Norzol 200mg/5ml Oral Suspension

Metronidazole Benzoate Ph Eur 320mg/5ml

Oral Suspension

Norzol is indicated in the prophylaxis and treatment of infections in which anaerobic bacteria have been identified or are suspected as the pathogen.

Norzol is active against a wide range of pathogenic micro-organisms, notably Trichomonas vaginalis, Entamoeba histolytica, Giardia lamblia, Balantidium coli and other species of bacteroides, fusobacteria, eubacteria, clostridia and anaerobic cocci.

It is indicated in:

1. The treatment of urogenital trichomoniasis in the female (trichomonal vaginitis) and in the male.

2. Bacterial vaginosis (also known as non-specific vaginitis, anaerobic vaginitis or Gardnerella vaginitis).

3. All forms of amoebiasis (intestinal and extra-intestinal disease and that of symptomless cyst passers).

4. Giardiasis.

5. Acute ulcerative gingivitis.

6. Anaerobically infected leg ulcers and pressure sores.

7. Acute dental infections (e.g. acute pericoronitis and acute apical infections).

8. The treatment of septicaemia, bacteraemia, brain abscess, necrotising pneumonia, osteomyelitis, puerperal sepsis, pelvic abscess, pelvic cellulitis, peritonitis and post-operative wound infections from which one or more pathogenic anaerobes have been isolated.

9. The prevention of post-operative infections caused by anaerobic bacteria particularly species of bacteroides and anaerobic streptococci.

For oral administration only.

A: Prophylaxis: against anaerobic infection- chiefly in the context of abdominal (especially colorectal) and gynaecological surgery.

Dosage: 400mg at 8 hourly intervals during the 24 hours preceding the operation followed by postoperative intravenous or rectal administration until the patient is able to take Norzol by mouth.

Children: 7.5mg/Kg every 8 hours.

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

B: Treatment of established anaerobic infection:

800mg followed by 400mg at 8 hourly intervals.

Children: 7.5mg/Kg every 8 hours.

C: Treatment of Protozoal and Other Infections:

(See Table).

Dosage is given in terms of metronidazole or metronidazole equivalent.

* Children and babies weighing less than 10Kg should receive proportionally smaller doses.

** Norzol is well tolerated by the elderly, but a pharmacokinetic study suggests cautious use of high dosage regimen in this age group.

Known hypersensitivity to Metronidazole and/or hydroxybenzoates.

If treatment for more than 10 days is considered to be necessary, regular clinical and laboratory monitoring are advised.

There is the possibility that after Trichomonas vaginalis has been eliminated a gonococcal infection might persist.

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 re-administered immediately after haemodialysis.

No routine adjustment in the dosage of Norzol need be made in patients with renal failure undergoing intermittent peritoneal dialysis (IPD) 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 encephalopathy.

Norzol should be administered with caution to patients with hepatic encephalopathy. The daily dosage may be reduced to one third and may be administered once daily.

Caution is advised in patients with active disease of the central nervous system other than brain abscess.

Norzol contains glucose, sucrose and sorbitol. Each 5ml contains 1.1g glucose, 0.6g sucrose and 0.6g sorbitol. Patients with hereditary fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine. The glucose and sucrose content should be taken into account in patients with diabetes mellitus. It may also be harmful to teeth.

Methyl, ethyl and propyl hydroxybenzoates are contained in this product which may cause allergic reactions (possibly delayed).

Patients should be advised not to take alcohol during metronidazole therapy and for at least 48 hours afterwards because of the possibility of a disulfiram-like (antabuse effect) reaction.

Some potentiation of anticoagulant therapy has been reported when metronidazole has been used with the warfarin type oral anti-coagulants. Dosage of the anticoagulant may require reducing. Prothrombin time should be monitored. No interactions have been reported of the heparin type.

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 concentration of lithium, creatinine and electrolytes should be monitored in patients under treatment with lithium while they receive metronidazole.

Patients receiving phenobarbital metabolise metronidazole at a much greater rate than normally, reducing the half life to approximately three hours.

Aspartate amino transferase assays may give spuriously low values in patients taking metronidazole, depending on the method used.

Clinicians who contemplate continuous therapy for the relief of chronic conditions, for periods no longer than those recommended, are advised to consider the possible therapeutic benefit against the risk of peripheral neuropathy.

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 coadministration is necessary.

Plasma levels of busulfan may be increased by metronidazole which may lead to severe busulfan toxicity.

There is inadequate evidence of the safety of metronidazole in pregnancy. Norzol should not therefore be given during pregnancy or during lactation unless the physician considers it essential, in these circumstances short, high dosage regimes are not recommended.

A significant amount of metronidazole is found in breast milk and breast feeding should be avoided after a large dose. This could give a bitter taste to the milk.

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.

Serious adverse reactions occur very rarely with standard recommended regimens. Unpleasant taste in the mouth, oral mucositis furred tongue, nausea, vomiting, gastro-intestinal disturbances, anorexia, urticaria and angioedema occur occasionally. Anaphylaxis may occur rarely. Erythema multiforme may occur, which may be reversed on drug withdrawal.

Abnormal liver function tests, cholestatic hepatitis, jaundice and pancreatitis, reversible on drug withdrawal have been reported but very rarely.

Agranulocytosis, neutropaenia, thrombocytopaenia and pancytopaenia, often reversible on drug withdrawal have been very rarely reported, although fatalities have occurred.

Drowsiness, dizziness, headache, ataxia, skin rashes, pustular eruptions, pruritus, inco-ordination of movement, darkening of the urine (due to metronidazole metabolite), myalgia, arthralgia and transient visual disorders such as diplopia and myopia have been reported but very rarely.

During intensive and/or prolonged metronidazole therapy a few instances of peripheral neuropathy or transient epileptiform seizures have been reported. In most cases neuropathy disappeared after treatment was stopped or when dosage was reduced. However, clinicians who contemplate continuous therapy for the relief of chronic conditions, for periods longer than those recommended are advised to consider the possible therapeutic benefit against the risk of peripheral neuropathy. A moderate leucopenia has been reported in some patients but the white cell count has always returned to normal before or after treatment has been completed.

Psychotic disorders, including confusion and hallucinations, have been reported very rarely.

Norzol contains glycerol, which can cause headache, gastro-intestinal disturbance and diarrhoea.

The parahydroxybenzoates used in Norzol may cause immediate or delayed hypersensitivity reactions.

Uneventful recovery has followed attempts at suicide with quantities of between 6 and 12g. There is no specific treatment for gross overdose of Norzol, however, early gastric lavage and symptomatic support is advised.

The selective action of this compound against anaerobes and anoxic and hypoxic cells is due to the mode of action. The nitro group of metronidazole acts as electron acceptor and is thus reduced to a chemically reactive drug form. This produces biochemical lesions in the cells, thus causing death. The major site of action is believed to be DNA, where it causes loss of the helical structure and inhibits synthesis.

It is readily absorbed from the gastro-intestinal tract and widely distributed in body tissues. Half life in plasma is about 8-10 hours. About 10% is bound to plasma proteins.

It penetrates well into body tissues and fluids, including vaginal secretions, seminal fluid, saliva and breast milk. Therapeutic concentrations are also achieved in cerebrospinal fluid.

Unchanged metronidazole and several metabolites are excreted in the urine, the liver is the main site of metabolism and the major metabolites are as a result of side chain oxidation, forming glucuronides.

Not applicable

Dispersible cellulose, colloidal silicon dioxide, sucrose, glucose, sorbitol solution, glycerine, polysorbate 80, methyl hydroxybenzoate, ethyl hydroxybenzoate, propyl hydroxybenzoate, propylene glycol, lemon flavour, orange flavour and purified water.

None known

24 months

Store below 25°C and protect from light.

Bottle: Amber (Type III) glass

Pack Sizes: 60ml, 100ml, 125ml and 150ml.

Keep out of the reach of children.

Shake the bottle well before use.

If a dose of under 5ml is required, the suspension should be administered using an oral dosing device.

Rosemont Pharmaceuticals Ltd

Rosemont House

Yorkdale Industrial Park

Braithwaite Street

Leeds

LS11 9XE

PL 00427/0068

18.5.84

24 June 2010