Butoconazole

Class: Azoles
ATC Class: G01AF15
VA Class: GU300
Chemical Name: (±)-1-[4-(4-Chlorophenyl)-2-[2,6-dichlorophenyl) thio]butyl]-1H-imidazole mononitrate
Molecular Formula: C19H17Cl3N2S•HNO3
CAS Number: 64872-77-1
Brands: Gynazole-1, Mycelex-3

Introduction

Antifungal; azole (imidazole derivative).1 2 3

Uses for Butoconazole

Vulvovaginal Candidiasis

Treatment of uncomplicated vulvovaginal candidiasis (mild to moderate, sporadic or infrequent, most likely caused by Candida albicans, occurring in immunocompetent women).1 4 6 7 24 29 30 31 48 51 A drug of choice.7 29 34 35 36 37 39 40 41 48 51

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Self-medication (OTC use) for treatment of uncomplicated vulvovaginal candidiasis in otherwise healthy, nonpregnant women who have been previously diagnosed by a clinician and are having recurrence of similar symptoms.29 47

Treatment of complicated vulvovaginal candidiasis, including infections that are recurrent (≥4 episodes in 1 year), severe (extensive vulvar erythema, edema, excoriation, fissure formation), caused by Candida other than C. albicans, or occurring in women with underlying medical conditions (uncontrolled diabetes mellitus, HIV infection, immunosuppressive therapy, pregnancy).7 29 35 36 37 41 46 Complicated infections generally require more prolonged treatment than uncomplicated infections.29 49 50

Optimal regimens for treatment of vulvovaginal candidiasis caused by Candida other than C. albicans (e.g., C. glabrata, C. krusei) not identified.29 48 CDC and others state these infections may respond to an intravaginal azole antifungal given for 7–14 days or to a 14-day regimen of intravaginal boric acid (not commercially available in the US).29 48 51

Butoconazole Dosage and Administration

Administration

Intravaginal Topical Administration

Administer intravaginally as a cream using the prefilled applicator provided by the manufacturer.1 47

Vaginal cream is for intravaginal administration only and should not be administered orally.47 Contact with the eyes should be avoided.47

Dosage

Pediatric Patients

Uncomplicated Vulvovaginal Candidiasis
Intravaginal

Mycelex-3: Children ≥12 years of age: One applicatorful of 2% cream (approximately 100 mg of the drug) once daily at bedtime for 3 consecutive days.29 47 May be used for self-medication.47

Adults

Uncomplicated Vulvovaginal Candidiasis
Intravaginal

Gynazole-1: One applicatorful of 2% cream (approximately 100 mg of the drug) as a single dose.1 29

Mycelex-3: One applicatorful of 2% cream (approximately 100 mg of the drug) once daily at bedtime for 3 consecutive days.29 47 May be used for self-medication.47

If clinical symptoms persist, tests should be repeated to rule out other pathogens, to confirm the original diagnosis, and to rule out other conditions that may predispose a patient to recurrent vaginal fungal infections.1

Complicated Vulvovaginal Candidiasis
Vulvovaginal Candidiasis in HIV-infected Women
Intravaginal

Use same intravaginal regimen recommended for women without HIV infection; however29 41 46 49 some experts recommend a duration of 3–7 days.49 Maintenance regimen of an intravaginal azole can be considered for those with recurrent episodes;49 routine primary or secondary prophylaxis (long-term suppressive or chronic maintenance therapy) not recommended.29 49

Recurrent Vulvovaginal Infections Caused by Candida albicans
Intravaginal

CDC and others recommend an initial intensive regimen (7–14 days of an intravaginal azole or 3-dose regimen of oral fluconazole) to achieve mycologic remission, followed by an appropriate maintenance regimen (6-month regimen of once-weekly oral fluconazole or, alternatively, an intravaginal azole given intermittently).7 29 35 36 37 41 46 48 50

Other Complicated Vulvovaginal Infections
Intravaginal

CDC and others recommend 7–14 days of an intravaginal azole for vulvovaginal candidasis that is severe, caused by Candida other than C. albicans, or occurring in women with underlying medical conditions.29 50

Cautions for Butoconazole

Contraindications

  • Known hypersensitivity to butoconazole or any ingredient in the formulation.1

Warnings/Precautions

Warnings

Use of Latex or Rubber Products

Butoconazole vaginal cream contains mineral oil that can weaken latex or rubber products (including condoms and vaginal contraceptive diaphragms).1 29 47 Use of such products within 72 hours following intravaginal butoconazole treatment not recommended.1

General Precautions

Selection and Use of Antifungals for Vulvovaginal Candidiasis

Prior to initial use of butoconazole in a woman with signs and symptoms of vulvovaginal candidiasis, confirm the diagnosis by demonstrating yeast or pseudohyphae with direct microscopic examination of vaginal discharge (saline or 10% potassium hydroxide [KOH] wet mount or Gram stain) or by culture.1 4 5 6 24 29 31

Candida identified by culture in the absence of symptoms is not an indication for antifungal treatment since approximately 10–20% of women harbor Candida or other yeasts in the vagina.29

If clinical symptoms persist after treatment or recur within 2 months, tests should be repeated to rule out other pathogens, to confirm the original diagnosis, and to rule out other conditions that may predispose a patient to recurrent vaginal fungal infections (e.g., pregnancy, HIV infection).1 47

Do not use for self-medication in women who have never had a vaginal yeast infection diagnosed by a clinician, in women who are or think they may be pregnant, or in women with diabetes, HIV infection, or HIV exposure.47

Specific Populations

Pregnancy

Category C.1

CDC states that a 7-day regimen of an intravaginal azole antifungal can be used, if necessary, for treatment of vulvovaginal candidiasis in pregnant women.29

Lactation

Not known whether intravaginal butoconazole is distributed into milk; use with caution in nursing women.1

Pediatric Use

Gynazole-1: Safety and efficacy not established in children.1

Mycelex-3: Safety and efficacy not established in children <12 years of age.47

Common Adverse Effects

Vulvar/vaginal burning, itching, soreness and swelling, pelvic or abdominal pain or cramping.1

Butoconazole Pharmacokinetics

Absorption

Bioavailability

Following intravaginal administration, only small amounts (1.3–2.2% of a dose) are absorbed systemically;1 4 peak plasma concentrations usually attained within 12–24 hours.1 4

Distribution

Extent

Crosses placenta in animals following intravaginal administration.1 Not known whether drug is distributed into milk.1

Elimination

Metabolism

Metabolic fate following intravaginal administration not fully characterized, but systemically absorbed drug appears to be extensively metabolized probably in the liver.4

Elimination Route

The systemically absorbed fraction of an intravaginal dose appears to be excreted in urine and feces.4

Stability

Storage

Intravaginal

Cream

25°C (may be exposed to 15–30°C).1 Avoid exposure to temperatures >30°1 47 and freezing.47

Actions and Spectrum

  • Imidazole-derivative azole antifungal.1 2 3

  • Usually fungistatic in action;3 8 16 22 can be fungicidal at high concentrations or against very susceptible organisms (e.g., Candida).1 3 8 16 22

  • Presumably exerts its antifungal activity by altering cellular membranes,1 8 9 17 22 resulting in increased membrane permeability, secondary metabolic effects, and growth inhibition.1 9 17 22 Interferes with ergosterol synthesis probably via inhibition of C-14 demethylation of sterol intermediates (e.g., lanosterol).1 3 9 16 17

  • Spectrum of antifungal activity includes many fungi, including yeasts and dermatophytes.2 15 17 23 Also has in vitro activity against some gram-positive bacteria.15 23

  • Candida: Active in vitro and in vivo against C. albicans15 23 , C. glabrata,23 and C. tropicalis.23

  • Dermatophytes and other fungi: Active in vitro against Trichophyton concentricum, T. mentagrophytes, T. rubrum, T. tonsurans, Epidermophyton floccosum, Microsporum canis, and M. gypseum.15 23 Also active in vitro against Aspergillus2 and Cryptococcus.23

  • Cross-resistance can occur among the azole antifungals.2

Advice to Patients

  • Importance of reading and understanding manufacturer’s patient instructions regarding use of applicator for intravaginal administration.1 47

  • Not for self-medication in women who have never had a vaginal yeast infection diagnosed by a clinician.47

  • Importance of discontinuing self-medication of vulvovaginal candidiasis and consulting clinician if fever, abdominal pain, or foul-smelling vaginal discharge develops; if symptoms do not improve within 3 days; if condition persists after therapy; or if symptoms recur within 2 months.29 47

  • Importance of not using latex or rubber products such as condoms or vaginal contraceptive diaphragms within 72 hours following butoconazole treatment.1

  • If used during menstruation, importance of using sanitary napkins instead of vaginal tampons.47

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and concomitant illnesses.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Butoconazole Nitrate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Vaginal

Cream

2%

Gynazole-1 (with parabens, propylene glycol, and microcrystalline wax; available with prefilled, disposable applicators)

Ther-Rx

Mycelex-3 (with parabens and propylene glycol; available with or without disposable applicators)

Bayer

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions August 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Ther-Rx Corporation. Gynazole-1 (butoconazole nitrate) vaginal cream prescribing information (dated 2003 Aug). In: Physicians’ desk reference. From the PDR electronic library website (http://pdrel.thomsonhc.com). Accessed 2006 Dec 4.

2. Odds FC, Webster CE, Abbott AB. Antifungal relative inhibition factors: BAY 1-9139, bifonazole, butoconazole, isoconazole, itraconazole (R 51211), oxiconazole, Ro 14-4767/002, sulconazole, terconazole and vibunazole (BAY n-7133) compared in vitro with nine established antifungal agents. J Antimicrob Chemother. 1984; 14:105-14. [PubMed 6094418]

3. Pye GW, Marriott MS. Inhibition of sterol C14 demethylation by imidazole-containing antifungals. Sabouraudia. 1982; 20:325-9. [PubMed 6760419]

4. Droegemueller W, Adamson DG, Brown D et al. Three-day treatment with butoconazole nitrate for vulvovaginal candidiasis. Obstet Gynecol. 1984; 64:530-4. [IDIS 191594] [PubMed 6384848]

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22. Thomas AH. Suggested mechanisms for the antimycotic activity of the polyene antibiotics and the N-substituted imidazoles. J Antimicrob Chemother. 1986; 17:269-79. [PubMed 3516967]

23. Matthews T. Butoconazole: pharmacologic considerations, chemistry and microbiology. J Reprod Med. 1986; 31(Suppl):655-7.

24. Van Dyck WA Jr. A comparative study of butoconazole, miconazole and placebo. J Reprod Med. 1986; 31(Suppl):662-3.

26. Reviewers’ comments (personal observations); 1986 Jul.

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30. Anon. Drugs for sexually transmitted infections. Treat Guidel Med Lett. 2004; 2:67-74. [PubMed 15529116]

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32. Sobel JD. Pathogenesis and treatment of recurrent vulvovaginal candidiasis. Clin Infect Dis. 1992; 14(Suppl 1):S148-53.

34. Hay RJ. Yeast infections. Dermatol Clin. 1996; 14:113-24. [PubMed 8821164]

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37. Sobel JD, Faro S, Force RW et al. Vulvovaginal candidiasis: epidemiologic, diagnostic, and therapeutic considerations. Am J Obstet Gynecol. 1998; 178:203-11. [IDIS 402301] [PubMed 9500475]

38. Bisschop MPJM, Merkus JMWM, Scheygrond H et al. Co-treatment of the male partner in vaginal candidosis: a double-blind randomized control study. Br J Obstet Gynecol. 1986; 93:79-81.

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42. Spinillo A, Capuzzo E, Gulminetti R et al. Prevalence of and risk factors for fungal vaginitis caused by non-albicans species. Am J Obstet Gynecol. 1997; 176: 138-41. [PubMed 9024104]

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45. Redondo-Lopez V, Lynch M, Schmitt C et al. Torulopsis glabrata vaginitis: clinical aspects and susceptibility to antifungal agents. Obstet Gynecol. 1990; 76: 651-5.

46. Reviewers’ comments (personal observations) on Tioconazole 84:04.08.

47. Mycelex-3 Vaginal Cream product information. From BayerCare.com (.) Accessed 2006 Dec 4.

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49. Centers for Disease Control and Prevention. Treating opportunistic infections among HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association/Infectious Diseases Society of America. MMWR Recomm Rep. 2004; 53(RR-15):1-112.

50. ACOG Committee on Practice Bulletins. ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists, number 72, May 2006: vaginitis. Obste Gynecol. 2006; 107:1195-296.

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b. AHFS Drug Information 2005. McEvoy, GK, ed. Butoconazole nitrate. Bethesda, MD: American Society of Health-System Pharmacists; 2005.

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