA — a 0.75% gel sold under the brand name Metrogel.¹²

1995: Oral metronidazole was approved in capsule form to be sold under the brand name Flagyl.¹³

1997: Flagyl ER was approved by the FDA. This has since been discontinued in the US, but generic extended-release metronidazole may still be available.¹⁴

Tips for taking metronidazole

• Follow your doctor or pharmacist’s instructions carefully. Not doing so could lead to antibiotic resistance.

• Never skip a dose. If you do, take the next dose immediately, except if it’s nearly time for the next dose.

• Inform your doctor of your medical history and any medication you’re currently taking before using metronidazole.

• Be aware that the drug can interact with some other drugs to cause adverse effects.

• Watch out for serious side effects like vision problems, dizziness, or yellowing eyes. Seek medical attention immediately if you notice severe adverse effects.

• Don’t stop taking metronidazole until you have finished your full course. Tell your doctor if your symptoms persist after this.