General
Preferred name
CLOTRIMAZOLE
Synonyms
B 5097, ba ()
BAY b 5097 ()
FB 5097 ()
CLOTRIMAZOLE23593-75-1 ()
BAY b 5097, FB 5097 ()
GNF-Pf-3499 ()
Fungederm ()
Trimysten ()
Candiden ()
Abtrim ()
Gyne-Lotrimin ()
Canesten AF ()
Canesten Crm Combi ()
Canesten VC ()
Gyne-Lotrimin Combination Pack ()
BAY 5097 ()
Svt-15652 ()
Privacom ()
Gyne-Lotrimin 3 ()
Lotrimin ()
Mycelex-7 Combination Pack ()
Trivagizole ()
BAY-5097 ()
Gynix ()
Canesten ()
Masnoderm ()
Trivagizole 3 ()
Gyne-Lotrimin 3 Combination Pack ()
Mycil Gold ()
Mycelex-7 ()
NSC-257473 ()
Mycelex-G ()
Canesten Internal ()
Actavall ()
Mycelex ()
Clotrimazole-d5 ()
P&D ID
PD002411
CAS
117829-71-7
23593-75-1
1185076-41-8
Tags
natural product
drug
available
Approved by
FDA
First approval
1975
Drug Status
approved
vet_approved
Drug indication
Antifungal
Fungal infection
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
ROE
Mainly hepatic [L5173].
PHARMACODYNAMICS
Clotrimazole is a broad-spectrum antifungal agent that inhibits the growth of pathogenic yeasts by changing the permeability of cell membranes. The action of clotrimazole is fungistatic at concentrations of drug up to 20 mcg/mL and may be fungicidal _in vitro_ against Candida albicans and other species of the genus Candida at higher concentrations [FDA label]. Unfortunately, resistance to clotrimazole, which was rare in the past, is now common in various patient populations [A174094]. Clotrimazole is generally considered to be a fungistatic, and not a fungicidal drug, although this contrast is not absolute, as clotrimazole shows fungicidal properties at higher concentrations [A174094].
METABOLISM
Hepatic (metabolized to inactive metabolites) [L5173].
ABSORPTION
Because clotrimazole is generally not significantly absorbed, drug interactions are not a major issue with its use [A174094].
PHARMACODYNAMICS
Clotrimazole is a broad-spectrum antifungal agent that inhibits the growth of pathogenic yeasts by changing the permeability of cell membranes. The action of clotrimazole is fungistatic at concentrations of drug up to 20 mcg/mL and may be fungicidal _in vitro_ against Candida albicans and other species of the genus Candida at higher concentrations [FDA label]. Unfortunately, resistance to clotrimazole, which was rare in the past, is now common in various patient populations [A174094]. ; ; Clotrimazole is generally considered to be a fungistatic, and not a fungicidal drug, although this contrast is not absolute, as clotrimazole shows fungicidal properties at higher concentrations [A174094].; ;
INDICATION
**Topical preparations**; ; Clotrimazole topical cream is indicated for the topical treatment of the following dermal infections [F3088], [F3121]:; ; Tinea pedis, tinea cruris, and tinea corporis due to _Trichophyton rubrum_, _Trichophyton mentagrophytes_, _Epidermophyton floccosum_; ; Candidiasis due to _Candida albicans_; ; Tinea versicolor due to _Malassezia furfur_; ; Diaper rash infected by _Candida albicans_; ; ; In some preparations, clotrimazole may be combined with betamethasone dipropionate, a corticosteroid [F3121]. ; ; **Oral preparations**; ; The oral troche preparation is indicated for the local treatment of oropharyngeal candidiasis [FDA label]. It is also indicated as a prophylactic drug to reduce the incidence of oropharyngeal candidiasis in patients immunocompromised by conditions such as chemotherapy, radiotherapy, or steroid therapy utilized in the treatment of leukemia, solid tumors, or renal transplantation [FDA label]. Troche preparations are not indicated for the treatment of any systemic mycoses [FDA label].
TOXICITY
Symptoms of overdose include erythema, stinging, blistering, peeling, edema, pruritus, urticaria, burning, and general irritation of the skin, and cramps. As with all topical agents, skin sensitization may result [F3088].; ; **Oral LD50 (rat)**: 708 mg/kg; **Intraperitoneal LD50 (rat)**: 445 mg/kg; **Subcutaneous LDLO (rat)**: 10 g/kg; **Oral LD50 (mouse)**: 761 mg/kg; **Subcutaneous LDLO (mouse)**: 10 g/kg; **Intraperitoneal LD50 (mouse)**: 108 mg/kg;[F3124]; ; **Overdose**; ; This drug poses no risk of acute intoxication, as it is unlikely to occur following a single vaginal or dermal application of an overdose (application over a large area under conditions favorable to absorption) or accidental oral ingestion. There is no specific antidote [F3100].; ; **Effects on Fertility**; ; No human studies of the effects of clotrimazole on fertility have been conducted; however, animal studies have not shown any effects on the drug on fertility [F3088].; ; **Use in Pregnancy**; ; There are limited data regarding the use of clotrimazole in pregnant women. Animal studies do not show direct or indirect harmful effects on reproduction. Although the topical application of clotrimazole may result in very low serum and tissue levels, the use of clotrimazole topical cream by pregnant women is not recommended unless it is advised by the prescribing physician. Clotrimazole topical cream should not be used in the first trimester of pregnancy unless it is considered by the physician to be essential to patient well-being [F3088].; ; **Use in Breastfeeding**; ; Available pharmacodynamic/toxicological studies in animals have shown excretion of clotrimazole/metabolites in breastmilk. Clotrimazole should not be administered during breastfeeding. Although the topical application of clotrimazole has resulted in very low serum and tissue levels, the use of clotrimazole topical cream by lactating women is not recommended unless it recommended by the prescribing physician [F3088].;
DESCRIPTION
Clotrimazole is an anti-fungal agent.
(GtoPdb)
MOA
Clotrimazole acts primarily by damaging the permeability barrier in the cell membrane of fungi. Clotrimazole causes inhibition of ergosterol biosynthesis, an essential constituent of fungal cell membranes. If ergosterol synthesis is either completely or partially inhibited, the cell is no longer able to construct an intact and functional cell membrane [F3088],[F3100]. Because ergosterol directly promotes the growth of fungal cells in a hormoneâlike fashion, rapid onset of the above events leads to dose-dependent inhibition of fungal growth [A174094]. Though decreased ergosterol, due to the inhibition of lanosterol 14-demethylase (also known as _CYP51_) [A174094] is accepted to be primarily responsible for the antimycotic properties of clotrimazole, this drug also shows other pharmacological effects. These include the inhibition of sarcoplasmic reticulum Ca2+âATPase, depletion of intracellular calcium, and blocking of calciumâdependent potassium channels and voltageâdependent calcium channels [A174094]. The action of clotrimazole on these targets accounts for other effects of this drug that are separate from its antimycotic activities [A174094].
INDICATION
**Topical preparations** Clotrimazole topical cream is indicated for the topical treatment of the following dermal infections [F3088], [F3121]: Tinea pedis, tinea cruris, and tinea corporis due to _Trichophyton rubrum_, _Trichophyton mentagrophytes_, _Epidermophyton floccosum_ Candidiasis due to _Candida albicans_ Tinea versicolor due to _Malassezia furfur_ Diaper rash infected by _Candida albicans_ In some preparations, clotrimazole may be combined with betamethasone dipropionate, a corticosteroid [F3121]. **Oral preparations** The oral troche preparation is indicated for the local treatment of oropharyngeal candidiasis [FDA label]. It is also indicated as a prophylactic drug to reduce the incidence of oropharyngeal candidiasis in patients immunocompromised by conditions such as chemotherapy, radiotherapy, or steroid therapy utilized in the treatment of leukemia, solid tumors, or renal transplantation [FDA label]. Troche preparations are not indicated for the treatment of any systemic mycoses [FDA label].
TOXICITY
Symptoms of overdose include erythema, stinging, blistering, peeling, edema, pruritus, urticaria, burning, and general irritation of the skin, and cramps. As with all topical agents, skin sensitization may result [F3088]. **Oral LD50 (rat)**: 708 mg/kg; **Intraperitoneal LD50 (rat)**: 445 mg/kg; **Subcutaneous LDLO (rat)**: 10 g/kg; **Oral LD50 (mouse)**: 761 mg/kg; **Subcutaneous LDLO (mouse)**: 10 g/kg; **Intraperitoneal LD50 (mouse)**: 108 mg/kg;[F3124] **Overdose** This drug poses no risk of acute intoxication, as it is unlikely to occur following a single vaginal or dermal application of an overdose (application over a large area under conditions favorable to absorption) or accidental oral ingestion. There is no specific antidote [F3100]. **Effects on Fertility** No human studies of the effects of clotrimazole on fertility have been conducted; however, animal studies have not shown any effects on the drug on fertility [F3088]. **Use in Pregnancy** There are limited data regarding the use of clotrimazole in pregnant women. Animal studies do not show direct or indirect harmful effects on reproduction. Although the topical application of clotrimazole may result in very low serum and tissue levels, the use of clotrimazole topical cream by pregnant women is not recommended unless it is advised by the prescribing physician. Clotrimazole topical cream should not be used in the first trimester of pregnancy unless it is considered by the physician to be essential to patient well-being [F3088]. **Use in Breastfeeding** Available pharmacodynamic/toxicological studies in animals have shown excretion of clotrimazole/metabolites in breastmilk. Clotrimazole should not be administered during breastfeeding. Although the topical application of clotrimazole has resulted in very low serum and tissue levels, the use of clotrimazole topical cream by lactating women is not recommended unless it recommended by the prescribing physician [F3088].
MOA
Clotrimazole acts primarily by damaging the permeability barrier in the cell membrane of fungi. Clotrimazole causes inhibition of ergosterol biosynthesis, an essential constituent of fungal cell membranes. If ergosterol synthesis is either completely or partially inhibited, the cell is no longer able to construct an intact and functional cell membrane [F3088],[F3100]. Because ergosterol directly promotes the growth of fungal cells in a hormoneâlike fashion, rapid onset of the above events leads to dose-dependent inhibition of fungal growth [A174094].; ; Though decreased ergosterol, due to the inhibition of lanosterol 14-demethylase (also known as _CYP51_) [A174094] is accepted to be primarily responsible for the antimycotic properties of clotrimazole, this drug also shows other pharmacological effects. These include the inhibition of sarcoplasmic reticulum Ca2+âATPase, depletion of intracellular calcium, and blocking of calciumâdependent potassium channels and voltageâdependent calcium channels [A174094]. The action of clotrimazole on these targets accounts for other effects of this drug that are separate from its antimycotic activities [A174094].
DESCRIPTION
Inosine monophosphate dehydrogenase inhibitor
(Tocris Bioactive Compound Library)
DESCRIPTION
Cytochrome P450 inhibitor; antifungal
(Tocriscreen Plus)
DESCRIPTION
Specific inhibitor of Ca2+-activated K+ channels
(LOPAC library)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
4
Organisms
11
Compound Sets
36
AdooQ Bioactive Compound Library
Axon Medchem Screening Library
ChEMBL Approved Drugs
ChEMBL Drugs
Concise Guide to Pharmacology 2017/18
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DrugBank Approved Drugs
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DrugCentral Approved Drugs
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DrugMAP Approved Drugs
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EU-OPENSCREEN Bioactive Compound Library
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LOPAC library
LSP-MoA library (Laboratory of Systems Pharmacology)
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NCATS Inxight Approved Drugs
NIH Clinical Collections (NCC)
NIH Mechanistic Set
Novartis Chemogenetic Library (NIBR MoA Box)
NPC Screening Collection
NURSA ligand set
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TargetMol Bioactive Compound Library
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ZINC Tool Compounds
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
47
Molecular Weight
344.11
Hydrogen Bond Acceptors
2
Hydrogen Bond Donors
0
Rotatable Bonds
4
Ring Count
4
Aromatic Ring Count
4
cLogP
5.38
TPSA
17.82
Fraction CSP3
0.05
Chiral centers
0.0
Largest ring
6.0
QED
0.45
Structural alerts
2
aggregator (Aggregator Advisor)
Aggregators
aggregator (ZINC)
Aggregators
Related compounds
Custom attributes
(extracted from source data)
Target Type
Enzymes
Selectivity
Ca2+-activated K+ channel
Pathway
Microbiology&virology
Anti-infection
Autophagy
Target
14-?? Demethylase
CYP3A4, KCNN4, NR1I2, NR1I3, TRPM2, TRPM4, TRPM8
Antifungal agent
antibiotic
Bacterial
Fungal
Antineoplastic and Immunosuppressive Antibiotics,Fungal
Primary Target
Cytochrome P450
MOA
Inhibitor
Intermediate Conductance K(Ca) 3.1 (IKCa1
Gardos channel, SK41, IK1) Channel Blockers
Lanosterol 14alpha-demethylase Inhibitors
Angiogenesis Inhibitors
cytochrome P450 inhibitor, imidazoline receptor ligand
Member status
member
Indication
vulvovaginal candidiasis, oropharyngeal candidiasis
Therapeutic Class
Antifungal Agents
Source data
