Metronidazole Tablets 200mg
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Metran 200 / Metronidazole Tablets 200 mg
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Metronidazole 200 mg.
For excipients see 6.1.
3 PHARMACEUTICAL FORM
Flat, white or creamy-white scored tablet.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Metronidazole Tablets 200mg is indicated in the prophylaxis and treatment of infections in which anaerobic bacteria have been identified or are suspected to be the cause.
Metronidazole Tablets 200mg is active against a wide range of pathogenic microorganisms, notably species of Bacteroides, Fusobacteria, Clostridia, Eubacteria, anaerobic cocci and Gardnerella vaginalis.
It is also active against Trichomonas vaginalis and other species of trichomonads, Entamoeba histolytica, Giardia lamblia, Balantidium coli and the causative organisms of acute ulcerative gingivitis.
Metronidazole Tablets 200mg is indicated in the oral treatment of:
The prevention of post-operative infections due to anaerobic bacteria, particularly species of Bacteroides and anaerobic streptococci.
The treatment of septicaemia, bacteraemia, peritonitis, brain abscess, necrotising pneumonia, osteomyelitis, puerperal sepsis, pelvic abscess, pelvic cellulitis and post-operative wound infections from which pathogenic anaerobes have been isolated.
Urogenital trichomoniasis in the female (trichomonal vaginitis) and in the male. The male consort of females suffering from urogenital trichomoniasis should be treated concurrently.
Bacterial vaginosis (also known as non-specific vaginitis, anaerobic vaginosis or Gardnerella vaginitis).
All forms of amoebiasis (intestinal and extra-intestinal disease, and that of symptomless cyst passers).
Giardiasis.
Acute ulcerative gingivitis.
Anaerobically-infected leg ulcers and pressure sores.
Acute dental infections (e.g. acute pericoronitis and acute apical infections).
Considerations should be given to official guidance on the appropriate use of antibacterial agents.
4.2 Posology and method of administration
Posology
Anaerobic infections: The duration of a course of Metronidazole Tablets 200mg treatment is about 7 days but it will depend upon the seriousness of the patient’s condition as assessed clinically and bacteriologically.
Prophylaxis against anaerobic infection: Chiefly in the context of abdominal (especially colorectal) and gynaecological surgery.
Adults: 400mg 8-hourly during 24 hours immediately preceding operation followed by postoperative intravenous or rectal administration until the patient is able to take the tablets.
Children: < 12 years: 20-30mg/kg as a single dose given 1-2 hours before surgery. Newborns with a gestation age of < 40 weeks: 10mg/kg body weight as a single dose before operation.
Treatment of established anaerobic infection:
Adults: 800mg followed by 400mg 8-hourly.
Children: Children > 8 weeks to 12 years of age: The usual dose is 20-30mg/kg/day as a single dose or divided into 7.5mg/kg every 8 hours. The daily dose may be increased to 40mg/kg, depending on the severity of the infection. Duration of treatment is usually 7 days.
Children < 8 weeks of age: 15mg/kg as a single dose daily or divided into 7.5mg/kg every 12hours. In newborns with a gestation < 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 therapy.
Protozoal and other infections
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Dosage is given in terms of metronidazole or metronidazole equivalent | |||||
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Duration of dosage in days |
Adults and children over 10 years |
Children | |||
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7 to 10 years |
3 to 7 years |
1 to 3 years | |||
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Urogenital Trichomoniasis Where infection is likely in adults the consort should receive similar course of treatment concurrently |
7 or 5-7 |
2000 mg as a single dose or 200 mg three times daily or 400 mg twice daily |
40 mg/kg orally as a single dose or 15-30 mg/kg/day divided in 2-3 doses; not to exceed 2000 mg/day | ||
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Bacterial vaginosis |
5-7 or |
400 mg twice daily | |||
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1 |
2000 mg as a single dose | ||||
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Amoebiasis (a) Invasive intestinal disease in susceptible subjects |
5 |
800 mg three times daily |
400 mg three daily mg times |
200 mg four daily mg times |
200 mg three times daily |
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(b) Intestinal disease in less susceptible subjects and chronic amoebic hepatitis |
5-10 |
400 mg three times daily |
200 mg three times daily |
100 mg four times daily |
100 mg Three times daily |
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(c) Amoebic liver abscess also other forms of extraintestinal amoebiasis |
5 |
400 mg three times daily |
200 mg three times daily |
100 mg four times daily |
100 mg Three times daily |
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(d) Symptomless cyst passers |
5-10 |
400-800 mg three times daily |
200-400 mg three times daily |
100-200 mg four times daily |
100-200 mg three times daily |
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Alternative 35 to 50 m exceed 240 |
y, doses may be expressed by body weight g/kg daily in 3 divided doses for 5 to 10 days, not to 0 mg/day | ||||
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Giardiasis |
3 |
2000 mg once daily or |
1000 mg once daily |
600-800 mg once daily |
500 mg once daily |
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5 |
400 mg three | ||||
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times daily or | |||||
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7-10 |
500 mg twice daily | ||||
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Alternative divided in 2 |
y, as expressed in mg per kg of body weight: 15-40 mg/kg/day .-3 doses. | ||||
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Acute ulcerative gingivitis |
3 |
200 mg three times daily |
100 mg three times daily |
100 mg twice daily |
50 mg three times daily |
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Acute dental infections |
3-7 |
200 mg three times daily | |||
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Leg ulcers and pressure sores |
7 |
400 mg three times daily | |||
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Children and infants weighing less than 10 kg should receive proportionally smaller dosages Elderly: Metronidazole is well tolerated by the elderly but a pharmacokinetic study suggests cautious use of high dosage regimens in this age group. | |||||
Eradication of Helicobacter _ pylori in _ paediatric _ patients:
As a part of a combination therapy, 20mg/kg/day not to exceed 500mg twice daily for 7-14 days. Official guidelines should be consulted before initiating therapy.
Method of administration
For oral use.
Metronidazole Tablets 200mg should be swallowed without chewing, with half a glassful of water, during or after meals.
4.3 Contraindications
Hypersensitivity to nitroimidazoles, metronidazole or any of the excipients.
4.4 Special warnings and precautions for use
Regular clinical and laboratory monitoring (especially leukocyte count) are advised if administration of Metronidazole Tablets 200mg for more than 10 days is considered to be necessary and patients should be monitored for adverse reactions such as peripheral or central neuropathy (such as paraesthesia, ataxia, dizziness, convulsive seizures)..
Metronidazole should be used with caution in patients with active or chronic severe peripheral and central nervous system disease due to the risk of neurological aggravation.
The possibility that an accompanying gonococcal infection might persist in a symptomatic state after Trichomonas vaginalis has been eliminated should be borne in mind.
The elimination half-life of metronidazole remains unchanged in the presence of renal failure. The dosage of metronidazole therefore needs no reduction. Such patients
however retain the metabolites of metronidazole. The clinical significance of this is not known at present.
In patients undergoing haemodialysis, metronidazole and metabolites are efficiently removed during an eight hour period of dialysis. Metronidazole should therefore be readministered immediately after haemodialysis.
No routine adjustment in the dosage of Metronidazole Tablets 200mg needs to be made in patients with renal failure undergoing intermittent peritoneal dialysis (IDP) or continuous ambulatory peritoneal dialysis (CAPD).
Metronidazole is mainly metabolised by hepatic oxidation. Substantial impairment of metronidazole clearance may occur in the presence of advanced hepatic insufficiency. Significant cumulation may occur in patients with hepatic encephalopathy and the resulting high plasma concentrations of metronidazole may contribute to the symptoms of the encephalopathy. Metronidazole should, therefore, be administered with caution to patients with hepatic encephalopathy. The daily dosage should be reduced to one third and may be administered once daily.
Patients should be warned that metronidazole may darken urine.
Patients with acute porphyria should not take this medicine.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Due to inadequate evidence on the mutagenicity risk in humans, the use of metronidazole for longer treatment than usually required should be carefully considered.
4.5 Interaction with other medicinal products and other forms of interaction
Patients should be advised not to take alcohol during therapy and for at least 48 hours
afterwards because of the possibility of a disulfiram-like (antabuse effect) reaction.
Concomitant administration of disulfiram has led to acute psychosis and confusional states.
The effects of warfarin type oral anticoagulants may be potentiated by metronidazole. The dose of warfarin type oral anticoagulants may require reducing. Prothrombin times should be monitored. There is no interaction with heparin.
Lithium retention accompanied by evidence of possible renal damage has been reported in patients treated simultaneously with lithium and metronidazole. Lithium treatment should be tapered or withdrawn before administering metronidazole. Plasma
concentrations of lithium, creatinine and electrolytes should be monitored in patients under treatment with lithium while they receive metronidazole.
Phenobarbital and Phenytoin causes increased metabolism of metronidazole, reducing the half-life to about three hours.
Metabolism of metronidazole is accelerated by primidone.
Metronidazole inhibits the metabolism of phenytoin (increased plasma concentration).
Metronidazole reduces the clearance of 5 fluorouracil and can therefore result in increased toxicity of 5 fluorouracil.
Patients receiving ciclosporin are at risk of elevated ciclosporin serum levels. Serum ciclosporin and serum creatinine should be closely monitored when co-administration is necessary.
Plasma levels of busulfan may be increased by metronidazole which may lead to severe busulfan toxicity.
Metronidazole possibly reduces bioavailability of mycophenolate.
The metabolism of metronidazole is inhibited by cimetidine.
Antibacterials that do not induce liver enzymes possibly reduce the contraceptive effect of oestrogens.
4.6 Fertility, Pregnancy and lactation
As there is insufficient evidence on safety of use in pregnancy or lactation, metronidazole should not be given in these circumstances unless it is considered essential by the physician. If it is used, then short-term high dosage therapy is not recommended.
4.7 Effects on ability to drive and use machines
Patients should be warned about the potential for drowsiness, dizziness, confusion, hallucinations, convulsions or transient visual disorders, and advised not to drive or operate machinery if these symptoms occur.
The frequency of adverse events listed below is defined using the following convention: very common (>1/10); common (> 1/100 to < 1/10); uncommon (> 1/1,000 to < 1/100); rare (> 1/10,000 to < 1/1000); very rare (< 1/10,000); not known (cannot be estimated from the available data).
Serious adverse reactions occur rarely with standard recommended regimens. Clinicians who contemplate continuous therapy for the relief of chronic conditions, for periods longer than those recommended, are advised to consider the possible risk of peripheral neuropathy.
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Blood and lymphatic system disorders: | |
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Very rare |
Agranulocytosis, neutropenia, thrombocytopenia, pancytopenia. |
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Not known |
Leucopenia. White blood cell counts return to normal once treatment is completed. |
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Immune system class: | |
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Rare |
Anaphylaxis |
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Not known |
Urticaria, angioedema, fever. |
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Metabolism and nutrition disorders: | |
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Not known |
Anorexia |
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Psychiatric disorders: | |
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Very rare |
Psychotic disorders, including hallucinations and confusion |
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Not known |
Depressed mood |
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Nervous system disorders: | |
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Very rare |
Encephalopathy (e.g. confusion, fever, headache, hallucinations, paralysis, light sensitivity, disturbances in sight and movement, stiff neck) and subacute cerebellar syndrome (e.g. ataxia, dysarthria, gait impairment, nystagmus and tremor), which may resolve on discontinuation of drug. Drowsiness, dizziness, convulsions, headaches |
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Not known |
During intensive and/or prolonged metronidazole therapy, peripheral sensory neuropathy or transient epileptiform seizures have been reported. These usually disappear after treatment is stopped or dosage reduced. Aseptic meningitis |
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Eye disorders: | |
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Very rare |
Diplopia and myopia (which in most cases |
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are transient). | |
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Not known |
Optic neuropathy/neuritis. |
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Gastrointestinal disorders: | |
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Not known |
Taste disorders (unpleasant taste in the mouth), oral mucositis, furred tongue, nausea, vomiting, gastrointestinal disturbances such as epigastric pain and diarrhoea. |
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Hepatobiliary disorders: | |
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Very rare |
Increase in liver enzymes (AST, ALT, alkaline phosphatase), cholestatic or mixed hepatitis and hepatocellular liver injury, jaundice and pancreatitis which is reversible on drug withdrawal. Cases of liver failure requiring liver transplant have been reported in patients treated with metronidazole in combination with other antibiotic drugs. |
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Skin and subcutaneous tissue disorders: | |
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Very rare |
Skin rashes, pustular eruptions, pruritus, flushing. |
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Not known |
Erythema multiforme, Stevens-Johnson syndrome or toxic epidermal necrolysis. |
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Musculoskeletal, connective tissue and bone disorders: | |
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Very rare |
Myalgia, arthralgia. |
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Renal and urinary disorders: | |
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Very rare |
Darkening of urine (due to a metabolite of metronidazole). |
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard
4.9 Overdose
Single oral doses of metronidazole, up to 12g have been reported in suicide attempts and accidental overdoses. Symptoms are limited to vomiting, ataxia and slight disorientation. There is no specific treatment for gross over dosage of metronidazole.
In cases of suspected massive overdose, symptomatic and supportive treatment should be instituted.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antibacterials for systemic use, ATC code: J01X D01
Metronidazole is an antimicrobial agent acting against a wide range of anaerobic bacteria and protozoa including Trichomonas vaginalis, Entamoeba histolytica and Giardia lamblia.
5.2 Pharmacokinetic properties
Metronidazole is rapidly absorbed from the gastro-intestinal tract. Peak plasma concentrations occur between twenty minutes and three hours.
The elimination half-life is 8.5±2.9 hours. Metronidazole can be used in chronic renal failure; it is rapidly removed from the plasma by dialysis. Metronidazole is excreted in milk but the intake of a suckling infant of a mother receiving normal dosage would be considerably less than the therapeutic dosage for infants.
5.3 Preclinical safety data
Metronidazole has been shown to be carcinogenic in the mouse and in the rat following chronic oral administration however similar studies in the hamster have given negative results. Epidemiological studies have provided no clear evidence of an increased carcinogenic risk in humans.
Metronidazole has been shown to be mutagenic in bacteria in vitro. In studies conducted in mammalian cells in vitro as well as in rodent or humans in vivo, there was inadequate evidence of a mutagenic effect of metronidazole, with some studies reporting mutagenic effects, while other studies were negative.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose
Maize Starch
Pregelatinised Maize Starch Sodium Starch Glycollate
6.2 Incompatibilities
None known.
6.3 Shelf life
36 months.
6.4 Special precautions for storage
Store in a dry place, below 25°C.
Keep container tightly closed, protect from light.
6.5 Nature and contents of container
High density polystyrene container with polytbene lids and/or Polypropylene containers with polypropylene or polythene lids and Polyurethane/polythene wads.
Pack sizes of 21, 28, 30, 50, 56, 60, 84, 90, 100, 112, 120, 140, 150, 168, 180, 250, 500, 1000, 5,000 or 50,000 tablets (not all packs are marketed)
6.6 Special precautions for disposal
None.
7 MARKETING AUTHORISATION HOLDER
Intrapharm Laboratories Limited,
The Courtyard Barns,
Choke Lane,
Cookham Dean,
Maidenhead,
Berkshire,
SL6 6PT,
UNITED KINGDOM.
8 MARKETING AUTHORISATION NUMBER(S)
PL 17509/0073
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
22/11/95
10
DATE OF REVISION OF THE TEXT
01/03/2015