GMP metronidazole Injection 0.5% 100ml

Metronidazole 500mg/100ml Intravenous Infusion is indicated in adults and children when oral medication is not possible for the following indications:

- The prophylaxis of postoperative infections due to sensitive anaerobic bacteria particularly species of Bacteroides and anaerobic Streptococci, during abdominal, gynaecological gastrointestinal or colorectal surgery which carries a high risk of occurrence of this type of infection. The solution may also be used in combination with an antibiotic active against aerobic bacteria.

- The treatment of severe intraabdominal and gynaecological infections in which sensitive anaerobic bacteria particularly Bacteriodes and anaerobic Streptococci have been identified or are suspected to be the cause.

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

Method of Administration

Metronidazole 500mg/100ml Intravenous Infusion should be infused intravenously at an approximate rate of 5 ml/minute (or one bag infused over 20 to 60 minutes). Oral medication should be substituted as soon as feasible.

Prophylaxis against postoperative infections caused by anaerobic bacteria:

Primarily in the context of abdominal, (especially colorectal) and gynaecological surgery.

Antibiotic prophylaxis duration should be short, mostly limited to the post operative period (24 hours but never more than 48 hours). Various schedules are possible.

Adults: Intra-venous injection of single dose of 1000mg-1500mg, 30-60 minutes preoperatively or alternatively 500mg immediately before, during or after operation, then 500mg 8 hourly.

Children < 12 years: 20-30 mg/kg as a single dose given 1-2 hours before surgery.

Newborns with a gestation age <40 weeks: 10 mg/kg body weight as a single dose before operation.

Anaerobic infections:

Intravenous route is to be used initially if patient symptoms preclude oral therapy. Various schedules are possible.

Adults: 1000mg – 1500mg daily as a single dose or alternatively 500mg every 8 hours.

Children > 8 weeks to 12 years of age: The usual daily dose is 20-30mg/kg/day as a single dose or divided into 7.5 mg/kg every 8 hours. The daily dose may be increased to 40 mg/kg, depending on the severity of the infection. Duration of treatment is usually 7 days.

Children < 8 weeks of age: 15 mg/kg as a single dose daily or divided into 7.5 mg/kg every 12 hours.

In newborns with a gestation age < 40 weeks, accumulation of metronidazole can occur during the first week of life, therefore the concentrations of metronidazole in serum should preferably be monitored after a few days of therapy.

Oral medication could be given, at the same dose regimen. Oral medication should be substituted as soon as feasible.

Duration of Treatment

Treatment for seven to ten days should be satisfactory for most patients but, depending upon clinical and bacteriological assessments, the physician might decide to prolong treatment e.g.; for the eradication of infection from sites which cannot be drained or are liable to endogenous recontamination by anaerobic pathogens from the gut, oropharynx or genital tract.

Bacterial vaginosis:

Adolescents: 400 mg twice daily for 5-7 days or 2000 mg as a single dose

Urogenital trichomoniasis

Adults and adolescents: 2000 mg as a single dose or 200 mg 3 times daily for 7 days or 400 mg twice daily for 5-7 days

Children < 10 years: 40 mg/kg orally as a single dose or 15 – 30 mg/kg/day divided in 2-3 doses for 7 days; not to exceed 2000 mg/dose

Giardiasis:

> 10 years: 2000 mg once daily for 3 days, or 400 mg three times daily for 5 days, or 500 mg twice daily for 7 to 10 days

Children 7 to 10 years: 1000 mg once daily for 3 days

Children 3 to 7 years: 600 to 800 mg once daily for 3 days

Children 1 to 3 years: 500 mg once daily for 3 days

Alternatively, as expressed in mg per kg of body weight: 15-40 mg/kg/day divided in 2-3 doses.

Amoebiasis:

> 10 years: 400 to 800 mg 3 times daily for 5-10 days

Children 7 to 10 years: 200 to 400 mg 3 times daily for 5-10 days

Children 3 to 7 years: 100 to 200 mg 4 times daily for 5-10 days

Children 1 to 3 years: 100 to 200 mg 3 times daily for 5-10 days

Alternatively, doses may be expressed by body weight 35 to 50 mg/kg daily in 3 divided doses for 5 to 10 days, not to exceed 2400 mg/day

Eradication of Helicobacter pylori in paediatric patients:

As a part of a combination therapy, 20 mg/kg/day not to exceed 500 mg twice daily for 7-14 days.

Official guidelines should be consulted before initiating therapy

Elderly Population

Caution is advised in the elderly, particularly at high doses, although there is limited information available on modification of dosage.

Patients with renal failure

Routine adjustments of the dosage of Metronidazole are not considered necessary in the presence of renal failure.

No routine adjustment in the dosage of Metronidazole needs to be made in patients with renal failure undergoing intermittent peritoneal dialysis (IDP) or continuous ambulatory peritoneal dialysis (CAPD). However dosage reduction may be necessary when excessive concentrations of metabolites are found.

In patients undergoing haemodialysis, Metronidazole should be re-administered immediately after haemodialysis

Patients with advanced hepatic insufficiency

In patients with advanced hepatic insufficiency a dosage reduction with serum level monitoring is necessary.

Hypersensitivity to the active substance, to other imidazole derivatives or to any of the excipients listed in section 6.1.

Liver disease:

Caution is needed in patients with severe hepatic impairment. The dose of metronidazole should be reduced as necessary. Metronidazole is mainly metabolised by hepatic oxidation. Substantial impairment of Metronidazole clearance may occur in the presence of advanced hepatic insufficiency. The risk/benefit ratio of using Metronidazole to treat trichomoniasis in such patients should be carefully considered (for dosage adjustment see section 4.2). Plasma levels of Metronidazole should be closely monitored.

Caution is needed in patients with hepatic encephalopathy. Patients with severe hepatic encephalopathy metabolize metronidazole slowly, with resultant accumulation of metronidazole. This may cause exacerbation of CNS adverse effects. The dose of metronidazole should be reduced as necessary.

Cases of severe hepatotoxicity/acute hepatic failure, including cases with a fatal outcome with very rapid onset after treatment initiation in patients with Cockayne syndrome have been reported with products containing metronidazole for systemic use. In this population, metronidazole should therefore be used after careful benefit-risk assessment and only if no alternative treatment is available. Liver function tests must be performed just prior to the start of therapy, throughout and after end of treatment until liver function is within normal ranges, or until the baseline values are reached. If the liver function tests become markedly elevated during treatment, the drug should be discontinued.

Patients with Cockayne syndrome should be advised to immediately report any symptoms of potential liver injury to their physician and stop taking metronidazole.

Active Central Nervous System disease:

Metronidazole should be used with caution in patients with active disease of the Peripheral and Central Nervous System. Severe neurological disturbances (including seizures and peripheral and optic neuropathies) have been reported in patients treated with metronidazole. Stop metronidazole treatment if any abnormal neurologic symptoms occur such as ataxia, dizziness, confusion or any other CNS adverse reaction. The risk of aggravation of the neurological state should be considered in patients with fixed or progressive paraesthesia, epilepsy and active disease of the central nervous system except for brain abscess.

Encephalopathy has been reported in association with cerebellar toxicity characterized by ataxia, dizziness, dysarthria, and accompanied by CNS lesions seen on magnetic resonance imaging (MRI). CNS symptoms and CNS lesions, are generally reversible within days to weeks upon discontinuation of metronidazole.

Aseptic meningitis can occur with metronidazole. Symptoms can start within hours of dose administration and generally resolve after metronidazole therapy is discontinued (see section 4.8).

Blood Dyscrasias

Metronidazole should be used with caution in patients with evidence or history of blood dyscrasia as agranulocytosis, leukopenia and neutropenia have been observed following metronidazole administration.

Renal Disease:

Metronidazole is removed during haemodialysis and should be administered after the procedure is finished.

Patients with renal impairment, including patients receiving peritoneal dialysis, should be monitored for signs of toxicity due to the potential accumulation of toxic metronidazole metabolites.

Sodium restricted patients:

This medicinal product contains 13.5 mmol (310 mg) sodium per 100 mL. To be taken into consideration by patients on a controlled sodium diet.

Alcohol:

Patients should be advised to discontinue consumption of alcoholic beverages or alcohol-containing products before, during, and up to 72hours after taking metronidazole because of a disulfram-like effect (abdominal cramps, nausea, headaches, flushing, vomiting and tachycardia). See section 4.5.

Intensive or prolonged Metronidazole therapy:

As a rule, the usual duration of therapy with i.v Metronidazole or other imidazole derivatives is usually less than 10 days. This period may only be exceeded in individual cases after a very strict benefit-risk assessment. Only in the rarest possible case should the treatment be repeated. Limiting the duration of treatment is necessary because damage to human germ cells cannot be excluded.

Intensive or prolonged Metronidazole therapy should be conducted only under conditions of close surveillance for clinical and biological effects and under specialist direction. If prolonged therapy is required, the physician should bear in mind the possibility of peripheral neuropathy or leucopenia. Both effects are usually reversible.

In case of prolonged treatment, occurrence of undesirable effects such as paraesthesia, ataxia, dizziness and convulsive crises should be checked. High dose regimes have been associated with transient epileptiform seizures.