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

+ [23]

Target-

Mechanism

fungal CYP51A1 inhibitors(Fungal CYP51A1 inhibitors)

Therapeutic Areas

Infectious DiseasesSkin and Musculoskeletal DiseasesUrogenital Diseases

Active Indication

CandidiasisTinea VersicolorTinea corporis+ [5]

Inactive Indication

Candidiasis, OralHuntington DiseaseInfective vaginitis+ [1]

Originator Organization

Bayer, Inc.

Active Organization

Nanjing Zeheng Pharmaceutical Technology Development Co., Ltd.Schering-Plough Corp.Bayer Vital GmbH

+ [4]

Inactive Organization

Bright Future Pharmaceuticals FactoryHong 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 (JP)

Login to view First Approval Timeline

Structure

Molecular FormulaC22H17ClN2

InChIKeyVNFPBHJOKIVQEB-UHFFFAOYSA-N

CAS Registry23593-75-1

Preterm birth is an important cause of death and disabilities. Bacterial vaginosis (BV) is a common vaginal dysbiosis or abnormal microbiota, with a predominance of anaerobic bacteria with a lack of Lactobacillus, with various diagnosis methods. Often asymptomatic, BV increases the risk of preterm birth according to the gestational age at diagnosis. BV is usually diagnosed by conventional diagnosis such as Nugent score. Molecular diagnosis of BV has been demonstrated to be more reproducible, more accurate and to better define dysbiosis.
The main objective of the study is to evaluate the effectiveness of an innovative screen-and-treat strategy for vaginal flora abnormalities by molecular biology using a Point of Care multiplex technology before 18 weeks' gestation to reduce the rate of preterm birth in a population of pregnant women at high risk of preterm birth.
The hypothesis is that a strategy for screening and treating vaginal flora abnormalities and their recurrences using molecular biology in women with a history of prematurity or late-term abortion could be effective in reducing premature births by 40%.

Start Date01 Aug 2024

Sponsor / Collaborator

Assistance Publique Hôpitaux de Marseille

CTRI/2024/03/063661 / RecruitingPhase 2/3IIT

A quasi-experimental trial on the antimicrobial efficacy of a value-added product developed from a polyherbal formulation in dermatophytic infections against Clotrimazole topical application - NIL

Start Date16 Mar 2024

Sponsor / Collaborator-

CTRI/2023/08/056043 / Not yet recruitingPhase 2IIT

Randomized comparative study of Anisoon Pimpinellaanisum L with Clotrimazole in Vulvovaginal Candidiasis - NIL

Start Date10 Aug 2023

Sponsor / Collaborator-

100 Clinical Results associated with Clotrimazole

Login to view more data

100 Translational Medicine associated with Clotrimazole

Login to view more data

100 Patents (Medical) associated with Clotrimazole

Login to view more data

2,858

Literatures (Medical) associated with Clotrimazole

01 Dec 2024·Antonie van Leeuwenhoek

Species distribution and antifungal susceptibility profiles of yeasts isolated from onychomycosis: a cross-sectional study with insights into emerging species

Article

Author: Kharazi, Mahboobeh ; Motamedi, Marjan ; Jabrodini, Ahmad ; Rezaei Arab, Maryam ; Shariat, Sahar ; Zomorodian, Kamiar ; Shabanzadeh, Shafigheh ; Ghasemi, Farnia ; Yazdanpanah, Somayeh

Candida onychomycosis is a common fungal infection affecting the nails, primarily caused by Candida (C.) species. Regarding the increasing trend of Candida onychomycosis and the antifungal resistant phenomenon in recent years, this study aims to evaluate the epidemiological characteristics of Candida onychomycosis, the distribution of emerging species, and the antifungal susceptibility profiles of isolates. Onychomycosis caused by yeast species was confirmed through direct examination and culture of nail scraping among all individuals suspected to have onychomycosis and referred to a medical mycology laboratory between June 2019 and March 2022. Species of yeast isolates were identified using the multiplex PCR and PCR-RFLP methods. The antifungal susceptibility of isolates to common antifungal agents and imidazole drugs was evaluated according to the M-27-A3 CLSI protocol. Among 101 yeast strains isolated from onychomycosis, Candida parapsilosis complex (50.49%) was the most common species, followed by C. albicans (20.79%) and C. tropicalis (10.89%). Rare species of yeasts such as C. guilliermondii and Saccharomyces cerevisiae were also identified by molecular methods. Results obtained from antifungal susceptibility testing showed significant differences in MIC values of isoconazole, fenticonazole, and sertaconazole among different species. Overall, a fluconazole-resistant rate of 3% was found among Candida species. Moreover, there was a statistically significant difference in MICs of fenticonazole and clotrimazole between the two most prevalent causative species, C. parapsilosis complex and C. albicans. Correct identification of the causative agents of onychomycosis and performing susceptibility testing could be helpful in choosing the most appropriate antifungal therapy.

01 Jun 2024·One Health

Prevalence and drug susceptibility of clinical Candida species in nasopharyngeal cancer patients in Vietnam

Article

Author: Vo, Thanh-Hoa ; Tran-Nguyen, Viet-Khoa ; Le, Minh-Tri ; Nguyen, Phuoc-Vinh ; Vu, Thao Thanh ; Nguyen, Bac V G ; Nguyen, Hau H N

In the nature, Candida species are normal inhabitants and can be observed in a wide variety of vertebrates. In humans, especially for cancer patients who fall prey to opportunistic pathogens, this group of susceptible multi-drug resistant and biofilm-forming yeasts, are among the commonest ones. In this study, Candida species in 76 oral lesion samples from Vietnamese nasopharyngeal-cancer patients were isolated, morphologically identified using CHROMagar™, germ tube formation, and chlamydospore formation tests, and molecularly confirmed by PCR-RFLP. The drug susceptibility of these isolates was then tested, and the gene ERG11 was DNA sequenced to investigate the mechanism of resistance. The results showed that Candida albicans remained the most prevalent species (63.16% of the cases), followed by Candida glabrata, Candida tropicalis, and Candida krusei. The rates of resistance of non-albicans Candida for tested drugs were 85.71%, 53.57%, and 57.14% to fluconazole, clotrimazole, and miconazole, respectively. Although the drug-resistance rate of Candida albicans was lower than that of non-albicans Candida, it was higher than expected, suggesting an emerging drug-resistance phenomenon. Furthermore, ERG11 DNA sequencing revealed different mutations (especially K128T), implying the presence of multiple resistance mechanisms. Altogether, the results indicate an alarming drug-resistance situation in Candida species in Vietnamese cancer patients and emphasize the importance of species identification and their drug susceptibility prior to treatment.

17 Apr 2024·ACS Applied Materials & Interfaces

Enhanced Solubility and Bioavailability of Clotrimazole in Aqueous Solutions with Hydrophobized Hyperbranched Polyglycidol for Improved Antifungal Activity

Article

Author: Kozanecki, Marcin ; Wielgus, Ewelina ; Ciesielska, Anita ; Kadlubowski, Slawomir ; Jaworska-Krych, Daria ; Gosecki, Mateusz ; Urbaniak, Malgorzata ; Gosecka, Monika ; Dzitko, Katarzyna

The poor solubility of clotrimazole in the aqueous medium and the uncontrolled removal of the drug-loaded suppository content limit its effectiveness in the treatment of vulvovaginal candidiasis. We present here the aqueous formulations of clotrimazole in the form of non-Newtonian structured fluids, i.e., Bingham plastic or pseudoplastic fluids constructed of hyperbranched polyglycidol, HbPGL, with a hydrophobized core with aryl groups such as phenyl or biphenyl. The amphiphilic constructs were obtained by the modification of linear units containing monohydroxyl groups with benzoyl chloride, phenyl isocyanate, and biphenyl isocyanate, while the terminal 1,2-diol groups in the shell were protected during the modification step, followed by their deprotection. The encapsulation of clotrimazole within internally hydrophobized HbPGLs using a solvent evaporation method followed by water addition resulted in structured fluids formation. Detailed Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) analyses performed for aryl-HbPGLs with clotrimazole revealed the difference in drug compatibility among polymers. Clotrimazole in biphenyl-enriched HbPGL, unlike phenyl derivatives, was molecularly distributed in both the dry and the hydrated states, resulting in transparent formulations. The shear-thinning properties of the obtained fluid formulations make them injectable and thus suitable for the intravaginal application. Permeability tests performed with the usage of the Franz diffusion cell showed a 5-fold increase in the permeability constant of clotrimazole compared to drugs loaded in a commercially available disposable tablet and a 50-fold increase of permeability in comparison to the aqueous suspension of clotrimazole. Furthermore, the biphenyl-modified HbPGL-based drug liquid showed enhanced antifungal activity against both Candida albicans and Candida glabrata that was retained for up to 7 days, in contrast to the phenyl-HbPGL derivatives and the tablet. With their simple formulation, convenient clotrimazole/biphenyl-HbPGL formulation strategy, rheological properties, and enhanced antifungal properties, these systems are potential antifungal therapeutics for gynecological applications. This study points in the synthetic direction of improving the solubility of poorly water-soluble aryl-enriched pharmaceuticals.

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

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
D00282	Clotrimazole	D01AC01 A01AB18 G01AF02	DB00257

R&D Status

Approved

10 top approved records.

Login

to view more data

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

Developing

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Oropharyngeal candidiasis	Phase 3	CN	Jiangsu Yabang Johnson & Johnson Pharmaceutical Co., Ltd.	26 Aug 2022
Oropharyngeal candidiasis	Phase 3	CN	Nanjing Zeheng Pharmaceutical Technology Development Co., Ltd.	26 Aug 2022
Candidiasis, Vulvovaginal	Phase 2	RU	Bayer AG	01 Sep 2008
Candidiasis, Oral	Phase 2	-	Boehringer Ingelheim GmbH	01 May 2001
Candidiasis, Vulvovaginal	Preclinical	RU	Bayer AG	01 Sep 2008
Candidiasis, Vulvovaginal	Preclinical	DE	Bayer AG	01 Sep 2008
Candidiasis, Vulvovaginal	Preclinical	DE	Bayer AG	01 Sep 2008
Infective vaginitis	Discovery	CN	Hong Kong Aomei Pharmaceutical Factory Co., Ltd. Beijing Representative Office	24 Mar 2014
Candidiasis, Oral	Discovery	-	Boehringer Ingelheim GmbH	01 May 2001

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02180828 (Pubmed \| Mycoses)	Phase 4	Candidiasis, Vulvovaginal	240	Clotrimazole vaginal tablet 500 mg	(lgvvmrgibs) = The adverse events of clotrimazole were mainly local snikpibjzb (vavqjdowch )	Positive	01 Jul 2016
				Oral fluconazole 150 mg
NCT00078559 (CTgov)	Phase 1/2	Renal transplant rejection \| Kidney Diseases	10	Kidney transplant+Acyclovir+Acetaminophen+Trimethoprim (TMP)/Sulfa (Bactrim, Septra)+Nystatin+Sirolimus+Clotrimazole+Diphenhydramine+Alemtuzumab+Valgancyclovir+Methylprednisolone (or equivalent)+Tacrolimus+Pentamidine	yiqgahtejg(jgphhlzjne) = vefhsfqzrk nmkwkvcbei (llhffkeyoj, vfjvwyeyda - zizbqlgaxp) View more	-	09 Jul 2012
NCT02242695 (Pubmed \| Arch Gynecol Obstet)	Phase 4	Recurrent candidiasis of vagina	150	Dequalinium chloride 10 mg	(bngrqhmllf): OR = 0.79 (95% CI, 0.56 - 1.1)	-	01 Jan 2021
				Clotrimazole 100 mg
NCT00390780 (CTgov)	Phase 3	Oropharyngeal candidiasis \| HIV Infections	578	Miconazole Lauriad (Miconazole Lauriad Buccal Tablet)	mocptjtprw(xpocgtsaps): comparison of proportion clinical cure = 0.15 (95% CI) View more	-	29 Aug 2013
				Clotrimazole (Clotrimazole Troches)
NCT02180828 (CTgov)	Phase 4	Candidiasis, Vulvovaginal	240	Clotrimazole vaginal tablet (Clotrimazole Vaginal Tablet)	rmxhqypgfn(ptqsiyzbgx) = rzvoynrngp bfzzeflzwq (bghcsejbuv, ecagocgihx - erftmqhprg) View more	-	30 Sep 2016
				fluconazole (Fluconazole)	rmxhqypgfn(ptqsiyzbgx) = banpkwmndi bfzzeflzwq (bghcsejbuv, hprqgxrmzm - dsavsdlysn) View more
NCT00629122 (CTgov)	Phase 4	Kidney Failure, Chronic	5	Nystatin+Tacrolimus (Arm A (Tacrolimus and Nystatin))	zdlybgzqvg(tbfxjoeniw) = vlrigbzmce ojopwmqsqc (nwxatrywwg, drmswuizpn - yvhaooroyu) View more	-	11 Dec 2017
				Tacrolimus+Clotrimazole (Arm B (Tacrolimus and Clotrimazole))	zdlybgzqvg(tbfxjoeniw) = ykskxmamih ojopwmqsqc (nwxatrywwg, ofqlkyovyw - fjbyxxyvar) View more
Pubmed	Not Applicable	Otomycosis	559	Clotrimazole	(rrqdyezhlc): RR = 0.8 (95% CI, 0.59 - 1.07) View more	-	25 May 2021
				Other types of azoles (eberconazole, fluconazole, miconazole)
AACR2009	Not Applicable	Neoplasms	-	Clotrimazole	egfagrsoke(ausfbztmkw) = beginning at 18h post-treatment jtzvpswoow (elptlhkxvz )	-	01 May 2009