TROSYL NAIL SOLUTION

Tioconazole 283 mg/ml.

For excipients, see 6.1.

Cutaneous solution. Clear pale yellow solution for topical application.

Tioconazole is a broad spectrum imidazole antifungal agent. Trosyl Nail Solution is indicated for the topical treatment of nail infections due to susceptible fungi (dermatophytes and yeasts) and bacteria.

Route of administration: Topical.

Adults The solution should be applied to the affected nails and immediately surrounding skin every twelve hours using the applicator brush supplied.

The duration of treatment is up to six months but may be extended to twelve months.

Use in the elderly No special precautions are required. Use the adult dose.

Use in children No special precautions are required. Use the adult dose.

Trosyl Nail Solution is contra-indicated in individuals who have been shown to be hypersensitive to imidazole antifungal agents, or to any of the components of the solution.

Use is contraindicated during pregnancy.

Trosyl Nail Solution is not for ophthalmic use.

None known.

Use DuringPregnancy: In animal studies tioconazole was not teratogenic. At high doses it increased the incidence of renal abnormalities in rat embryos, but this effect was minor and transient and was not evident in weaned animals.

There is insufficient evidence as to the drug's safety in human pregnancy although absorption after topical administration is negligible. Because of the extensive duration of treatment required for nail infections, the use of Trosyl Nail Solution is contra-indicated throughout pregnancy.

Use During Lactation: It is unknown whether this drug is excreted in human milk. Because many drugs are excreted in human milk, nursing should be temporarily discontinued while Trosyl is administered.

None known.

Trosyl Nail Solution is well tolerated upon local application. Symptoms of local irritation have been reported by some patients, but are usually seen during the first week of treatment and are transient and mild. Systemic allergic reactions are uncommon.

However, if a sensitivity reaction develops with the use of Trosyl Nail Solution, treatment should be discontinued and appropriate therapy instituted.

The undesirable effects listed below were reported with frequencies corresponding to Common (1/100, 1/10), Uncommon (1/1000, <1/100), Rare (1/10,000 to <1/1,000), or Very rare (<1/10,000) not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

No cases of overdosage with Trosyl Nail Solution have been reported. Overdosage by topical application of tioconazole is unlikely because of negligible systemic absorption. In the event of excessive oral ingestion, gastrointestinal symptoms may occur. Appropriate means of gastric lavage should be considered.

Pharmacotherapeutic group: Imidazole and triazole derivatives; ATC-code: D01AC07.

Tioconazole is an imidazole which is active against commonly occurring dermatophyte and yeast-like fungal species. It is fungicidal in murine models vs. Candida spp., T. rubrum and T. mentacrophytes. In vitro it is fungicidal to pathenogenic dermatophytes, yeasts and other fungi. All dermatophytes and Candida spp. were inhibited by 6.25 or 12.5 mg/l respectively. It is also inhibitory vs. Staph. spp. and Strep. spp. at 100 mg/l or less.

Oral doses (200 mg/kg) did not affect behaviour in rats but 25 mg/kg i.v. produced dose-related respiratory distress, gasping, tremors and prostration. Slight but dose-related impairment of performance of mice on the rotating rod occurred from 25 mg/kg. Slight anti-cholinergic and anti-histamine (H₁) activity was recorded in vitro but no effect on mice pupil size in vivo. Oral tioconazole prolonged alcohol and pentobarbital sleeping time at 150 and 37.5 mg/kg respectively.

In the anaesthetised cat i.v. tioconazole 2.5 - 10 mg/kg produced brief falls in blood pressure and increased heart rate, haematuria, tremors and twitches.

Absorption is rapid and extensive on oral administration to rats, monkeys and man, the major metabolite being a glucuronide conjugate of tioconazole. Tissue uptake in rat and monkey was highest in liver, kidney and intestinal tract with excretion in all species mainly in faeces.

Rat studies using oral, dermal and vaginal administration of C¹⁴ labelled tioconazole confirm significantly lower absorption via the topical route.

In man, oral formulations of tioconazole (500mg) gave plasma concentrations of 1300ng/ml. Topical administration of dermal cream 1% (20mg/day) for 28 days, or vaginal cream 2% (100mg/day) for 30 days gave negligible mean peak plasma levels, i.e. 10.1 and 11.5ng/ml respectively.

After single dose administration of tioconazole vaginal ointment 6.5% w/w (tioconazole 300mg) the mean peak plasma concentration was 18ng/ml in humans, achieved approximately 8 hours post dose.

None relevant to the prescriber.

Undecylenic acid, ethyl acetate.

Not applicable.

24 months.

Do not store above 25ºC. Avoid flame and heat. Do not refrigerate.

Trosyl Nail Solution is contained in an amber glass bottle with a screw cap fitted with an applicator containing 12 ml.

No special instructions are required.

Pfizer Limited

Ramsgate Road

Sandwich

Kent

CT13 9NJ

United Kingdom

PL 00057/0236

21 July 1999

January 2009

POM

TY6_0