Clotrimazole

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Clotrimazole
Clotrimazole.svg
Clotrimazole-xtal-3D-balls.png
Clinical data
Trade names Desenex, CalmYourself, others
AHFS/Drugs.com Monograph
MedlinePlus a682753
Pregnancy
category
  • AU:A
Routes of
administration
Topical, throat lozenge
ATC code
Legal status
Legal status
  • US: OTC (topical), Rx-only (by mouth)
Pharmacokinetic data
Bioavailability Poor absorption by mouth (lozenge), negligible absorption through intact skin (topical)
Protein binding 90%
Metabolism Liver
Elimination half-life 2 hours
Identifiers
  • 1-[(2-Chlorophenyl)(diphenyl)methyl]-1H-imidazole
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.041.589 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C22H17ClN2
Molar mass 344.84 g·mol−1
3D model (JSmol)
Melting point 147 to 149 °C (297 to 300 °F)
  • Clc1ccccc1C(c2ccccc2)(c3ccccc3)n4ccnc4
  • InChI=1S/C22H17ClN2/c23-21-14-8-7-13-20(21)22(25-16-15-24-17-25,18-9-3-1-4-10-18)19-11-5-2-6-12-19/h1-17H Yes check.svgY
  • Key:VNFPBHJOKIVQEB-UHFFFAOYSA-N Yes check.svgY
   (verify)

Clotrimazole, sold under the brand name Lotrimin, among others, is an antifungal medication. [1] It is used to treat vaginal yeast infections, oral thrush, diaper rash, tinea versicolor, and types of ringworm including athlete's foot and jock itch. [1] It can be taken by mouth or applied as a cream to the skin or in the vagina. [1]

Contents

Common side effects when taken by mouth include nausea and itchiness. [1] When applied to the skin, common side effects include redness and a burning sensation. [1] In pregnancy, use on the skin or in the vagina is believed to be safe. [1] There is no evidence of harm when used by mouth during pregnancy but this has been less well studied. [1] When used by mouth, greater care should be taken in those with liver problems. [1] It is in the azole class of medications and works by disrupting the fungal cell membrane. [1]

Clotrimazole was discovered in 1969. [2] It is on the World Health Organization's List of Essential Medicines. [3] It is available as a generic medication. [1] In 2021, it was the 273rd most commonly prescribed medication in the United States, with more than 900,000 prescriptions. [4] [5]

Medical uses

It is commonly available without a prescription in various dosage forms, such as a topical cream, ointment, or vaginal suppository. [1] [6] It is also available as an oral troche or throat lozenge as a prescription only. Topically, clotrimazole is used for vulvovaginal candidiasis (yeast infection) or yeast infections of the skin. For vulvovaginal candidiasis, clotrimazole tablets and creams are inserted into the vagina.[ medical citation needed ]

An effective treatment option for mixed infectious vaginitis is a combination of clotrimazole and metronidazole. [7]

Topical clotrimazole is usually not effective in treatment of fungal infections of the scalp or nails.[ citation needed ] When using over-the-counter drug clotrimazole products, use should be discontinued if condition does not improve after treatment for 2 weeks for jock itch or after 4 weeks for athlete's foot or ringworm. [8]

Throat lozenge preparations are used for oropharyngeal candidiasis (oral thrush) or prevention of oral thrush in people with neutropenia. [8]

Clotrimazole is usually used five times daily for 14 days for oral thrush, twice daily for 2 to 8 weeks for skin infections, and once daily for 3 or 7 days for vaginal infections. [9]

Clotrimazole may be compounded with a glucocorticoid, such as betamethasone, in a topical cream for the treatment of tinea corporis (ringworm), tinea cruris (jock itch) and tinea pedis (athlete's foot). Although FDA approved, clotrimazole–betamethasone combination cream is not the preferred treatment for dermatophyte infections due to increased side effects from the topical glucocorticoid. [ citation needed ]Although temporary relief and partial suppression of symptoms may be observed with the combination therapy, glucocorticoids can elicit an immunosuppressive response and rebound effect that results in more severe infection typically requiring systemic antifungal agents to treat the disease. Combination creams are best avoided in order to improve treatment outcome, reduce the possibility of skin atrophy associated with prolonged topical glucocorticoid use, and to limit the cost of treatment. It can be effective in treating chronic paronychia. The preferred treatment of tinea infections is therefore with clotrimazole monotherapy. [10]

Topical clotrimazole cream, when combined with mechanical reduction of the nail, has been demonstrated to be effective in the treatment of onychomycosis - fungal infection of the fingernails and toenails. [11]

Topical and oral clotrimazole can be used in both adults and children.[ citation needed ]

Additionally, clotrimazole may be used to treat the sickling of cells (related to sickle cell anemia). [12] [13]

Pregnancy

Topical clotrimazole is categorized as pregnancy category B. [14] Small amounts of clotrimazole may be absorbed systemically following topical and vaginal administration. However, topical clotrimazole is still considered safe to use to treat yeast infections in pregnant women and is a safer alternative to other antifungals. [14] [15]

Side effects

Side effects of the oral formulation include itching, nausea, and vomiting. Less than 10% of patients using the oral formulation may have abnormal liver function tests. Side effects include rash, hives, blisters, burning, itching, peeling, redness, swelling, pain or other signs of skin irritation. [1] For this reason, liver function tests should be monitored periodically when taking the oral clotrimazole (troche). When used to treat vulvovaginal candidiasis (yeast infection), less than 10% of patients have vulvar or vaginal burning sensation. Less than 1% of patients have the following side effects: burning or itching of penis of sexual partner; polyuria; vulvar itching, soreness, edema, or discharge. [9] [6] [16]

Clotrimazole creams and suppositories contain oil which may weaken latex condoms and diaphragms. [15]

For topical formulations, should be used externally and should be discontinued if irritation or sensitivity develops at the site of administration. [17]

Interactions

There are no known significant drug interactions with topical clotrimazole. However, with oral (troche) clotrimazole, there are multiple interactions as the medication is a CYP450 enzyme inhibitor, primarily CYP3A4. Thus, any medication that is metabolized by the CYP3A4 enzyme will potentially have elevated levels when oral clotrimazole is used. The prescribing physician should be aware of any medication the patient is taking prior to starting oral clotrimazole. Certain medications should not be taken with oral clotrimazole. [16]

Pharmacology

Pharmacodynamics

Clotrimazole is an imidazole derivative which works by inhibiting the growth of individual Candida or fungal cells by altering the permeability of the fungal cell wall. [6] The drug impairs the biosynthesis of ergosterol, a critical component of the fungal cell membrane, by inhibiting the P450 enzyme lanosterol 14-alpha demethylase. [18] Clotrimazole may slow fungal growth or result in fungal cell death. [1]

Sales volume

Canesten brand Clotrimazole antifungal cream Canesten.jpg
Canesten brand Clotrimazole antifungal cream

Clotrimazole is available as a generic medication, [1] and in 2016 Canesten brand Clotrimazole was one of the biggest-selling branded over-the-counter medications sold in Great Britain, with sales of £39.2 million. [19]

Related Research Articles

<span class="mw-page-title-main">Candidiasis</span> Fungal infection due to any type of Candida

Candidiasis is a fungal infection due to any species of the genus Candida. When it affects the mouth, in some countries it is commonly called thrush. Signs and symptoms include white patches on the tongue or other areas of the mouth and throat. Other symptoms may include soreness and problems swallowing. When it affects the vagina, it may be referred to as a yeast infection or thrush. Signs and symptoms include genital itching, burning, and sometimes a white "cottage cheese-like" discharge from the vagina. Yeast infections of the penis are less common and typically present with an itchy rash. Very rarely, yeast infections may become invasive, spreading to other parts of the body. This may result in fevers, among other symptoms.

Vaginitis, also known as vulvovaginitis, is inflammation of the vagina and vulva. Symptoms may include itching, burning, pain, discharge, and a bad smell. Certain types of vaginitis may result in complications during pregnancy.

<span class="mw-page-title-main">Antifungal</span> Pharmaceutical fungicide or fungistatic used to treat and prevent mycosis

An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as cryptococcal meningitis, and others. Such drugs are usually obtained by a doctor's prescription, but a few are available over the counter (OTC). The evolution of antifungal resistance is a growing threat to health globally.

<span class="mw-page-title-main">Nystatin</span> Antifungal medication

Nystatin, sold under the brand name Mycostatin among others, is an antifungal medication. It is used to treat Candida infections of the skin including diaper rash, thrush, esophageal candidiasis, and vaginal yeast infections. It may also be used to prevent candidiasis in those who are at high risk. Nystatin may be used by mouth, in the vagina, or applied to the skin.

<span class="mw-page-title-main">Miconazole</span> Chemical compound

Miconazole, sold under the brand name Monistat among others, is an antifungal medication used to treat ring worm, pityriasis versicolor, and yeast infections of the skin or vagina. It is used for ring worm of the body, groin, and feet. It is applied to the skin or vagina as a cream or ointment.

<span class="mw-page-title-main">Athlete's foot</span> Skin infection caused by fungus

Athlete's foot, known medically as tinea pedis, is a common skin infection of the feet caused by a fungus. Signs and symptoms often include itching, scaling, cracking and redness. In rare cases the skin may blister. Athlete's foot fungus may infect any part of the foot, but most often grows between the toes. The next most common area is the bottom of the foot. The same fungus may also affect the nails or the hands. It is a member of the group of diseases known as tinea.

<span class="mw-page-title-main">Terbinafine</span> Antifungal medication

Terbinafine, sold under the brand name Lamisil among others, is an antifungal medication used to treat pityriasis versicolor, fungal nail infections, and ringworm including jock itch and athlete's foot. It is either taken by mouth or applied to the skin as a cream or ointment. The cream and ointment are not effective for nail infections.

Dermatophyte is a common label for a group of fungus of Arthrodermataceae that commonly causes skin disease in animals and humans. Traditionally, these anamorphic mold genera are: Microsporum, Epidermophyton and Trichophyton. There are about 40 species in these three genera. Species capable of reproducing sexually belong in the teleomorphic genus Arthroderma, of the Ascomycota. As of 2019 a total of nine genera are identified and new phylogenetic taxonomy has been proposed.

<span class="mw-page-title-main">Tinea corporis</span> Medical condition

Tinea corporis is a fungal infection of the body, similar to other forms of tinea. Specifically, it is a type of dermatophytosis that appears on the arms and legs, especially on glabrous skin; however, it may occur on any superficial part of the body.

<span class="mw-page-title-main">Terconazole</span> Chemical compound

Terconazole is an antifungal drug used to treat vaginal yeast infection. It comes as a lotion or a suppository and disrupts the biosynthesis of fats in a yeast cell. It has a relatively broad spectrum compared to azole compounds but not triazole compounds. Testing shows that it is a suitable compound for prophylaxis for those that suffer from chronic vulvovaginal candidiasis.

<span class="mw-page-title-main">Dermatophytosis</span> Fungal infection of the skin

Dermatophytosis, also known as ringworm, is a fungal infection of the skin (Dermatomycosis). Typically it results in a red, itchy, scaly, circular rash. Hair loss may occur in the area affected. Symptoms begin four to fourteen days after exposure. Multiple areas can be affected at a given time.

<span class="mw-page-title-main">Tioconazole</span> Chemical compound

Tioconazole is an antifungal medication of the imidazole class used to treat infections caused by a fungus or yeast. It is marketed under the brand names Trosyd and Gyno-Trosyd. Tioconazole ointments serve to treat women's vaginal yeast infections. They are available in one day doses, as opposed to the 7-day treatments commonly used in the past.

<span class="mw-page-title-main">Tinea faciei</span> Medical condition

Tinea faciei is a fungal infection of the skin of the face. It generally appears as a photosensitive painless red rash with small bumps and a raised edge appearing to grow outwards, usually over eyebrows or one side of the face. It may feel wet or have some crusting, and overlying hairs may fall out easily. There may be a mild itch.

<span class="mw-page-title-main">Fenticonazole</span> Chemical compound

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 dermatophyte pathogens, 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.

<span class="mw-page-title-main">Tinea incognita</span> Fungal skin infection caused by the presence of a topical immunosuppressive agent

Tinea incognita, also spelled tinea incognito, is a fungal infection of the skin that generally looks odd for a typical tinea infection. The border of the skin lesion is usually blurred and it appears to have florid growth.

<span class="mw-page-title-main">Vaginal yeast infection</span> Medical condition

Vaginal yeast infection, also known as candidal vulvovaginitis and vaginal thrush, is excessive growth of yeast in the vagina that results in irritation. The most common symptom is vaginal itching, which may be severe. Other symptoms include burning with urination, a thick, white vaginal discharge that typically does not smell bad, pain during sex, and redness around the vagina. Symptoms often worsen just before a woman's period.

<span class="mw-page-title-main">Ibrexafungerp</span> Medication

Ibrexafungerp, sold under the brand name Brexafemme, is an antifungal medication used to treat vulvovaginal candidiasis (VVC). It is taken orally. It is also currently undergoing clinical trials for other indications via an intravenous (IV) formulation. An estimated 75% of women will have at least one episode of VVC and 40 to 45% will have two or more episodes in their lifetime.

Topical antifungaldrugs are used to treat fungal infections on the skin, scalp, nails, vagina or inside the mouth. These medications come as creams, gels, lotions, ointments, powders, shampoos, tinctures and sprays. Most antifungal drugs induce fungal cell death by destroying the cell wall of the fungus. These drugs inhibit the production of ergosterol, which is a fundamental component of the fungal cell membrane and wall.

<span class="mw-page-title-main">Oteseconazole</span> Chemical compound

Oteseconazole, a novel orally bioavailable and selective inhibitor of fungal cytochrome P450 enzyme 51 (CYP51), has shown promising efficacy in the treatment of recurrent vulvovaginal candidiasis (RVVC) in patients.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 American Society of Health-System Pharmacists (8 February 2016). "Clotrimazole Monograph for Professionals". www.drugs.com. Archived from the original on 28 October 2016. Retrieved 28 October 2016.
  2. Walker SR (2012). Trends and Changes in Drug Research and Development. Springer Science & Business Media. p. 109. ISBN   9789400926592. Archived from the original on 14 September 2016.
  3. World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl: 10665/325771 . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  4. "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
  5. "Clotrimazole - Drug Usage Statistics". ClinCalc. Archived from the original on 18 January 2024. Retrieved 14 January 2024.
  6. 1 2 3 "Clotrimazole (Oral)". Lexicomp Online. Archived from the original on 23 January 2015. Retrieved 17 April 2014.
  7. Huang Y, Shen C, Shen Y, Cui H (January 2024). "Assessing the Efficacy of Clotrimazole and Metronidazole Combined Treatment in Vaginitis: A Meta-Analysis". Altern Ther Health Med. 30 (1): 186–191. PMID   37773671.
  8. 1 2 "UpToDate". www.uptodate.com. Archived from the original on 17 October 2019. Retrieved 7 August 2019.
  9. 1 2 "Clotrimazole: MedlinePlus Drug Information". The American Society of Health-System Pharmacists, Inc. Archived from the original on 18 April 2014. Retrieved 17 April 2014.
  10. Moriarty B, Hay R, Morris-Jones R (July 2012). "The diagnosis and management of tinea". BMJ. 345: e4380. doi:10.1136/bmj.e4380. PMID   22782730. S2CID   38106083.
  11. Davies KJ (1 March 2006). "Study to determine the efficacy of Clotrimazole 1% cream for the treatment of onychomycosis in association with the mechanical reduction of the nail plate". The Foot. 16 (1): 19–22. doi:10.1016/j.foot.2005.10.004. ISSN   0958-2592.
  12. Marieb EN, Hoehn K. Human Anatomy and Physiology. Toronto: Pearson. p. 643.
  13. Rodgers G. "Hydroxyurea and other disease-modifying therapies in sickle cell disease". UpToDate. Archived from the original on 15 April 2014. Retrieved 14 April 2014.
  14. 1 2 Patel VM, Schwartz RA, Lambert WC (September 2017). "Topical antiviral and antifungal medications in pregnancy: a review of safety profiles". Journal of the European Academy of Dermatology and Venereology. 31 (9): 1440–1446. doi:10.1111/jdv.14297. PMID   28449377. S2CID   544751.
  15. 1 2 "Diseases Characterized by Vaginal Discharge". CDC. Archived from the original on 28 April 2014. Retrieved 17 April 2014.
  16. 1 2 "Clotrimazole". DrugBank. Archived from the original on 17 April 2014. Retrieved 17 April 2014.
  17. "DailyMed - CLOTRIMAZOLE ANTIFUNGAL- clotrimazole cream". dailymed.nlm.nih.gov. Archived from the original on 30 July 2020. Retrieved 7 August 2019.
  18. Crowley PD, Gallagher HC (September 2014). "Clotrimazole as a pharmaceutical: past, present and future". Journal of Applied Microbiology. 117 (3): 611–617. doi:10.1111/jam.12554. PMID   24863842. Archived from the original on 25 January 2024. Retrieved 19 October 2023.
  19. "A breakdown of the over-the-counter medicines market in Britain in 2016". Pharmaceutical Journal. 28 April 2017. Archived from the original on 22 October 2019. Retrieved 29 May 2017.