Clotrimazole

Pharmacological properties

Antifungal drug used to treat vaginal infections caused by fungi of the genus candida, trichomonas vaginalis, the main types of gram-positive and gram-negative bacteria. The pharmacological effect of the gel is due to the properties of clotrimazole, which is part of it. Clotrimazole is susceptible to dermatophytes, yeast fungi (candida, torulopsis glabarata, rhodotorula), mold fungi, as well as causative agents of colorful lichen (pityriasis versicolor) and erythrasma. in addition, clotrimazole has an antimicrobial effect against gram-positive (staphylococci, streptococci) and gram-negative bacteria (bacteroides, gardnerella vaginalis), as well as against trichomonas vaginalis, malasseria furfur, corinebacterium minussimum. the effect of clotrimazole is associated with a violation of the synthesis of ergosterol, which is part of the cell membrane of fungi. as a result, the structure and properties of the membranes change, cell lysis is noted.

Pharmacokinetics Not studied.

Indications

Genital infections caused by pathogens sensitive to the drug: vaginal candidiasis, vaginal trichomoniasis, mixed vaginal infections, bacterial vaginitis and infectious leukorrhea.

Application

In the treatment of genital infections, about 5 g of gel (1 full applicator) is administered as deep as possible into the vagina in the evening (before bedtime) for 6 days. treatment should not be carried out during menstruation and therefore should be completed by its beginning.

Contraindications

Hypersensitivity to the components of the drug, i trimester of pregnancy.

Side effects

Local allergic reactions from the vaginal mucosa, redness, burning sensation.

special instructions

Candid in the form of a gel is not used during menstruation.

To prevent re-infection, simultaneous treatment of both partners is necessary.

Candid does not stain skin and underwear.

During pregnancy (II and III trimester) and breastfeeding, Candid is used with caution and only under the supervision of a doctor.

Interactions

When combined with amphotericin B, nystatin, the activity of candida gel decreases.

Overdose

Due to the low absorption of the drug, an overdose is unlikely

Storage conditions

In the dark place at a temperature of no higher than 25 ° C.

Actual information

Clotrimazole is a broad-spectrum antifungal drug that is used mainly to treat candida albicans diseases and other fungal infections. synthetic azole antimycotic clotrimazole is widely prescribed as a medicine for the treatment of tinea pedis (athletes foot), as well as vulvovaginal and oropharyngeal candidiasis. it exhibits fungistatic antifungal activity, disrupts the biosynthesis of ergosterol, which is part of the cell membrane of fungi, thereby inhibiting their growth. In addition to its antifungal activity, clotrimazole is interesting in a number of other diseases, such as sickle cell anemia, malaria and some types of cancer. complexes of clotrimazole compounds with metals were obtained (studies with several drugs), they showed better pharmacological efficacy. in addition, several new modified release pharmaceutical formulations are also under development. Clotrimazole is a well-tolerated drug. it has a small number of side effects. however, drug resistance may be observed in some groups of patients (immunocompromised). its antimycotic properties were discovered in the late 1960s. as an active ingredient, it is sold under various brand names, various pharmaceutical companies around the world. in addition to its antimycotic activity, clotrimazole is used to treat metronidazole-resistant trichomoniasis, to alleviate its symptoms (cudmore et al., 2004) and is active against certain gram-positive bacteria (alsterholm et al., 2010). this is a compound obtained by synthesis.

Clotrimazole is considered a chemically distinct compound. It consists of four aromatic rings bonded to a tetrahedral (sp3-hybridized) carbon atom.One of the aromatic groups is the imidazole ring, and, as you know, it mediates electron transfer reactions in biological systems (Eaton and Wilkins, 1978; Eaton and Wilson, 1979). The remaining aromatic rings form a triphenylmethyl radical, which is known to form and stabilize the radical intermediate (Hicks, 2007). One of these rings is chlorine substituted at position C2. Although clotrimazole is an achiral molecule, its two phenyl rings are called enantiotopic (from the point of view of symmetry, enantiotopic rings are groups that translate one into another by reflection in the mirror plane). These enantiotopic groups can be differentiated by interaction with a chiral molecule (they are found only in such molecules) (Eliel et al., 1994).

Azoles represent the largest class of antifungal drugs used in clinical practice, and can be further divided into two classes depending on their chemical structure: imidazoles and triazoles. Clotrimazole belongs to a subclass of imidazoloazole drugs. Along with econazole and miconazole, clotrimazole is the drug of choice for topical treatment of dermatophytosis (athletes foot), inguinal dermatomycosis and dermatomycosis caused by isolates of Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum, Microsporum Canis and et al. Albicans. It is also actively prescribed for local therapy of vulvovaginal and oropharyngeal candidiasis.

Brief description of antimicrobial activity

Clotrimazole acts primarily by damaging the permeability barrier in the cell membrane of fungi. Clotrimazole inhibits the biosynthesis of ergosterol, an essential component of fungal cell membranes. If ergosterol synthesis is fully or partially inhibited, the cell is no longer able to create an intact and functional cell membrane. Candid (clotrimazole) is a broad-spectrum antifungal that inhibits the growth of pathogens by altering the permeability of cell membranes. The effect of clotrimazole is fungistatic at drug concentrations up to 20 μg / ml and may be fungicidal in vitro against Candida albicans and other species of the genus Candida at higher concentrations. Unfortunately, resistance to clotrimazole, which was rare in the past, is now common among different patient groups.

Similar drugs

There are a number of antimycotic drugs of azole that are closely associated with clotrimazole, including imidazole preparations: miconazole, econazole and ketoconazole, as well as triazole preparations: fluconazole and itraconazole. All of them are broad-spectrum antimycotics and, as a rule, are poorly absorbed by oral administration, with the exception of ketoconazole and itraconazole (review by Odds et al., 2003; Gelone and O’Donnell, 2006; Lorand and Kocsis, 2007). In clinical conditions, the effects of miconazole and econazole are very similar to those of fluconazole; in the treatment of local fungal infections. Unlike other azoles, itraconazole is active against aspergillus.

Dosage Forms

In the European Union, clotrimazole is available in the form of a cream, pessary under various trademarks. In the USA, additional drugs are available, namely clotrimazole lotions, powders, lozenges, topical solutions and vaginal tablets. Clotrimazole is sometimes combined with steroids hydrocortisone or betamethasone. In Ukraine, clotrimazole under one of the trademarks is a drug Candid - applied in the form of several dosage forms. This is a cream, skin powder, solution for external use, a solution for the oral cavity.

Adverse Reactions Types of interactions

All dosage forms of the drug Candid (clotrimazole) are available without a prescription. Several cases of contact allergic dermatitis have been reported during the application of cream with clotrimazole.It was found that this reaction is not associated with auxiliary components of the drug, namely with the active substance - clotrimazole (Kalb and Grossman, 1985). Intravaginal clotrimazole, used as a pessary, can damage the condom (additional contraceptive measures must be applied).

The most significant adverse reactions for clotrimazole preparations are currently those that are used as oral lozenges for the treatment of candidiasis in the oral cavity. These include nausea, vomiting, discomfort in the mouth, itching, and elevated liver enzymes (rev. Ellepola and Samaranayake, 2000). Clotrimazole lollipops are not sold in the European Union, but are widely available in the United States and other countries. Clotrimazole tablets or capsules intended for swallowing are no longer prescribed, because against the background of their use, gastrointestinal disorders occur, dysuria and the development of depression can occur. In particular, due to the very limited solubility of clotrimazole in water and toxicity to the gastrointestinal tract, other antifungal imidazole derivatives replaced clotrimazole for oral administration in capsule form.

The drug does not affect a persons ability to drive vehicles or work with other mechanisms. Pessaries are not recommended for use in children. Candid (clotrimazole) is prescribed for the treatment of the elderly, nursing.

findings

Ironically, this trend, namely the growth of fungal infections, partially reflects clinical success in other areas, such as the treatment of human immunodeficiency virus (HIV), cancer, and an increase in the number of transplant recipients. Clotrimazole resistance, which was a rare occurrence, is now quite common in some groups of patients with candidiasis (Pelletier et al., 2000). Although these epidemiological trends are unlikely to have a significant impact on the widespread use of clotrimazole and related drugs in the general population. The rational development of new drugs with improved activity spectra continues. And it is anticipated that these new drugs will replace clotrimazole for the treatment of invasive fungal infections in selected high-risk patient groups.

Nevertheless, at present, the continued use of clotrimazole as a medicine is an area of ​​intensive research. There are prospects both for its use in new indications, and for the development of new compositions. Clotrimazole is used as the basis for the development and synthesis of new antimalarial drugs that are cheap and easy to synthesize (Gemma et al., 2007, 2008). Palladium-clotrimazole complexes, which exhibit increased cytotoxicity against tumor cell lines compared to clotrimazole alone, are being studied as new antitumor agents (Navarro et al., 2006). Some other metal-clotrimazole complexes, such as ruthenium-clotrimazole and platinum-clotrimazole, also show promising antitumor characteristics (Navarro et al., 2009; Robles-Escajeda et al., 2013). There is also great interest in using clotrimazole and its metabolites as lead compounds in the strategic development of new treatments for sickle cell anemia, as they can reduce red blood cell dehydration in vivo by inhibiting the so-called Gardos, calcium-dependent potassium channel (Brugnara et al., 1996; Brugnara and De Franceschi, 2006; Gbotosho et al., 2013).

New approaches to the type of dosage form of clotrimazole include a buccal bioadhesive film containing clotrimazole, which has been shown to inhibit oral candidiasis for up to 6 hours (Singh et al., 2008). As well as a vaginal gel with slow release of clotrimazole. This type of slow-release drug may be more effective than other vaginal delivery systems, as traditional vaginal creams, pessaries, and tablets tend to have a short residence time in the vagina due to the natural cleansing process that takes place there. In conclusion, it should be noted that the drug Candid (clotrimazole) is effective, safe and well tolerated.It is sold in most developed countries around the world under various brand names, and a large number of medicines are available that include clotrimazole. Although the emerging resistance to clotrimazole may limit the future use of this drug in certain groups of patients, its widespread use is likely to continue in the general population. The ongoing development of clotrimazole as a drug is aimed at finding new clinical indications for the use of the drug, its use as the main substance in studies on the development of drugs based on it, and the optimization of dosage forms to improve drug delivery (Crowley P.D., 2014).