Zidoval^TM 7.5 mg/g vaginal gel

Metronidazole 0.75% w/w, 7.5 mg/g

For excipients, see 6.1.

Vaginal gel

A colourless to straw coloured gel

Zidoval vaginal gel is indicated for the treatment of bacterial vaginosis.

For vaginal administration.

Adults

One application of Zidoval vaginal gel (5g) inserted into the vagina once daily, at bedtime, for 5 consecutive days.

Directions for use: Pierce sealed end of tube and screw open end of applicator tightly onto tube of gel. Squeeze tube, filling the applicator with gel. Remove applicator from tube and gently insert applicator into vagina as far as it will comfortably go. Push the plunger to release the gel. Dispose of applicator as instructed.

Elderly

Bacterial vaginosis is not commonly seen in the elderly population and consequently clinical assessment in this age group has not been carried out.

Children

Not recommended for use in children and adolescents under 18 years since safety and efficacy have not been established.

Zidoval vaginal gel is contraindicated in patients with a prior history of hypersensitivity to metronidazole, other nitroimidazoles, parabens or any other ingredient of the gel.

Use during menses is not recommended.

Known or previously unrecognised candidiasis may present more prominent symptoms during therapy with Zidoval vaginal gel and may require treatment with a candicidal agent.

Metronidazole is a nitroimidazole and should be used with care in patients with evidence of a history of blood dyscrasias.

As with all vaginal infections, sexual intercourse during the infection and during treatment with Zidoval vaginal gel is not recommended.

Oral metronidazole has been associated with a disulfiram-like reaction in combination with alcohol. Acute psychotic reactions and confusion have occurred during concomitant use of disulfiram with oral metronidazole. At the low serum concentrations which result from the use of Zidoval vaginal gel, the possibility of similar reactions is unlikely although cannot be excluded.

Oral metronidazole has been shown to increase the plasma concentrations of warfarin, lithium, cyclosporin and 5-fluorouracil. Similar effects after vaginal administration of metronidazole are not expected due to the low plasma concentrations but cannot be completely ruled out.

Metronidazole may interfere with certain types of determination of serum chemistry values, such as aspartate aminotransferase (AST, SGOT), alanine aminotransferase (ALT, SGPT), lactic dehydrogenase (LDH), triglycerides and hexokinase glucose. Values of zero may be observed.

Pregnancy

Data on a large number (several hundred) of exposed pregnancies indicate no adverse effects of metronidazole on the foetus/newborn child. There have been no formal studies with Zidoval vaginal gel in pregnant women. Caution should, therefore, be exercised when prescribing to pregnant women.

Lactation

The ratio of serum concentrations of Zidoval vaginal gel/oral metronidazole is approximately 0.02. Metronidazole is excreted in milk at concentrations similar to those in maternal serum and the ratio of serum concentrations of metronidazole in the breastfed infant/mother is approximately 0.15. Caution should be exercised when prescribing to lactating women.

None.

In controlled clinical trials involving 759 patients, the most commonly reported ADRs were urogenital (26%) and gastrointestinal (14%).

There is no human experience of overdosage with Zidoval vaginal gel. There is no specific treatment. Metronidazole is readily removed from the plasma by haemodialysis.

ATC classification: G01 AF01

Metronidazole is a synthetic antibacterial agent which also possesses amoebicidal activity. Zidoval vaginal gel has been shown in vivo to be active against the vaginal pathogens Gardnerella vaginalis and bacteroides species.

Significant increases in lactobacilli are observed in bacterial vaginosis patients following therapy with Zidoval.

Bioavailability studies on the administration of a single 5 gram dose of Zidoval vaginal gel into the vagina of 12 normal subjects showed a mean C_max serum concentration of 237 nanogram/ml or about 2% of the mean maximum serum concentration of a 500 mg tablet taken orally (mean C_max = 12,785 ng/ml). Under normal usage, the formulation therefore affords minimal serum concentrations of metronidazole.

Metronidazole has a large apparent volume of distribution and has the ability to penetrate the blood brain barrier and blood cerebro-spinal fluid barrier at concentrations similar to serum concentrations.

Metronidazole is metabolised in the liver by side chain oxidation and glucuronide formation and a large portion of the absorbed dose is excreted as metabolites. Both unchanged drug and metabolites are excreted mainly in the urine.

At high doses metronidazolehas been found to be mutagenic in bacteria but not in mammalian cells in vitro or in vivo. A carcinogenic potential has been demonstrated in mouse and rat but not in hamster. In epidemiological studies, no evidence of increased risk of cancer as a consequence of exposure to metronidazole has been observed.

Carbomer (Carbopol) 974P, disodium edetate, methyl parahydroxybenzoate, propyl parahydroxybenzoate, propylene glycol, sodium hydroxide, purified water.

None known

3 years

Do not store above 25 ^oC.

Aluminium tubes lined with an epoxy phenolic resin with polyethylene screw caps containing 40 g product. The product is packaged with 5 disposable vaginal applicators, each to deliver 5 g of gel.

Not applicable.

Meda Pharmaceuticals Ltd

249 West George Street

Glasgow

G2 4RB

Trading as:

Meda Pharmaceuticals Ltd

Skyway House

Parsonage Road

Takeley

Bishop's Stortford

CM22 6PU

PL 15142/0100

31 January 1997 / 16 February 2005

10th September 2009