Butoconazole nitrate 2%

Gynazole-1 (Arrow Pharmaceuticals)
single dose applicator containing 5 g of cream
Approved indication: local treatment of candidal vulvovaginitis
Australian Medicines Handbook section 17.11.1

Candida albicans is a common cause of vulvovaginitis.^1,2These infections are usually treated with imidazole antifungal drugs. Butoconazole nitrate is the fifth imidazole agent to be registered in Australia, after clotrimazole, ketoconazole, miconazole and econazole. These drugs come in a number of different formulations (including cream, pessaries and oral tablets) and dosing regimens. Although butoconazole nitrate 2% cream is a new product in Australia, it was first introduced in the USA as a prescription drug in 1986 and is currently marketed there as an over-the-counter product.

Depending on the formulation, up to 6% of an intravaginal dose is absorbed, with peak plasma levels being reached 12-24 hours after administration. The drug is excreted mainly as metabolites in the urine and faeces.

The Australian butoconazole cream has been formulated to adhere to the vaginal wall for longer than the standard butoconazole cream.³The prolonged retention time means that this formulation can be given as a single-dose application rather than a three-day course.

In a randomised open-label trial of 181 American women with vulvovaginal candidiasis, a single application of butoconazole cream was compared to a single 150 mg oral tablet of fluconazole. Twelve hours after treatment, 44.4% of women given topical butoconazole experienced first relief of symptoms compared with 29% of women given oral fluconazole. The time to complete relief of symptoms was similar in both treatment groups. Yeast cultures to confirm the presence or absence of candida were not performed in this study so the true microbiological cure rates could not be assessed. The most common butoconazole-related adverse events were vulvovaginal pruritis (3 events) and vulvovaginal burning (3 events). In the fluconazole group, headache (6 events), diarrhoea, nausea, skin sensitivity and upset stomach were the most common drug-related adverse events.⁴

In another trial, a single-dose butoconazole cream was compared to a seven-day miconazole cream. Similar levels of drug efficacy in both treatment groups were observed with regard to clinical symptoms and microbiological cultures.⁵

Two unpublished studies compared butoconazole nitrate 2% cream with a clotrimazole pessary (500 mg) in women with confirmed vulvovaginal Candida albicans infection. Microbiological and symptomatic signs of candidiasis were resolved 30 days after treatment in 79 of 118 (67%) women treated with butoconazole compared with 71 of 116 (61%) given clotrimazole.

In trials comparing butoconazole and clotrimazole vaginal treatments, irritation of the vulva, vagina or urethra were the most common drug-related adverse event. These were reported by approximately 1% of patients receiving either treatment.

The use of latex or rubber products such as condoms or contraceptive diaphragms is not recommended within 72 hours of butoconazole application. Additional topical antifungal cream may be required for the treatment of external vulval or perianal areas.

In Australia, 10% clotrimazole is the only single-dose cream already available for the treatment of candidal vulvovaginitis. It is not known whether the single-dose butoconazole formulation will be more effective.

manufacturer provided additional useful information

The Transparency Score ( ) is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.