Clotrimazole
G01A - Antiinfectives and antiseptics, excl. combinations with corticosteroids
ATC G01AF02
Small molecule
approved 1975
Oral
Topical
Natural product
JFDA label: Canesten Vaginal Tab
Mechanism of Action
Inhibitor of Lanosterol 14-alpha demethylase — Cytochrome P450 51 inhibitor
| Target | Action | Gene / class |
|---|---|---|
| Lanosterol 14-alpha demethylase efficacy | INHIBITOR | ERG11 |
Indications
Approved
- Candidiasis — candidiasis
- Infections — infection
- Mycoses — fungal infectious disease
- Pruritus — Pruritus
- Skin Diseases, Infectious — skin infection
- Tinea — tinea
- Tinea Cruris — tinea
- Tinea Pedis — tinea pedis
Off-label
- Candidiasis, Oral
- Candidiasis, Vulvovaginal
- Folliculitis
- HIV Infections
- Otomycosis
- Vaginal Discharge
- Vaginitis
- Vaginosis, Bacterial
Antimicrobial Spectrum
Expected / intrinsic spectrum (EUCAST breakpoints & labels) — not local resistance. Source: openfda-label.
Bacteria
| Organism | Activity | MIC |
|---|---|---|
| Candida albicans | Active | — |
| Candida guilliermondi | Active | — |
| Epidermophyton floccosum | Active | — |
| Epidermophyton fluoccosum | Active | — |
| Malassezia furfur | Active | — |
| Microsporum canis | Active | — |
| Trichophyton mentagrophytes | Active | — |
| Trichophyton rubrum | Active | — |
Class profile
| antifungalClass | Azole (topical) |
|---|---|
| targetMolecule | Lanosterol 14-alpha-demethylase (CYP51) |
| isFungicidal | 0 |
| spectrumCandida | S (topical) |
| spectrumAspergillus | Not used systemically |
| spectrumCryptococcus | Not used systemically |
| spectrumDermatophytes | S (topical) |
| resistanceMechanisms | ERG11 mutations (local),Efflux pumps |
| source | Pappas2016/Lass-Florl2011 |
Contraindications
Source: openFDA
- Clotrimazole is contraindicated in patients who are hypersensitive to any of its components. Absolute
Adverse Reactions
Very Common >10%Common 1–10%Uncommon 0.1–1%
Rare 0.01–0.1%Very Rare <0.01%Not Known
Vascular disorders (1)
Not Known Haemorrhage
Hepatobiliary disorders (2)
Not Known Aspartate aminotransferase increased · Liver function test abnormal
Renal and urinary disorders (1)
Not Known Pollakiuria
Blood and lymphatic system disorders (1)
Not Known Haemoglobin
Gastrointestinal disorders (5)
Not Known Abdominal distension · Abdominal pain · Flatulence · Nausea · Vomiting
Skin and subcutaneous tissue disorders (7)
Not Known Blister · Dermatitis · Dermatitis bullous · Erythema · Rash · Skin exfoliation · Urticaria
Musculoskeletal and connective tissue disorders (1)
Not Known Muscle spasms
Reproductive system and breast disorders (1)
Not Known Vulvovaginal burning sensation
Infections and infestations (1)
Not Known Cystitis noninfective
General disorders and administration site conditions (6)
Not Known Bladder pain · Burning sensation · Cystitis · Oedema · Pain · Skin irritation
Dosing
Source: openFDA
Clotrimazole is administered only as a lozenge that must be slowly dissolved in the mouth. The recommended dose is one troche five times a day for fourteen consecutive days. Only limited data are available on the safety and effectiveness of the clotrimazole troche after prolonged administration; therefore, therapy should be limited to short term use, if possible. For prophylaxis to reduce the incidence of oropharyngeal candidiasis in patients immunocompromised by conditions that include chemotherapy, radiotherapy, or steroid therapy utilized in the treatment of leukemia, solid tumors, or renal transplantation, the recommended dose is one troche three times daily for the duration of chemotherapy or until steroids are reduced to maintenance levels.
Warnings & Precautions
Source: openFDA
Warnings & Precautions
Clotrimazole is not indicated for the treatment of systemic mycoses including systemic candidiasis.
Pregnancy & Lactation
Pregnancy
Lactation
Caution
Hale L3
Only water-miscible cream or gel products should be applied to the breast because ointments may expose the infant to high levels of mineral paraffins via licking.
Monitoring
| Efficacy | Fungal culture and species identification; minimum inhibitory concentration (MIC) where available; clinical response (temperature, imaging for invasive fungal disease) |
|---|---|
| Toxicity | LFTs (hepatotoxicity — azoles in particular); renal function; ECG for QT prolongation (azoles); drug levels if available (itraconazole, voriconazole) |
| Clinical pearl | Voriconazole levels are highly variable due to CYP2C19 polymorphism — TDM recommended (target trough 2–5 mg/L). Check for drug interactions with CYP3A4 substrates. |
| Counseling | Report visual disturbances (voriconazole), jaundice, or rash. Take azoles with food or as directed to optimise absorption. |
Chemistry & Properties
| Formula | C22H17ClN2 |
|---|---|
| Molecular weight | 344.85 g/mol |
| IUPAC name | 1-[(2-chlorophenyl)-diphenylmethyl]imidazole |
| CAS | 23593-75-1 |
| PubChem CID | 2812 |
| InChIKey | VNFPBHJOKIVQEB-UHFFFAOYSA-N |
| logP | 5.38 (XLogP 5.0) |
| Polar surface area | 17.82 Ų |
| H-bond acceptors / donors | 2 / 0 |
| Drug-likeness (QED) | 0.45 |
| Lipinski violations | 1 |
SMILES
Clc1ccccc1C(c1ccccc1)(c1ccccc1)n1ccnc1Biology & Pharmacokinetics
Pharmacokinetics
| BBB penetrant | No |
|---|
Enzyme interactions
| Enzyme | Role | Detail |
|---|---|---|
| CYP1A2 | Inhibitor | IC₅₀ 1.2499999999999996 µM |
| CYP1A2 | Substrate | — |
| CYP2B6 | Inhibitor | — |
| CYP2C19 | Inhibitor | IC₅₀ 0.34432542746651734 µM |
| CYP2C8 | Inhibitor | IC₅₀ 0.8029999999999998 µM |
| CYP2C9 | Inhibitor | IC₅₀ 0.04664761515876238 µM |
| CYP2D6 | Inhibitor | IC₅₀ 0.883 µM |
| CYP3A4 | Inhibitor | IC₅₀ 0.05023977365036584 µM |
| CYP3A4 | Substrate | — |
Receptor binding (top 2)
| Target | Action | Affinity |
|---|---|---|
| Constitutive androstane receptor (NR1I3) | Antagonist | pIC50 6.2 |
| KCa1.1 (KCNMA1) | Channel blocker | pIC50 5.5 |
Transporters
BCRP (Inhibitor)BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MATE1 (Inhibitor)MDR1 (Inhibitor)MRP (Inhibitor)MRP1 (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)OATP2B1 (Inhibitor)OCT1 (Inhibitor)P-gp (Inhibitor)BSEP (Substrate)MDR1 (Substrate)P-gp (Substrate)
Drug–drug interactions (100+, DDInter)
| Interacting drug | Severity | Management |
|---|---|---|
| Alfentanil | major | |
| Amiodarone | major | |
| Astemizole | major | |
| Benzhydrocodone | major | |
| Brexpiprazole | major | |
| Butorphanol | major | |
| Eliglustat | major | |
| Eplerenone | major | |
| Fentanyl | major | |
| Halofantrine | major | |
| Hydrocodone | major | |
| Ivabradine | major | |
| Leflunomide | major | |
| Lemborexant | major | |
| Levacetylmethadol | major | |
| Lomitapide | major | |
| Lonafarnib | major | |
| Mipomersen | major | |
| Neratinib | major | |
| Oxycodone | major | |
| Pexidartinib | major | |
| Ranolazine | major | |
| Sirolimus | major | |
| Sonidegib | major | |
| Tacrolimus | major | |
| Terfenadine | major | |
| Teriflunomide | major | |
| Valbenazine | major | |
| Abemaciclib | moderate | |
| Acalabrutinib | moderate | |
| Alfuzosin | moderate | |
| Aliskiren | moderate | |
| Alprazolam | moderate | |
| Amlodipine | moderate | |
| Apixaban | moderate | |
| Aprepitant | moderate | |
| Aripiprazole | moderate | |
| Asparaginase Erwinia chrysanthemi | moderate | |
| Asparaginase Escherichia coli | moderate | |
| Atazanavir | moderate |
Showing 40 of 100+.
Registered Products (24)
| Brand | Form / strength | Pack | Agent | Citizen (JOD) |
|---|---|---|---|---|
| Dermatin Cream | Cream 0.01 g/1 g | 14 gm | Modern Drug Store | 0.970 |
| Clozole Cream | Cream 1 %w/w | 15 g tube | PHILADELPHIA PHAEMACEUTICALS.COMP/JORDAN | 1.030 |
| Dermatin Solution | Solution 0.01 g/1 ml | 20 ml | Modern Drug Store | 1.170 |
| clotrimox powder | Powder 1 % | 15 g | MIDDLE EAST PHARMA&CHEMICAL IND/JORDAN | 1.200 |
| Mycoten-HC Cream | Cream 1 %, 1 % | 15 g tube | Sukhtian Group | 1.480 |
| NEWTRIMAZOLE | Cream 0.2 g/20 g | 20 GM/1 TUB | AlGadeed Pharmaceutical Industries | 1.550 |
| Clotrim | Solution 1 % | 20 ml | JORDAN RIVER PHARMA.IND(JORIVER)/JORDAN | 2.070 |
| Vatrim Vaginal Tablet | Tablet 500 mg | 1 Vaginal Tab | Sukhtian Pharma Co. (SP) | 2.180 |
| Mycoten | Tablet 500 mg | 1 tab | Sukhtian Group | 2.480 |
| Clotrim Vaginal Tab | Tablet 500 mg | 1 tab | JORDAN RIVER PHARMA.IND(JORIVER)/JORDAN | 2.490 |
| Clotrex otic solution | Ear Drops 0.2 g/20 ml | 20 ml | Hayat Pharmaceutical Industries CO.PLC/JORDAN | 2.550 |
| gyno-clotrimox vaginal tablet | Tablet 100 mg | 6 tab | MIDDLE EAST PHARMA&CHEMICAL IND/JORDAN | 2.600 |
| Clotrim 100mg vag tab | Tablet 100 mg | 6 Vag.Tab | JORDAN RIVER PHARMA.IND(JORIVER)/JORDAN | 2.640 |
| Otozol ear drops | Eye/Ear Drops 1 % | 10 ml | Amman Pharmaceutical Indusries | 2.700 |
| CANESTEN CREAM | Cream 1 % | 20 g tube | The Jordan Drugstore Co | 2.730 |
| Newtrimazole | Solution 10 mg/1 ml | 25 ml | Al-Gadeed Pharmaceutical Industries/JORDAN | 2.950 |
| Vatrim Vaginal Tablet | Tablet 200 mg | 3 Vaginal Tab | Sukhtian Pharma Co. (SP) | 3.070 |
| Clozole Topical Solution | Solution 1 %w/v | 30 ml | PHILADELPHIA PHAEMACEUTICALS.COMP/JORDAN | 3.100 |
| Dermazol Topical Solution | Solution 1 % | 30 ml | Amman Pharmaceutical Indusries | 3.100 |
| Canesten Vaginal Tab | Tablet 500 mg | 1 tab | The Jordan Drugstore Co | 3.110 |
| CANESTEN VAGINAL Tab | Tablet 100 mg dose | 6+appl. | The Jordan Drugstore Co | 3.250 |
| Mycoten | Tablet 200 mg | 3 tab | Sukhtian Group | 3.960 |
| Clozole Vaginal Cream | Cream 1 % | 50 g tube | PHILADELPHIA PHAEMACEUTICALS.COMP/JORDAN | 4.000 |
| Gentazole-B | Cream Betamethasone Dipropionate 0.064 %WW, Clotrimazole 1.00 %WW, Gentamicin Sulphate 0.1 %WW | (30 GM) / TUB | Sana Pharmaceutical Industry Co. | 4.800 |