VA Class: GU300
Chemical Name: cis - 1 - [4 - [2 - (2,4 - Dichlorophenyl) - 2 - (1H - 1,2,4 - triazol - 1 - ylmethyl) - 1,3 - dioxolan - 4 - yl]methoxy]phenyl] - 4 - (1 - methylethyl)piperazine
Molecular Formula: C26H31Cl2N5O3
CAS Number: 67915-31-5
Uses for Terconazole
Treatment of uncomplicated vulvovaginal candidiasis (mild to moderate, sporadic or infrequent, most likely caused by Candida albicans, occurring in immunocompetent women).1 3 5 15 16 17 18 19 20 21 22 23 24 27 33 37 47 49 65 67 68 A drug of choice.37 47 51 52 53 54 56 57 58 65 67 68
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).47 53 54 56 57 58 67 68 Complicated infections generally require more prolonged treatment than uncomplicated infections.47 66 67 68
Optimal regimens for treatment of vulvovaginal candidiasis caused by Candida other than C. albicans (e.g., C. glabrata, C. krusei) not identified.47 68 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).47 68 69
Terconazole Dosage and Administration
Intravaginal Topical Administration
Administer intravaginally as a cream or suppository.1
Uncomplicated Vulvovaginal Candidiasis
Complicated Vulvovaginal Candidiasis
Recurrent Vulvovaginal Infections Caused by Candida albicansIntravaginal
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).47 52 54 58 64 67 68
Other Complicated Vulvovaginal InfectionsIntravaginal
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.47 67
HIV-infected patients: Use same regimen recommended for other patients.47 66 Some experts recommend a duration of 3–7 days.66 Maintenance regimen of an intravaginal azole can be considered for those with recurrent episodes;66 routine primary or secondary prophylaxis (long-term suppressive or chronic maintenance therapy) not recommended.47 66
No specific dosage recommendations at this time.a
No specific dosage recommendations at this time.a
No specific dosage recommendations at this time.a
Cautions for Terconazole
Known hypersensitivity to terconazole or any ingredient in the formulation.1
Possible flu-like syndrome, characterized by fever, chills, headache, and/or hypotension and occasionally by vertigo and nausea.45 May be immunoallergenic45 or may be a reaction to the dying fungi (similar to the Jarisch-Herxheimer reaction observed during penicillin therapy for syphilis).46
If irritation, sensitization, fever, chills, or flu-like symptoms occur and appear to be drug related, discontinue and do not reinstitute terconazole therapy.1
Photosensitivity reactions reported following repeated topical application to the skin of 0.8 or 2% terconazole cream and exposure to filtered artificial ultraviolet light; not reported to date following intravaginal administration of 0.4 or 0.8% cream or 80-mg suppositories.1 3
Use of Latex/Rubber Contraceptive Diaphragms
Hydrogenated vegetable oil base contained in terconazole vaginal suppositories may interact with certain rubber or latex products such as vaginal contraceptive diaphragms; concurrent use not recommended.1 Consider use of terconazole vaginal cream as an alternative to the suppositories.43 44
Selection and Use of Antifungals for Vulvovaginal Candidiasis
Prior to initial use of terconazole 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 47
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.47
If clinical symptoms persist, tests should be repeated to rule out other pathogens and to confirm the original diagnosis.1
Because terconazole is absorbed systemically following intravaginal administration, manufacturer states the drug should not be used during the first trimester of pregnancy unless the clinician considers it essential to the welfare of the patient.1 CDC and others state that a 7-day regimen of an intravaginal azole antifungal can be used, if necessary, for treatment of vulvovaginal candidiasis in pregnant women.47 67
Insufficient experience from clinical studies to determine whether patients ≥65 years of age respond differently than younger adults.1 Other clinical experience has not identified age-related differences in response.1
Common Adverse Effects
Interactions for Terconazole
Small amounts of terconazole (about 5–16% of a dose) are slowly absorbed systemically following intravaginal administration.1 3 14 The amount of drug absorbed is proportional to the dose (regardless of dosage form)3 14 and absorption is similar in women with or without vulvovaginal candidiasis.3
Distribution into body tissues and fluids following intravaginal administration has not been determined.a
Following oral administration, half-life is 6.9 hours.1
Presumably exerts its antifungal activity by altering cellular membranes resulting in increased membrane permeability, leakage of essential elements (e.g., amino acids, potassium), and impaired uptake of precursor molecules (e.g., purine and pyrimidine precursors to DNA).3 4 8 12 34 Inhibits cytochrome P-450 14-α-desmethylase in susceptible fungi, which leads to accumulation of C-14 methylated sterols (e.g., lanosterol) and decreased concentrations of ergosterol.3 4 6 8 12 28 34
Spectrum of antifungal activity includes many fungi, including yeasts and dermatophytes.3 7 8 10 11 12 14 15 31 At high concentrations, has some in vitro activity against gram-positive and -negative bacteria.7 11 25 31 34
Dermatophytes and other fungi: Active in vitro against Trichophyton mentagrophytes,3 11 31 T. rubrum,3 11 31 T. tonsurans,3 11 T. verrucosum,3 11 and Epidermophyton floccosum.3 11 Also active against Cryptococcus neoformans.3 11 31
Advice to Patients
Importance of reading and understanding manufacturer’s patient instructions regarding use of applicator for intravaginal administration.1
Importance of informing clinicians if irritation, sensitization, fever, chills, or flu-like symptoms occur.1
Importance of women following clinician's advice regarding sexual intercourse and informing partner to seek medical advice if penile itching, redness, or discomfort occurs.1
Importance of not using rubber or latex products such as vaginal contraceptive diaphragms when using terconazole vaginal suppositories;1 use of terconazole vaginal cream should be considered as an alternative.43 44
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.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. (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Terazol 7 (with propylene glycol; with applicator)
Terconazole Vaginal Cream
Terazol 3 (with propylene glycol; with applicator)
Terconazole Vaginal Cream
Terazol 3 (in a hydrogenated vegetable oil base; with applicator)
Terconazole Vaginal Suppositories (in a hydrogenated vegetable oil base; with applicator)
AHFS DI Essentials. © Copyright, 2004-2016, Selected Revisions July 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
1. Ortho-McNeil Pharmaceutical, Inc. Terazol 7 (terconazole) vaginal cream 0.4%, Terazol 3 (terconazole) vaginal cream 0.8%, and Terazol 3 (terconazole) vaginal suppositories prescribing information. Raritan, NJ; 2003 Apr.
3. Ortho Pharmaceutical Corporation. Terazol (terconazole 0.4% cream/80 mg suppositories) clinical monograph. Raritan, NJ; 1988 Jun.
4. Wilborn WH, Shields RL, Hyde BM et al. Mode of action of terconazole on Candida albicans as shown by scanning and transmission electron microscopy during treatment for vulvovaginal candidiasis. Am J Gynecol Health. 1988; 2:51-6.
5. Kjaeldgaard A, Larsson B. Single-blind comparative clinical trial of short-term therapy with terconazole versus clotrimazole vaginal tablets in vulvovaginal candidiasis. Curr Ther Res Clin Exp. 1985; 38:939-44.
6. Borgers M, Van den Bossche H, De Brabander M. The mechanism of action of the new antimycotic ketoconazole. Am J Med. 1983; 74(Suppl 1B):2-8. [IDIS 165048] [PubMed 6295147]
7. Isaacson DM, Foleno B, Tolman EL et al. In vitro studies with terconazole. Gynakol Rundsch. 1985; 25(Suppl 1):12-25. [PubMed 3891537]
8. Tolman EL, Isaacson DM, Rosenthale ME et al. Anticandidal activities of terconazole, a broad-spectrum antimycotic. Antimicrob Agents Chemother. 1986; 29:986-91. [PubMed 3729366]
9. Smith KJ, Warnock DW, Kennedy CTC et al. Azole resistance in Candida albicans. J Med Vet Mycol. 1986; 24:133-44. [PubMed 3014106]
10. Cauwenbergh G. New and prospective developments in antifungal drugs. Acta Derm Venereol. 1986; 121(Suppl):147-53.
11. Van Cutsem J, Van Gerven F, Zaman R et al. Terconazole—a new broad-spectrum antifungal. Chemotherapy. 1983; 29:322-31. [PubMed 6617296]
12. Isaacson DM, Tolman EL, Tobia AJ et al. Selective inhibition of 14α-desmethyl sterol synthesis in Candida albicans by terconazole, a new triazole antimycotic. J Antimicrob Chemother. 1988; 21:333-43. [PubMed 3129389]
13. Turner CA, Turner A, Warnock DW. High performance liquid chromatographic determination of ketoconazole in human serum. J Antimicrob Chemother. 1986; 18:757-63. [PubMed 3546244]
14. Kennedy BK, Friedmann N. Terconazole cream and suppositories: plasma terconazole following vaginal administration. Gynakol Rundsch. 1985; 25(Suppl 1):26-32. [PubMed 4007621]
15. Del Palacio-Hernanz, Sanz-Sanz F, Rodriquez-Noriega A. Double-blind investigation of R-42470 (terconazole cream 0.4%) and clotrimazole (cream 1%) for the topical treatment of mycotic vaginitis. Chemioterapia. 1984; 3:192-5. [PubMed 6529776]
16. Loendersloot EW. Demonstration of effectiveness and tolerability of terconazole 80-mg vaginal suppositories (3 days) versus terconazole 240-mg vaginal suppositories (1 day) versus clotrimazole 200-mg vaginal tablets (3 days) in non-pregnant women with vulvovaginal candidosis. Gynakol Rundsch. 1985; 25(Suppl 1):99-104. [PubMed 4007627]
17. Munnich W, Hiltl BP. Single-day topical treatment of vaginal candidosis: an open evaluation of terconazole 240-mg vaginal suppositories versus isoconazole tablets 600 mg. Gynakol Rundsch. 1985; 25(Suppl 1):90-8. [PubMed 4007626]
18. Grice G, Spencer RC, Steele CE et al. One-day treatment of vaginal candidosis: comparison of terconazole 240-mg suppository with clotrimazole 500-mg vaginal tablet. Gynakol Rundsch. 1985; 25(Suppl 1):83-9. [PubMed 3891541]
19. Goormans E. Comparative double-blind evaluation of the efficacy and tolerability of terconazole 240-mg suppository (1 day) and 80-mg suppositories (3 days) versus clotrimazole 200-mg (3 days) in pregnant patients with vulvovaginal candidosis. Gynakol Rundsch. 1985; 25(Suppl 1):74-82. [PubMed 3891540]
20. Wesel S, Benijts G, Ubachs JMH et al. Comparative open evaluation of efficacy and tolerability of terconazole 0.8% cream in a 5-day regimen versus clotrimazole 100-mg tablets in a 6-day regimen. Gynakol Rundsch. 1985; 25(Suppl 1):67-73. [PubMed 4007625]
21. Litschgi M. Assessment of clinical efficacy and tolerability of terconazole 240-mg vaginal suppositories. Gynakol Rundsch. 1985; 25(Suppl 1): 59-66. [PubMed 4007623]
22. Nahmanovici C. Treatment of vaginal candidosis with three 80-mg terconazole vaginal suppositories: results of a multicentre study in France. Gynakol Rundsch. 1985; 25(Suppl 1):52-8. [PubMed 3891539]
23. Delecour M. Advantages of a 6- to 7-day treatment with 40-mg vaginal suppositories of terconazole against vaginal candidosis: conclusions drawn from a phase II multicentre study in France. Gynakol Rundsch. 1985; 25(Suppl 1):42-51. [PubMed 3891538]
24. Siedentopf HG. Terconazole 0.8% vaginal cream (5 days) versus clotrimazole 1% (6 days): efficacy and tolerability in an open study. Gynakol Rundsch. 1985; 25(Suppl 1):33-41. [PubMed 4007622]
25. Cartwright RY. Terconazole, a new triazole antifungal agent. Gynakol Rundsch. 1985; 25(Suppl 1):6-11. [PubMed 4007624]
26. Hirsch HA. Vulvovaginal candidosis: definition of the disease and its special problems and treatment in pregnancy. Gynakol Rundsch. 1985; 25(Suppl 1):1-5. [PubMed 4007619]
27. Martinek G. Summary of clinical studies with vaginal formulations of terconazole. Gynakol Rundsch. 1985; 25(Suppl 1):105-13. [PubMed 3891536]
28. Saag MS, Dismukes WE. Azole antifungal agents: emphasis on new triazoles. Antimicrob Agents Chemother. 1988; 32:1-8. [IDIS 243869] [PubMed 2831809]
29. Holmberg K. In vitro assessment of antifungal drug resistance. Acta Derm Venereol. 1986; 121:131-8.
30. Odds FC, Cheesman SL, Abbott AB. Suppression of ATP in Candida albicans by imidazole and derivative antifungal agents. Sabouraudia. 1985; 23:415-24. [PubMed 3913012]
31. Heeres J, Hendrickx R, Van Cutsem J. Antimycotic azoles: 6. Synthesis and antifungal properties of terconazole, a novel triazole ketal. J Med Chem. 1983; 26:611-3. [PubMed 6834396]
32. Odds FC, Webster CE, Abbott AB. Antifungal relative inhibition factors: BAY 1-9139, bifonazole, butoconazole, isoconazole, itraconazole (R 51211), oxiconazole, Ro 14-4767002, sulconazole, terconazole and vibunazole (BAY n-7133) compared in vitro with nine established antifungal agents. J Antimicrob Chemother. 1984; 14:105-14. [PubMed 6094418]
33. Vartiainen E, Widholm O. Single-dose therapy of vulvovaginal candidosis: comparison of terconazole and clotrimazole. Curr Ther Res. 1988; 44:185-8.
34. Vanden Bossche H, Lauwers W, Willemsens G et al. Molecular basis for the antimycotic and antibacterial activity of N-substituted imidazoles and triazoles: the inhibition of isoprenoid biosynthesis. Pestic Sci. 1984; 15:188-98.
35. Anon. Discussion. Gynakol Rundsch. 1985; 25(Suppl 1):114-7. [PubMed 4007620]
36. Hay RJ. Recent advances in the management of fungal infections. Quarterly J Med. 1987; 64(No. 244):631-9.
37. Anon. Drugs for sexually transmitted diseases. Treat Guidel Med Lett. 2004; 2:67-74. [PubMed 15529116]
38. 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]
39. Beggs WH, Andrews FA, Sarosi GA. Minireview: action of imidazole-containing antifungal drugs. Life Sci. 1981; 28:111-8. [PubMed 7019609]
40. Borgers M. Mechanism of action of antifungal drugs, with special reference to the imidazole derivatives. Rev Infect Dis. 1980; 2:520-34. [IDIS 124096] [PubMed 7003674]
41. Sud IJ, Feingold DS. Mechanisms of action of the antimycotic imidazoles. J Invest Dermatol. 1981; 76:438-41. [IDIS 133194] [PubMed 7017013]
42. Pye GW, Marriott. Inhibition of sterol C14 demethylation by imidazole-containing antifungals. Sabouraudia. 1982; 20:325-9. [PubMed 6760419]
43. Murphy RJ. (Ortho Pharmaceutical Corporation, Raritan, NJ): Personal communication; 1988 Dec.
44. Reviewers’ comments (personal observations); 1988 Dec.
45. Moebius UM. Influenza-like syndrome after terconazole. Lancet. 2:966-7. Letter.
46. Geiger AJ. Influenza-like syndrome after terconazole. Lancet. 1988; 2:1192. [IDIS 248142] [PubMed 2903397]
47. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep. 2006; 55(No. RR-11):1-96.
49. Doering PL, Santiago TM. Drugs for treatment of vulvovaginal candidiasis: comparative efficacy of agents and regimens. DICP. 1990; 24:1078-83. [IDIS 274670] [PubMed 2275233]
50. Sobel JD. Pathogenesis and treatment of recurrent vulvovaginal candidiasis. Clin Infect Dis. 1992; 14(Suppl 1):S148-53.
51. Hay RJ. Yeast infections. Dermatol Clin. 1996; 14:113-24. [PubMed 8821164]
52. Doering PL, Santiago TM. Drugs for the treatment of vulvovaginal candidiasis: comparative efficacy of agents and regimens. DICP. 1990; 24:1078-83. [IDIS 274670] [PubMed 2275233]
53. Sobel JD. Vaginitis. N Engl J Med. 1997; 337:1896-903. [IDIS 401347] [PubMed 9407158]
54. 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]
55. 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.
56. Bohannon NJV. Treatment of vulvovaginal candidiasis in patients with diabetes. Diabetes Care. 1998; 21:451-6. [IDIS 402373] [PubMed 9540031]
57. Tobin MJ. Vulvovaginal candidiasis: topical vs. oral therapy. Am Fam Physician. 1995; 51:1715-24. [IDIS 348350] [PubMed 7754931]
58. Sobel JD. Controversial aspects in the management of vulvovaginal candidiasis. J Am Acad Dermatol. 1994; 31: S10-3. [IDIS 335764] [PubMed 8077494]
59. 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]
60. Chaim W. Fungal vaginitis caused by nonalbicans species. Am J Obstet Gynecol. 1997; 177: 485. [IDIS 393344] [PubMed 9290485]
61. Spinillo A, Capuzzo E. Fungal vaginitis caused by nonalbicans species. Am J Obstet Gynecol. 1997; 177: 485-6.
62. 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.
63. Sobel JD. Pathogenesis and treatment of recurrent vulvovaginal candidiasis. Clin Infect Dis. 1992; 14(Suppl 1):S148-53.
64. Reviewers’ comments (personal observations) on Tioconazole 84:04.08.
65. Anon. Drugs for vulvovaginal candidiasis. Med Lett Drugs Ther. 2001; 43:3-4. [PubMed 11151090]
66. 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.
67. 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.
68. Pappas GP, Rex JR, Sobel JD et al. Guidelines for treatment of candidiasis. Clin Infect Ids. 2004; 38:161-89.
69. Anon. Antifungal drugs. Treat Guidel Med Lett. 2005; 3:7-14. [PubMed 15671963]
a. AHFS drug information 2003. McEvoy GK, ed. Terconazole. Bethesda, MD: American Society of Health-System Pharmacists; 2003:3365-69.
More about terconazole topical
- Terconazole (FDA)
- Terconazole Vaginal Cream (FDA)
- Terconazole Vaginal Cream 0.8% (FDA)
- Terconazole (Wolters Kluwer)