Metrolex

METROLEX TABLET 200 MG: Each tablet contains Metronidazole 200 mg.
METROLEX TABLET 400 MG: Each tablet contains Metronidazole 400 mg.
METROLEX Injection 500 MG/100 ML: Each 100 ml contains Metronidazole 500 mg, 0.9% Sodium chloride solution as isotonic vehicle, Water for injection qs. 100 ml.

Pharmacology: Pharmacodynamics: Metronidazole is active against anaerobic bacteria. The drug is readily taken up by bacterial cells and reduced by intracellular electron transport proteins. This generates free radicals which interacting with cell components and leads to bacterial cell death.
Pharmacokinetics: Metronidazole is well absorbed and distributed into cerebrospinal fluid, saliva and breast milk in concentrations equal to concurrent plasma concentrations of the drug.
The drug is metabolized in the liver and excreted mostly in urine and some in feces as unchanged drug and metabolites.
Metronidazole is active in vitro against many susceptible microorganisms as following; Anaerobic gram-negative bacilli: Bacteroides species including Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus and Fusobacterium species.
Anaerobic gram-positive bacilli: Clostridium species and some strains of Eubacterium species.
Anaerobic gram-positive cocci: Peptococcus niger and Peptostreptococcus species.
Moreover the drug also has activity against Gardnerella vaginalis, Entamoeba histolytica, Trichomonas vaginalis, Giardia lamblia and Balantidium coli.
Injection: It is also distributed to hepatic abscess in concentration similar to concentration in plasma. Metronidazole is less than 20% bound to plasma proteins.

Metronidazole is used in the prevention/prophylaxis and treatment of infectious diseases caused by susceptible anaerobic bacteria as follows: Urogenital (tablet)/sexually transmitted (injection) infection in either male or female caused by Trichomonas sp.
Bacterial vaginosis caused by Trichomonas sp. and anaerobic bacterial infection in vagina including non-specific vaginitis, anaerobic vaginosis, or Gardnerella vaginitis.
Amoebiasis, both intestinal and extraintestinal disease, caused by Entamoeba histolytica.
Diarrhea caused by Giardia sp. (Giardiasis).
Anaerobic bacterial septicemia, such as septicemia and bacteremia, caused by Bacteroides sp. and Clostridium sp.
Intra-abdominal anaerobic bacterial infections including peritonitis, intra-abdominal abscess, and liver abscess caused by Bacteroides sp., Clostridium sp., Eubacterium sp., Peptococcus niger and Peptostreptococcus sp.
Central nervous system anaerobic bacterial infections including brain abscess and meningitis caused by Bacteroides sp.
Lower respiratory tract anaerobic bacterial infections including pneumonia, empyema, and lung abscess caused by Bacteroides sp.
Skin and skin structure anaerobic bacterial infections including bone and joint infections caused by Bacteroides sp., Clostridium sp., Peptococcus niger, Peptostreptococcus sp. and Fusobacterium sp.
Acute necrotizing ulcerative gingivitis.
Prevention of post-operative infections due to anaerobic bacteria particularly caused by Bacteroides sp.
Tablet: Acute dental infections (e.g. acute pericoronitis and acute apical infections).
Injection: This includes severe infection as well as intraoperative and postoperative surgical prophylaxis to reduce incidence of infection. Metronidazole is effective in Bacteroides fragilis infection which failed to respond to clindamycin, chloramphenicol, penicillin.

Dosage and duration of therapy depend on severity of infection and patient's condition.
Administration in renal impairment: Dosage reductions are not usually recommended for patient with renal impairment who undergoing peritoneal dialysis because Metronidazole is removed during 8 hours of hemodialysis. Metronidazole should therefore be re-administered immediately after hemodialysis.
Administration in hepatic impairment: Metronidazole is metabolized by liver; so patients with hepatic impairment should use METROLEX with caution because accumulation of the drug is likely in patients with impaired hepatic function especially patient with hepatic encephalopathy. Metronidazole may increase symptoms of encephalopathy. One-third of the usual daily dose may be given once daily in these patients. Moreover, signs of Metronidazole toxicity and plasma concentrations of the drug should be monitored.
Metronidazole tablets should be swallowed with plenty of water. It is recommended that the tablets should be taken during or after a meal.
Prophylaxis against anaerobic bacterial infections, in the context of abdominal and gynaecological surgery: Adults: 400 mg every 8 hours for 3-4 days followed by postoperative intravenous until the patient is able to take tablets. Shorter preoperative course and higher oral dose (up to 1 g) have been used.
Children: 7.5 mg/kg every 8 hours.
Treatment of established anaerobic bacterial infection: Adults: 800 mg initially followed by 400 mg every 8 hours.
Children: 7.5 mg/kg every 8 hours.
Duration of action is approximately 7-10 days based on patient symptom and severity of disease.
Urogenital trichomoniasis (the consort should receive a similar course of treatment concurrently to prevent re-infection): Adults and children over 10 years: 200 mg three times daily for 7 days or 400 mg twice daily for 7 days or 800 mg in the morning and 1200 mg in the evening for 2 days; 2 g as a single dose for 1 day.
*Children 7-10 years: 100 mg three times daily for 7 days; 3-7 years: 100 mg twice daily for 7 days; 1-3 years: 50 mg three times daily for 5-10 days.
Bacterial vaginosis: Adults and children over 10 years: 400 mg twice daily for 7 days or 2 g as a single dose for 1 day.
Amoebiasis: Invasive intestinal disease in susceptible subject: Adults and children over 10 years: 800 mg three times daily for 5 days.
*Children 7-10 years: 400 mg three times daily for 5 days; 3-7 years: 200 mg four times daily for 5 days; 1-3 years: 200 mg three times daily for 5 days.
Intestinal disease in less susceptible subjects and chronic amoebic hepatitis: Adults and children over 10 years: 400 mg three times daily for 5-10 days.
*Children 7-10 years: 200 mg three times daily for 5-10 days; 3-7 years: 100 mg four times daily for 5-10 days; 1-3 years: 100 mg three times daily for 5-10 days.
Symptomless cyst passers: Adults and children over 10 years: 400-800 mg three times daily for 5-10 days.
*Children 7-10 years: 200-400 mg three times daily for 5-10 days; 3-7 years: 100-200 mg four times daily for 5-10 days; 1-3 years: 100-200 mg three times daily for 5-10 days.
Giardiasis: Adults and children over 10 years: 2 g once daily for 3 days.
*Children 7-10 years: 1 g once daily for 3 days; 3-7 years: 600 to 800 mg once daily for 3 days; 1-3 years: 500 mg once daily for 3 days.
Acute ulcerative gingivitis: Adults and children over 10 years: 200 mg three times daily for 3 days.
*Children 7-10 years: 100 mg three times daily for 3 days; 3-7 years: 100 mg twice daily for 3 days; 1-3 years: 50 mg three times daily for 3 days.
Acute dental infections: Adults and children over 10 years: 200 mg three times daily for 3-7 days.
Leg ulcers and pressure sores: Adults and children over 10 years: 400 mg three times daily for 7 days.
*Children and infants weighing less than 10 kg should receive proportionately smaller dosages.
Injection: The usual duration of therapy is 7-10 days.
Anaerobic bacterial infections of the bone and joint, lower respiratory tract, and endocardium may require longer treatment.
Prophylactic use of Metronidazole during and after surgery should not be continued for more than 12 hours after surgery.
Metronidazole is administered by continuous or intermittent IV infusion.
Metronidazole should not be mixed with solution containing other drugs. And avoid contact drug solution with equipment or container containing aluminum.
IV infusions are usually given over 1 hour.
METROLEX injection is a ready-to-use isotonic solution that dilution is not required before IV infusion.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. With concern of microbial contamination, the drug should be used promptly after the preparation and use within 24 hours and the remaining unused solution should be discarded.
For the treatment of severe anaerobic bacterial infection: Adults: Adults should receive an initial METROLEX IV loading dose of 15 mg/kg, IV infusions are usually given over 1 hour (approximately 1 g for a 70 kg adult). After 6 hours of first infusion followed by IV maintenance doses of 7.5 mg/kg every 6 hours (approximately 500 mg for a 70 kg adult).
IV infusions are usually given over 1 hour.
The maximum adult dose within 24 hours is 4 g.
Oral Metronidazole is substituted when the condition of the patient warrants, based upon the severity of the disease and the patient's condition. The usual adult oral dosage is 7.5 mg/kg every 6 hours (METROLEX TABLET 400 mg three times a day for 7 days).
For perioperative and postoperative prophylaxis: One hour prior to the procedure, adults receive METROLEX injection 15 mg/kg by IV infusion over 30-60 minutes. The initial preoperative dose must be completely infused approximately 1 hour prior to surgery to ensure adequate serum and tissue concentrations of Metronidazole. After that, patients receive 7.5 mg/kg by IV infusion over 30-60 minutes at 6 and 12 hours after initial dose.
Oral Metronidazole is substituted when the condition of the patient warrants, based upon the severity of the disease and the patient's condition. The usual adult oral dosage is 7.5 mg/kg every 6 hours (METROLEX TABLET 400 mg three times a day for 7 days).

Overdose of Metronidazole can cause symptoms: nausea, vomiting, ataxia, central nervous system depression, seizures and peripheral neuropathy.
Treatment for overdose: Metronidazole does not have a specific antidote. If acute overdose of Metronidazole occurs, symptomatic and supportive treatment should be initiated. Moreover, cardiovascular system and respiratory system should be monitored closely.
Metronidazole is removed by hemodialysis.

Hypersensitivity to Metronidazole, nitroimidazole derivatives, or any components of the formulation; pregnant patients (first trimester).

Metronidazole should be used with caution in patients with central nervous system disease. Continuous therapy for periods longer than those recommended are advised to consider the risk of peripheral neuropathy.
Metronidazole was carcinogenic in mice and rats. Unnecessary use of Metronidazole should be avoided, and the drug should be used only as stated in indication.
Use the drug with caution in the elderly and in reduced dosage in patients with hepatic impairment. Plasma Metronidazole concentration should be monitored regularly.
METROLEX should be used with caution in patients with a history of blood dyscrasias, and leukocyte counts should be performed before and after treatment with the drug.
Concurrent use of METROLEX and alcoholic beverage is contraindicated. Disulfiram-like reactions have occurred in some patients who ingested alcohol while receiving METROLEX.
Injection: This Metronidazole injection product should be used with caution in patients who need restrict sodium content, in patients receiving corticosteroids and in patients predisposed to edema because the Metronidazole injection contains 0.9% sodium chloride solution.
Candidiasis infection maybe more prominent during Metronidazole treatment, antifungal treatment required.

There are no adequate or well-controlled studies to date using Metronidazole in pregnant women. The drug should not be used in pregnant women especially using during the first trimester.
Metronidazole is distributed into milk. Breast-feeding should be avoided in women requiring treatment with Metronidazole.

The adverse effects are taste disorders (unpleasant metallic taste), furred tongue, nausea, vomiting, gastrointestinal disturbance, diarrhea, epigastric distress, abdominal pain, constipation, stomatitis, gastritis, vulvovaginal candidiasis, drowsiness, dizziness, headache, urticaria, angioedema, pruritus, erythema multiforme, flattening of the T-wave in ECG tracings, dry mouth, flushing, fever, transient leukopenia, transient thrombocytopenia, dysuria, cystitis, polyuria, incontinence, urine may be dark or reddish brown in color which result from metabolism of Metronidazole, ataxia, confusion, depression, insomnia, weakness.
Moreover, maybe found anaphylaxis, convulsion and peripheral neuropathy which characterized by weakness and numbness. In this case, the drug should be discontinued. Another adverse effects including encephalopathy presenting as confusion, ataxia, dysarthria, gait impairment, nystagmus, tremor. These symptoms may disappear after discontinuing the drug. Peripheral neuropathy, leukopenia and transient epileptiform seizures have been associated with high doses of Metronidazole or prolonged treatment. Stopping Metronidazole or lowering the dose usually results in complete resolution.
Injection: Other adverse effects: Thrombophlebitis. Breast and colon cancer may be found in patients with Crohn's disease who have been treated with high dosage of Metronidazole for prolonged periods. Patients with Crohn's disease are known to have an increased incidence of gastroinstestinal and certain extraintestinal cancers including breast and colon cancer. Use of Metronidazole must be avoided in patient with Crohn's disease.

Concomitant uses of warfarin and Metronidazole may increase the serum concentration of warfarin. If concomitant therapy cannot be avoided, prothrombin times should be monitored and dosage of warfarin adjusted accordingly. There is no interaction between Metronidazole and heparin.
If Metronidazole is used in patients receiving lithium; Metronidazole may increase the serum lithium concentrations, resulting in signs of lithium toxicity. Lithium should be discontinued before Metronidazole is used in treatment. If concomitant therapy cannot be avoided, plasma concentration of lithium, creatinine and electrolytes should be monitored.
Concomitant use of Metronidazole and phenobarbital appears to decrease the serum half-life of Metronidazole/Metronidazole is metabolized with a much greater rate than normal. Serum concentrations of Metronidazole have been decreased.
Administration of disulfiram and Metronidazole has been associated with acute psychoses and confusion in some patients; therefore, the drugs should not be used concomitantly and 2 weeks should elapse following discontinuance of disulfiram prior to initiating Metronidazole therapy.
Disulfiram-like reactions including flushing, nausea, vomiting, palpitation and tachycardia have occurred in some patients who ingested alcohol while receiving Metronidazole. Alcohol should not be consumed during or for at least 1 day (or 3 days) following completion of Metronidazole therapy.
Concomitant use of Metronidazole and cimetidine appears to increase the plasma half-life and decrease total plasma clearance of Metronidazole. Serum concentrations of Metronidazole have been increased.
Concomitant use of Metronidazole and hydantoins may increase the serum concentration of phenytoin.
Injection: Metronidazole may interfere with aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), triglycerides and hexokinase glucose testing.

Store below 30°C and protect from light.
Injection: Do not freeze the solution.

Antiamoebics / Other Antibiotics / Preparations for Vaginal Conditions

P01AB01 - metronidazole ; Belongs to the class of nitroimidazole derivatives antiprotozoals. Used in the treatment amoebiasis and other protozoal diseases.
J01XD01 - metronidazole ; Belongs to the class of imidazole derivative antibacterials. Used in the systemic treatment of infections.

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