Metronidazole

Metronidazole is a nitroimidazole antimicrobial that works against anaerobic bacteria and certain parasites. It passes into the organism, where it is chemically reduced into short-lived free radicals that damage DNA and kill the cell. The precise mechanism is not fully understood. Metronidazole has no clinically relevant activity against obligate aerobes or facultative anaerobes, the bacteria behind most everyday urinary and chest infections, which is why it is not used for those.

Metronidazole is approved to treat:

• symptomatic trichomoniasis in adult women and men, confirmed by laboratory testing
• asymptomatic trichomoniasis in women when the organism is associated with endocervicitis, cervicitis or cervical erosion
• trichomoniasis in asymptomatic sexual partners, treated at the same time as the patient to prevent reinfection
• amebiasis, both acute intestinal amebiasis (amoebic dysentery) and amebic liver abscess, in adults and children
• serious anaerobic bacterial infections, including intra-abdominal, skin, gynecologic, lower respiratory, central nervous system, and bloodstream infections, endocarditis, and bone and joint infections as add-on therapy
• preventing infection after elective bowel surgery. Metronidazole injection given before, during and after contaminated or potentially contaminated colorectal surgery can reduce postoperative infection. It is stopped within 12 hours of surgery
• bacterial vaginosis in non-pregnant women

Because trichomoniasis is sexually transmitted, sexual partners should be treated at the same time even if they have no symptoms, since a woman can be reinfected by an untreated partner and the organism is hard to detect in men.

Metronidazole is well absorbed by mouth, with peak blood levels 1 to 2 hours after a tablet and an average half-life of about 8 hours. It starts working quickly, but it may take a couple of days before you feel better. Finish the whole course even if your symptoms improve, because stopping early makes the treatment less effective and makes resistant bacteria more likely.

Metronidazole was first approved by the FDA in 1963.

Take metronidazole exactly as prescribed and read all medication guides.

• Regular tablets, capsules, and the suspension may be taken with or without food. Extended-release tablets must be taken on an empty stomach, at least 1 hour before or 2 hours after a meal
• Shake the oral suspension well before each dose and measure it with a calibrated oral dosing device, not a household teaspoon or tablespoon
• Swallow extended-release tablets whole. Do not crush, chew or break them
• Keep taking metronidazole even if you feel better quickly. Skipping doses reduces how well it works and makes resistant bacteria more likely
• Do not share this medicine with anyone else
• If you are being treated for trichomoniasis, your sexual partner should be treated at the same time so you are not reinfected
• The dose is reduced by 50% if you have severe liver impairment. If you are on hemodialysis, an extra dose may be given after a session

The injection is given by slow infusion into a vein by a healthcare provider. For most serious anaerobic infections treatment starts this way and switches to tablets once you are well enough.

Metronidazole carries a Boxed Warning for cancer-causing potential.

Cancer-causing potential

Metronidazole has been shown to cause cancer in mice and rats. Tumours of the liver, lung, mammary and lymphatic tissues were seen in several animal studies, though not in hamsters.

Because of this, unnecessary use of metronidazole should be avoided. It should be reserved for the conditions it is approved to treat: trichomoniasis, amebiasis and anaerobic bacterial infections.

Metronidazole will not treat a viral infection, such as a cold or flu, and it will not treat a vaginal yeast infection. Do not use it for any condition your doctor has not assessed.

Do not use metronidazole if you are allergic to it or to other nitroimidazole medicines such as secnidazole or tinidazole, or if you:

• have taken disulfiram (Antabuse) in the past 2 weeks
• drink alcohol, or use products containing alcohol or propylene glycol, during treatment or for at least 3 days afterwards
• have Cockayne syndrome

Tell your healthcare provider about all your medical conditions, including if you have:

• liver disease
• kidney disease, or if you are on dialysis
• a heart rhythm disorder
• a stomach or intestinal disease such as Crohn's disease
• a blood cell disorder, or any history of blood problems
• a condition affecting the brain or nerves
• a yeast or fungal infection anywhere in your body

Pregnancy

Published case-control studies, cohort studies, and two meta-analyses covering more than 5,000 pregnancies, many involving first-trimester exposure, have not established a link between metronidazole and major birth defects or miscarriage. One study reported an increased risk of cleft lip, with or without cleft palate, but this was not confirmed. Metronidazole crosses the placenta and reaches the baby's circulation rapidly.

Metronidazole tablets are contraindicated in the first trimester for treating trichomoniasis. For other infections, discuss the benefits and risks with your doctor.

Breastfeeding

Metronidazole passes into breast milk at levels similar to those in the mother's blood, and levels in a breastfed infant can approach those used to treat infants. You may choose to pump and discard your milk during treatment and for 48 hours after your last dose, feeding your baby stored milk or formula instead. Discuss the best option with your healthcare provider.

Use in children

For oral metronidazole, safety and effectiveness in children have been established only for amebiasis. Metronidazole injection is also established for treating intra-abdominal infections in babies from birth to under 4 months of age; it has not been established in children of 4 months and older, or for other anaerobic infections or surgical prophylaxis in babies under 4 months. Metronidazole is not approved to treat vaginal infections in girls who have not begun having menstrual periods.

Older adults

Monitoring is recommended in elderly patients, and reduced liver function may mean the dose needs adjusting.

Metronidazole may cause the following serious side effects.

• Severe skin reactions. Serious and sometimes fatal skin reactions have been reported, including toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). Stop taking metronidazole and seek medical attention if you develop any kind of rash.
• Nervous system effects. Encephalopathy, aseptic meningitis, seizures, and nerve damage affecting the limbs or the optic nerve have been reported. Stop taking metronidazole and contact your doctor immediately if you develop seizures, headache, visual changes, weakness, numbness, tingling, unsteadiness or slurred speech. Symptoms usually resolve within days to weeks after stopping, but nerve damage has persisted in some people on long courses.
• Alcohol and propylene glycol. Do not drink alcohol or use products containing alcohol or propylene glycol during treatment and for at least 3 days after your last dose. The combination can cause abdominal cramps, nausea, vomiting, headache and flushing. Do not take metronidazole if you have used disulfiram (Antabuse) in the past 2 weeks, as the combination has caused psychotic reactions.
• Cockayne syndrome. Metronidazole is contraindicated in people with this rare genetic condition. Severe, irreversible liver failure with fatal outcomes has occurred, sometimes within 2 days of starting.
• Metronidazole should be used with care if you have a history of blood disorders, and your white cell counts may be checked before and after treatment.
• Pregnancy and trichomoniasis. Metronidazole tablets are contraindicated during the first trimester in women being treated for trichomoniasis. If treatment later in pregnancy is unavoidable, the one-day 2 g regimen should not be used, because it produces higher blood levels that reach the baby's circulation.
• The intravenous solution contains 13.5 mEq of sodium per container, so it is used with care in people taking corticosteroids or prone to fluid retention.

Get emergency medical help if you have signs of a serious allergic reaction to metronidazole: swelling of the face, lips or throat, difficulty breathing, or a sudden drop in blood pressure. Milder allergic reactions include hives, an erythematous rash, flushing, nasal congestion, dryness of the mouth, vagina or vulva, and fever.

Stop taking metronidazole and seek medical attention if you have:

• any type of skin rash, or blisters, peeling skin, sores in your mouth, redness or swelling of your face, hands or soles, fever, muscle or joint aches, or swollen glands. These can be signs of a severe skin reaction
• nervous system problems such as seizures, confusion, unsteadiness, slurred speech, headache, changes in vision, or numbness or tingling in your hands or feet. Your doctor will weigh the benefits and risks of continuing

Call your doctor promptly if you have:

• severe stomach pain spreading to your back, with nausea and vomiting, which can be a sign of pancreatitis
• ringing in the ears, hearing changes, or hearing loss
• signs of a low white cell count, such as fever, chills, or sore throat, or unusual bruising or bleeding
• new or worsening vaginal itching or discharge, which may be a yeast infection needing separate antifungal treatment. Keep taking your metronidazole unless your doctor tells you otherwise
• if you have Cockayne syndrome, any sign of liver failure, such as nausea, pain in the upper right side of your stomach, clay-coloured stools or jaundice (yellowing of the skin or eyes). Stop taking metronidazole and contact your doctor at once

Common side effects

The most common side effects of metronidazole are:

• nausea, vomiting, diarrhea
• headache
• loss of appetite
• upper abdominal pain, cramping, epigastric discomfort, constipation.

Other side effects of metronidazole include:

• a sharp, unpleasant metallic taste, which the labeling describes as not unusual
• furry tongue, sore mouth or tongue, often linked to Candida overgrowth
• rash, itching, hives, blistering, fixed drug eruption, flushing, heavy sweating, nasal congestion, dryness of the mouth, vagina or vulva, and fever
• reversible falls in white cells or platelets, and a rise in eosinophils
• dizziness, vertigo, unsteadiness, fainting, insomnia, irritability, low mood, and rarely psychosis
• raised liver enzymes, and jaundice
• QT prolongation, an abnormal heart rhythm, particularly alongside other medicines that affect the QT interval
• painful or frequent urination, incontinence, or a sense of pelvic pressure
• darkened urine, reported in roughly 1 in 100,000 people and thought to be harmless
• vaginal thrush, painful sex, reduced libido, proctitis, hiccups, and fleeting joint pains
• with the injection, inflammation of the vein at the drip site.

People with Crohn's disease have a higher background rate of bowel and other cancers. There have been reports in the medical literature of breast and colon cancer in people with Crohn's disease treated with high-dose metronidazole over long periods, but no cause-and-effect relationship has been established. Crohn's disease is not an approved use for metronidazole.

These are not all the possible side effects. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Metronidazole dose for trichomoniasis in adults

Treatment should be individualised. Usual regimens are:

• One-day treatment: 2 g as a single oral dose, or as two divided doses of 1 g each given on the same day
• Seven-day course: 250 mg three times daily for 7 consecutive days

A seven-day course may give higher cure rates and gives sexual contacts time to be treated, while single-dose treatment can help with adherence. Treat sexual partners at the same time to prevent reinfection. If a repeat course is needed, an interval of 4 to 6 weeks is recommended, the infection should be reconfirmed by laboratory testing, and white cell counts should be checked before and after re-treatment.

Metronidazole dose for amebiasis

• Adults, acute intestinal amebiasis: 750 mg three times daily for 5 to 10 days
• Adults, amebic liver abscess: 500 mg or 750 mg three times daily for 5 to 10 days. Metronidazole does not remove the need for aspiration or drainage of pus
• Children: 35 to 50 mg/kg per 24 hours, divided into three doses, for 10 days, up to a maximum of 2,250 mg per 24 hours and 750 mg per dose

Metronidazole dose for anaerobic bacterial infections in adults

Intravenous metronidazole is usually given first for serious anaerobic infections.

By mouth: 7.5 mg/kg every 6 hours, roughly 500 mg for a 70 kg adult, for 7 to 10 days.

By infusion: a loading dose of 15 mg/kg infused over one hour, about 1 g for a 70 kg adult, then 7.5 mg/kg infused over one hour every 6 hours, starting 6 hours after the loading dose.

Do not exceed 4 g in any 24-hour period. Bone and joint, lower respiratory tract and endocardial infections may need longer treatment. Where an infection involves both aerobic and anaerobic bacteria, an additional antibiotic active against the aerobic organisms should be used, and any necessary surgery should still be performed.

Metronidazole dose for prevention of infection after colorectal surgery

Metronidazole injection 15 mg/kg infused over 30 to 60 minutes, finishing about one hour before surgery, then 7.5 mg/kg over 30 to 60 minutes at 6 and 12 hours after the first dose. Preventive use is limited to the day of surgery.

Dose adjustments

Severe liver impairment (Child-Pugh C): reduce the dose by 50%. Mild to moderate impairment needs no change, but monitoring is advised.

In end-stage kidney disease, metronidazole metabolites can build up, so monitoring is recommended. A hemodialysis session lasting 4 to 8 hours removes 40 to 65% of a dose, so if dosing cannot be separated from the session a supplemental dose may be given afterwards.

No adjustment is needed for continuous ambulatory peritoneal dialysis, and the dose is not specifically reduced in people who produce no urine, because accumulated metabolites are rapidly cleared by dialysis.

Take it as soon as you can, but skip the missed dose if it is almost time for your next one. Do not take two doses at once.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. Single doses of up to 15 g have been reported, causing nausea, vomiting, and unsteadiness. Seizures and nerve damage have followed repeated very high doses. There is no specific antidote, and treatment is supportive. Metronidazole can be removed by dialysis.

Do not drink alcohol or use products containing alcohol or propylene glycol during treatment and for 3 days after your last dose.

Tell your doctor about all the medicines you take, including over-the-counter medicines, vitamins and herbal products. Not all possible interactions are listed here.

• Disulfiram (Antabuse), which must not have been taken in the previous 2 weeks
• Alcohol and products containing propylene glycol
• Warfarin and other oral anticoagulants, whose blood-thinning effect metronidazole increases. Prothrombin time and INR need careful monitoring
• Lithium, which can rise to toxic levels. Lithium and creatinine levels are monitored for several days after starting metronidazole
• Busulfan, whose levels metronidazole raises, increasing the risk of serious toxicity
• Cimetidine and other drugs that slow liver enzymes, which can prolong metronidazole's half-life
• Phenytoin and phenobarbital, which speed up the clearance of metronidazole and may make it less effective. Metronidazole can also slow the clearance of phenytoin
• Medicines that prolong the QT interval

Metronidazole can interfere with some blood tests, including AST, ALT, LDH, triglycerides, and glucose, sometimes producing a result of zero. Tell any doctor who treats you that you are taking it.

Tablets: store at 20°C to 25°C (68°F to 77°F) and protect from light. Keep in a tight, light-resistant container with a child-resistant closure.

Oral suspension: store at 20°C to 25°C (68°F to 77°F), with brief exposure to 15°C to 30°C (59°F to 86°F) permitted. Do not freeze. Keep in a tight container and shake before each dose. Discard any unused Likmez suspension 60 days after opening the bottle.

Injection: stored by the hospital or clinic at 20°C to 25°C (68°F to 77°F), protected from light until use and from freezing. It is not refrigerated, and any unused portion is discarded.

Keep metronidazole and all medicines out of the reach of children.