M-400400 mg

M-400 is a nitroimidazole antimicrobial used to treat a range of anaerobic bacterial and protozoal infections. Its indications can be grouped by strength of evidence:

Established/FDA-approved uses

• Anaerobic bacterial infections of the abdomen, pelvis, skin/soft tissue, bone/joint, CNS, lower respiratory tract, and bloodstream caused by susceptible organisms (e.g., Bacteroides species, Clostridium species, Fusobacterium species, Peptococcus/Peptostreptococcus species).
• Trichomoniasis (symptomatic and asymptomatic) in both male and female patients, including simultaneous treatment of sexual partners.
• Intestinal amoebiasis and amoebic liver abscess caused by Entamoeba histolytica.
• Surgical prophylaxis to reduce the incidence of postoperative infection in contaminated or potentially contaminated colorectal surgery.

Guideline-supported uses

• Bacterial vaginosis.
• Giardiasis (infection with Giardia duodenalis/lamblia).
• Clostridioides difficile-associated diarrhea (mild-to-moderate disease per some guidelines, though vancomycin/fidaxomicin are now generally preferred first-line).

Adjunct/combination-therapy uses

• Helicobacter pylori eradication, always used together with other antibiotics (e.g., clarithromycin or amoxicillin) and a proton pump inhibitor as part of a combination regimen — never as monotherapy for this indication.

Off-label uses (commonly used, not FDA-approved for this route/form)

• Certain dermatologic conditions such as rosacea (topical formulations); use only on a physician's advice.

Each Metronidazole formulation contains Metronidazole as the active ingredient, available in various strengths (commonly 200 mg, 250 mg, 400 mg, and 500 mg tablets, oral suspension 200 mg/5 mL, vaginal gel, topical gel/cream, suppositories, and intravenous infusion 500 mg/100 mL), along with standard pharmaceutical excipients.

M-400 is a synthetic nitroimidazole derivative with broad-spectrum antibacterial activity against anaerobic bacteria and antiprotozoal activity against certain parasites. It is available in Bangladesh and worldwide as oral tablets, oral suspension, intravenous infusion, vaginal gel/tablets, and topical preparations, and is widely used for anaerobic infections, protozoal infections, and as part of combination regimens such as H. pylori eradication.

M-400 belongs to the nitroimidazole class of antimicrobials, which has both antibacterial (anti-anaerobic) and antiprotozoal (antiparasitic) activity.

Metronidazole is a prodrug that diffuses into anaerobic bacterial and protozoal cells, where its nitro group is reduced by intracellular electron-transport proteins found only in anaerobic/microaerophilic organisms. This reduction generates cytotoxic intermediates and free radicals that bind to microbial DNA, causing strand breakage, disruption of the helical structure, and inhibition of nucleic acid synthesis, ultimately leading to cell death. Because this reductive activation requires a low-redox-potential environment, Metronidazole is selectively active against anaerobic bacteria and certain protozoa (e.g., Entamoeba histolytica, Giardia duodenalis, Trichomonas vaginalis) and has little activity against aerobic organisms.

Pharmacokinetics: Metronidazole is well absorbed orally (bioavailability greater than 90%), widely distributed into body tissues and fluids (including CSF, bone, and abscess cavities), metabolized in the liver, and eliminated mainly via the kidneys. Its elimination half-life is approximately 6-8 hours in adults with normal hepatic function.

M-400 tablets/capsules can be taken with or without food; taking with food or milk may reduce stomach upset. Tablets should be swallowed whole with a full glass of water and not crushed or chewed unless directed. The oral suspension should be shaken well before use and measured with an accurate dosing device. Vaginal gel/tablets should be inserted as directed, and topical preparations applied to clean, dry skin. Intravenous M-400 is administered by slow infusion under medical supervision. Complete the full course of M-400 as prescribed even if symptoms improve early.

M-400 has several clinically significant drug interactions:

• Alcohol: concurrent use with alcohol can cause a disulfiram-like reaction (flushing, nausea, vomiting, headache, tachycardia); avoid alcohol during M-400 treatment and for at least 24-72 hours after the last dose.
• Disulfiram: concurrent use, or use within the previous two weeks, may cause psychotic reactions or confusion; do not combine with M-400.
• Warfarin and other oral anticoagulants: M-400 potentiates anticoagulant effect, prolonging prothrombin time and increasing bleeding risk; monitor INR closely and adjust anticoagulant dose if needed.
• Lithium: M-400 can raise serum lithium levels, increasing the risk of lithium toxicity; monitor lithium levels.
• Phenytoin, phenobarbital, and other CYP-inducing drugs: may accelerate M-400 metabolism and reduce its effectiveness.
• Cimetidine and other CYP inhibitors: may decrease M-400 clearance and prolong its half-life, increasing exposure.
• Busulfan: M-400 may increase busulfan plasma levels, raising the risk of serious busulfan toxicity.

Common side effects of M-400 include:

• Metallic or bitter taste in the mouth (common, benign)
• Nausea, vomiting, loss of appetite, abdominal discomfort/cramping
• Diarrhea
• Headache and dizziness
• Dry mouth or glossitis (furry tongue)
• Darkened (reddish-brown) urine — harmless

Less common but important effects:

• Peripheral neuropathy (numbness, tingling in hands/feet) and CNS effects such as seizures and encephalopathy — rare, generally associated with prolonged or high-dose M-400 therapy; discontinue M-400 and seek medical attention if neurological symptoms occur (see Precautions and Warnings).
• Clostridioides difficile-associated diarrhea/colitis, ranging from mild diarrhea to severe colitis, which can occur during or after M-400 treatment.
• Rash, urticaria, and rarely severe hypersensitivity reactions.
• Leukopenia (usually reversible).

Pregnancy: M-400 crosses the placenta. It is classified under the former FDA pregnancy category B. M-400 should be used during pregnancy only if clearly needed and the potential benefit justifies the potential risk to the fetus; consult a physician before use, particularly avoiding use of M-400 in the first trimester for trichomoniasis (see Contraindications). Single high-dose M-400 regimens are generally avoided in pregnancy in favor of longer, lower-dose courses.

Lactation: M-400 is excreted in breast milk in concentrations similar to maternal plasma. Because of concerns raised by carcinogenicity findings in animal studies, a decision should be made, in consultation with a physician, either to temporarily discontinue breastfeeding (with pumping and discarding milk for 12-24 hours after a single M-400 dose) or to avoid M-400, weighing the importance of the drug to the mother.

Take M-400 exactly as prescribed by your physician; do not stop, extend, skip doses, or share this medicine with others without medical advice.

• Alcohol: avoid alcohol during M-400 treatment and for at least 24-72 hours afterward due to risk of a disulfiram-like reaction (see Interactions).
• Neurological effects: peripheral neuropathy, seizures, and encephalopathy have been reported rarely with M-400, mainly with prolonged or high-dose use; stop M-400 and seek medical attention if numbness, tingling, confusion, or seizures occur.
• Candida overgrowth: M-400 use may lead to overgrowth of Candida, requiring antifungal treatment.
• Clostridioides difficile-associated diarrhea: may occur during or after M-400 treatment; seek medical advice for severe or persistent diarrhea.
• Hepatic impairment: use M-400 with caution and consider dose reduction in patients with severe liver disease.
• Blood dyscrasias: a history of blood disorders warrants monitoring of white blood cell counts during prolonged M-400 therapy.
• Metallic taste and darkened urine may occur with M-400 and are harmless (see Side Effects).

Overdose of M-400 may cause nausea, vomiting, and ataxia (unsteady gait); very high doses of M-400 have rarely been associated with peripheral neuropathy and seizures. There is no specific antidote. If M-400 overdose is suspected, seek immediate medical attention or contact emergency services/a poison control center; treatment is supportive and symptomatic.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Elderly: no specific dose adjustment of M-400 is generally required, but elderly patients may be more susceptible to neurological side effects; use with caution and monitor.

Renal impairment: generally no adjustment needed for mild-to-moderate impairment; consider M-400 dose reduction in severe renal impairment or dialysis patients (a supplemental post-dialysis dose may be required).

Hepatic impairment: reduced M-400 doses and monitoring recommended in severe hepatic impairment, as M-400 is extensively hepatically metabolized.

Pregnancy and lactation: see Pregnancy and Lactation.

Pediatric patients: see Pediatric Uses.

Duration of M-400 treatment depends on the indication, ranging from a single dose (e.g., 2 g for trichomoniasis) to 5-10 days for most infections, and longer courses (occasionally several weeks) for certain bone, joint, or CNS infections as directed by a physician. Complete the full prescribed course of M-400 even if symptoms resolve early.

Nitroimidazole antimicrobial (antibacterial and antiprotozoal agent)

Metronidazole is reduced intracellularly by anaerobic and microaerophilic organisms to reactive intermediates that damage microbial DNA, causing strand breakage and inhibiting nucleic acid synthesis, which leads to cell death of susceptible anaerobic bacteria and protozoa.

Category B

M-400 is used in children for indications such as amoebiasis, giardiasis, and anaerobic bacterial infections, with doses calculated on a mg/kg basis by a pediatrician. For amoebiasis, a commonly used pediatric dose of M-400 is approximately 35-50 mg/kg/day in three divided doses for 10 days; lower doses are used for giardiasis. Safety and efficacy of M-400 for indications and age groups not specifically studied have not been established, and pediatric use should always be guided and supervised by a physician.