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Fenticonazole
Fenticonazole
Fenticonazole
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Fenticonazole
Clinical data
Trade namesLomexin, Gynoxin
AHFS/Drugs.comInternational Drug Names
Routes of
administration		Topical (ovule, spray, cream)
ATC code
Legal status
Legal status
  • UK: POM (Prescription only)
  • US: Not approved
  • In general: ℞ (Prescription only)
Identifiers
  • 1-[2-(2,4-dichlorophenyl)-2-{[4-(phenylsulfanyl)phenyl]methoxy}ethyl]-1H-imidazole
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEBI
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC24H20Cl2N2OS
Molar mass455.40 g·mol−1
3D model (JSmol)
  • c1ccc(cc1)Sc2ccc(cc2)COC(Cn3ccnc3)c4ccc(cc4Cl)Cl
  • InChI=1S/C24H20Cl2N2OS/c25-19-8-11-22(23(26)14-19)24(15-28-13-12-27-17-28)29-16-18-6-9-21(10-7-18)30-20-4-2-1-3-5-20/h1-14,17,24H,15-16H2 ☒N
  • Key:ZCJYUTQZBAIHBS-UHFFFAOYSA-N ☒N
 ☒NcheckY (what is this?)  (verify)

Fenticonazole is an imidazole antifungal drug, used locally as the nitrate in the treatment of vulvovaginal candidiasis. It is active against a range of organisms including Trichophyton mentagrophytes, Malassezia furfur, and Candida albicans. Fenticonazole has also been shown to exhibit antibacterial action, with a spectrum of activity that includes bacteria commonly associated with superinfected fungal skin and vaginal infections, and antiparasitic action against the protozoan Trichomonas vaginalis.[1]

Uses and administration

[edit]

A 200 mg pessary is inserted into the vagina at bedtime for 3 nights or a 600 mg pessary is inserted once only at bedtime. The fenticonazole nitrate vaginal capsule is not greasy, does not soil and can easily be removed with water.[2] Fenticonazole nitrate can also be applied topically as a 2% cream or solution for the treatment of fungal skin infections.[citation needed]

Pregnancy and lactation

[edit]

Oral administration of fenticonazole in rats has been reported to produce prolonged gestation and embryotoxic effects after doses above 40 mg/kg/day. Fenticonazole does not interfere with the function of male and female gonads and does not modify the first phases of reproduction. Fenticonazole has shown no teratogenic effects in rats and rabbits. Fenticonazole or its metabolites cross the placental barrier in pregnant rats and rabbits after vaginal application and are excreted in milk of lactating rats. Since there is no experience of use during pregnancy or lactation, fenticonazole nitrate vaginal capsules should not be used unless the physician considers if essential to the welfare of the patient.[2]

Adverse effects

[edit]

Burning and itching have been reported after the application of fenticonazole nitrate.[citation needed]

Intravaginal preparations of fenticonazole may damage latex contraceptives and additional contraceptive measures are therefore necessary during local administration.[citation needed]

See also

[edit]

References

[edit]

Further reading

[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Fenticonazole

View on Grokipedia
from Grokipedia
Fenticonazole is a synthetic derivative agent with a broad spectrum of activity against dermatophytes, yeasts (including Candida species), , and the parasite , primarily employed for topical treatment of superficial fungal infections in dermatological and gynecological contexts. Its involves inhibiting the release of fungal proteases, disrupting cytoplasmic membranes, blocking P450-dependent enzymes to impair essential for fungal cell walls, and interfering with oxidases and peroxidases, resulting in fungal cell death. Due to its low systemic absorption when applied topically, fenticonazole achieves prolonged retention in the skin's and vaginal mucosa (up to 72 hours), minimizing the risk of widespread side effects while effectively targeting localized infections. In clinical practice, it is indicated for conditions such as vulvovaginal , , mixed vaginal infections, , versicolor, tinea infections, cutaneous , and , with formulations including 2% creams, 600 mg vaginal ovules or capsules, and combination products for enhanced efficacy in polymicrobial cases. Studies demonstrate high cure rates, with mycological eradication exceeding 95% in dermatological mycoses and 75–100% in vaginal infections, often comparable to established agents like clotrimazole or miconazole, and rapid symptom relief within days of treatment. Fenticonazole is generally well-tolerated, with adverse events limited to mild, transient local such as burning or itching in less than 7% of users, and no significant systemic observed in preclinical or . As part of initiatives, its topical profile helps curb the development of resistance to oral azoles by reducing unnecessary systemic exposure, positioning it as a first-line option for uncomplicated superficial infections.

Medical use

Indications

Fenticonazole is primarily indicated for the topical treatment of vulvovaginal caused by and other sensitive Candida species. This application leverages its broad-spectrum antifungal activity against yeasts, making it a standard choice for acute and recurrent vaginal yeast infections. It is also indicated for vulvovaginal infections due to trichomoniasis (Trichomonas vaginalis), bacterial vaginosis, and mixed vaginal infections involving fungal, bacterial, and parasitic pathogens. Secondary indications include the treatment of superficial dermatophytoses, such as tinea pedis and tinea cruris, as well as cutaneous candidiasis, pityriasis versicolor caused by sensitive fungi, and erythrasma. These uses extend to dermatological applications where topical formulations effectively target localized fungal overgrowth on the skin. Clinical studies have demonstrated high efficacy in vulvovaginal , with mycological cure rates ranging from 80% to 92% following 3- to 6-day treatments using vaginal ovules or cream. For instance, in comparative trials against other imidazoles, fenticonazole achieved clinical resolution in approximately 80% of patients at follow-up assessments. Off-label use of fenticonazole has been explored for mixed involving both fungal and bacterial components, with limited evidence suggesting empiric topical application may aid in eradication, though rates vary around 67% overall.

Administration

Fenticonazole is available in several formulations for topical and intravaginal use, including a 2% vaginal cream (20 mg/g fenticonazole nitrate), vaginal ovules or capsules in 200 mg and 600 mg strengths, and a 2% topical cream for cutaneous application. For the treatment of vulvovaginal candidiasis, the recommended dosage includes a single 600 mg vaginal ovule administered intravaginally or 5 g of 2% vaginal cream applied twice daily for 3 days. Alternatively, 200 mg vaginal ovules may be used once daily for 3 consecutive days, or a single 600 mg dose with a possible second dose after 3 days if symptoms persist. For maintenance therapy in recurrent cases, a 200 mg ovule may be administered weekly. Treatment durations can extend to 6 days for more severe infections, with the full course completed to prevent recurrence. For superficial infections such as dermatophytoses or , the 2% topical is applied to the affected area once or twice daily for 2 to 4 weeks, depending on the severity and response. of ovules or should occur at bedtime, with the product inserted as deeply as possible using an applicator or finger to ensure retention. During treatment, patients should avoid , use, or douching to maximize efficacy and minimize irritation. For topical use, clean and dry the area before application, and wash hands afterward. Fenticonazole products should be stored at , not exceeding 25–30°C, in a cool, dry place away from moisture, heat, and direct light, and kept out of reach of children. Do not use after the expiry date.

Pharmacology

Mechanism of action

Fenticonazole, an antifungal agent, primarily exerts its therapeutic effect by inhibiting lanosterol 14α-demethylase (CYP51 or ERG11), a key in the fungal biosynthesis pathway. This inhibition prevents the conversion of to , a critical component of fungal s, resulting in depleted levels and accumulation of toxic precursors. Consequently, the integrity of the fungal is compromised, leading to increased permeability, leakage of cellular contents, and ultimately fungal cell death. In addition to its primary target, fenticonazole demonstrates multifaceted antifungal activity through secondary mechanisms. It impairs the secretion of aspartyl proteinases by , enzymes essential for fungal adherence and tissue invasion, thereby attenuating fungal virulence. Fenticonazole also directly damages the fungal cytoplasmic membrane and blocks cytochrome oxidases and peroxidases, enzymes involved in oxidative processes, further disrupting and inducing that contribute to microbicidal effects. These actions enhance its efficacy beyond simple depletion. The drug exhibits a broad spectrum of activity against various fungal pathogens, including Candida species (such as C. albicans, C. glabrata, C. parapsilosis, and C. krusei), dermatophytes (Trichophyton and Microsporum spp.), and Malassezia furfur. At low concentrations, fenticonazole acts in a fungistatic manner by halting fungal growth, while higher concentrations are fungicidal, effectively killing the organisms. As a member of the class, resistance to fenticonazole may arise through mechanisms common to azole antifungals, such as point mutations in the CYP51 gene that reduce drug binding affinity or overexpression of efflux pumps (e.g., ABC transporters or major facilitator superfamily proteins) that expel the drug from fungal cells. However, such resistance remains rare in clinical settings, particularly with topical formulations that limit systemic exposure and selective pressure.

Pharmacokinetics

Fenticonazole demonstrates minimal systemic absorption following topical or vaginal administration, with the extent of absorption typically less than 10% of the applied dose. In women with vulvovaginal , vaginal absorption after a single 1 g dose was approximately 1.81 ± 0.57% of the administered dose, compared to 0.58 ± 0.28% in those with normal vaginal mucosa. For topical cutaneous application, systemic uptake is around 0.5% of the dose. Plasma concentrations remain low due to this limited absorption; after of a 100 mg dose (as 2% gel), peak plasma levels (Cmax) reached 5.96 ± 2.04 ng/mL at approximately 9.4 hours, while application of the same dose yielded much lower Cmax values of 0.50 ± 0.24 ng/mL at 16.9 hours. In most cases, plasma levels become undetectable within 24 hours post-administration. Distribution of fenticonazole is predominantly local to the vaginal mucosa or skin at the site of application, with high tissue concentrations maintained for up to 12 hours post-vaginal ovule administration (200–1000 mg doses). Systemic distribution is negligible owing to the low plasma penetration, and no significant accumulation occurs in other tissues even with repeated dosing. Vaginal tissue levels at 3 hours post-administration show no dose-dependent differences across 200 mg, 600 mg, and 1000 mg ovules, but at 12 hours, higher doses (600 mg and 1000 mg) yield significantly elevated concentrations compared to 200 mg. The drug's local retention supports its therapeutic efficacy at the application site for 72 hours. Limited data exist on the metabolism of systemically absorbed fenticonazole due to its minimal bioavailability; however, as an imidazole antifungal, it is expected to undergo hepatic biotransformation similar to related compounds, though specific pathways have not been detailed in human studies. The absorbed fraction exhibits rapid clearance, with no evidence of active metabolites contributing to systemic effects. Elimination of absorbed fenticonazole occurs primarily through renal and fecal routes. Over 5 days following vaginal administration, urinary excretion accounts for 0.4–1.5% of the dose, while fecal excretion represents 0.18–0.32%. The terminal elimination half-life for the absorbed fraction is approximately 26–27 hours after both intravaginal and percutaneous administration. Plasma detectability persists for up to 96 hours in some cases, aligning with the drug's prolonged local action. Factors such as vaginal mucosa integrity and influence local retention and absorption; absorption is higher (1.81% vs. 0.58%) in candidiasis-affected mucosa compared to normal tissue, likely due to compromised . Minimal transcutaneous absorption is observed in humans and animals, further emphasizing route-specific kinetics.

Safety profile

Adverse effects

Fenticonazole, when used topically or intravaginally for fungal infections, is generally well tolerated, with adverse effects primarily limited to local reactions at the site of application. Common local effects, occurring in more than 1% of users, include vaginal burning sensation, irritation, itching, . These effects are typically mild, transient, and resolve spontaneously after treatment discontinuation. Rare local effects, reported in less than 1% of cases, encompass and vulvar , often identified through post-marketing surveillance. These reactions are usually associated with and may require prompt discontinuation of . Systemic effects are extremely rare owing to the drug's low systemic absorption (approximately 0.5% under normal conditions), with no systemic adverse reactions reported in clinical data. Overall, adverse events occur in approximately 5% of users across clinical and real-world studies, predominantly mild and self-limiting without leading to serious complications or frequent treatment interruptions. Management involves symptomatic relief with emollients for minor and immediate discontinuation if severe or persistent symptoms arise, particularly in patients with prior .

Contraindications and precautions

Fenticonazole is contraindicated in patients with to the active substance, other antifungals, or any excipients in the formulation. The vaginal capsule formulation contains soya lecithin, which precludes its use in individuals allergic to or soya products. Precautions are necessary for patients with a history of or prior to vaginal antifungals, as excipients such as parahydroxybenzoates may elicit allergic reactions, including delayed ; treatment must be halted if local develops. Those using barrier contraceptives, including condoms or diaphragms, should opt for non- alternatives, since the lipid-based excipients and oils in fenticonazole can degrade and compromise contraceptive . Concurrent use with other intravaginal products, such as spermicides, douches, or additional antifungals, is not recommended to prevent potential interference with treatment or heightened local . Due to its topical administration and negligible systemic absorption, fenticonazole does not require routine laboratory monitoring, including assessments for hepatic function, even in patients with underlying liver conditions. In cases of recurrent infections or persistence of symptoms beyond one week, patients—particularly those who are immunocompromised—should seek medical evaluation to rule out underlying issues.

Special populations

Pregnancy and lactation

Animal reproduction studies in rats and rabbits with showed placental transfer but no teratogenic effects, though embryotoxic and fetotoxic effects occurred at very high doses exceeding 20 mg/kg daily. Limited human data from the EFEMERIS database, involving 7,209 exposed (including 2,082 in the first trimester), revealed no increased risk of major congenital anomalies (adjusted 0.91, 95% CI 0.68-1.21), with a 2.5% malformation rate among first-trimester exposures comparable to 2.6% in unexposed . Fenticonazole should be used during only if the potential benefits outweigh the risks, and under physician supervision. Regarding lactation, animal studies via the oral route demonstrated excretion of fenticonazole into milk, but vaginal administration results in negligible systemic absorption, suggesting minimal transfer to human . No specific human data exist on into following topical or vaginal use, though the low pharmacokinetic absorption limits potential infant exposure. Limited data exist, but due to negligible systemic absorption, minimal transfer to is expected. It is considered compatible with ; however, consultation with a physician is recommended, and avoid applying the product to .

Drug interactions

Due to its primarily topical application and low systemic absorption, fenticonazole exhibits minimal risk of systemic drug interactions, including no significant effects on enzymes. A key interaction involves barrier contraceptives, as the —particularly vaginal capsules containing fat excipients or oils—can damage in condoms and diaphragms, reducing their effectiveness; patients should use alternative contraception methods during treatment and for a short period thereafter. Concurrent administration with other topical or systemic azole antifungals is not recommended, as it may lead to additive local irritation or enhanced side effects. Other vaginal products, such as spermicides or intravaginal douches, may increase the risk of local irritation when used alongside fenticonazole, and their combined use should be avoided. No clinically relevant interactions with or alcohol have been identified, consistent with the drug's limited absorption. To manage potential interactions, applications of fenticonazole should be spaced from other vaginal treatments, and patients monitored for signs of heightened local reactions such as increased burning or itching.

Chemistry and development

Chemical structure and properties

Fenticonazole is classified as a broad-spectrum agent primarily used in topical formulations. It belongs to the subclass of azoles, characterized by an ring in its core structure that contributes to its properties. The of fenticonazole features a central ring substituted at the 1-position with a 2-(2,4-dichlorophenyl)-2-{[4-(phenylsulfanyl)benzyl]oxy}ethyl group. Its IUPAC name is 1-[2-(2,4-dichlorophenyl)-2-[(4-phenylsulfanylphenyl)methoxy]ethyl]. Fenticonazole exists as a due to a chiral center at the carbon bearing the 2,4-dichlorophenyl and benzyloxy groups. The molecular of the is C24H20Cl2N2OS, with a molecular weight of 455.4 g/mol. The commonly used salt has the C24H21Cl2N3O4S and a molecular weight of 518.4 g/mol. In its physical form, fenticonazole appears as a white to pale yellow crystalline powder. It exhibits poor , with values below 0.1 mg/mL, rendering it practically insoluble in aqueous media; however, it is freely soluble in and . The calculated logP value is approximately 6.7, indicating high , which supports its suitability for topical applications. The salt form is preferred in pharmaceutical preparations to enhance compatibility, despite the base's inherent low .

History and regulatory status

Fenticonazole was developed by Recordati S.p.A., an Italian pharmaceutical company based in , as part of research into imidazole-based antifungal agents during the late 1970s. The compound, chemically known as 1-[2-(2,4-dichlorophenyl)-2-[(4-phenylthiophenyl)methoxy]ethyl], was synthesized through a multi-step process involving the of 1-(2,4-dichlorophenyl)-2-(1-imidazolyl)ethanol with a 4-(chloromethyl)phenyl phenyl sulfide derivative, typically in a solvent like using a base such as ; this method was patented by Recordati in 1979 under US Patent 4,221,803. Initial clinical trials for its use in treating vaginal began in the early 1980s, demonstrating efficacy against Candida species with minimal systemic absorption. The drug was first launched in in 1986 under the brand name Lomexin (also marketed as Gynoxin in some regions), marking a key milestone in therapy for gynecological and dermatological infections. Subsequent regulatory approvals followed across Europe through the (EMA), with authorizations in countries including , , , and the by the late and . It gained further approvals in (e.g., , , ), Asia (e.g., , , , ), and other regions such as the and , expanding its availability for vulvovaginal treatment. However, fenticonazole has not received approval from the U.S. (FDA), limiting its use in the United States. Following the expiry of the original in the late , generic versions of fenticonazole nitrate emerged in various formulations, including creams, ovules, and sprays, broadening access in approved markets. In 2021, Recordati launched an improved 2% cream formulation in with enhanced texture for better application. As of , the drug remains commercially available in over 30 countries worldwide, primarily as a prescription , with ongoing formulations by Recordati and generics supporting its role in reproductive .

References

  1. https://pubmed.ncbi.nlm.nih.gov/18840006/
  2. https://www.europeanreview.org/wp/wp-content/uploads/2749-2756-Fenticonazole-as-the-first-step-of-antifungal-stewardship-program.pdf
  3. https://go.drugbank.com/drugs/DB13434
  4. https://assets.hpra.ie/products/Human/21553/Licence_PA0812-004-002_23092020150729.pdf
  5. https://assets.hpra.ie/products/Human/21546/LicenseSPC_PA0812-002-001_30012010225621.pdf
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  12. https://patient.info/medicine/fenticonazole-for-vaginal-thrush
  13. https://medex.com.bd/attachments/1r5SbPDsM18hdyccWtYdxajNQxYtsB/fenticonazole-nitrate-vaginal-capsules-prescribing-information
  14. https://pmc.ncbi.nlm.nih.gov/articles/PMC6591636/
  15. https://pmc.ncbi.nlm.nih.gov/articles/PMC7847387/
  16. https://europepmc.org/article/med/2635139
  17. https://pmc.ncbi.nlm.nih.gov/articles/PMC2790137/
  18. https://pubmed.ncbi.nlm.nih.gov/2019858/
  19. https://www.sciencedirect.com/science/article/pii/S2095177916300788
  20. http://article.scholarena.com/Topical-Fenticonazole-Exposure-in-Pregnant.pdf
  21. https://pubmed.ncbi.nlm.nih.gov/3069750/
  22. https://www.researchgate.net/publication/23304454_Topical_Fenticonazole_in_Dermatology_and_Gynaecology
  23. https://medcraveonline.com/PPIJ/the-efficacy-and-safety-of-fenticonazole-in-the-treatment-of-mixed-vaginitis.html
  24. https://www.ijss-sn.com/uploads/2/0/1/5/20153321/ijss_apr_oa20_-_2018.pdf
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  34. https://patents.google.com/patent/US4221803A/en
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  37. https://pillintrip.com/ar/medicine/lomexin-2
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  39. https://www.pharmacompass.com/active-pharmaceutical-ingredients/fenticonazole-nitrate
  40. https://datahorizzonresearch.com/fenticonazole-market-5016
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