INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo COMPU METRONIDAZOLE 400

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

COMPU METRONIDAZOLE 400

COMPOSITION:
Each tablet contains 400 mg
metronidazole.

PHARMACOLOGICAL CLASSIFICATION:
A 20.2.6 Antimicrobials: Medicines against protozoa.

PHARMACOLOGICAL ACTION:
Metronidazole has antiprotozoal activity against Trichomonas vaginalis and other protozoa, including Entamoeba histolytica and Giardia lamblia. It does not affect the acidophilic flora of the vagina and it has no effect on Candida species. Metronidazole has bactericidal activity against obligate anaerobic bacteria, whether they are gram-positive or negative and bacilli or cocci. It has no antibacterial activity against aerobic and facultative anaerobic bacteria. Metronidazole does not interfere with the activity of antibacterial agents which are active against a variety of aerobes and facultative anaerobes.
Metronidazole is well absorbed from the gastro-intestinal tract and widely distributed in body tissues. Approximately 30 - 40% of a dose is metabolised in the liver and excreted in the urine, together with the unchanged compound. Metronidazole is able to pass the blood/brain barrier. It reaches therapeutic concentrations in most other body fluids i.e. saliva, bile, urine, amniotic fluid, breast milk and in abscess cavities.
The following has been proposed as the mode of action of Metronidazole: The parent compound penetrates the cell membrane unchanged, but once inside the cell the nitro group is reduced in the redox conditions prevalent in the anaerobic cell.
The reduced product is known to damage DNA-causing eventual death of the organism.

INDICATIONS:
A - In the oral treatment of:
  - urogenital trichomoniasis
  - all forms of amoebiasis except asymptomatic carrier state
  - giardiasis
  - acute ulcerative gingivitis (Vincents’s)
  - acute pericoronitis
B - Treatment of infections, in which anaerobic bacteria have been identified or are suspected as pathogens, particularly Bacteroides fragilis and other species of bacteroides and including other species for which metronidazole is bactericidal, such as fusobacteria, clostridia, eubacteria and anaerobic streptococci.
METRONIDAZOLE has been used successfully for anaerobic infections in the following conditions: pelvic inflammatory disease and postoperative wound infections. Combined therapy is often indicated as there are usually mixed infections.
C - Prevention of postoperative infections due to anaerobic bacteria:
i)        Given before and after gynaecological surgery
ii)        Given before and after appendicectomy
iii)        Given before and after colonic surgery

CONTRA-INDICATIONS:
Hypersensitivity to metronidazole. Safety in pregnancy and lactation has not been established.
Patients with blood dyscrasias or with active disease of the central nervous system.

WARNINGS:
Patients should be advised not to take alcohol during metronidazole therapy and for at least one day afterwards because of the possibility of a disulfiram-like reaction.
Metronidazole enhances the effect of warfarin.

DOSAGE AND DIRECTIONS FOR USE:
Administration:
Tablets should be swallowed (without chewing) with half a glassfull of water.
The tablets should be taken with or after food.
Immature children and babies weighing less than 10 kg should receive proportionally smaller doses, as advised by the physician.
Children over 10 years may be given a suitable proportion of the adult dosage according to bodymass.

  DURATION ADULTS CHILDREN                       
  OF DOSAGE
IN DAYS
  7 TO 10 YEARS 3 TO 7 YEARS 1 TO 3 YEARS
UROGENITAL TRICHOMONIASIS
Where re-infection is likely, in adults the consort should receive a similar course of treatment concurrently.
        1 2g as a single dose 
          7 200 mg three times daily or 400 mg twice daily 100 mg three times daily 100 mg twice daily 50 mg three times daily
          2 800 mg in the morning and 1,2 g in the evening 
NON-SPECIFIC VAGINITIS         7 400 mg twice daily 
          OR 1 2 g as a single dose  
AMOEBIASIS
a) Invasive intestinal disease in susceptible subjects
        5 800 mg three times daily 400 mg three times daily 200 mg four times daily 200 mg three times daily
AMOEBIASIS
b) Intestinal disease in less susceptible subjects and “chronic amoebic hepatitis”
        5 to 10 400 mg three times daily 200 mg three times daily 100 mg four times daily 100 mg three times daily
AMOEBIASIS
c) Amoebic liver abscess, also other forms of extra-intestinal amoebiasis
        5 400 mg three times daily 200 mg three times daily 100 mg four times daily 100 mg three times daily
AMOEBIASIS
d) Symptomless cyst passers
        5 to 10 400 to 800 mg three times daily 200 to 400 mg three times daily 100 to 200 mg four times daily 100 to 200 mg three times daily
GIARDIASIS
A second course of treatment may be necessary for some patients two weeks after the end of the first course
        3 2g once daily 1g once daily 600 to 800 mg once daily 500 mg once daily
ACUTE ULCERATIVE GINGIVITIS         3 200 mg three times daily 100 mg three times daily 100 mg twice daily 50 mg three times daily
ACUTE PERICORONITIS         3 to 7 200 mg three times daily 

Anaerobic infections:
a) Treatment:
COMPU METRONIDAZOLE TABLETS may be given alone or concurrently with other bacteriologically appropriate antibacterial agents. They should be given for 7 days or longer depending on clinical and bacteriological assessments of the patient’s condition.
Adults: Initially, 800 mg followed by 400 mg by mouth every 8 hours.
Children: 7,5 mg/kg bodymass by mouth every 8 hours
b) Prevention:
Adults: Administered in doses similar to those used for the treatment of established infection. 400 mg may be given every 8 hours in the 24 hours before surgery followed postoperatively by intravenous or rectal administration until oral therapy is possible.
Children: as for treatment (a)

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Side-effects:
The adverse effects of metronidazole are generally dose-related. The most common are gastro-intestinal disturbances, especially nausea and an unpleasent metallic taste; nausea is sometimes accompanied by headache, anorexia and vomiting. Diarrhoea, dry mouth, a furred tongue, glossitis and stomatitis may also occur. There have also been rare reports of antibiotic-associated with metronidazole.
Peripheral neuropathy, usually presenting as numbness or tingling in the extremities, and epileptiform seizures are serious adverse effects on the nervous system that have been associated especially with high doses of metronidazole or prolonged treatment. Psychiatric disturbances such as confusion and hallucinations have been reported. Weakness, dizziness, attaxia, drowsiness, insomnia, and changes in mood or mental state such as depression or confusion have also been reported.
Temporary moderate leucopenia may occur in some patients receiving metronidazole. Skin rashes and pruritus occur occasionally and anaphylaxis has been reported rarely. Other side-effects include urethral discomfort and darkening in the urine. Raised liver enzyme values have occasionally been reported.
Exceptional and reversible cases of pancreatitis have been reported.
Special precautions:
Metronidazole should be used with great care in patients with blood dyscrasias or with active disease of the central nervous system. All patients receiving metronidazole for more than 10 days should be monitored and treatment discontinued if signs of peripheral neuropathy or central nervous system toxicity develop. Doses should be reduced in patients with severe liver disease.
When given in conjunction with alcohol, metronidazole may provoke a disulfiram-like reaction is some individuals; reactions have occured after the administration of pharmaceutical preparations formulated with alcohol, including injections, as well as after drinking alcohol. Acute psychoses or confusion have been associated with the concomitant use of metronidazole and disulfiram.
Although metronidazole had no effect on the elimination of antipyrine in healthy subjects and, by interference, has little effect of hepatic drug-metabolising enzymes, it enhances the anticoagulant effect of warfarin and may impair the clearance of phenytoin, of lithium and of fluorouracil. There is some evidence that phenytoin might accelerate the metabolism of metronidazole. Plasma concentrations of metronidazole are decreased by the concomitant administration of phenobarbitone, with a consequent reduction in the effectiveness of metronidazole. Cimetidine has increased plasma concentrations of metronidazole and might increase the risk of neurological side-effects.
Metronidazole has anti-treponemal activity and may mask the immunological response seen in untreated early syphilis, contracts of syphilis receiving metronidazole should probably be screened for an additional 4 to 8 weeks.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
See “Side-effects and Special Precautions”above. Treatment is symptomatic and supportive.

IDENTIFICATION:
Biconvex white tablets with score on one side.

PRESENTATION:
10 x 400 mg tablets (white securitainers with snap-on lids)
100 x 400 mg tablets (white securitainers with snap-on lids)
250 x 400 mg tablets (white securitainers with snap-on lids)
500 x 400 mg tablets (white securitainers with snap-on lids)
5 000 x 400 mg tablets (turquoise bucket with snap-on lid)

STORAGE INSTRUCTIONS:
Store in below 25°C. Protect from light.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER:
27/20.2.2/0142

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
Brainware Compu (Pty) Ltd
476 Kings Highway
Lynnwood
Pretoria

DATE OF PUBLICATION OF THIS PACKAGE INSERT:

Updated on this site: April 2000

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