Clotrimazole

Clotrimazole is an Imidazole derivative belonging to Antifungal Agent.

Clotrimazole is a topical broad-spectrum antifungal agent used for the treatment of a wide variety of dermatophyte infections and candidiasis.

Clotrimazole well absorbed from the gastrointestinal tract. Minimally absorbed from the skin and vagina. Time to peak plasma concentration is approximately 24 hours (vaginal cream). The topical form is minimally absorbed in the serum and tissues. Clotrimazole is a lipophilic drug and has been shown to be secreted in breastmilk in animal studies. Clotrimazole is metabolized in the liver to inactive compounds. Clotrimazole excreted via faeces and urine.

Clotrimazole shows common side effects like Blistering, redness, swelling, itching, burning, stinging, peeling, hives, or skin cracks.

Clotrimazole is available in the form of Oral lozenge or troche, Topical cream, Intravaginal tablet, and Topical solution.

Clotrimazole is available in India, US, China, Japan, Singapore, France, Canada, Italy, and Australia.

Clotrimazole belongs to the Antifungal Agent acts as an Imidazole derivative.

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. Because ergosterol directly promotes the growth of fungal cells in a hormone‐like fashion, rapid onset of the above events leads to dose-dependent inhibition of fungal growth.

Though decreased ergosterol, due to the inhibition of lanosterol 14-demethylase (also known as CYP51) 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+‐ATPase, depletion of intracellular calcium, and blocking of calcium‐dependent potassium channels and voltage‐dependent calcium channels. The action of clotrimazole on these targets accounts for other effects of this drug that are separate from its antimycotic activities.

The Data of onset and duration of action of Clotrimazole is not clinically established.

The Tmax of Clotrimazole is approximately 24 hours (vaginal cream).

Clotrimazole is available in the form of Oral lozenge or troche, Topical cream, Intravaginal tablet, and Topical solution.

Clotrimazole lozenge or troche are taken orally, allow troche to dissolve slowly in the mouth.

Clotrimazole Cream: May also be applied externally for itching and irritation of surrounding areas. Do not use tampons, douches, spermicides, or other vaginal products or have vaginal intercourse during treatment.

Clotrimazole Vaginal tablet: Should be inserted deep into the vagina to ensure tablet dissolves completely. If tablet does not dissolve completely within one night, consider use of a vaginal cream.

Clotrimazole is an antifungal medication that is used to treat fungal infections and prevent them from further spread. Its topical form (tablet, gel, cream, ointment, powder, soap and lotion) is used to treat fungal infections of your skin such as diaper rash, nail infections and rash in folds of your skin etc. Clotrimazole throat paint and lozenges are used to treat oral thrush (sore patches in your mouth) and ear drops to treat external ear infections.

Clotrimazole is an Imidazole derivative belonging to Antifungal Agent.

Clotrimazole is an imidazole antifungal that exerts its antimicrobial activity by binding to phospholipids in the cell membrane and altering cell wall permeability, thereby causing a loss in essential intracellular elements.

Clotrimazole is approved for use in the following clinical indications

• Adult indication

Oral

• Oropharyngeal, mild disease, treatment
• Oropharyngeal, chronic suppression for recurrent infection

Topical

• Candidiasis, vulvovaginal
• Cutaneous candidiasis
• Otomycosis
• Tinea infections

• Pediatric indication

Oral

• Candidiasis, oropharyngeal; treatment

Topical

• Cutaneous candidiasis
• Tinea corporis, tinea cruris, and tinea pedis
• Vulvovaginal candidiasis

• Adult Dose

Oral

• Oropharyngeal, mild disease, treatment

Oral: 10 mg dissolved slowly 5 times daily for 7 to 14 days.

• Oropharyngeal, chronic suppression for recurrent infection

Oral: 10 mg dissolved slowly 3 times daily for the duration of immunosuppression (eg, chemotherapy or high-dose steroids).

Topical

• Candidiasis, vulvovaginal

Cream 1%

Intravaginal: Insert 1 applicatorful (~5 g) once daily (at bedtime) for 7 days. May also apply externally twice daily for 7 days, as needed, for itching and irritation.

Canesten 6-day intravaginal cream 1%

Intravaginal: Insert 1 applicatorful (~5 g) once daily (at bedtime) for 6 days.

Cream 2%

Intravaginal: Insert 1 applicatorful (~5 g) once daily (at bedtime) for 3 days. May also apply externally twice daily for 7 days, as needed, for itching and irritation.

Cream 10%

Intravaginal: Insert 1 applicatorful (~5 g) as a single dose (at bedtime).

200 mg tablet

Intravaginal: Insert 1 vaginal tablet once daily for 3 days (at bedtime).

500 mg tablet

Intravaginal: Insert 1 vaginal tablet as a single dose (at bedtime).

• Cutaneous candidiasis

Cream 1%, solution 1%: Apply to affected area twice daily; if no improvement occurs after 4 weeks of therapy, re-evaluate diagnosis.

Ointment 1% (OTC labeling): Apply to affected area twice daily for 2 weeks.

• Otomycosis (off-label)

Topical: Solution 1%: Instill 4 to 5 drops into the affected ear(s) twice daily for 10 to 14 days; application should begin after thorough cleansing of the ear canal by the provider. Reassess after completion of therapy; if fungal elements are still present, repeat cleansing of the ear canal followed by another 10- to 14-day course of clotrimazole and reassessment. Several cycles of ear cleansing followed by topical therapy and reassessment may be required; persistent otomycosis should be managed by an otolaryngologist.

• Tinea infections

Tinea corporis/tinea cruris (OTC labeling)

Topical: Cream 1%, ointment 1%, solution 1%: Apply to affected and surrounding area(s) twice daily until clinical resolution, typically 1 to 4 weeks.

Tinea pedis (OTC labeling)/tinea manuum (off-label use)

Topical: Cream 1%, ointment 1%, solution 1%: Apply to affected and surrounding area(s) twice daily until 1 week after clinical resolution, typically for 4 weeks total.

Tinea versicolor

Topical: Cream 1%, solution 1%: Apply to affected area(s) and immediate surrounding skin twice daily for 2 weeks.

• Pediatric Dose

Oral

• Candidiasis, oropharyngeal; treatment

Children ≥3 years and Adolescents: Oral: 10 mg troche dissolved slowly 5 times daily for 14 consecutive days.

Topical

• Cutaneous candidiasis

Topical ointment: Children ≥2 years and Adolescents: Topical: Apply twice daily (morning and night) for 2 weeks.

• Tinea corporis, tinea cruris, and tinea pedis

Topical cream, ointment, or solution: Children ≥2 years and Adolescents: Topical: Apply twice daily (morning and night). Duration: 2 weeks for tinea cruris; 4 weeks for tinea corporis and tinea pedis.

• Vulvovaginal candidiasis

Children ≥12 years and Adolescents: Intravaginal

Cream (1%): Insert 1 applicatorful of 1% vaginal cream daily (preferably at bedtime) for 7 consecutive days; some patients may require 14 days (CDC [Workowski 2015]). May also apply externally twice daily for 7 days as needed for itching and irritation.

Cream (2%): Insert 1 applicatorful of 2% vaginal cream daily (preferably at bedtime) for 3 consecutive days. May also apply externally twice daily for 7 days as needed for itching and irritation.

Clotrimazole is available in various strengths as 10mg, 1%, 2%, 10%, 100mg and 200mg.

Clotrimazole is available in the form of Oral lozenge or troche, Topical cream, Intravaginal tablet, and Topical solution.

Clotrimazole is contraindicated in patients with

• Hypersensitivity to clotrimazole or any component of the formulation.

• Hepatic effects: Abnormal LFTs have been reported, including abnormal aspartate aminotransferase (AST). Elevations are usually minimal. Monitor LFTs periodically, especially in patients with preexisting hepatic impairment.
• Systemic fungal infection: Clotrimazole should not be used for treatment of systemic fungal infection.
• Local irritation: If irritation/sensitivity develops, discontinue therapy and institute appropriate alternative therapy.

Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk. Because many drugs are excreted in human milk, caution should be exercised when Clotrimazole Cream or Lotion is administered to a nursing woman.

Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Common

● Abnormal liver function tests, Pruritus, Nausea, vomiting, Vulvovaginal burning.

Rare

● Burning sensation of the penis (of sexual partner), polyuria, pruritus vulvae, vaginal discharge, vulvar pain, vulvar swelling.

• Alprazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Alprazolam.
• Carbamazepine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Carbamazepine.
• Cyclosporine (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Cyclosporine (Systemic).
• Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide.
• Everolimus: Clotrimazole (Oral) may increase the serum concentration of Everolimus.
• Finerenone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Finerenone.
• Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin.
• Ixabepilone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ixabepilone.
• Lemborexant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of Lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors.
• Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day.
• Lonafarnib: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lonafarnib. Management: Avoid concurrent use of lonafarnib with weak CYP3A4 inhibitors. If concurrent use is unavoidable, reduce the lonafarnib dose to or continue at a dose of 115 mg/square meter. Monitor for evidence of arrhythmia, syncope, palpitations, or similar effects.
• Methysergide: Clotrimazole (Oral) may increase the serum concentration of Methysergide.
• Midazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Midazolam.
• Nimodipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Nimodipine.
• Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide.
• Simvastatin: CYP3A4 Inhibitors (Weak) may increase serum concentrations of the active metabolite(s) of Simvastatin. CYP3A4 Inhibitors (Weak) may increase the serum concentration of Simvastatin.
• Sirolimus (Conventional): Clotrimazole (Oral) may increase the serum concentration of Sirolimus (Conventional).
• Sirolimus (Protein Bound): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Protein Bound). Management: Reduce the dose of protein bound sirolimus to 56 mg/m² when used concomitantly with a weak CYP3A4 inhibitor.
• Tacrolimus (Systemic): Clotrimazole (Oral) may increase the serum concentration of Tacrolimus (Systemic).
• Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam.
• Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (given at least 2 hours later if needed) of ubrogepant should be limited to 50 mg.
• Progesterone: Antifungal Agents (Vaginal) may diminish the therapeutic effect of Progesterone.

● Tacrolimus (Systemic): Clotrimazole (Topical) may increase the serum concentration of Tacrolimus (Systemic).

The common side effects of Clotrimazole include the following

Common side effects

● Blistering, redness, swelling, itching, burning, stinging, peeling, hives, or skin cracks.

• Pregnancy

Pregnancy Category B and C

There have been no teratogenic studies performed in animals or humans with the combination of clotrimazole and betamethasone dipropionate. Corticosteroids are generally teratogenic in laboratory animals when administered at relatively low dosage levels.

• Nursing Mothers

Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk. Because many drugs are excreted in human milk, caution should be exercised when Clotrimazole Cream or Lotion is administered to a nursing woman.

• Pediatric Use

Adverse events consistent with corticosteroid use have been observed in patients under 12 years of age treated with Clotrimazole Cream. In open-label studies, 17 of 43 (39.5%) evaluable pediatric patients (aged 12 - 16 years old) using Clotrimazole Cream for treatment of tinea pedis demonstrated adrenal suppression as determined by cosyntropin testing. In another open-label study, 8 of 17 (47.1%) evaluable pediatric patients (aged 12 - 16 years old) using Clotrimazole Cream for treatment of tinea cruris demonstrated adrenal suppression as determined by cosyntropin testing. The use of Clotrimazole cream or lotion in the treatment of patients under 17 years of age or patients with diaper dermatitis is not recommended.

• Geriatric Use

Clinical studies of Clotrimazole Cream and Lotion did not include enough subjects aged 65 and over to determine whether they respond differently from younger subjects. Post market adverse event reporting for Clotrimazole Cream in patients aged 65 and above includes reports of skin atrophy and rare reports of skin ulceration. Caution should be exercised with the use of these corticosteroid-containing topical products on thinning skin. The use of Clotrimazole cream or lotion under occlusion, such as in diaper dermatitis, is not recommended.

Symptoms: Dizziness, nausea, or vomiting.

Management: Perform gastric lavage only if life-threatening amount has been ingested, symptoms become apparent and if the airway can be adequately protected.

Pharmacodynamic

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. Unfortunately, resistance to clotrimazole, which was rare in the past, is now common in various patient populations. 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.

Pharmacokinetics

• Absorption

Clotrimazole well absorbed from the gastrointestinal tract. Minimally absorbed from the skin and vagina. Time to peak plasma concentration is approximately 24 hours (vaginal cream).

• Distribution

The topical form is minimally absorbed in the serum and tissues. Clotrimazole is a lipophilic drug and has been shown to be secreted in breastmilk in animal studies.

• Metabolism and Excretion

Clotrimazole is metabolized in the liver to inactive compounds. Clotrimazole excreted via faeces and urine.

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• https://www.rxlist.com/mycelex-drug.htm#dosage
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