Vaginyl
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
VAGINYL/Metronidazole Tablets 200 mg
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Metronidazole BP 200 mg
3 PHARMACEUTICAL FORM
Tablet
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Metronidazole is indicated in the prophylaxis of infections in which anaerobic bacteria have been identified or are suspected to be the cause.
Metronidazole is active against a wide range of pathogenic micro-organisms, notably species of Bacteroides, Fusobacteria, Clostridia, Eubacteria, anaerobic cocci and Gardnerella vaginalis.
It is also active against Tricholonas vaginalis and other species of trichomonads, Entamoeba histolytica, Giardia lamblia, Balantidium coli and the causative organisms of acute ulcerative gingivitis.
Metronidazole is indicated in adults and children for the following indications:
1. The prevention of post-operative infections due to anaerobic bacteria, particularly species of Bacteroides and anaerobic streptococci.
2. 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.
3. Urogenital trichomoniasis in the female (trichomonal vaginitis) and in the male. The male consort of females suffering from urogenital trichomoniasis should be treated concurrently.
4. Bacterial vaginosis (also known as non-specific vaginitis, anaerobic vaginosis or Gardnerella vaginitis).
5. All forms of amoebiasis (intestinal and extra-intestinal disease and that of symptomless cyst passers).
6. Giardiasis.
7. Acute ulcerative gingivitis.
8. Anaerobically-infected leg ulcers and pressure sores
9. 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
Metronidazole tablets should be swallowed, without chewing, with half a glassful of water during or after meals.
Prophylaxis against postoperative infections caused by anaerobic infection:
Chiefly in the context of abdominal (especially colorectal) and gynaecological surgery
Adults: 400 mg 8 hourly during 24 hours immediately preceding operation
followed by postoperative intravenous or rectal administration until the patient is able to take tablets.
Children: < 12 years: 20-30mg/kg as a single dose given 1-2 hours before
surgery
Newborns with a gestation age < 40 weeks: 10mg/kg body weight as a single dose before operation
Anaerobic infections: The duration of a course of metronidazole treatment is about 7 days but it will depend upon the seriousness of the patient's condition as assessed clinically and bacteriologically.
Treatment of established anaerobic infection:
Adults: 800 mg followed by 400 mg 8 hourly.
Children: >8 weeks to 12 years of age: The usual dose is 20-30 mg/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.
<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, thus the concentrations of metronidazole in serum should preferable be monitored after a few days therapy.
Protozoal and other infections: • Urogenital trichomoniasis:
Adults and adolescents:
200 mg, 3 times daily for 7 days; or 400 mg, twice daily for 5-7 days; or 2000mg as a single dose for 7 days
To prevent re-infection, the consort should receive the same course of treatment concurrently.
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
• Bacterial vaginosis:
Adults and adolescents:
400 mg, twice daily for 5-7 days; or 2000 mg as a single dose
• Amoebiasis:
Adults and children over 10 years:
a) Invasive intestinal disease in susceptible subjects, 800 mg three times daily for 5 days, or 2000 mg once daily for three days.
b) Intestinal disease in less susceptible subjects and chronic amoebic hepatitis, 400 mg three times daily for 5-10 days or 2000 mg once daily for 2 days.
c) Amoebic liver abscess, also forms of extra-intestinal amoebiasis, 400 mg three times daily for 5 days or 2000 mg once daily for two days.
d) Symptomless cyst passers. The upper ranges of dosage and duration of treatment seem to be necessary in temperate climate countries. 400-800 mg three times daily for 5-10 days
Children:
7-10 years: 200-400 mg 3 times daily for 5-10 days
3-7 years: 100-200 mg 4 times daily for 5-10 days
1-3 years: 100-200 mg 3 times daily for 5-10 days
Alternatively, dose may be expressed by body weight: 35-50 mg/kg daily in 3 divided doses for 5-10 days, not to exceed 2400 mg/day
• Giardiasis:
Adults and children over 10 years:
2000 mg once daily for 3 days or 400 mg three times daily for 5 days or 500 mg twice daily for 7-10 days Children:
7-10 years: 1000 mg once daily for 3 days 3-7 years: 600-800 mg once daily for 3 days
1-3 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
• Acute ulcerative gingivitis:
Adults and adolescents: 200 mg, 3 times daily for 3 days
• Acute dental infections:
Adults and adolescents: 200 mg, 3 times daily for 3-7 days.
• Leg ulcers and pressure sores:
Adults and adolescents: 400 mg, 3 times daily for 7 days.
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 500 mg twice daily for 7-14 days. Official guidelines should be consulted before initiating therapy.
This formulation is appropriate, where the dosage is 100 mg or multiples thereof.
To be taken orally.
4.3 Contraindications
Known hypersensitivity to metronidazole.
4.4 Special warnings and precautions for use
The possibility that an accompanying gonococcal infection might persist in a symptomless state after Trichomonas vaginalis has been eliminated should be borne in mind.
Metronidazole is mainly metabolised by hepatic oxidation. Substantial impairment of Metronidazole clearance may occur in patients with severe liver disease and significant accumulation of Metronidazole and its metabolites in the plasma may contribute to the symptoms of hepatic encephalopathy. In such patients, the total daily dose should be reduced to one-third, and given once daily. Metronidazole should be used with caution in patients with active disease of the central nervous system.
Clinical and laboratory monitoring is advised if treatment exceeds 10 days. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
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 possibility of a disulfiram-like reaction.
When Warfarin is used, this may be potentiated by Metronidazole. Dosage of Warfarin may require reducing.
Phenobarbitone causes increased metabolisation of Metronidazole reducing the half-life to about 3 hours.
Metronidazole inhibits the metabolism of phenytoin Metronidazole inhibits the metabolism of florouracil.
Lithium treatment should be tapered or withdrawn before administering Metronidazole, as lithium retention accompanied by evidence of possible renal damage has been reported in patients treated simultaneously with Metronidazole and lithium.
Cimetidine inhibits the metabolism of metronidazole.
4.6 Pregnancy and lactation
As there is insufficient evidence of the safety of Metronidazole in pregnancy, Metronidazole should not be given during pregnancy or during lactation unless considered essential by a physician; in such circumstances 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 dizziness, drowsiness, confusion, convulsions or hallucinations, and advised not to drive or operate machinery if these symptoms occur.
4.8 Undesirable effects
Frequency, type and severity of adverse reactions in children are the same as in adults.
Unpleasant taste in the mouth, furred tongue, nausea, vomiting, gastro-intestinal disturbance, anorexia, urticaria and angiodema occur occasionally.
Anaphylaxis may occur rarely.
Very rarely drowsiness, dizziness, headache, ataxia, pruritus, pustular eruptions, darkening of the urine (due to the metronidazole metabolite), incoordination of
movement, myalgia, arthralgia and transient visual disorders such as myopia and diplopia have been reported.
Psychotic disorders including confusion and hallucinations have very rarely been reported.
During intensive or prolonged therapy, a few instances of peripheral neuropathy, transient epileptiform seizures have been reported. This usually disappears after treatment is stopped or dosage reduced.
Leucopenia has been reported but the white cell count always returns to the normal after treatment has been completed.
Metronidazole may result in hepatotoxicity and reactions such as abnormal liver function tests, cholestatic hepatitis and jaundice, which may be reversed upon drug withdrawal. There have been reports of bone marrow depression disorders such as agranulocytosis, neutropenia, thrombocytopenia, pancytopenia and aplastic anaemia, which may be reversed on drug withdrawal although fatalities have been reported. Metronidazole may be associated with erythema multiforme, which may be reversed on drug withdrawal.
4.9 Overdose
There is no specific treatment for gross overdosage of Metronidazole.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Metronidazole is an anti-microbial drug primarily active against obligate anaerobic micro-organisms, both bacteria and protazoa. The 5-nitro group undergoes reductive transformation to an active intermediate which exerts an inhibitory or lethal effect against DNA and subsequent DNA strand breakage. Other reduction-oxidation processes within anaerobic organisms may also be inhibited (an example is the phosphoroclastic reaction in clostridia).
Metronidazole is very active against trichomonas vaginalis, gardia lamblia and E-histolytica, with minimal inhibition concentrations. Metronidazole is also especially active against strains of bacteroides fragilis and related species. It is moderately active against the facultative anaeobes gardnerella vaginates and cambylobacter fetus.
5.2 Pharmacokinetic properties
The bio-availability of oral Metronidazole produces 90-100%. Peak plasma levels of Metronidazole after a single 500 mg oral dose ranges between 9 and 13 mg/l and occurs 0.33-3 hours after the dose. With multiple oral doses, there is some drug accumulation on day 3 after a dose of 500 mg 6-hourly, with no evidence of further accumulation by day 7. Serum levels are directly proportional to the dose over a broad therapeutic range.
Pre-systemic metabolism is negligible. The plasma half-life range is 7.9-9.8 hours. Plasma protein binding 0%-20%. Volume of distribution of 0.76-1.02 l/kg reflects the wide distribution throughout the body.
5.3 Preclinical safety data
Not applicable.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose Maize starch
Pregelatinised maize starch Sodium starch glycollate Magnesium stearate
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 in well closed containers. Protect from light.
6.5 Nature and contents of container
High density polystyrene or polypropylene securitainer type containers with lids for polythene or polypropylene with polythene bellows and/or polyurethane wads.
Pack sizes:
28, 30, 50, 56, 60, 84, 90, 100, 112, 120, 140, 150, 168, 180, 500, 1000, 5000, 50000
6.6 Special precautions for disposal
No special instructions.
7 MARKETING AUTHORISATION HOLDER
Chelonia Healthcare Limited
Boumpoulinas 11, 3 rd Floor
NICOSIA
CYPRUS
PC. 1060
CYPRUS
8 MARKETING AUTHORISATION NUMBER(S)
PL 33414/0064
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
19/06/72 19/06/96
DATE OF REVISION OF THE TEXT
10
07/04/2011
11 DOSIMETRY (IF APPLICABLE)
12 INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS (IF APPLICABLE)