Sertaconazole Nitrate : An Overview

Drug Overview

Sertaconazole nitrate is an antifungal medication used topically to treat various fungal infections, including interdigital tinea pedis. With broad-spectrum activity against fungi, it inhibits ergosterol synthesis, disrupting cell membrane integrity and effectively alleviating symptoms associated with dermatophyte infections. Sertaconazole nitrate was approved for topical use by the United States FDA (Food and Drug Administration) in 2003.

For Patients:

Interdigital tinea pedis, commonly known as athlete's foot, is a fungal infection that affects the skin on the feet. It is one of the most common fungal infections caused by various dermatophyte fungi, such as Trichophyton and Epidermophyton. These fungi thrive in warm and moist environments, making the spaces between the toes ideal for infection.

What Are the Clinical Indications Of Sertaconazole Nitrate?

Sertaconazole nitrate is clinically indicated for treating interdigital tinea pedis, commonly known as athlete's foot, effectively addressing fungal infections between the toes and relieving associated symptoms.

What Is the Dosage of Sertaconazole Nitrate?

Sertaconazole nitrate cream, two percent, consists of 17.5 milligram (mg) of Sertaconazole (as Sertaconazole nitrate, 20 mg) per gram. As for the dosage of Sertaconazole nitrate typically involves applying a thin layer of the two percent cream to the affected area once daily, as directed by a healthcare professional. The exact dosage and duration of treatment may differ depending on the fungal infection's severity and individual patient factors.

What Are the Things to Inform the Doctor Before Taking the Drug?

The patient must inform the doctor if they are on other medications before starting this drug. They should also inform them about the below-mentioned conditions:

• Pregnancy.

• Heart disease.

• Liver disease.

• Migraines.

• Seizures (uncontrolled electrical activity).

• Kidney diseases.

• Stroke (brain damage).

• Cancer.

• Depression (unexplainable grief).

• Breastfeeding.

• Diabetes (enhanced blood sugar level).

How Is Sertaconazole Nitrate Administered?

Sertaconazole nitrate is administered by:

• Apply a thin layer of the two percent cream.

• Administer topically to the affected skin or area with the fungal infection.

• Apply once daily.

• Follow specific instructions for dosage and application provided by the healthcare professional.

• The duration of treatment varies based on the severity of the infection and individual factors.

What Are the Side Effects of Sertaconazole Nitrate?

• Redness.

• Itching.

• Dry skin.

• Burning.

• Blistering.

• Swelling.

• Drainage.

• Skin tenderness at the treated skin areas.

Missed Dose:

• If a dose is missed, apply it as soon as remembered.

• If it is almost time for the next dose, skip the missed one and resume the regular schedule.

• Avoid taking an extra dose to compensate for a missed one.

Overdose:

• The patient might feel increased severity of side effects such as redness, itching, burning, and worsening skin irritation or discomfort.

• If overdosed, seek medical attention or contact a poison control center immediately.

• Do not apply more than the prescribed amount to compensate for a missed dose.

Storage:

Keeping the drug in its original package and container is necessary. It must be safely secured and out of the children's reach. This action ensures their safety. Since bathrooms have substantial moisture levels, never keep or store drugs there. It should always be kept for storage at the optimal room temperature.

For Doctors:

Indication:

Sertaconazole nitrate cream, two percent, is an azole antifungal prescribed for the topical therapy of interdigital tinea pedis in immunocompetent individuals, both adults and pediatric patients aged 12 years and older, caused by Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum.

Dose:

Sertaconazole topical formulation of two percent strength is recommended to be used at a frequency of twice daily for four weeks.

Dosing Considerations:

• Apply Sertaconazole nitrate cream, two percent, twice daily for four weeks.

• Use enough to cover affected areas between the toes and surrounding healthy skin.

• Follow the full treatment time the physician recommends, regardless of symptom improvement.

• Ensure the affected area is thoroughly dry before application, especially after bathing.

• Wash hands after use.

• Avoid using occlusive dressings or wrappings.

• Designed for topical use only.

• Not intended for use in the eyes, mouth, or vagina.

What Are the Pharmacological Aspects of Sertaconazole Nitrate?

Mechanism of Action:

• Inhibition of Cytochrome P450 Enzymes: Sertaconazole demonstrates a selective inhibition of specific cytochrome P450 enzymes, with a notable impact on 14α-demethylase. This particular enzyme, 14α-demethylase, plays a pivotal role in converting lanosterol to ergosterol within the fungal cell membrane. The targeted inhibition of 14α-demethylase is significant as it disrupts a key step in synthesizing ergosterol, an essential sterol contributing to the structural integrity and fluidity of the fungal cell membrane.

• Disruption of Ergosterol Synthesis: The mechanism of action involves the inhibition of 14α-demethylase by Sertaconazole, leading to a consequential disruption in the biosynthesis of ergosterol. Ergosterol, a vital sterol, is integral to maintaining the structural integrity and fluidity of the fungal cell membrane. The interference with this biosynthetic pathway represents a critical aspect of Sertaconazole's antifungal activity, compromising the fungal cell's membrane structure and function. This disruption is instrumental in hindering the fungal organism's growth, reproduction, and overall survival.

• Accumulation of Ergosterol Precursors: The inhibitory effect on ergosterol synthesis by Sertaconazole leads to the buildup of abnormal sterol intermediates, notably 14α-methylsterols. This accumulation disrupts the typical composition and function of the fungal cell membrane, introducing aberrations that impede normal cellular processes.

• Alteration of Membrane Permeability: The disturbance in ergosterol synthesis induces changes in the composition of the fungal cell membrane, resulting in heightened permeability. This increased permeability, in turn, prompts the leakage of cellular contents, thereby compromising the structural integrity of the fungal cell. The alteration in membrane permeability is a pivotal event in the antifungal action of Sertaconazole.

• Fungal Growth Inhibition: The combined impact of disrupted ergosterol synthesis and changes in membrane structure culminates in preventing normal fungal growth, reproduction, and overall survival. This inhibition of fungal growth underscores the therapeutic efficacy of Sertaconazole in addressing various fungal infections.

• Antifungal Activity Against Various Pathogens: Sertaconazole nitrate showcases a comprehensive spectrum of antifungal activity, extending its effectiveness against diverse pathogens. It proves productive against dermatophytes like Trichophyton and Epidermophyton, yeasts including Candida, and molds. This broad-spectrum activity reinforces the versatility of Sertaconazole nitrate in targeting a wide range of fungal organisms responsible for various dermatological infections.

Pharmacokinetics:

• Absorption: Sertaconazole nitrate is predominantly administered topically, emphasizing its application on the skin as a critical aspect of its pharmacokinetics. The drug is absorbed through the skin through this topical route, initiating its journey into systemic circulation. However, the absorption into the systemic circulation remains notably limited, primarily attributed to the localized application on the skin.

• Distribution: Once absorbed, the drug may undergo distribution within the local tissues, where it actively exerts its antifungal activity. This distribution focuses on the application site's immediate vicinity, facilitating targeted action against fungal infections in the localized area. The systemic distribution of Sertaconazole nitrate is restricted, aligning with its primary therapeutic target being the specific application site. The localized distribution emphasizes the drug's efficacy in treating fungal infections directly at the application site while minimizing broader systemic effects.

• Metabolism: Sertaconazole nitrate undergoes potential hepatic metabolism, suggesting that enzymes in the liver may play a role in its metabolic processes. The liver's enzymatic activity may contribute to the transformation of the drug, a process that commonly occurs with various medications. The resulting metabolites, if present, are anticipated to exhibit lower pharmacological activity than the original compound, indicating that the parent drug retains primary therapeutic significance.

• Elimination: The elimination of Sertaconazole nitrate involves hepatic metabolism as well as excretion through the feces. This dual route of elimination reflects the interplay between metabolic processes in the liver and the removal of the drug and its metabolites via fecal excretion. Notably, renal elimination, typically a major route for many systemic drugs, is expected to be a minor pathway for Sertaconazole nitrate due to its predominantly topical administration. This emphasizes the localized nature of elimination, aligning with the targeted application of the drug.

• Half-life: The elimination half-life is a crucial pharmacokinetic parameter representing the duration required for half of the administered drug to be cleared from the body. While specific details about the half-life of Sertaconazole nitrate may be available in the product-specific prescribing information, understanding this parameter aids in determining the drug's duration of action and the frequency of dosing. A longer half-life suggests a more sustained presence in the body, potentially influencing dosing intervals and overall therapeutic efficacy.

• Special Populations: Pharmacokinetics in special populations, such as the elderly or individuals with hepatic or renal impairment, may vary. Consultation with healthcare professionals is essential for appropriate dosing in these populations.

Pharmacodynamics:

• Spectrum of Activity: Sertaconazole nitrate exhibits a broad spectrum of antifungal activity, targeting dermatophytes like Trichophyton species, yeasts including Candida species, and molds. This versatility allows for its efficacy against a range of fungal infections. Its effectiveness extends to treating diverse fungal infections, including interdigital tinea pedis (athlete's foot), tinea corporis (ringworm), and cutaneous candidiasis. This makes it a versatile choice for various dermatological conditions.

• Fungal Cell Membrane Disruption: Interference with ergosterol synthesis by Sertaconazole nitrate induces structural and functional alterations in the fungal cell membrane. This leads to changes in membrane permeability, causing leakage of cellular contents and compromising the overall integrity of the fungal cell.

• Time-Dependent Action: The antifungal activity of Sertaconazole nitrate relies on a time-dependent mechanism. Sustained exposure to the medication is crucial for optimal effectiveness. Prolonged exposure contributes to the ongoing disruption of fungal cell membranes, inhibiting growth and promoting comprehensive antifungal efficacy.

Clinical Studies And Efficacy:

In two randomized, double-blind clinical trials, participants aged 12 years and above with interdigital tinea pedis applied either Sertaconazole nitrate cream, two percent, or a placebo (vehicle) twice daily for four weeks. Those with moccasin-type (plantar) tinea pedis or onychomycosis were not part of the trial. Evaluation occurred two weeks after completing the treatment (six weeks from the start), focusing on signs and symptoms associated with interdigital tinea pedis. The assessment criteria were as follows:

• Complete Cure: Patients achieving complete clearance of both signs and symptoms and mycological cure.

• Effective Treatment: Patients exhibit minimal residual signs and symptoms of interdigital tinea pedis, along with a mycological cure.

• Mycological Cure: Patients demonstrate negative results in microscopic KOH (potassium hydroxide) preparation and fungal culture.

These criteria were utilized to assess the effectiveness of the treatments in addressing interdigital tinea pedis, encompassing clinical and mycological outcomes.

What Are the Contraindications of Sertaconazole Nitrate?

There are no contraindications of the drug recorded.

Warnings and Precautions:

Local Adverse Reactions: In the event of irritation, cease the treatment and initiate suitable therapeutic measures. Physicians should use caution when prescribing Sertaconazole nitrate cream, two percent, to individuals with a known sensitivity to azole antifungals, as there is a potential for cross-reactivity.

Specific Considerations

1. Pregnancy: Information regarding the application of Sertaconazole nitrate cream, two percent, in pregnant women is unavailable, posing a challenge in evaluating the potential risks of significant birth defects, miscarriage, or adverse outcomes for both the mother and fetus associated with the drug. Animal reproduction studies involving oral administration of Sertaconazole nitrate to pregnant rats and rabbits during organogenesis at doses 40 and 80 times the maximum recommended human dose (MRHD) based on body surface area (BSA) comparison revealed no observable adverse developmental effects.

In rats, where maternal dosing continued until weaning, a reduction in live birth indices and an increase in still-born pups were noted at doses 20 and 40 times the MRHD based on BSA comparison. The baseline risk of major birth defects and miscarriage for the specific population under consideration remains unknown. In the general United States population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is approximately two to four percent and 15 to 20 percent, respectively.

2. Lactation:There needs to be more data on the presence of Sertaconazole in human or animal milk, its impact on the breastfed infant, or its influence on milk production. When contemplating the use of Sertaconazole nitrate cream, two percent, it is essential to evaluate the developmental and health benefits of breastfeeding in conjunction with the mother's clinical necessity for the medication. Additionally, potential adverse effects on the breastfed infant from either Sertaconazole nitrate cream, two percent, or the underlying maternal condition should be considered.

3. Pediatric Use: The safety and efficacy of Sertaconazole nitrate cream, two percent, have not been established in pediatric patients under the age of 12 years.

4. Geriatric Use: Clinical trials of Sertaconazole nitrate cream, two percent, did not enroll an adequate number of participants aged 65 and older to ascertain if their response differs from that of younger subjects.