Delving into the Latest Updates on Clotrimazole with Synapse

Overview

Basic Info

SummaryClotrimazole, a diminutive molecule of pharmacological relevance, exerts its influence as an astoundingly powerful CYP51A1 inhibitor. This enzyme, paramount in the biosynthesis of ergosterol, a fundamental building block of fungal cell membranes, is the key target for clotrimazole's inhibitory prowess. Through its blockade of this enzyme, clotrimazole elicits a destructive effect on the integrity of fungal cell membranes, ultimately leading to their demise. The manifold fungal infections for which clotrimazole is primarily utilized as a treatment modality are tinea corporis, tinea cruris, tinea pedis, tinea, candidiasis, and tinea versicolor, amongst others. Initially developed and marketed by Bayer Vital GmbH and Schering-Plough Corp., this highly efficacious drug is presently manufactured and vended by Bayer Pharma AG. Since its first approval in 1981, clotrimazole has established itself as a widely employed antifungal agent, attaining this status on account of its superlative potency and exceptional safety profile, with an exceedingly low incidence of adverse effects.

Drug Type

Small molecule drug

Synonyms

1-((2-Chlorophenyl)diphenylmethyl)-1H-imidazole, 1-(o-Chloro-α,α-diphenylbenzyl)imidazole, 1-(o-Chlorotrityl)imidazole

+ [25]

Target

fungal CYP51A1

Mechanism

fungal CYP51A1 inhibitors(Fungal CYP51A1 inhibitors)

Therapeutic Areas

Infectious DiseasesSkin and Musculoskeletal DiseasesUrogenital Diseases

Active Indication

CandidiasisTinea VersicolorTinea corporis+ [5]

Inactive Indication

Candidiasis, OralHIV InfectionsHuntington Disease

Originator Organization

Bayer, Inc.

Active Organization

Schering-Plough Corp.

Nanjing Zeheng Pharmaceutical Technology Development Co., Ltd.Bayer Vital GmbH

+ [4]

Inactive Organization

THINQ Pharma-CRO Ltd.Hong Kong Aomei Pharmaceutical Factory Co., Ltd. Beijing Representative Office

Medinova AG

+ [4]

Drug Highest PhaseApproved

First Approval Date

US (03 Feb 1975),

Mycoses

RegulationOrphan Drug (US), Orphan Drug (JP)

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Structure

Molecular FormulaC22H17ClN2

InChIKeyVNFPBHJOKIVQEB-UHFFFAOYSA-N

CAS Registry23593-75-1

Vulvovaginal candidiasis is a yeast infection commonly caused by the overgrowth of Candida species in and around the vulva and vagina. Abnormal vaginal discharge, itching and irritation, swelling and redness of the vaginal area, pain during sexual intercourse, and dyspareunia are important clinical findings of the infection. Currently, the infection is one of the growing burdens to married women. Moreover, the infection with antifungal-resistant Candida species adds challenges to managing the disease. Hence, this study was conducted to identify the different Candida species causing vulvovaginal candidiasis and to determine its susceptibility pattern against different antifungal drugs. A hospital-based cross-sectional and quantitative study was conducted for the period of six months from September 2022 to March 2023 among symptomatic married women in the Gynecology and Obstetrics Department of Bharatpur Hospital, Chitwan. A total of 300 symptomatic cases were enrolled in the study. Candida species were isolated from vaginal swabs following standard microbiological procedures and antifungal susceptibility testing was performed with different antifungal agents. The total prevalence of vulvovaginal candidiasis was found to be 37.3 % (112/300). Among different isolates, Candida albicans was found to be the most predominant (52.6 %), followed by Candida glabrata (29.3 %) among non-albicans. Women from the age group 25-35 years were found to be more infected (47.3 %) and the relationship between contraceptive use and vulvovaginal candidiasis was found to be statistically significant (p < 0.05). Candida species showed higher susceptibility toward Amphotericin-B (68.1 %), followed by fluconazole (Diflucan), and Clotrimazole (50.9 %). Whereas the least susceptibility was observed to Voriconazole (27.6 %) and Itraconazole (35.30 %). Candida albicans was comparatively more susceptible to different antifungal drugs than non-albicans species. Candida parapsilosis was only susceptible to Amphotericin-B and the increasing incidence of vaginal candidiasis due to non-albicans Candida indicates the need for routine speciation of Candida.

01 Dec 2024·MYCOPATHOLOGIA

Three-Dose Antifungal Treatment Improves the Efficacy for Severe Vulvovaginal Candidiasis

Article

Author: Liang, Yiheng ; Zhu, Yuxia ; Xiao, Zhansong ; Huang, Liting ; Zhang, Xiaowei ; Fan, Shangrong

Vulvovaginal candidiasis (VVC) is a prevalent gynecological infection characterized by high incidence and recurrent episodes, causing significant distress in women. This study aims to assess the effectiveness of different clotrimazole and fluconazole treatment regimens for severe vulvovaginal candidiasis (SVVC). A retrospective analysis was conducted on 1303 cases of SVVC among first-time visitors to the gynecology outpatient department at Peking University Shenzhen Hospital between January 2013 and December 2022. Vaginal secretions were systematically collected for fungal culture, with species identification conducted using Chromogenic culture medium and API Candida test reagents. Mycological cure rates were assessed at days 7-14, days 25-35, and day 35 to 6 months after treatment. The three-dose clotrimazole regimen demonstrated significantly higher mycological cure rates (85.7%, 80.0% and 74.6% at three follow-up periods, respectively) compared to the two-dose clotrimazole regimen (76.0%, 61.6%, and 59.8%, all P < 0.05). The three-dose fluconazole regimen showed no significant difference to three-dose clotrimazole regimen, with cure rates of 82.8%, 79.3%, and 75.9% (all P > 0.05). The two-dose fluconazole regimen had cure rates of 74.3%, 56.4% and 51.1%, with no significant difference from two-dose clotrimazole regimen at days 7-14 and 25-35, but lower than three-dose fluconazole regimen at days 25-35 and 35 to 6 months. The three-dose clotrimazole regimen demonstrated higher cure rates in Candida albicans and non-albicans Candida SVVC cases than two-dose regimen. These findings suggest that three-dose antifungal regimens may be more efficacious than two-dose regimens for SVVC. The three-dose clotrimazole regimen could serve as a promising alternative for SVVC management.

01 Dec 2024·ENVIRONMENTAL POLLUTION

Septic tanks as a pathway for emerging contaminants to the aquatic environment–Need for alternative rural wastewater treatment?

Article

Author: Cartmell, Elise ; Yates, Kyari ; Petrie, Bruce ; Wilschnack, Maike

Septic tanks (STs) as a decentralised approach to community wastewater treatment were investigated as a pathway for emerging contaminants (ECs) entering the aquatic environment. A broad range of ECs were examined in five community STs (population equivalents 217-475) and receiving rivers in Scotland over 12 months. All 68 studied ECs were detected at least once in ST influent or effluent at a broad concentration range from ng L^-1 - μg L^-1 which can surpass freshwater predicted no-effect concentrations. Pharmaceuticals with acute use, such as antibiotics and antifungals, had high monthly variability and concentrations can exceed those previously found in centralised wastewater treatment works. Differences between the STs demonstrate the impact of localised prescription and population behaviour on EC concentrations. The similarities in concentrations between influent and effluent, suggest limited or no removal of ECs in STs. Hence, dilution of the discharges is required to mitigate environmental risk. Although the contribution of ECs sorbed to suspended solids to the total EC concentration was generally small (<10%), higher contributions (>30%) were observed for fluoroquinolone antibiotics (ofloxacin and ciprofloxacin), antidepressants (fluoxetine), and antifungals (clotrimazole). A wide range of ECs were also detected in rivers upstream and downstream of the ST discharge points, and concentrations increased by up to 95% downstream. In general, risk quotients (RQs) in the rivers were low, indicating small risk for the environment. However, higher RQs (>1) were found for ibuprofen, diclofenac and ciprofloxacin in a few samples. Therefore, reducing their concentration by improving ST performance or through sustainable medicines use may be needed at low dilution locations to mitigate any risk.

6

News (Medical) associated with Clotrimazole

11 Jan 2024

·www.drugs.com

Overuse of Antifungal Skin Meds Could Be Driving Drug-Resistant Disease

THURSDAY, Jan. 11, 2024 -- U.S. doctors are prescribing antifungal creams to patients with skin complaints at rates so high they could be contributing to the rise of drug-resistant infections, new research shows. These are "severe antimicrobial-resistant superficial fungal infections , which have recently been detected in the United States," noted a team led by Jeremy Gold, a researcher at the U.S. Centers for Disease Control and Prevention. One of the biggest emerging threats: Drug-resistant forms of ringworm (a form of dermatophytosis). In Southeast Asia, major outbreaks of this itchy, circular rash have occurred that are not responding to either topical antifungal creams or pills. Cases of ringworm resistant to drugs have also now been spotted in 11 U.S. states, Gold's team noted. This is leading to "patients experiencing extensive lesions and delays in diagnosis," the team said. As is seen with the overuse of antibiotics, fungi naturally build up resistance to antifungal meds the more they are exposed to them. The CDC team believes that antifungal topical creams are being overprescribed. Looking at 2021 Medicare Part D data, they found that 6.5 million prescriptions for creams containing antifungals, such as ketoconazole, nystatin and clotrimazole-betamethasone, were prescribed that year. In sheer numbers, primary care doctors wrote the biggest percentage of these prescriptions, but dermatologists and podiatrists had much higher rates on a prescriptions-per-doctor basis. One of the big issues, according to Gold's team, is that most doctors diagnose a skin condition simply by looking at it, a method that is "frequently incorrect," even among board-certified dermatologists. "Confirmatory diagnostic testing" of a skin lesion beyond just looking at it is rarely done, they added. A small percentage of physicians are prescribing antifungal drugs at exceedingly high rates. In 2021, "10% of antifungal prescribers prescribed nearly one half of these medications," Gold's group found. The new study probably only captures a fraction of the overuse of antifungals, since "most topical antifungals can be purchased over the counter without a prescription," the researchers noted. The high use of clotrimazole-betamethasone, in particular, is thought to be a big factor in the emergence of drug-resistant ringworm. This drug (a combination of a steroid and an antifungal) can also "cause skin damage if applied to intertriginous areas," meaning areas where the skin folds onto itself, such as occurs around the groin, buttocks and armpits. Long-term, extensive use of clotrimazole-betamethasone can also trigger hormonal problems, Gold's team said. The bottom line, according to the CDC team: "Health care providers should be judicious in prescribing topical antifungals" for suspected fungal skin infections, and go beyond a visual diagnosis when possible. Doctors should also try to "educate patients about the correct use of topical antifungals and combination antifungal-cortoicosteroids" to help reduce overprescribing and the danger of drug-resistant fungal disease, they added. The findings were published in the Jan. 11 issue of the CDC journal Morbidity and Mortality Weekly Report . Sources Morbidity and Mortality Weekly Report, Jan. 11, 2024 Disclaimer: Statistical data in medical articles provide general trends and do not pertain to individuals. Individual factors can vary greatly. Always seek personalized medical advice for individual healthcare decisions. Posted January 2024 More news resources FDA Medwatch Drug Alerts Daily MedNews News for Health Professionals New Drug Approvals New Drug Applications Drug Shortages Clinical Trial Results Generic Drug Approvals Subscribe to our newsletter Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

22 Aug 2023

·medcitynews.com

Teva, Glenmark To Pay $255M, Divest Cholesterol Drug to Settle DOJ Price Fixing Charges

On Monday, Teva Pharmaceuticals and Glenmark Pharmaceuticals became the sixth and seventh drugmakers to resolve criminal charges as a result of the Department of Justice’s yearslong investigation into generic drug price fixing. The settlement agreement requires both companies to pay hefty fines as well as divest their drug lines for pravastatin, a widely used statin that lowers cholesterol. In 2019, the DOJ showed that it was serious about cracking down on generic drug price fixing by issuing two multi-million dollar fines to Heritage Pharmaceuticals and Rising Pharmaceuticals. The legal case at the center of Monday’s settlement dates back to 2020, when the DOJ indicted Teva over alleged price fixing conspiracies with four other generic drugmakers — Glenmark, Sandoz, Apotex and Taro Pharmaceuticals. The indictment charged the pharma companies with raising prices, rigging bids and allocating customers for generic drugs. These medications included pravastatin, as well as generic drugs for autoimmune diseases, pain, cancer and cystic fibrosis. In 2020, Taro, Sandoz and Apotex admitted their roles in the alleged schemes and paid fines respectively totaling $205.7 million, $195 million and $24.1 million. With Monday’s settlement, Teva and Glenmark have also admitted to their roles in running a price fixing scheme and agreed to pay criminal penalties. The DOJ ordered Teva to pay a $225 million penalty, which the department said is the largest fine to date for “a domestic antitrust cartel.” As for Glenmark, the DOJ issued the firm a $30 million fine. The settlement agreement also requires both Teva and Glenmark to divest their respective drug lines for pravastatin, which was at the center of the companies’ alleged price fixing scheme. In addition to the $225 million penalty, the DOJ ordered Teva to donate $50 million worth of drugs to humanitarian organizations. Those drugs are antifungal medication clotrimazole and antibiotic drug tobramycin The prices of both were affected by the conspiracy, the DOJ said. If either company violates the terms of their settlement agreement, they will face prosecution. If convicted, they would likely get banned from federal healthcare programs like Medicare and Medicaid, according to the DOJ’s statement. “When a firm is criminally convicted, it is barred from participating in U.S. federal healthcare programs. Teva Pharmaceuticals is one of the largest generic pharmaceutical firms in the world, so barring it from much of the healthcare industry would be dangerous. The right response is to shrink the firm and force it to disgorge illicit profits, which is what the antitrust division did,” Matt Stoller, director of research at the antitrust advocacy group American Economic Liberties Project, said in a statement. In a press release issued Monday, Teva said it “fosters a culture of compliance” and “has robust and consistent compliance controls in place” to prevent price fixing schemes from recurring in the future. Glenmark did not respond to MedCity News’ request for comment. In 2019, Heritage agreed to pay more than $7 million to settle its price fixing case, and Rising was issued a penalty totaling more than $3 million. Collectively, seven drugmakers have agreed to pay nearly $700 million as a result of the DOJ’s crackdown on generic drug price fixing.

Patent Infringement

22 Aug 2023

·www.fiercepharma.com

Teva, Glenmark ⁠reach $255M price-fixing settlement with DOJ, agree to offload certain meds

The government has reached price-fixing settlements with seven companies totaling more than $681 million. After admitting to running a price-fixing scheme as part of a deal with the Department of Justice, not only will generic makers Teva and Glenmark Pharmaceuticals pay hefty fines, but they'll also be forced to divest certain products. The two companies reached a deferred prosecution agreement (DPA) with the government, meaning the U.S. will charge the companies but it won’t move forward with the case as long as Teva and Glenmark follow certain terms. If they hold up their end of the agreement, the charges will then be dismissed. The consequences of a conviction could be disastrous as they would likely include exclusion from federal healthcare programs such as Medicare and Medicaid. To avoid such punishment, Teva will pay a fine of $225 million over five years. Glenmark, for its part, must pay $30 million. Teva’s penalty is “the largest to date for a domestic antitrust cartel,” the DOJ wrote in its recent release. Aside from the financial penalty, Teva must also donate $50 million worth of generic versions of antifungal cream clotrimazole and antibiotic tobramycin to humanitarian organizations. The company will also divest its generic cholesterol med pravastatin to a third-party buyer in what the government called an “extraordinary remedy." Glenmark must also divest its own version of pravastatin. In the DPA, Teva confessed that one of its former employees agreed with competitors that the company wouldn’t bid on contracts to sell certain drugs three times between 2013 and 2015. The scheme affected the markets for clotrimazole, tobramycin and pravastatin, and the employee left Teva in 2016. Meanwhile, Glenmark admitted to participating in a conspiracy to lower the price of pravastatin, according to the DOJ. Teva has “robust and consistent” controls in place meant to prevent such activity from happening again and it pledges to maintain these provisions, the company said in a statement. “The company is pleased to put these charges behind us and believes that we remain well-positioned to defend against related civil claims,” the statement continued. As part of its long-running effort to stamp out price-fixing in the generic industry, the DOJ has collected settlements totaling $681 million.

Patent Infringement

100 Deals associated with Clotrimazole

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External Link

KEGG	Wiki	ATC	Drug Bank
D00282	Clotrimazole	D01AC01 A01AB18 G01AF02	DB00257

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Candidiasis	JP	Bayer Pharma AG	08 May 2009
Tinea Versicolor	JP	Bayer Pharma AG	08 May 2009
Tinea corporis	US	Schering-Plough Corp.	27 Oct 1989
tinea cruris	US	Schering-Plough Corp.	27 Oct 1989
Tinea Pedis	US	Schering-Plough Corp.	27 Oct 1989
Tinea	CN	Mayinglong Pharmaceutical Group Co., Ltd.	01 Jan 1981
Mycoses	US	Schering-Plough Corp.	03 Feb 1975

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Candidiasis, Vulvovaginal	Phase 3	DE	Bayer AG	01 Sep 2008
Candidiasis, Vulvovaginal	Phase 3	RU	Bayer AG	01 Sep 2008
Candidiasis, Oral	Phase 3	-	Boehringer Ingelheim GmbH	01 May 2001
HIV Infections	Phase 3	-	Boehringer Ingelheim GmbH	01 May 2001
Oropharyngeal candidiasis	Phase 3	-	Boehringer Ingelheim GmbH	01 May 2001
Huntington Disease	Discovery	US	FORUM Pharmaceuticals, Inc.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


Pubmed	Not Applicable	Otomycosis	-	1% Clotrimazole Cream	eqduojnlgg(irothswxze) = wdiceyxdcy umsfcprinf (dnjgceayww ) View more	-	01 Apr 2023
NCT00629122 (CTgov)	Phase 4	Kidney Failure, Chronic	5	Nystatin+Tacrolimus (Arm A (Tacrolimus and Nystatin))	hdsdoyxufg(dghjsxxhhh) = ogqztbbpix efjyadtzay (ogijkvkapm, ffrwuyfzkg - dglortxsbm) View more	-	11 Dec 2017
				Tacrolimus+Clotrimazole (Arm B (Tacrolimus and Clotrimazole))	hdsdoyxufg(dghjsxxhhh) = uflekfhqeq efjyadtzay (ogijkvkapm, czzegptdax - dvsadskbrc) View more
NCT02180828 (CTgov)	Phase 4	Candidiasis, Vulvovaginal	240	Clotrimazole vaginal tablet (Clotrimazole Vaginal Tablet)	wyptxltzwd(uvidwofait) = jvvioxpeab twxcwaflau (avxooqmykt, wriaukxpev - zguvbzjssu) View more	-	30 Sep 2016
				fluconazole (Fluconazole)	wyptxltzwd(uvidwofait) = hqqqdhscar twxcwaflau (avxooqmykt, ympaxsyikh - wjuxszdxgx) View more
NCT02180828 (Pubmed \| Mycoses)	Phase 4	Candidiasis, Vulvovaginal	240	Clotrimazole vaginal tablet 500 mg	xewdyscdqn(gpyirvlcoo) = The adverse events of clotrimazole were mainly local qktyvvkvyd (dywjnfkfgo )	Positive	01 Jul 2016
				Oral fluconazole 150 mg
NCT00078559 (CTgov)	Phase 1/2	Kidney Diseases \| Renal transplant rejection	10	Kidney transplant+Acyclovir+Acetaminophen+Nystatin+Sirolimus+Clotrimazole+Trimethoprim (TMP)/Sulfa (Bactrim, Septra)+Diphenhydramine+Alemtuzumab+Valgancyclovir+Methylprednisolone (or equivalent)+Tacrolimus+Pentamidine	tdkjirivbq(cdgnglifes) = jbivitjogq oakgrcvtkh (eytgmwipgp, gahyadfcao - frmkktpqgs) View more	-	09 Jul 2012
AACR2009	Not Applicable	Neoplasms	-	Clotrimazole	lpmjhtdjdu(zilsfxnvfz) = beginning at 18h post-treatment wltjpseryc (rpxegqthnz )	-	01 May 2009