indication

For the local treatment of oropharyngeal candidiasis and vaginal yeast infections, also used in fungal infections of the skin such as ringworm, athlete's foot, and jock itch.

pharmacology

Clotrimazole, an imidazole derivative with a broad spectrum of antimycotic activity, inhibits biosynthesis of the sterol ergostol, an important component of fungal cell membranes. Its action leads to increased membrane permeability and apparent disruption of enzyme systems bound to the membrane. Betamethasone and clotrimazole are used together to treat cutaneous tinea infections. In studies in fungal cultures, the minimum fungicidal concentration of clotrimazole caused leakage of intracellular phosphorous compounds into the ambient medium with concomitant breakdown of cellular nucleic acids, and accelerated potassium etflux. Both of these events began rapidly and extensively after addition of the drug to the cultures. The primary action of clotrimazole is against dividing and growing organisms.

mechanism of action

Clotrimazole interacts with yeast 14-α demethylase, a cytochrome P-450 enzyme that converts lanosterol to ergosterol, an essential component of the membrane. In this way, clotrimazole inhibits ergosterol synthesis, resulting in increased cellular permeability. Clotrimazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms and the uptake of purine, impair triglyceride and/or phospholipid biosynthesis, and inhibit the movement of calcium and potassium ions across the cell membrane by blocking the ion transport pathway known as the Gardos channel.

toxicity

Symptoms of overdose include erythema, stinging, blistering, peeling, edema, pruritus, urticaria, burning, and general irritation of the skin, and cramps.

biotransformation

Hepatic (metabolized to inactive metabolites)

absorption

Poorly and erratically absorbed orally, minimal vaginal or topical absorption.

half life

2 hours

drug interactions

Budesonide: CYP3A4 Inhibitors (Moderate) such as clotrimazole may increase the serum concentration of Budesonide (Systemic, Oral Inhalation). Consider reducing the oral budesonide dose when used together with a CYP3A4 inhibitor. This interaction is likely less severe with orally inhaled budesonide. Any patient receiving both budesonide and a moderate CYP3A4 inhibitor should be monitored closely for signs/symptoms of corticosteroid excess.

Colchicine: CYP3A4 Inhibitors (Moderate) such as clotrimazole may increase the serum concentration of colchicine. Reduce colchicine dose (for gout flares: to 1.2 mg x 1 dose, with next dose no sooner than 3 days later; for Familial Mediterranean Fever: to no more than 1.2 mg/day) when using in combination with a moderate CYP3A4 inhibitor such as erythromycin or verapamil. Increase monitoring for colchicine-related toxicity when using such combinations. Use extra caution in patients with impaired renal and/or hepatic function.

Everolimus: CYP3A4 Inhibitors (Moderate)such as clotrimazole may increase the serum concentration of everolimus. The prescribing information for the Afinitor branded everolimus product lists indication-specific recommendations for managing this interaction.

Fentanyl: CYP3A4 Inhibitors (Moderate) such as clotrimazole may increase the serum concentration of fentanyl. Concurrent use of fentanyl with any CYP3A4 inhibitor may result in increased fentanyl concentrations and could increase or prolong adverse effects, including potentially fatal respiratory depression. Patients receiving fentanyl and any CYP3A4 inhibitor should be closely monitored for several days following initiation of the combination, and fentanyl dosage reductions should be made as appropriate.

Halofantrine: CYP3A4 Inhibitors (Moderate) such as clotrmazole may increase the serum concentration of halofantrine. Extreme caution, with possibly increased monitoring of cardiac status (e.g., ECG), should be used with concurrent use of halofantrine with any moderate CYP3A4 inhibitor(s).

Ranolazine: CYP3A4 Inhibitors (Moderate) such as clotrimazole may increase the serum concentration of ranolazine. Limit the ranolazine dose to a maximum of 500mg twice daily in patients concurrently receiving moderate CYP3A4 inhibitors (e.g., diltiazem, verapamil, erythromycin, etc.). Monitor for increased effects/toxicity of ranolazine during concomitant use.

Tacrolimus: The antifungal, Clotrimazole, may increase serum concentrations of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Clotrimazole therapy is initiated, discontinued or altered.

Tamsulosin: Clotrimazole, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Clotrimazole is initiated, discontinued, or dose changed.

Tolterodine: Clotrimazole may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.

Tramadol: Clotrimazole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.

Trazodone: The CYP3A4 inhibitor, Clotrimazole, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Clotrimazole is initiated, discontinued or dose changed.