Metrogyl 400

Metrogyl 400 contains metronidazole. It is sold by JB Pharma.

Metronidazole belongs to nitroimidazole pharmacological class and acts as an antibiotic/antimicrobial/antiprotozoal therapeutic agent.

Metrogyl 400 is used to treat trichomoniasis, amebiasis, inflammatory lesions of rosacea, and bacterial infections, as well as prevent postoperative infections.

Metrogyl 400 is  rapidly and almost completely absorbed from the gastrointestinal tract. Food may delay absorption. The time to peak plasma concentration is approximately 1-2 hours (oral); 20 minutes (IV); 5-12 hours (rectal); 8 hours (intravaginal gel). The Bioavailability found to be 60-80% (rectal); 20-25% (vag pessaries); 56% (intravaginal gel). Metronidazole is the major component appearing in the plasma, with lesser quantities of metabolites also being present. Less than 20% of the circulating metronidazole is bound to plasma proteins. Metronidazole appears in cerebrospinal fluid, saliva, and breast milk in concentrations like those found in plasma. The metabolites of metronidazole result primarily from side-chain oxidation [1-(βhydroxyethyl)-2- hydroxymethyl-5-nitroimidazole and 2-methyl-5-nitroimidazole-1-ylacetic acid] and glucuronide conjugation. Both the parent compound and the hydroxyl metabolite possess in vitro antimicrobial activity. The major route of elimination of metronidazole and its metabolites is via the urine (60 to 80% of the dose), with approximately 20% of the amount excreted appearing as unchanged metronidazole. Renal clearance of metronidazole is approximately 10 mL/min/1.73 m2. Fecal excretion accounts for 6 to 15% of the dose.

Metrogyl 400 shows common side effects like Vomiting, nausea, Diarrhoea, constipation, upset stomach, stomach cramps, loss of appetite, headache, dry mouth, sharp, unpleasant metallic taste, furry tongue, mouth, or tongue irritation.

Metrogyl 400 is available in the form of Oral Tablet

Metronidazole is available in India, US, China, Japan, Singapore, France, Spain, Italy, Malaysia, Russia, and Australia.

Metrogyl 400 contains Metronidazole 400 mg. Metronidazole belongs to nitroimidazole pharmacological class and acts as an antibiotic/antimicrobial/antiprotozoal therapeutic agent.

Metronidazole, a nitroimidazole, exerts antibacterial effects in an anaerobic environment against most obligate anaerobes. Once metronidazole enters the organism by passive diffusion and activated in the cytoplasm of susceptible anaerobic bacteria, it is reduced; this process includes intra-cellular electron transport proteins such as ferredoxin, transfer of an electron to the nitro group of the metronidazole, and formation of a short-lived nitroso free radical. Because of this alteration of the metronidazole molecule, a concentration gradient is created and maintained which promotes the drug’s intracellular transport. The reduced form of metronidazole and free radicals can interact with DNA leading to inhibition of DNA synthesis and DNA degradation leading to death of bacteria. The precise mechanism of action of metronidazole is unclear.

The onset of action of Metronidazole is not clinically established.

The duration of action for Metronidazole is around 12 hours.

The Tmax of Metronidazole is approximately 1-2 hours (via Oral).

Metrogyl 400 contains Metronidazole 400 mg is approved for use in the following clinical indications

Adult Dose

Oral

• Amebiasis, intestinal or extraintestinal
• Skin and soft tissue infection
• Surgical prophylaxis
• Intra-abdominal infection
• Intracranial abscess
• Pneumonia, aspiration

Although not approved, there have been certain off-label indications. These include

• Balantidiasis
• Bite wound infection, prophylaxis or treatment, animal or human bite
• Clostridioides difficile infection, treatment
• Crohn disease
• Dientamoeba fragilis infection
• Giardiasis
• Helicobacter pylori eradication
• Odontogenic infection
• Pouchitis, acute
• Sexually transmitted infections
• Tetanus

Pediatric Dose

Oral

• Amebiasis
• Appendicitis, perforated
• Balantidiasis
• Catheter; exit-site or tunnel infection
• Clostridioides difficile infection
• Dientamoeba fragilis
• Giardiasis
• Helicobacter pylori eradication
• Inflammatory bowel disease
• Intra-abdominal infection
• Pelvic inflammatory disease
• Peritonitis
• Prophylaxis against sexually transmitted diseases following sexual assault
• Surgical prophylaxis
• Tetanus
• Trichomoniasis; treatment
• Vaginosis, bacterial

Metrogyl 400 contains Metronidazole 400 mg is administered as

Adult Dose

Amebiasis, intestinal or extraintestinal

Oral: 400 to 750 mg every 8 hours for 7 to 10 days followed by an intraluminal agent (eg, paromomycin).

Intra-abdominal infection

Oral: 400 mg every 8 hours as part of an appropriate combination regimen. Duration of therapy is 4 to 5 days following adequate source control; for diverticulitis or uncomplicated appendicitis managed without intervention, duration is 10 to 14 days.

Pneumonia, aspiration

Oral: 400 mg 3 times daily in combination with an appropriate beta-lactam (eg, oral amoxicillin, IV penicillin, or an IV third-generation cephalosporin) for 7 days.

Although not approved, there have been certain off-label indications. These include

• Balantidiasis

Oral: Initial dose- 400 mg, increase up to 750 mg 3 times daily for 5 days.

• Bite wound infection, prophylaxis or treatment, animal or human bite

Oral: Initial dose- 400 mg every 8 hours. Duration is 3 to 5 days for prophylaxis; duration of treatment for established infection is typically 5 to 14 days and varies based on clinical response and patient-specific factors.

• Clostridioides difficile infection, treatment

Nonsevere (ie, WBC ≤15,000 cells/mm3 and serum creatinine <1.5 mg/dL), initial episode

Oral: Initial dose- 400 mg 3 times daily for 10 to 14 days.

• Crohn disease

Management after surgical resection

Monotherapy: Oral: 20 mg/kg/day (in 3 divided doses) or 1 to 2 g/day in divided doses for 3 months; begin as soon as oral intake is resumed after surgery.

Treatment of simple perianal fistulas

Adjunctive agent: Oral: Initial dose- 400 mg twice daily for 4 weeks initially; if clinical response (ie, cessation of drainage and closure of fistula), continue at 250 mg 3 times daily for an additional 4 weeks or 10 to 20 mg/kg/day in divided doses for 4 to 8 weeks with or without ciprofloxacin.

• Dientamoeba fragilis infection

Oral: Initial dose- 400 mg, increase up to 750 mg 3 times daily for 10 days.

• Giardiasis

Oral: Initial dose- 400 mg 2 times daily for 5 to 7 days.

• Helicobacter pylori eradication

Clarithromycin triple regimen

Oral: Initial dose- 400 mg 3 times daily in combination with clarithromycin 500 mg twice daily and a standard-dose or double-dose proton pump inhibitor (PPI) twice daily; continue regimen for 14 days.

Bismuth quadruple regimen

Oral: Initial dose- 400 mg 3 or 4 times daily in combination with either bismuth subsalicylate 300 to 524 mg or bismuth subcitrate 120 to 300 mg 4 times daily, tetracycline 500 mg 4 times daily, and a standard-dose PPI twice daily; continue regimen for 10 to 14 days.

Concomitant regimen

Oral: Initial dose- 400 mg twice daily in combination with clarithromycin 500 mg twice daily, amoxicillin 1 g twice daily, and a standard-dose PPI twice daily; continue regimen for 10 to 14 days.

Sequential regimen (alternative regimen)

Oral: Amoxicillin 1 g twice daily plus a standard-dose PPI twice daily for 5 to 7 days; then follow with clarithromycin 500 mg twice daily, Metronidazole initial dose- 400 mg and a standard-dose PPI twice daily for 5 to 7 days; some experts prefer the 10-day sequential regimen (amoxicillin for 5 days, followed by metronidazole and clarithromycin for 5 days) over the 14-day sequential regimen (amoxicillin for 7 days, followed by metronidazole and clarithromycin for 7 days) due to the lack of data showing superiority of the 14-day regimen over the 10-day regimen in North America.

Hybrid regimen (alternative regimen)

Oral: Amoxicillin 1 g twice daily plus a standard-dose PPI twice daily for 7 days; then follow with amoxicillin 1 g twice daily, clarithromycin 500 mg twice daily, metronidazole initial dose- 400 mg twice daily, and a standard-dose PPI twice daily for 7 days.

• Odontogenic infection

Acute simple gingivitis, plaque-associated

Oral: Initial dose- 400 mg every 8 hours in combination with penicillin V for 5 to 7 days.

Periodontitis, severe, plaque-associated

Oral: Initial dose- 400 mg every 8 hours in combination with amoxicillin for 14 days or until clinical resolution; use in addition to periodontal debridement.

Pyogenic odontogenic soft tissue infection (alternative agent)

Oral: Initial dose- 400 mg every 8 hours as part of an appropriate combination regimen until resolution, typically for 7 to 14 days. Use in addition to appropriate surgical management (eg, drainage and/or extraction).

• Pouchitis, acute

Initial therapy (alternative agent)

Oral: Initial dose- 400 mg every 12 hours for 14 days.

Refractory disease

Oral: Initial dose- 400 mg every 12 hours in combination with ciprofloxacin for 28 days.

• Sexually transmitted infections

Bacterial vaginosis

Oral: 400 mg twice daily for 7 days. For multiple disease recurrences, 400 mg twice daily for 7 days in combination with or prior to a multi-week course of boric acid, followed by suppressive topical therapy.

Empiric treatment following sexual assault in females

Oral: Initial dose- 400 mg twice daily for 7 days, as part of an appropriate combination regimen.

Pelvic inflammatory disease

Oral: Initial dose- 400 mg every 12 hours for 14 days as part of an appropriate combination regimen.

Trichomoniasis (index case and sex partner)

Initial treatment:

Females: Oral: Initial dose- 400 mg twice daily for 7 days.

Males: Oral: Initial dose- 400 mg can increase up to 2 g as a single dose.

Refractory infection:

Oral: Initial dose- 400 mg, increase up to 2 g once daily for 7 days.

Tetanus

Oral: Initial dose- 400 mg every 6 to 8 hours for 7 to 10 days in combination with supportive therapy.

Pediatric Dose

Oral

• Amebiasis

Infants, Children, and Adolescents: Oral: 35 to 50 mg/kg/day in divided doses every 8 hours for 7 to 10 days; maximum dose: 750 mg/dose; for severe infection or extraintestinal disease, IV may be necessary.

• Appendicitis, perforated

Divided dosing: Children and Adolescents: IV: 10 mg/kg/dose every 8 hours.

Once-daily dosing: Children and Adolescents: IV: 30 mg/kg/dose once daily in combination with ceftriaxone; maximum reported daily dose: 1,500 mg/day; however, other pediatric trials did not report a maximum; in adult patients, a maximum daily dose of 1,500 mg/day for once-daily dosing is suggested; in pediatric patients, once-daily metronidazole in combination with ceftriaxone has been shown to have similar efficacy as triple-combination therapy with ampicillin, clindamycin, and gentamicin.

• Balantidiasis

Infants, Children, and Adolescents: Oral: 35 to 50 mg/kg/day in divided doses every 8 hours for 5 days; maximum dose: 750 mg/dose.

• Catheter; exit-site or tunnel infection

Infants, Children, and Adolescents: Oral: 10 mg/kg/dose 3 times daily. Maximum dose: 500 mg/dose.

• Clostridioides difficile infection

Infants: Mild to moderate infection: Oral: 7.5 mg/kg/dose every 6 hours for 10 days.

Children and Adolescents

Non-severe infection, initial or first recurrence: Oral: 7.5 mg/kg/dose 3 to 4 times daily for 10 days; maximum dose: 500 mg/dose.

Severe/fulminant infection, initial: IV: 10 mg/kg/dose every 8 hours for 10 days; maximum dose: 500 mg/dose; use concomitantly with oral or rectal vancomycin.

• Dientamoeba fragilis

Infants, Children, and Adolescents: Oral: 35 to 50 mg/kg/day in divided doses every 8 hours for 10 days; maximum dose: 750 mg/dose.

• Giardiasis

Infants, Children, and Adolescents: Oral: 5 to 10 mg/kg/dose every 8 hours for 5 to 7 days; maximum dose: 250 mg/dose.

• Helicobacter pylori eradication

Weight-directed dosing: Children and Adolescents: Oral: 10 to 15 mg/kg/dose twice daily; maximum dose: 500 mg/dose.

Fixed dosing: Children and Adolescents:

25 to <25 kg: Oral: 250 mg twice daily.

25 to <35 kg: Oral: 500 mg in the morning and 250 mg in the evening or 375 mg twice daily (if using liquid preparation).

≥35 kg: Oral: 500 mg twice daily.

• Inflammatory bowel disease

Crohn disease, perianal disease; induction: Children and Adolescents: Oral: 7.5 mg/kg/dose 3 times daily for 6 weeks with or without ciprofloxacin; maximum dose: 500 mg/dose.

Ulcerative colitis, pouchitis, persistent: Children and Adolescents: Oral: 20 to 30 mg/kg/day in divided doses 3 times daily for 14 days with or without ciprofloxacin or oral budesonide; maximum dose: 500 mg/dose.

• Intra-abdominal infection

Infants, Children, and Adolescents: IV: 30 to 40 mg/kg/day in divided doses 3 times daily as part of combination therapy; maximum dose: 500 mg/dose.

• Pelvic inflammatory disease

Adolescents: Oral: 500 mg twice daily for 14 days; give with doxycycline plus a cephalosporin.

• Peritonitis

Prophylaxis: Gastrointestinal or genitourinary procedures: Infants, Children, and Adolescents: IV: 10 mg/kg once prior to procedure in combination with cefazolin; Maximum dose: 1,000 mg/dose.

Treatment: Infants, Children, and Adolescents: Oral: 10 mg/kg/dose 3 times daily. Maximum daily dose: 1,200 mg/day.

• Prophylaxis against sexually transmitted diseases following sexual assault

Adolescents: Oral: 2,000 mg as a single dose in combination with azithromycin and ceftriaxone.

• Surgical prophylaxis

Children and Adolescents: 15 mg/kg as a single dose 30 to 60 minutes prior to procedure; maximum single dose: 500 mg.

• Tetanus

Infants, Children, and Adolescents: Oral: 30 mg/kg/day in divided doses 4 times daily for 7 to 10 days; maximum daily dose: 4,000 mg/day.

• Trichomoniasis; treatment

Children <45 kg: 45 mg/kg/day in divided doses 3 times daily for 7 days; maximum daily dose: 2,000 mg/day.

Children ≥45 kg and Adolescents: 500 mg twice daily for 7 days or 2,000 mg as a single dose once.

• Vaginosis, bacterial

Children >45 kg and Adolescents: Initial dose- 400 mg twice daily for 7 days.

Metrogyl 400 is available in the dose of 400 mg.

Metrogyl 400 contains Metronidazole.

Metrogyl 400 is available in the form of Oral Tablets.

Dosage Adjustment in Kidney Patient

Oral

CrCl ≥10 mL/minute: No dosage adjustment necessary; however, monitor closely for adverse effects due to accumulation of metabolites in patients with more severe impairment (CrCl <30 mL/minute), particularly with prolonged courses of therapy.

CrCl <10 mL/minute: No dosage adjustment necessary; however, monitor closely for adverse effects due to accumulation of metabolites, particularly with prolonged courses of therapy. A dose of 500 mg every 12 hours may be adequate to achieve therapeutic plasma levels for nonsevere non-Clostridioides difficile infections.

Metrogyl 400 which contains Metronidazole 400 mg is contraindicated in patients with

Hypersensitivity

Metronidazole Tablets is contraindicated in patients with a prior history of hypersensitivity to metronidazole or other nitroimidazole derivatives. In patients with trichomoniasis, Metronidazole Tablets is contraindicated during the first trimester of pregnancy.

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.

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.

Cockayne Syndrome

Metronidazole Tablets are contraindicated in patients with Cockayne syndrome. Severe irreversible hepatotoxicity/acute liver failure with fatal outcomes have been reported after initiation of metronidazole in patients with Cockayne syndrome.

Metrogyl 400 which contains Metronidazole 400 mg should be used with certain warnings and precautions

The treating physician must closely monitor the patient and keep pharmacovigilance as follows

 Superinfection

Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Carcinogenic

Possibly carcinogenic based on animal data. Unnecessary use should be avoided.

CNS effects

Aseptic meningitis, encephalopathy, seizures, and neuropathies (peripheral and optic) have been reported with systemic metronidazole, especially with increased doses and chronic treatment; peripheral neuropathy has also been reported with topical products; monitor and consider discontinuation of therapy if signs/symptoms occur. Use with caution in patients with CNS diseases. Discontinue immediately if abnormal neurologic signs develop.

Eye irritation

May cause tearing of the eye; avoid contact with the eyes. In the event of accidental contact, wash out immediately.

Hepatic impairment

Use with caution in patients with severe liver impairment due to potential accumulation.

Avoid consuming alcohol while taking Metrogyl 400 as it may enhance the adverse/toxic effect of Alcohol (Ethyl). A disulfiram-like reaction may occur which leads to symptoms like fast heartbeat, warmth, headache, and breathing difficulty.

Metrogyl 400 which contains Metronidazole 400 mg is present in human milk at concentrations like maternal serum levels, and infant serum levels can be close to or comparable to infant therapeutic levels. Because of the potential for tumorigenicity shown for metronidazole in mouse and rat. studies, a decision should be made whether to discontinue nursing or to discontinue the drug, considering the importance of the drug to the mother. Alternatively, a nursing mother may choose to pump and discard human milk for the duration of metronidazole therapy, and for 24 hours after therapy ends and feed her infant stored human milk or formula.

Metrogyl 400 contains Metronidazole 400 mg. Metronidazole crosses the placenta and rapidly distributes into the fetal circulation following oral administration. The amount of metronidazole available systemically following topical application is less in comparison to oral doses. Most studies have not shown an increased risk of adverse events to the fetus following maternal use during pregnancy.

The adverse reactions related to Metrogyl 400 can be categorized as

Common

Nausea, Vaginitis, Headache, Genital pruritus, Abdominal pain, diarrhea, xerostomia, Dysmenorrhea, urinary tract infection, urine abnormality, Bacterial infection, candidiasis, Dizziness, metallic taste, Flu-like symptoms, pharyngitis, rhinitis, sinusitis, upper respiratory tract infection.

Rare

Chest pain, facial edema, flattened T-wave on ECG, flushing, palpitations, peripheral edema, syncope, tachycardia, Erythematous rash, hyperhidrosis, pruritus, urticaria, Decreased libido, Abdominal cramps, anorexia, constipation, decreased appetite, dysgeusia, epigastric discomfort, glossitis, hairy tongue, proctitis, stomatitis, vomiting, Cystitis, dark urine, dyspareunia, dysuria, urinary incontinence, urine discoloration, vaginal dryness, vulvovaginal candidiasis, Agranulocytosis, eosinophilia, Drug reaction with eosinophilia and systemic symptoms, Inflammation at injection site, injection site reaction, Chills, depression, drowsiness, epilepsy, hypoesthesia, insomnia, irritability, malaise, numbness, psychosis, Arthralgia, asthenia, muscle spasm, myalgia, Abnormal eye movements (saccadic), nystagmus disorder, Polyuria, Dyspnea, nasal congestion, Fever.

The clinically relevant drug interactions of Metrogyl 400 is briefly summarized here

Disulfiram

Psychotic reactions have been reported in alcoholic patients who are using metronidazole and disulfiram concurrently. Metronidazole should not be given to patients who have taken disulfiram within the last two weeks.

Alcoholic Beverages

Abdominal cramps, nausea, vomiting, headaches, and flushing may occur if alcoholic beverages or products containing propylene glycol are consumed during or following metronidazole therapy.

Warfarin And Other Oral Anticoagulants

Metronidazole has been reported to potentiate the anticoagulant effect of warfarin and other oral coumarin anticoagulants, resulting in a prolongation of prothrombin time. When METRONIDAZOLE is prescribed for patients on this type of anticoagulant therapy, prothrombin time and INR should be carefully monitored.

Lithium

In patients stabilized on relatively high doses of lithium, short-term metronidazole therapy has been associated with elevation of serum lithium and, in a few cases, signs of lithium toxicity. Serum lithium and serum creatinine levels should be obtained several days after beginning metronidazole to detect any increase that may precede clinical symptoms of lithium intoxication.

Busulfan

Metronidazole has been reported to increase plasma concentrations of busulfan, which can result in an increased risk for serious busulfan toxicity. Metronidazole should not be administered concomitantly with busulfan unless the benefit outweighs the risk. If no therapeutic alternatives to metronidazole are available, and concomitant administration with busulfan is medically needed, frequent monitoring of busulfan plasma concentration should be performed and the busulfan dose should be adjusted accordingly.

Drugs That Inhibit CYP450 Enzymes

The simultaneous administration of drugs that decrease microsomal liver enzyme activity, such as cimetidine, may prolong the half-life and decrease plasma clearance of metronidazole.

Drugs That Induce CYP450 Enzymes

The simultaneous administration of drugs that induce microsomal liver enzymes, such as phenytoin or phenobarbital, may accelerate the elimination of metronidazole, resulting in reduced plasma levels; impaired clearance of phenytoin has also been reported.

Drugs That Prolong the QT interval

QT prolongation has been reported, particularly when metronidazole was administered with drugs with the potential for prolonging the QT interval.

The common side effects of Metrogyl 400 which contains Metronidazole includes the following

Common side effects

Vomiting, nausea, Diarrhea, constipation, upset stomach, stomach cramps, loss of appetite, headache, dry mouth, sharp, unpleasant metallic taste, furry tongue, mouth, or tongue irritation.

Rare side effects

Numbness, pain, burning, or tingling in your hands or feet, seizures, Rash, itching, Hives, peeling or blistering skin, flushing, stuffy nose, fever, sore throat, or other signs of infection, joint pain, dizziness, difficulty speaking, problems with coordination, Confusion, agitation.

Metrogyl 400 contains Metronidazole 400 mg

Pregnancy Category B

Teratogenic Effects: There are no adequate and well controlled studies of Metronidazole in pregnant women. There are published data from case-control studies, cohort studies, and 2 meta-analyses that include more than 5000 pregnant women who used metronidazole 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 ten randomized placebo-controlled clinical trials enrolled more than 5000 pregnant women to assess the use of antibiotic treatment (including metronidazole) for bacterial vaginosis on the incidence of preterm delivery. Most studies did not show an increased risk for congenital anomalies or other adverse fetal outcomes following metronidazole exposure during pregnancy. Three studies conducted to assess the risk of infant cancer following metronidazole exposure during pregnancy did not show an increased risk; however, the ability of these studies to detect such a signal was limited. Metronidazole crosses the placental barrier and its effects on the human fetal organogenesis are not known. Reproduction studies have been performed in rats, rabbits, and mice at doses similar to the maximum recommended human dose based on body surface area comparisons. There was no evidence of harm to the fetus due to metronidazole.

Nursing Mothers

Metronidazole is present in human milk at concentrations similar to maternal serum levels, and infant serum levels can be close to or comparable to infant therapeutic levels. Because of the potential for tumorigenicity shown for metronidazole in mouse and rat. studies, a decision should be made whether to discontinue nursing or to discontinue the drug, considering the importance of the drug to the mother. Alternatively, a nursing mother may choose to pump and discard human milk for the duration of metronidazole therapy, and for 24 hours after therapy ends and feed her infant stored human milk or formula.

Pediatric Use

In one study newborn infants appeared to demonstrate diminished capacity to eliminate metronidazole. The elimination half-life, measured during the first three days of life, was inversely related to gestational age. In infants whose gestational ages were between 28 and 40 weeks, the corresponding elimination half-lives ranged from 109 to 22.5 hours.

Geriatric Use

Following a single oral dose of metronidazole, subjects >70 years old with no apparent renal or hepatic dysfunction had a 40% to 80% higher mean AUC of hydroxy metronidazole (active metabolite), with no apparent increase in the mean AUC of metronidazole (parent compound), compared to young healthy controls < 40 years old. In geriatric patients, monitoring for metronidazole associated adverse events is recommended.

The physician should be vigilant about the knowledge pertaining to the identification and treatment of overdosage of Metrgyl 400. The use of 27 mg/kg three times a day for 20 days, and the use of 75 mg/kg as a single loading dose followed by 7.5 mg/kg maintenance doses. No adverse reactions were reported in either of the two cases. Single oral doses of metronidazole, up to 15 g, have been reported in suicide attempts and accidental overdoses. Symptoms reported included nausea, vomiting, and ataxia. Oral metronidazole has been studied as a radiation sensitizer in the treatment of malignant tumors. Neurotoxic effects, including seizures and peripheral neuropathy, have been reported after 5 to 7 days of doses of 6 to 10.4 g every other day.

Metrogyl 400 contains Metronidazole 400 mg.

Pharmacodynamics

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.

Pharmacokinetics

Absorption

Metronidazole rapidly and almost completely absorbed from the gastrointestinal tract. Food may delay absorption. The time to peak plasma concentration is approximately 1-2 hours (oral); 20 minutes (IV); 5-12 hours (rectal); 8 hours (intravaginal gel). The Bioavailability found to be 60-80% (rectal); 20-25% (vag pessaries); 56% (intravaginal gel).

Distribution

Metronidazole is the major component appearing in the plasma, with lesser quantities of metabolites also being present. Less than 20% of the circulating metronidazole is bound to plasma proteins. Metronidazole appears in cerebrospinal fluid, saliva and breast milk in concentrations similar to those found in plasma. Bactericidal concentrations of metronidazole have also been detected in pus from hepatic abscesses. Following a single intravenous dose of metronidazole 500 mg, 4 healthy subjects who underwent gastrointestinal endoscopy had peak gastric juice metronidazole concentrations of 5 to 6 mcg/mL at one-hour post-dose. In patients receiving intravenous metronidazole in whom gastric secretions are continuously removed by nasogastric aspiration, sufficient metronidazole may be removed in the aspirate to cause a reduction in serum levels.

Metabolism and Excretion

The metabolites of metronidazole result primarily from side-chain oxidation [1-(βhydroxyethyl)-2- hydroxymethyl-5-nitroimidazole and 2-methyl-5-nitroimidazole-1-ylacetic acid] and glucuronide conjugation. Both the parent compound and the hydroxyl metabolite possess in vitro antimicrobial activity. The major route of elimination of metronidazole and its metabolites is via the urine (60 to 80% of the dose), with approximately 20% of the amount excreted appearing as unchanged metronidazole. Renal clearance of metronidazole is approximately 10 mL/min/1.73 m2. Fecal excretion accounts for 6 to 15% of the dose