NIRMET* (Metronidazole Intravenous Infusion BP)

NIRMET* (Metronidazole Intravenous Infusion BP)

NIRMET* (Metronidazole Intravenous Infusion BP)

Nirmet* contains metronidazole, which is nitroimidazole, most potent anaerobic eradicator. It is a synthetic broad-spectrum antimicrobial agent for intravenous (I.V) administration.

Mechanism of action

Metronidazole exerts antibacterial effects in an anaerobic environment by the following possible mechanism: Once metronidazole enters the organism, the drug is reduced by intracellular electron transport proteins. Because of this alteration to the metronidazole molecule, a concentration gradient is maintained which promotes the drug’s intracellular transport. Presumably, free radicals are formed which in turn, react with cellular relevant activity against facultative anaerobes or obligate aerobes.


Metroniodazole has shown to be active against most isolates of the following bacteria

Gram-positive anaerobes

Clostridium species

Eubacterium species

Peptococcus species

Peptostreptococcus species

Gram-negative anaerobes

Bacteriodes fragilis group (B.fragilis, B.distasonis, B.ovatus, B.thetaitaomicron, B.vulgatus)

Fusobacterium species


  • Treatment of anaerobic infections: Metronidazole  infusion is indicated in the treatment of serious infections caused by susceptible anaerobic bacteria. Indicated surgical procedures should be performed in conjugation with metronidazole infusion therapy. In a mixed aerobic and anaerobic infection, antibiotics appropriate for the treatment of the aerobic infection should be used in additional to metronidazole. Infusion is effective in bacteriodes fragilis infections resistant to clindamycin, chloramphenicol and penicillin.
  • Intra-abdominal infections: Including peritonitis, intra-abdominal abscess and liver abscess, cause by bacteriodes species including the B.fragilis group (B.fragilis, B.distasonis, B.thetaiotaomicron, B.vulgatus), Clostridium species, uebacterium species, peptococcus species and peptostreptococcus species.
  • Gynecological infections: including endometritis, endomyometritis, tuboovarian abscess and postsurgical vaginal cuff infection, caused by bacteriodes species including the B.fragilis group, Clotridium species, peptostreptococcus species and fusobacterium species.
  • Skin and skin structure infections: caused by bacteriodes species including the B.fragilis, clostridium species, peptococcus species, peptostreptococcus species and fusobacterium species.
  • Bacterial septicaemia
  • Bone and joint infections
  • Central nervous system infections
  • Lower respiratory tract infections
  • Endocarditis
  • Prophylaxis

The prophylaxis administration of metronidazole preoperatively and postoperatively may reduce the incidence of postoperative infection in patients undergoing elective colorectal surgery which is classified as contaminated or potentially contaminated. Prophylactic use of metronidazole should be discontinued within 12 hours after surgery. If there are signs of infection, specimens for cultures should be obtained for the identification of the causative organism(s) so that appropriate therapy may be given. To reduce the development of drug resistant bacteria and maintain the effectiveness of metronidazole and other antibacterial drugs, metronidazole should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiological and susceptibility patterns may contribute to the empiric selection of therapy.


Dosage and administration

Treatment of Anaerobic Bacterial Infections

The recommended dosage schedule for adults is:

  • Loading dose: 15mg/kg infused over 1 hour (approximately 1 g for a 70kg adult).
  • Maintenance dose: 7.5 mg/kg infused over 1 hour every 6 hours (approximately 500mg for a 70kg adult). The first maintenance dose should be instituted 6 hours following the initial loading dose.

Parenteral therapy may be changed to oral Metronidazole when conditions warrant, based upon the severity of the disease and the response of the patient to metronidazole treatment. The usual adult oral dosage is 75mg/kg every 6 hours (approximately 500mg for a 70kg adult).

A maximum of 4 g should not be exceeded during a 24-hour period.

The usual duration of therapy is 7 to 10 days, however, infections of the bone and joint, lower respiratory tract and endocardium may require longer  treatment.

Patients with severe hepatic impairment, the metronidazole dose should be reduced by 50%.

Patients undergoing hemodialysis: Hemodialysis removes significant amounts of metronidazole from systemic circulation. The clearance of metronidazole will depend on the type of dialysis membrane used, the duration of the dialysis session, and other factors. If the administration of metronidazole cannot be separated from the hemodialysis session, supplementation of metronidazole dosage following the hemodialysis session should be considered, depending on the patient’s clinical situation.

Prophylaxis: For surgical prophylactic use, to prevent postoperative infection in contaminated or potentially contaminated colorectal surgery, the recommended dosage schedule for adults is:

  1. 15mg/kg infused over 30 to 60 minutes and completed approximately 1 hour before surgery.
  2. 7.5mg/kg infused over 30 to 60 minutes at 6 and 12 hours after the initial dose

It is important that

  1. Administration of the initial preoperative dose be completed approximately 1 hour before surgery so that adequate drug levels are present in the serum and tissues at the time of initial incision, and
  2. Metronidazole be administered, if necessary, at 6-hour intervals to maintain effective drug levels. Prophylactic use of metronidazole should be limited to the day of surgery only. Following the above guidelines.


  • Hypersensitivity: metronidazole is contraindicated inn patients with a prior history of hypersensitivity to metronidazole or other nitroimidazole derivatives.
  • Psychotic reaction with disulfiram: use of 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 metronidazole is associated with a disulfiram-like reaction to alcohol, including abdominal cramps, nausea, vomiting, headache, and flushing. Discontinue consumption of alcohol and products containing propyleneglycol during and for at least three days after therapy with metronidazole.


Metronidazole infusion is to be administered by slow intravenous drip infusion only; either as a continuous or intermittent infusion. Additives should not be introduced into metronidazole infusion.

Warnings and precautions

Central and peripheral nervous system effects: Encephalopathy may occur in association with cerebellar toxicity characterized byy ataxia, dizziness and dysarthria. CNS symptoms are generally reversible within days to weeks upon discontinuation of metronidazole.

Peripheral neuropathy, mainly of sensory type may occur and is characterized by numbness or paresthesia of an extremity.

Convulsive seizures may occur in patients treated with metronidazole.

Aseptic meningitis: Symptoms can occur within hours of dose administration and generally resolve after metronidazole therapy is discontinued.

The appearance of abnormal neurological signs and symptoms demands the prompt evaluation of the benefits/risk ratio of the continuation of the therapy.


Hepatic impairment: Patients with hepatic impairment metabolize metronidazole slowly, with resultant accumulation oof metronidazole in the plasma. For patients with severe hepatic impairment, a reduced dose of metronidazole is recommended. For patients with mild to moderate hepatic impairment, no dosage adjustment is needed but these patients should be monitored for metronidazole associated adverse events.

Renal impairment: patients with end-stage renal disease may excrete metronidazole and metabolise slowly in the urine, resulting in significant accumulation of metronidazole metabolites. Monitoring of metronidazole associated adverse events is recommended.

Fungal superinfections: known or previously unrecognized conditions may present more prominent symptoms during therapy with metronidazole and requires treatment with a candidacidal agent.

Use in patients with blood dyscrasias: metronidazole is a nitroimidazole and it should be used with caution in patients with evidence of or history of blood dyscrasias. As per published reviewed, a mild leucopenia has been observed during its administration; however, no persistent hematologic abnormalities attributable to metronidazole have been observed.

Monitoring of leucopenia: total and differential leukocyte counts are recommended before and after prolonged or repeated courses of metronidazole therapy.

Sodium retention: administration of solution containing sodium ions may result in sodium retention. Care should be taken when administering metronidazole to patients receiving corticosteroids or to patients predisposed to edema.

Drug-resistant bacteria and parasites: use of metronidazole in the absence of a proven or strongly suspected bacterial or prophylactic indications is unlikely to provide benefit to the patients and increases the risk of the development of  drug-resistant bacteria.

 Drug interactions

Disulfiram: Psychotic reactions may occur in alcoholic patients who are using metronidazole and disulfiram concurrently. Metronidazole should not be given to patients who have taken disulfiram with 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 may potentiate the anticoagulant effect of warfarin and other oral coumarin anticoagulants, resulting in a prolongation of prothrombin time and INR should careful be monitored.

Lithium: in patients stabilized on relatively high doses of lithium, short-term metronidazole therapy may be associated with elevation of serum lithium and, in 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 increases plasma concentration 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.

Drug/laboratory test effects

Metronidazole may interfere with certain types of determination of serum chemistry values, such as aspartame aminotrasferase (AST, SGOT), alanine aminotransferase (ALT, SGPT), lactate dehydrogenase (LDH), triglycerides and glucose hexokinase. Values of xero may be observed . all of the assay in which interference may involve enzymatic coupling of the assay to oxidation reduction of nicotinamide adenine dinucleotide (NAD+↔NADH). Interference is due to the similarity in absorbance peaks of NADH (340 nm) and metronidazole (322 nm) at pH 7.


Teratogenic effects: Pregnancy category B

As per literature reviewed, there are no adequate and well controlled studies of Mteronidazole in pregnant women. Most studies did not show an increased risk for congenital anomalies or other adverse fetal outcomes following metronidazole exposure during pregnancy. Metronidazole crosses the placental barrier and its effects on the human ffetal organogenesis are not known. 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. A decision should be made whether to discontinue nursing or discontinue the drug, taking into account 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.

Geriatric use: In geriatric patients, monitoring for metronidazole associated adverse events is recommended. Decreased liver function in geriatric patients can result in increased concentrations of metronidazole that may necessitate adjustment of metronidazole dosage.

Pediatric use: safety and effectiveness in pediatric patients have not been established.


1 thought on “NIRMET* (Metronidazole Intravenous Infusion BP)”

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