Tioconazole

Class: Azoles
ATC Class: D01AC07
VA Class: GU300
Chemical Name: 1-[2-[(2-Chloro-3-thienyl)methoxy]-2-(2,4-dichlorophenyl)ethyl]-1H-imidazole
Molecular Formula: C16H13Cl3N2OS
CAS Number: 65899-73-2
Brands: 1-Day, Vagistat-1

Introduction

Antifungal; azole (imidazole derivative).2 3 49 65

Uses for Tioconazole

Vulvovaginal Candidiasis

Treatment of uncomplicated vulvovaginal candidiasis (mild to moderate, sporadic or infrequent, most likely caused by Candida albicans, occurring in immunocompetent women).1 2 108 127 128 A drug of choice.4 30 74 75 76 92 93 104 108 127 128

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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.1 108 123 124

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).108 127 128 Complicated infections generally require more prolonged treatment than uncomplicated infections.108 126 127 128

Optimal regimens for treatment of vulvovaginal candidiasis caused by Candida other than C. albicans (e.g., C. glabrata, C. krusei) not identified.108 128 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).108 128 129

Tioconazole Dosage and Administration

Administration

Intravaginal Topical Administration

Administer intravaginally as a 6.5% ointment using the prefilled applicator provided by the manufacturer.1 108 123 124

Vaginal ointment is for intravaginal administration only; do not administer orally.1 Avoid contact with the eyes.1

Administer dose intravaginally high in the vaginal vault at bedtime.1 123 124

Open applicator just prior to administration to prevent contamination.1 123 124

Dosage

Pediatric Patients

Uncomplicated Vulvovaginal Candidiasis
Intravaginal

Children ≥12 years of age: One applicatorful of 6.5% ointment (approximately 300 mg of tioconazole) as a single dose at bedtime.1 123 124 May be used for self-medication.1 123 124

If clinical symptoms do not improve within 3 days, persist for >7 days, or recur within 2 months, discontinue self-medication and consult a clinician.1 108 123 124 Confirm diagnosis and rule out other pathogens and conditions that may predispose a patient to recurrent vaginal fungal infections.1 108

HIV-infected Adolescents
Intravaginal

Use same regimen recommended for other patients.108 126 Some experts recommend a duration of 3–7 days.126 Maintenance regimen of an intravaginal azole can be considered for those with recurrent episodes;126 routine primary or secondary prophylaxis (long-term suppressive or chronic maintenance therapy) not recommended.126 108

Complicated Vulvovaginal Candidiasis
Recurrent Vulvovaginal Infections Caused by Candida albicans
Intravaginal

Adolescents: 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).108 127 128

Other Complicated Vulvovaginal Infections
Intravaginal

Adolescents: CDC and others recommend 7–14 days of an intravaginal azole for vulvovaginal candidiasis that is severe, caused by Candida other than C. albicans, or occurring in those with underlying medical conditions.108 127

Adults

Uncomplicated Vulvovaginal Candidiasis
Intravaginal

One applicatorful of 6.5% ointment (approximately 300 mg of tioconazole) as a single dose at bedtime.1 123 124 May be used for self-medication.1 123 124

If clinical symptoms do not improve within 3 days, persist for >7 days, or recur within 2 months, discontinue self-medication and consult a clinician.1 108 123 124 Confirm diagnosis and rule out other pathogens and conditions that may predispose a patient to recurrent vaginal fungal infections.1 108

HIV-infected Adults
Intravaginal

Use same regimen recommended for other patients.108 126 Some experts recommend a duration of 3–7 days.126 Maintenance regimen of an intravaginal azole can be considered for those with recurrent episodes;126 routine primary or secondary prophylaxis (long-term suppressive or chronic maintenance therapy) not recommended.108 126

Complicated Vulvovaginal Candidiasis
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).108 127 128

Other Complicated Vulvovaginal Infections
Intravaginal

CDC and others recommend 7–14 days of an intravaginal azole for vulvovaginal candidiasis that is severe, caused by Candida other than C. albicans, or occurring in women with underlying medical conditions.108 127

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.a

Renal Impairment

No specific dosage recommendations at this time.a

Geriatric Patients

No specific dosage recommendations at this time.a

Cautions for Tioconazole

Contraindications

Known hypersensitivity to tioconazole, other imidazoles, or any ingredient in the formulation.1 117

Warnings/Precautions

Warnings

Use of Latex or Rubber Products

Tioconazole vaginal ointment contains petroleum base that can weaken latex or rubber products (including condoms and vaginal contraceptive diaphragms).1 108 Use of such products within 72 hours following intravaginal tioconazole treatment not recommended.1 108 124

Sensitivity Reactions

Hypersensitivity Reactions

Contact dermatitis reported following topical application of tioconazole45 46 47 48 50 51 100 or other imidazole-derivative azole antifungals.47 49 113 114

Possible cross-sensitization among the imidazoles.45 46 47 48 49 50 51 100 113

General Precautions

Selection and Use of Antifungals for Vulvovaginal Candidiasis

Prior to initial use in a woman with signs and symptoms of vulvovaginal candidiasis, confirm diagnosis by direct microscopic examination of vaginal discharge (saline or potassium hydroxide [KOH] wet mount or Gram stain) and/or cultures.1 2 108

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.108

If clinical symptoms persist after treatment, repeat tests to rule out other pathogens, confirm the original diagnosis, and rule out other conditions that may predispose a patient to recurrent vaginal fungal infections (e.g., HIV infection).1 2

Do not use for self-medication in women who are or think they may be pregnant or in those with diabetes mellitus, HIV infection, or HIV exposure.1 123 124

Specific Populations

Pregnancy

Category C.1

Lactation

Not known whether tioconazole is distributed into milk after intravaginal administration; temporarily discontinue nursing during treatment.1 2 117

Pediatric Use

Safety and efficacy not established in children <12 years of age.1 123 124

Common Adverse Effects

Vulvovaginal burning,1 2 10 86 123 irritation,10 123 vaginitis,1 pruritus,1 2 10 86 123 headache.1

Interactions for Tioconazole

Weak inducer of CYP450 isoenzymes.61 63

Drugs Metabolized by Hepatic Microsomal Enzymes

Potential pharmacokinetic interaction with drugs metabolized by CYP450 isoenzymes;61 63 interaction unlikely with usual single-dose intravaginal tioconazole regimen117 since only low amounts of the drug absorbed systemically.1 2

Specific Drugs

Drug

Interaction

Comments

Oral contraceptives

Efficacy of intravaginal tioconazole not affected by concomitant oral contraceptives1

Tioconazole Pharmacokinetics

Absorption

Bioavailability

Following intravaginal administration, only small amounts absorbed systemically;1 2 3 18 84 peak plasma concentrations usually attained within 2–24 hours.84

Distribution

Extent

Unabsorbed drug persists in vaginal fluid for 24–72 hours following an intravaginal dose.2 18 84 87

Not known whether tioconazole is distributed into milk.1

Elimination

Elimination Route

Does not appear to be metabolized in vaginal fluid.2 After oral administration of radiolabeled tioconazole, systemically absorbed drug excreted in urine as metabolites (25–27% of the oral dose) and in feces as unchanged drug (59% of the oral dose).2 6

Stability

Storage

Intravaginal

Ointment

15–30°C;1 123 124 expires 3 years following the date of manufacture.91

Actions and Spectrum

  • Imidazole-derivative azole antifungal.2 3 49 65

  • Usually fungistatic in action; can be fungicidal at high concentrations or against very susceptible organisms (e.g., Candida).2 7 8 37 39 59 81

  • Presumably exerts its antifungal activity by altering cellular membranes, resulting in increased membrane permeability, secondary metabolic effects, and growth inhibition.59 62 68 69 77 81 90 111 Interferes with ergosterol synthesis probably via inhibition of C-14 demethylation of sterol intermediates (e.g., lanosterol).12 59 62 68 69 77 81 90 111

  • Spectrum of antifungal activity includes many fungi, including yeasts and dermatophytes.1 3 64 Also has in vitro activity against some gram-positive and gram-negative bacteria,3 53 87 Trichomonas,3 22 and Chlamydia.22

  • Candida: Active in vitro and in vivo against C. albicans,2 23 24 25 43 44 62 C. glabrata (formerly Torulopsis glabrata),2 24 101 C. krusei,2 24 C. parapsilosis,2 24 C. pseudotropicalis,2 24 and C. tropicalis.2

  • Dermatophytes and other fungi: Active in vitro against Epidermophyton floccosum,3 43 44 53 64 E. stockdaleae,53 Microsporum canis,3 23 44 64 M. gypseum,3 23 64 Trichophyton mentagrophytes,3 23 43 44 64 T. rubrum,3 23 43 44 54 103 T. tonsurans.3 64 Also active against Aspergillus3 23 87 and Cryptococcus neoformans.3 23 24 64

  • Bacteria: Active in vitro against Corynebacterium minutissimum, Enterococcus faecalis (formerly Streptococcus faecalis),87 Gardnerella vaginalis (formerly Haemophilus or Corynebacterium vaginalis),3 87 H. ducreyi ,87 Helicobacter pylori,52 , Mobiluncus,87 Moraxella catarrhalis (formerly Branhamella catarrhalis),87 Neisseria gonorrhoeae,87 N. meningitidis,87 Staphylococcus aureus,87 S. epidermidis,87 and some streptococci.3 87

  • Other organisms: Active against Chlamydia trachomatis,3 Lymphogranuloma venereum,3 and Trichomonas vaginalis.3 22

  • C. albicans, C. glabrata, C. krusei, C. tropicalis, and C. parapsilosis with reduced susceptibility to tioconazole reported.2 31 32 34 90 101 111

  • Cross-resistance can occur among the azole antifungals.31 32 34 90 111

Advice to Patients

  • Importance of reading and understanding manufacturer’s patient instructions regarding use of applicator for intravaginal administration.117 123 124

  • Not for self-medication in women who have never had a vaginal yeast infection diagnosed by a clinician.1 123 124

  • Not for self-medication in women who think they are pregnant or have been exposed to HIV.1 123 124

  • Importance of discontinuing self-medication of vulvovaginal candidiasis and consulting clinician if fever, abdominal pain, or foul-smelling discharge develops; if symptoms do not improve within 3 days, if condition persists beyond 7 days, or if symptoms recur within 2 months.1 72 108 123 124

  • Importance of informing clinicians if irritation, sensitization, fever, chills, or flu-like symptoms occur.1 123 124

  • Advise patients that a single intravaginal dose of tioconazole 6.5% ointment generally is effective,1 2 3 108 but complete relief may not occur on the day of treatment.123 124 Most women experience some relief of symptoms within 1 day and complete relief within 7 days.123 124

  • Importance of not using latex or rubber products such as condoms or vaginal contraceptive diaphragms within 72 hours following tioconazole treatment.1 108 124

  • Importance of not having vaginal intercourse, douching, using spermicides, or other vaginal products after an intravaginal dose of tioconazole.10 123 124

  • If used during menstruation,1 56 72 117 importance of using sanitary napkins instead of vaginal tampons.1 56 72 123 124

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

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1 123 124

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

Preparations

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

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Tioconazole

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Vaginal

Ointment

6.5%*

1-Day (available in prefilled, disposable applicators)

Personal Products

Tioconazole Vaginal Ointment (available in prefilled, disposable applicators)

Perrigo

Vagistat-1 (available in prefilled, disposable applicators)

Novartis

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

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