Metronidazole

Metronidazole Uses, Dosage, Side Effects, Food Interaction and all others data.

Metronidazole, a nitroimidazole has an extremely broad spectrum antiprotozoal and antimicrobial activities, with high activity against anaerobic bacteria and protozoa. Metronidazole is usually completely and rapidly absorbed after oral administration. The half-life in plasma is about 8 hours. About 10% of the drug is bound to plasma proteins. Metronidazole penetrates well into body tissues and fluids. The liver is the main site of metabolism. Both unchanged Metronidazole and metabolites are excreted in various proportions in the urine after oral administration.

Metronidazole treats amebiasis, trichomoniasis, and giardiasis, exerting both antibacterial and antiprotozoal activities. Metronidazole is an effective treatment for some anaerobic bacterial infections. Metronidazole has shown antibacterial activity against the majority of obligate anaerobes, however, during in vitro studies, it does not demonstrate significant action against facultative anaerobes or obligate aerobes. The nitro group reduction of metronidazole by anaerobic organisms is likely responsible for the drug's antimicrobial cytotoxic effects, causing DNA strand damage to microbes.

A note on convulsions and neuropathy and carcinogenesis

It is important to be aware of the risk of peripheral neuropathy and convulsions associated with metronidazole, especially at higher doses. If convulsions or numbness of an extremity occur, discontinue the drug immediately. Metronidazole has been found to be carcinogenic in mice and rats. The relevance to this effect in humans is unknown. It is advisable to only administer metronidazole when clinically necessary and only for its approved indications.

Trade Name Metronidazole
Availability Prescription only
Generic Metronidazole
Metronidazole Other Names Metronidazol, Métronidazole, Metronidazole, Metronidazolum
Related Drugs amoxicillin, prednisone, omeprazole, pantoprazole, doxycycline, ciprofloxacin, cephalexin, azithromycin, clindamycin, ceftriaxone
Weight 200mg, 400mg, 200mg/5ml, 500mg/100ml, , 5mg/ml, 375mg, 100mg/ml, 50mg/ml, 250mg, 500mg, 750mg, 0.75%, 1%, 0.75%cleanser, 140mg + 125mg + 125mg, 262.4mg + 250mg + 500mg
Type Injection, Tablet, Oral Suspension, Iv Infusion, Tablets, Solution, Intravenous Solution, Oral Capsule, Oral Tablet, Extended Release, Intravenous, Topical Cream, Topical Gel, Topical Kit, Topical Lotion, Oral Kit, Oral, Infusion
Formula C6H9N3O3
Weight Average: 171.154
Monoisotopic: 171.064391169
Protein binding

Metronidazole is less than 20% bound to plasma proteins.

Groups Approved
Therapeutic Class Amoebicides, Anti-diarrhoeal Antiprotozoal
Manufacturer Claris Lifesciences Limited, Munawar Pharma (pvt) Ltd, , Essential Drugs Company Ltd, Albion Pharmaceuticals Ltd, Aurobindo Pharma - Milpharm Ltd, Intrapharm Laboratories Limited, Zentiva, Pharmaceutical Solution Industries (psi), B, Braun, Hospira Inc, Finusolprima Farma Internasional, Bernofarm, Pratapa Nirmala, Axa Parenterals Ltd
Available Country India, Pakistan, Bangladesh, United Kingdom, Australia, Saudi Arabia, United States, Indonesia, Nigeria
Last Updated: September 19, 2023 at 7:00 am
Metronidazole
Metronidazole

Uses

Metronidazole is used for:

  • All forms of amoebiasis (intestinal and extra-intestinal disease including liver abscess and that of symptomless cyst passers)
  • Trichomoniasis
  • Giardiasis
  • Bacterial vaginosis
  • Acute ulcerative gingivitis
  • Anaerobic infections including septicaemia, bacteraemia, peritonitis, brain abscess, necrotising pneumonia, osteomyelitis, puerperal sepsis, pelvic abscess, pelvic cellulitis etc.
  • Anaerobically-infected leg ulcers and pressure sores
  • Acute dental infections (e.g. acute pericoronitis and acute apical infections)
  • Surgical prophylaxis (prevention of postoperative infections due to anaerobic bacteria, particularly species of bacteroides and anaerobic streptococci
  • Chronic symptomatic peptic ulcer disease (as an agent of triple therapy to eradicate H. pylori-the most important aetiological factor of peptic ulcer)

Metronidazole is also used to associated treatment for these conditions: Abscess, Intra-Abdominal, Acne Rosacea, Amebiasis, Anaerobic Infection, Bacteremia, Bacterial Endocarditis, Bacterial Peritonitis, Bacterial Vaginosis (BV), Balantidiasis, Bloodstream Infections, Bone and Joint Infections, Brain abscess, CNS Infection, Candidal Vulvovaginitis, Clostridium Difficile Infection (CDI), Empyema, Endometritis, Endomyometritis, Facial Rosacea, Giardiasis, Gynaecological infection, Helicobacter Pylori Infection, Infection, Bacteroides, Intraabdominal Infections, Lower Respiratory Infection, Lower respiratory tract infection bacterial, Lung Abscess, Meningitis, Mixed Vaginal Infections, Parasitic infection NOS, Periodontitis, Pneumonia, Postoperative Infections, Pouchitis, Septicemia bacterial anaerobic, Skin and Subcutaneous Tissue Bacterial Infections, Tetanus, Trichomonal Vaginitis, Trichomonas Vaginitis, Tubo-ovarian abscess, Urethritis, Vulvovaginitis, Asymptomatic Trichomoniasis, Entamoeba histolytica, Hepatic abscess, Refractory Sinusitis, Skin and skin-structure infections, Symptomatic Trichomoniasis, Asymptomatic Infections

How Metronidazole works

The exact mechanism of action of metronidazole has not been fully established, however, it is possible that an intermediate in the reduction of metronidazole which is only made by anaerobic bacteria and protozoa, binds deoxyribonucleic acid and electron-transport proteins of organisms, blocking nucleic acid synthesis. After administration, metronidazole enters cells by passive diffusion. Following this, ferredoxin or flavodoxin reduce its nitro group to nitro radicals. The redox potential of the electron transport portions of anaerobic or microaerophilic microorganisms renders metronidazole selective to these organisms, which cause nitro group reduction, leading to the production of toxic metabolites. These include N-(2-hydroxyethyl) oxamic acid and acetamide, which may damage DNA of replicating organisms.

Dosage

Metronidazole dosage

Tablet and Suspension:

Amoebic dysentery: Duration 5-10 Days; 

  • For Tablet: Adults- 750 mg t.i.d. Children- (7-10 years) 500 mg t.i.d. (3-7 years) 250 mg q.i.d. (1-3 years) 250 mg t.i.d.
  • For Suspension: Adults- 800 mg t.i.d. Children- (7-10 years) 500 mg t.i.d. (3-7 years) 200 mg q.i.d. (1-3 years) 200 mg t.i.d.

Asymptomatic amoebiasis: Duration 5-10 Days;

  • For Tablet: Adults- 500-750 mg t.i.d. Children- (7-10 years) 250-500 mg t.i.d. (3-7 years) 250 mg q.i.d. (1-3 years) 250 mg t.i.d.
  • For Suspension: Adults- 500-800 mg t.i.d. Children- (7-10 years) 200-500 mg t.i.d.; (3-7 years) 200 mg q.i.d.; (1-3 years) 200 mg t.i.d.

Hepatic extraintestinal amoebiasis : Duration 5-10 Days (or 2days); 

  • For Tablet: Adults- 500-750 mg t.i.d.; Children- (7-10 years) 250-500 mg t.i.d.; (3-7 years) 250 mg q.i.d.; (1-3 years) 250 mg t.i.d.
  • For Suspension: Adults- 500-800 mg t.i.d.; Children- (7-10 years) 200-500 mg t.i.d.; (3-7 years) 200 mg q.i.d.; (1-3 years) 200 mg t.i.d.

Giardiasis: Duration 3 Days;

  • For Tablet: Adults- 2 g once daily; Children-(7-10 years) 1g once daily; (3-7 years) 750 mg once daily; (1-3 years) 500 mg once daily.
  • For suspension: Adults- 2 g once daily; Children-(7-10 years) 1g once daily; (3-7 years) 800 mg once daily; (1-3 years) 500 mg once daily.

Trichomoniasis: Duration 7 Days;

  • For Tablet: Adults- 250 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.
  • For Suspension: Adults- 200 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.

Trichomoniasis: Duration 1 Day;

  • For Tablet: Adults- 2 g single dose;
  • For Suspension: Adults- 2 g single dose;

Vincent's infection (Ulceration of mucous membrane of respiratory tract & mouth): Duration 3 Days;

  • For Tablet: Adults- 250 mg t.i.d. or 500 mg b.i.d; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.
  • For Suspension: Adults- 200 mg t.i.d. or 500 mg b.i.d; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.

Periodontal infection: Duration 3 Days;

  • For Tablet: Adults- 250 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.
  • For Suspension: Adults- 200 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.

Severe dental infection: Duration 3 Days;

  • For Tablet: Adults- 500 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.
  • For Suspension: Adults- 500 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.

Anaerobic infection: Duration 7 Days;

  • For Tablet: Adults- 500 mg t.i.d.; Children- 7.5 mg/kg body weight t.i.d.
  • For Suspension: Adults- 500 mg t.i.d.; Children- 7.5 mg/kg body weight t.i.d.

Postoperative anaerobic infection (specially in operation abdominal or gynecological surgery): Duration 7 Days;

  • For Tablet: Adults- 500 mg t.i.d. before and after operation; Children- 7.5 mg/kg body weight t.i.d.
  • For Suspension: Adults- 500 mg t.i.d. before and after operation; Children- 7.5 mg/kg body weight t.i.d.

Bacterial vaginitis: Duration 7 Days;

  • For Tablet: Adults- 500 mg b.i.d.
  • For Suspension: Adults- 500 mg b.i.d.

Leg ulcers: Duration 1 Day;

  • For Tablet: Adults- 2 g as a single dose
  • For Suspension: Adults- 2 g as a single dose

Pressure sores: Duration 7 Days;

  • For Tablet: Adults- 500 mg t.i.d.
  • For Suspension: Adults- 500 mg t.i.d.

H. pylori infection: Duration 7 Days;

  • For Tablet: Adults- 500 mg b.i.d
  • For Suspension: Adults-500 mg b.i.d

Antibiotic Associated Pseudomembranus colitis: Duration 7 Days;

  • For Tablet: Adults- 500 mg b.i.d
  • For Suspension: Adults- 500 mg b.i.d

Vaginal Gel:

The recommended dose is one applicator full of Metronidazole GEL (approximately 5 grams containing approximately 37.5 mg of Metronidazole) intravaginally once or twice a day for 5 days. For once a day dosing, Metronidazole GEL should be administered at bedtime.

Suppository:

Anaerobic infections:

  • Adult: 1 g 8 hrly for 3 days, then 12 hrly thereafter until oral medication is possible.
  • Child: 5-10 yr 500 mg. All doses to be given 8 hrly for 3 days, then 12 hrly thereafter until oral medication is possible.

Prophylaxis of postoperative anaerobic bacterial infections:

  • Adult: 1 g 2 hr before surgery, repeated 8 hrly for 3 days, then 12 hrly thereafter until oral medication is possible.
  • Child: 5-10 yr 500 mg 2 hr before surgery, repeated 8 hrly for 3 days, then 12 hrly thereafter until oral medication is possible.

IV Infusion:

Metronidazole injection should be infused intravenously at an approximate rate of 5 ml/min. Oral medication should be substituted as soon as feasible. Treatment for 7 days should be satisfactory for most patients, but the physician might decide to prolong treatment.

  • For bacterial infections: Adults: 500 mg (100 ml) 8 hourly. Children: 7.5 mg/kg (1.5 ml/kg) 8 hourly.
  • For treatment before and during surgery: Adults: 500 mg (100 ml) shortly before operation, repeated 8 hourly. Children: 7.5 mg/kg (1.5 ml/kg) 8 hourly

Side Effects

Side effects of Metronidazole include gastrointestinal discomfort, nausea, coated tongue, dryness of mouth and unpleasant metallic or bitter taste, headache, pruritus and skin rashes and less frequently, vertigo, depression, insomnia, drowsiness, urethral discomfort, and darkening of the urine. Occasionally there may be temporary moderate leucopenia. Peripheral neuropathy has been reported in patients on prolonged therapy.

Toxicity

LD50 information

The oral LD50 of metronidazole in rats is 5000 mg/kg

Overdose information

Adverse effects that may be exaggerated with an overdose include peripheral neuropathy, central nervous system toxicity, seizures, disulfiram-like effect (if combined with alcohol) dark urine, a metallic taste in the mouth, nausea, epigastric discomfort, and vertigo, in addition to neutropenia. There is no specific antidote for metronidazole overdose. Symptomatic and supportive treatment should be employed in addition to the administration of activated charcoal to remove the unabsorbed drug from the gastrointestinal tract. In addition to the above measures, contact the local poison control center for updated information on the management of a metronidazole overdose.

Precaution

Metronidazole should not be used in patients with blood dyscrasia. It is suggested that it should not be given in the first three months of pregnancy. When given in conjunction with alcohol, Metronidazole may provoke a disulphiram like effect.

Interaction

Metronidazole interacts with warfarin, nicoumalone, phenytoin, phenobarbitone, fluorouracil, disulfiram, lithium, cimetidine etc.

Food Interaction

  • Avoid alcohol. Unpleasant symptoms such as nausea, vomiting, and abdominal distress may occur with alcohol.
  • Take with or without food. The extended release formulation should, however, be taken without food.

[Major] CONTRAINDICATED: Use of alcohol or products containing alcohol during nitroimidazole therapy may result in a disulfiram-like reaction in some patients.

There have been a few case reports involving metronidazole, although data overall are not convincing.

The presumed mechanism is inhibition of aldehyde dehydrogenase (ALDH) by metronidazole in a manner similar to disulfiram.

Following ingestion of alcohol, inhibition of ALDH results in increased concentrations of acetaldehyde, the accumulation of which can produce an unpleasant physiologic response referred to as the 'disulfiram reaction'.

Symptoms include flushing, throbbing in head and neck, throbbing headache, respiratory difficulty, nausea, vomiting, sweating, thirst, chest pain, palpitation, dyspnea, hyperventilation, tachycardia, hypotension, syncope, weakness, vertigo, blurred vision, and confusion.

Severe reactions may result in respiratory depression, cardiovascular collapse, arrhythmia, myocardial infarction, acute congestive heart failure, unconsciousness, convulsions, and death.

However, some investigators have questioned the disulfiram-like properties of metronidazole.

One study found neither elevations in blood acetaldehyde nor objective or subjective signs of a disulfiram-like reaction to ethanol in six subjects treated with metronidazole (200 mg three times a day for 5 days) compared to six subjects who received placebo.

MANAGEMENT: Because clear evidence is lacking concerning the safety of ethanol use during nitroimidazole therapy, patients should be apprised of the potential for interaction.

Consumption of alcoholic beverages and products containing propylene glycol is specifically contraindicated during and for at least 3 days after completion of metronidazole and benznidazole therapy according to their product labeling.

Metronidazole Hypertension interaction

[Moderate] Flagyl I.V. RTU (brand of metronidazole ready-to-use injection) contains 14 mEq of sodium per each 500 mg dose of metronidazole.

The sodium content should be considered when this product is used in patients with conditions that may require sodium restriction, such as congestive heart failure, hypertension, and fluid retention.

Volume of Distribution

Metronidazole is widely distributed throughout the body and various body fluids. They include the bile, saliva, breastmilk, cerebrospinal fluid, and the placenta. Steady-state volume distribution of metronidazole in adults ranges from 0.51 to 1.1 L/kg. It attains 60 to 100% of plasma concentrations in various tissues, such as the central nervous system, however, is not measured in high concentrations in the placental tissue.

Elimination Route

After the intravenous infusion of a 1.5g dose, peak concentration was reached within 1 hour and was peak level of 30-40 mg/L. When a multiple-dose regimen of 500mg three times a day administered intravenously, steady-state concentrations were achieved within about 3 days and peak concentration was measured at 26 mg/L. When administered orally in the tablet form, metronidazole is absorbed entirely absorbed, showing a bioavailability of greater than 90%. One resource indicates that Cmax after a single oral dose of 500mg metronidazole ranges from 8 to 13 mg/L, with a Tmax of 25 minutes to 4 hours. The AUC following a single 500mg oral dose of metronidazole was 122 ± 10.3 mg/L • h.

A note on the absorption of topical preparations

Insignificant percutaneous absorption of metronidazole occurs after the application of 1% metronidazole cream topically. Healthy volunteers applied one 100 mg dose of 14C-labelled metronidazole 2% cream to unbroken skin. After 12 hours, metronidazole was not detected in the plasma. Approximately 0.1% to 1% of the administered metronidazole was measured in the urine and feces.

Half Life

The elimination half-life of metronidazole is 7.3 ± 1.0 after a single 500mg IV dose in healthy subjects. Another resource indicates that the elimination half-life for metronidazole ranges from 6 to 10 hours.

Clearance

Dose adjustments may be required in patients with hepatic impairment, as clearance is impaired in these patients. The clearance of metronidazole in the kidneys is estimated at 10 mL/min/1.73 m2. The total clearance from serum is about 2.1 to 6.4 L/h/kg.

Elimination Route

Metronidazole and metabolites are 60 to 80% eliminated in the urine, and 6-15% excreted in the feces.

Pregnancy & Breastfeeding use

Not recommended during first & later trimesters. Breast feeding should be delayed until 48 hours after discontinuing metronidazole in the mother.

Contraindication

Metronidazole is contraindicated in patients with prior history of hypersensitivity to Metronidazole or other Nitroimidazole derivatives.

Storage Condition

Store in a cool and dry place. Protect from light and moisture. Keep out of the reach of children

Innovators Monograph

You find simplified version here Metronidazole

Metronidazole contains Metronidazole see full prescribing information from innovator Metronidazole Monograph, Metronidazole MSDS, Metronidazole FDA label

FAQ

What are the side effects of Metronidazole?

Metronidazole side effects are notorious for causing an upset stomach and killing your appetite. For many people, the nausea and even vomiting can occur just from the bad taste. Heartburn, constipation, and diarrhea can occur, too.

Side effects of Metronidazole include gastrointestinal discomfort, nausea, coated tongue, dryness of mouth and unpleasant metallic or bitter taste, headache, pruritus and skin rashes and less frequently, vertigo, depression, insomnia, drowsiness, urethral discomfort, and darkening of the urine. Occasionally there may be temporary moderate leucopenia. Peripheral neuropathy has been reported in patients on prolonged therapy.

What bacteria does Metronidazole kill?

Metronidazole has activity against protozoans like Entamoeba histolytica, Giardia lamblia and Trichomonas vaginalis, for which the drug was first approved as an effective treatment. Anaerobic bacteria which are typically sensitive are primarily Gram-negative anaerobes belonging to the Bacteroides and Fusobacterium spp.

When Metronidazole is prescribed?

Metronidazole is a drug used to treat infections caused by parasites (amoeba) and anaerobe bacteria. It can be given to treat diarrhea caused by Entamoeba histolytica, Giardia lamblia, or Clostridium difficile. It can also be used to treat vaginal infections or various types of bacterial infections.

How should this drug be taken?

Metronidazole is available as 250 mg tablets and 500 mg capsules. It is also available as vaginal creams and inserts as well as a cream to apply on the skin. If needed, Metronidazole can also be given intravenously (by the veins). The recommended dose of Metronidazole will vary depending on the type of infection that is being treated. Metronidazole can be taken with or without food. You should NOT take any alcohol during your treatment and for at least 24 hours following the end of the treatment.

What should I do if I forget to take Metronidazole?

If you miss a dose of Metronidazole, take it as soon as possible. However, if it is time for your next dose, do not double the dose, just carry on with your regular schedule.

Why should I do not forget to take Metronidazole?

If you miss doses of Metronidazole, the infection will continue and possibly worsen. Therefore, it is extremely important that you take Metronidazole for the entire duration of the treatment.

Does Metronidazole make you sleepy?

Metronidazole oral tablet doesn't cause drowsiness, but it can cause other side effects.

Can Metronidazole treat yeast infection?

Metronidazole vaginal will not treat a vaginal yeast infection. You may even develop a new vaginal yeast infection after using this medicine. Watch for symptoms such as itching or discharge during or after treatment with Metronidazole vaginal.

*** Taking medicines without doctor's advice can cause long-term problems.
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