What is topical clotrimazole used for. How to apply clotrimazole cream or liquid. What precautions should be taken when using clotrimazole. What side effects can clotrimazole cause. How to store and handle clotrimazole properly.

Understanding Topical Clotrimazole: An Antifungal Medication

Clotrimazole is a widely used antifungal medication that belongs to the imidazole class. It’s primarily prescribed for treating various fungal skin infections. The topical form of clotrimazole comes as a cream or liquid and is applied directly to the affected area of the skin.

How does clotrimazole work? This medication functions by inhibiting the growth of fungi responsible for causing infections. By doing so, it effectively treats conditions such as ringworm, jock itch, and athlete’s foot.

Common Brand Names for Clotrimazole

• Lotrimin
• Mycelex
• Canesten

Primary Uses of Topical Clotrimazole

Topical clotrimazole is prescribed for several fungal skin infections. Here are the main conditions it treats:

1. Tinea corporis (ringworm): A fungal infection causing red, scaly rashes on various body parts
2. Tinea cruris (jock itch): A fungal infection affecting the groin and buttocks area
3. Tinea pedis (athlete’s foot): A fungal infection of the feet and between toes

Can clotrimazole be used for other conditions? Yes, in some cases, doctors may prescribe topical clotrimazole for tinea versicolor (a fungal infection causing discolored spots on the skin) or yeast infections of the skin. However, it’s crucial to consult a healthcare professional before using it for these purposes.

Proper Application of Topical Clotrimazole

To ensure the effectiveness of topical clotrimazole, it’s essential to apply it correctly. Here’s a step-by-step guide:

1. Wash and thoroughly dry the affected area
2. Apply a thin layer of cream or liquid to cover the affected skin
3. If treating athlete’s foot, pay special attention to the spaces between toes
4. Apply twice daily, typically in the morning and at night

Is clotrimazole safe for use on all parts of the body? While clotrimazole is generally safe for external use, it should not be applied to the scalp or nails. Additionally, avoid getting it in your eyes or swallowing the medication.

Treatment Duration and Expected Results

The duration of treatment with topical clotrimazole varies depending on the condition being treated:

• For jock itch: Symptoms should improve within 2 weeks of treatment
• For athlete’s foot or ringworm: Expect improvement over 4 weeks of treatment

When should you consult a doctor during treatment? If your symptoms don’t improve within these timeframes or if they worsen at any point during treatment, it’s crucial to seek medical advice.

Precautions and Special Considerations

Before using topical clotrimazole, it’s important to be aware of certain precautions:

• Inform your doctor about any allergies, especially to clotrimazole or its ingredients
• Disclose all medications, supplements, and herbal products you’re taking
• Notify your doctor if you’re pregnant, planning to become pregnant, or breastfeeding

Should you adjust your diet while using clotrimazole? Generally, no dietary changes are necessary unless specifically instructed by your doctor.

Potential Side Effects of Topical Clotrimazole

While clotrimazole is generally well-tolerated, it can cause side effects in some individuals. Common side effects may include:

• Blistering
• Redness
• Swelling
• Itching
• Burning or stinging sensation
• Peeling
• Hives
• Skin cracking

What should you do if you experience side effects? If you notice any of these symptoms, discontinue use and contact your healthcare provider promptly.

Proper Storage and Handling of Clotrimazole

To maintain the effectiveness and safety of clotrimazole, proper storage is crucial:

• Keep the medication in its original container, tightly closed
• Store at room temperature, away from excess heat and moisture
• Keep out of reach of children
• Avoid storing in the bathroom

Why is proper storage important? Correct storage ensures the medication remains effective and prevents accidental ingestion by children.

Missed Doses and Overdose Information

If you miss a dose of clotrimazole, apply it as soon as you remember. However, if it’s almost time for your next scheduled application, skip the missed dose and continue with your regular dosing schedule. It’s important not to apply a double amount to make up for a missed dose.

Is overdose a concern with topical clotrimazole? While topical overdose is unlikely, it’s still important to use the medication as directed. In case of accidental ingestion, contact poison control or seek emergency medical attention.

Reporting Adverse Events

If you experience serious side effects from clotrimazole, you or your doctor can report them to the FDA’s MedWatch Adverse Event Reporting program. This can be done online at the FDA website or by phone at 1-800-332-1088.

Additional Tips for Managing Fungal Infections

While using clotrimazole, consider these additional measures to manage fungal infections effectively:

• Keep the affected area clean and dry
• Wear breathable, well-fitting shoes and change socks daily if treating athlete’s foot
• Avoid sharing personal items like towels or shoes
• Use antifungal powders in shoes to prevent recurrence
• Maintain good overall hygiene

How can you prevent fungal infections in the future? Regular hygiene practices, avoiding prolonged moisture on the skin, and using preventive measures in public areas like locker rooms can help reduce the risk of future fungal infections.

When to Seek Further Medical Advice

While clotrimazole is effective for many fungal infections, there are instances where you should consult a healthcare professional:

• If symptoms persist or worsen after the recommended treatment duration
• If you experience severe side effects
• If the infection spreads to other parts of the body
• If you have underlying health conditions that might complicate treatment

Why is professional medical advice important in these cases? A healthcare provider can assess whether a different treatment approach is necessary or if there are underlying conditions contributing to persistent infections.

Clotrimazole in Combination Products

Clotrimazole is sometimes combined with other medications for enhanced effectiveness or to treat multiple symptoms. These combination products may include:

• Clotrimazole with hydrocortisone for added anti-inflammatory effects
• Clotrimazole with antibacterial agents for mixed infections

Are combination products more effective? While combination products can be beneficial in certain cases, they should only be used under the guidance of a healthcare professional, as they may have different side effects and precautions.

Off-Label Uses of Clotrimazole

While primarily used for fungal skin infections, clotrimazole may sometimes be prescribed for off-label uses. These could include:

• Treatment of certain types of diaper rash
• Management of superficial fungal nail infections
• As part of a treatment regimen for certain oral conditions

Is it safe to use clotrimazole for off-label purposes? Always consult with a healthcare provider before using clotrimazole for any purpose other than its primary indications. They can provide guidance on the appropriateness and safety of off-label use in your specific situation.

Comparing Clotrimazole to Other Antifungal Medications

Clotrimazole is one of several topical antifungal medications available. Understanding how it compares to others can help in choosing the most appropriate treatment:

• Miconazole: Similar to clotrimazole, used for various fungal infections
• Terbinafine: Often preferred for certain types of athlete’s foot
• Ketoconazole: Used for both fungal and certain inflammatory skin conditions

How does the effectiveness of clotrimazole compare to other antifungals? While clotrimazole is effective for many common fungal infections, the choice of antifungal may depend on the specific type of infection, its severity, and individual patient factors. Your healthcare provider can guide you on the most suitable option for your condition.

Cost and Accessibility Considerations

When choosing an antifungal treatment, cost and accessibility are important factors to consider:

• Clotrimazole is available over-the-counter in many countries
• Generic versions are often more affordable than brand-name products
• Some insurance plans may cover prescription-strength clotrimazole

How can patients manage the cost of antifungal treatment? Discussing generic options with your healthcare provider, checking for discount programs, and comparing prices at different pharmacies can help manage the cost of treatment.

The Role of Clotrimazole in Public Health

Clotrimazole plays a significant role in public health by providing an accessible and effective treatment for common fungal infections. Its availability as an over-the-counter medication in many regions allows for prompt treatment, potentially reducing the spread of fungal infections in communities.

How does the widespread use of antifungals like clotrimazole impact public health? By providing easy access to effective treatment, these medications can help reduce the overall burden of fungal infections on healthcare systems and improve quality of life for many individuals.

Research and Future Developments

Ongoing research continues to explore new applications and formulations of clotrimazole:

• Development of extended-release formulations for longer-lasting effects
• Investigation of clotrimazole’s potential in treating resistant fungal strains
• Exploration of combination therapies for enhanced efficacy

What potential advancements might we see in antifungal treatments? Future developments could lead to more effective treatments, reduced treatment durations, and potentially new applications for antifungal medications like clotrimazole.

Environmental Considerations and Proper Disposal

Proper disposal of medications, including clotrimazole, is important for environmental protection:

• Do not flush medications down the toilet or drain unless specifically instructed
• Check for local medication take-back programs
• If no take-back program is available, mix the medication with an undesirable substance (like coffee grounds) and dispose of it in a sealed container in the trash

Why is proper disposal of medications important? Correct disposal methods help prevent environmental contamination and reduce the risk of accidental ingestion by children or pets.

Patient Education and Self-Care

Effective use of clotrimazole goes hand in hand with patient education and self-care practices:

• Understanding the causes and prevention of fungal infections
• Recognizing early signs of infection for prompt treatment
• Learning proper application techniques for topical medications
• Implementing lifestyle changes to reduce the risk of recurrent infections

How can healthcare providers enhance patient education about antifungal treatments? Providing clear instructions, using visual aids, and encouraging patients to ask questions can improve understanding and adherence to treatment protocols.

Clotrimazole Topical: MedlinePlus Drug Information

pronounced as (kloe trim’ a zole)

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Topical clotrimazole is used to treat tinea corporis (ringworm; fungal skin infection that causes a red scaly rash on different parts of the body), tinea cruris (jock itch; fungal infection of the skin in the groin or buttocks), and tinea pedis (athlete’s foot; fungal infection of the skin on the feet and between the toes). Clotrimazole is in a class of antifungal medications called imidazoles. It works by stopping the growth of fungi that cause infection.

Topical clotrimazole comes as a cream and liquid to apply to the skin. It is usually applied twice a day (morning and night). Follow the directions on the package label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Use clotrimazole exactly as directed. Do not use more or less of it or use it more often than directed on the package or as directed by your doctor.

Topical clotrimazole is only for use on the skin. Do not let clotrimazole get into your eyes and do not swallow the medication. Clotrimazole does not work on the scalp or nails.

If you are using clotrimazole to treat jock itch, your symptoms should improve over 2 weeks of treatment. If you are using clotrimazole to treat athlete’s foot or ringworm, your symptoms should improve over 4 weeks of treatment. Call your doctor if your symptoms do not improve during this time or if your symptoms get worse at any time during your treatment.

To use topical clotrimazole, wash the affected area and dry thoroughly. Then apply a small amount of cream or liquid to cover the affected area of skin with a thin layer.

If you are treating athlete’s foot, pay special attention to the spaces between the toes when applying clotrimazole. Also, be sure to wear well-fitting shoes that allow for air circulation, and change shoes and socks at least once a day.

If you are using the liquid, do not apply it to any severely cracked or irritated areas.

Topical clotrimazole may be used to treat tinea versicolor (fungal infection of the skin that causes brown or light colored spots on the chest, back, arms, legs, or neck) or yeast infections of the skin. Talk to your doctor about the risks of using this medication for your condition.

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

Before using topical clotrimazole,

• tell your doctor and pharmacist if you are allergic to clotrimazole, any other medications, or any of the ingredients in clotrimazole cream or liquid. Ask your pharmacist for a list of the ingredients.
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take.
• tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while using clotrimazole, call your doctor.

Unless your doctor tells you otherwise, continue your normal diet.

Apply the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not apply a double amount to make up for a missed dose.

Clotrimazole may cause side effects. If you experience any of these symptoms, stop using clotrimazole and call your doctor:

• blistering, redness, swelling, itching, burning, stinging, peeling, hives, or skin cracks

Clotrimazole may cause other side effects. Call your doctor if you have any unusual problems while using this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration’s (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA’s Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

If someone swallows clotrimazole topical, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

• Lotrimin^® AF Athlete’s Foot Cream
• Lotrimin^® AF Jock Itch Cream
• Lotrimin^® AF Ringworm Cream
• Lotrimin^® Solution^¶

• Lotrisone^® Cream (containing Betamethasone, Clotrimazole)
• Lotrisone^® Lotion (containing Betamethasone, Clotrimazole)

^¶ This branded product is no longer on the market. Generic alternatives may be available.

Last Revised – 11/15/2018

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Clotrimazole topical Uses, Side Effects & Warnings

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Generic name: clotrimazole topical [ kloe-TRIM-a-zole ]
Brand names: Anti-Fungal Liquid, FungiCURE Pump Spray, Lotrimin AF Cream, Lotrimin Jock Itch Powder, MPM Anti-Fungal, Prescription Strength Cruex
Dosage forms: topical cream (1%), topical powder (1%), topical solution (1%), topical spray (1%)
Drug classes: Topical antifungals, Vaginal anti-infectives

Medically reviewed by Drugs.com on Feb 28, 2023. Written by Cerner Multum.

What is clotrimazole topical?

Clotrimazole topical is an antifungal medication that fights infections caused by fungus.

Clotrimazole topical (for the skin) is used to treat skin infections such as athlete’s foot, jock itch, ringworm, and yeast infections.

Clotrimazole topical may also be used for purposes not listed in this medication guide.

Warnings

Follow all directions on your medicine label and package. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

Before taking this medicine

You should not use clotrimazole topical if you are allergic to it.

Clotrimazole topical is not expected to harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether clotrimazole topical passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

How should I use clotrimazole topical?

Use exactly as directed on the label, or as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended.

Do not take by mouth. Clotrimazole topical is for use only on the skin.

Wash your hands before and after using clotrimazole topical, unless you are using it to treat a hand infection.

Clean and dry the affected area. Apply a small amount of the cream (usually twice daily) for 2 to 4 weeks.

Do not cover the treated skin area unless your doctor tells you to. Avoid using bandages or dressings that do not allow air circulation. A light cotton-gauze dressing may be used to protect clothing.

Use this medicine for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared. Skipping doses may also increase your risk of further infection that is resistant to antifungal medicine.

Call your doctor if your symptoms get worse, or if your condition does not improve after 4 weeks of treatment.

Store at room temperature away from moisture and heat.

What happens if I miss a dose?

Apply the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

What happens if I overdose?

An overdose of clotrimazole topical is not expected to be dangerous. Seek emergency medical attention or call the Poison Help line at 1-800-222-1222 if anyone has accidentally swallowed the medication.

What should I avoid while using clotrimazole topical?

Avoid getting this medication in your eyes, nose, or mouth.

Avoid using other skin medications on the areas you treat with clotrimazole topical unless your doctor tells you to.

Avoid wearing tight-fitting, synthetic clothing that doesn’t allow air circulation. Wear clothing made of loose cotton and other natural fibers until the infection is healed.

Clotrimazole topical side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Clotrimazole topical may cause serious side effects. Stop using clotrimazole topical and call your doctor at once if you have:

• severe blistering of treated skin;

• swelling, redness, or oozing; or

• severe burning, itching, or other irritation.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect clotrimazole topical?

It is not likely that other drugs you take orally or inject will have an effect on topically applied clotrimazole. But many drugs can interact with each other. Tell each of your health care providers about all medicines you use, including prescription and over-the-counter medicines, vitamins, and herbal products.

Frequently asked questions

• What are the most common skin conditions? (with photos)

More about clotrimazole topical

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Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer

Copyright 1996-2023 Cerner Multum, Inc. Version: 4.02.

Clotrimazol cream, 20g – InternetAptieka.lv

Clotrimazolum GSK cream 10 mg/g is intended for topical use. It contains the active substance clotrimazole, which destroys most of the fungi that cause infection in humans. Clotrimazole belongs to the group of imidazole derivatives. Medication is especially effective against yeast-like fungi and dermatophytes. Clotrimazolum cream is used for topical treatment in the following cases: fungal infections of the skin of the palms …

Product details

Before using the medicine, read the instructions for use or the relevant information on the packaging. Talk to your doctor or pharmacist about taking the medicine.

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cream for external use, cream, ointment for external use, gel for external use, vaginal cream, solution for external use, suppositories…

gel for external use 1% aluminum tube —
In a place protected from light, at a temperature not exceeding 18 ° C.
(do not freeze).
topical solution 1% vial —
In a place protected from light, at a temperature not exceeding 30 ° C (do not freeze).
topical cream 1% tube —
Store in a dry, dark place at temperatures below 25°C.
topical ointment 1% aluminum tube —
In a dry place, at a temperature of 5-25 °C.
topical cream 1% tube —
At a temperature not exceeding 25 ° C, in the original packaging (pack of cardboard).
topical cream 1% aluminum tube —
At a temperature not higher than 25 °C.
Do not freeze.
topical cream 1% aluminum tube —
In a dry, dark place, at a temperature of 15–25 °C.
Do not freeze.

Keep out of reach of children.

topical gel 1% aluminum tube – 2 years.
cream for external use 1% aluminum tube – 3 years.
topical cream 1% tube – 4 years.

Do not use after the expiry date which is stated on the packaging.

Clotrimazole is a white to pale yellow, slightly alkaline crystalline substance, melting point 145°C, soluble in acetone, chloroform and ethanol, and practically insoluble in water. Forms stable salts with both inorganic and organic acids. It is not photosensitive, but slightly hygroscopic and may hydrolyze in acidic environments. Molecular weight 344.84 Da.

Mechanism of action

Clotrimazole is an antifungal agent. Violates the permeability of the cell membrane of fungi, causes inhibition of the biosynthesis of ergosterol, an important component of fungal cell membranes. With complete or partial inhibition of ergosterol synthesis, the cell is no longer able to build an intact cell membrane, which leads to the death of the fungus.

The effect of clotrimazole on Candida albicans leads to the release of intracellular phosphorus compounds from the cell with concomitant destruction of cellular nucleic acids and the outflow of potassium. After the application of clotrimazole, its effect on the body manifests itself quickly and extensively and causes time- and concentration-dependent inhibition of fungal growth.

Pharmacodynamics

Clotrimazole is an antifungal drug with a wide spectrum of action. In general, the activity of clotrimazole in vitro”\u003e in vitro is similar to the activity of tolnaftate, griseofulvin and pyrrolnitrin against dermatophytes (Trichophyton species , Microsporum and Epidermophyton ) and the activity of polyenes, amphotericin B and nystatin against budding forms of yeast-like fungi (Candida species and Histoplasma ).

In vitro clotrimazole is fungistatic against most isolates of pathogenic fungi at concentrations from 0.02 to 10 µg/ml. It has a fungicidal effect against many isolates of species Trichophyton, Microsporum, Epidermophyton and Candida at a concentration of 0.1 to 2 μg / ml.

With consecutive passages C.albicans, C.krusei, C.pseudotropicalis, T.mentagrophytes, T.rubrum, Cryptococcus neoformans, Aspergillus niger and A.nidulans neither one-stage nor multi-stage secondary resistance to clotrimazole developed. Only a few isolates have been identified as having primary resistance to clotrimazole: one isolate C. guilliermondii , six isolates C. neoformans , three isolates Paracoccidioides brasiliensis and two isolates Blakeslea trispora . The potential for development of secondary resistance to clotrimazole was determined for several microorganisms by successive passages in liquid medium, successive passages on solid medium, or the Warburg proliferation test. Growth of dermatophytes and yeasts on Shibalsky’s plates has also been used as a method to determine the development of secondary resistance. No change in sensitivity was observed for C. albicans in none of the secondary resistance tests. Sensitivity for Trichophyton mentagrophytes, T.rubrum, C.krusei, C.pseudotropicalis, C.neoformans, Aspergillus niger or A.nidulans did not change after successive passages on liquid and solid media. Possible development of resistance has been noted in successive passages of Torulopsis glabrata and other species Torulopsis . Data from cultivation on Shibalski’s plates and other tests have shown that dermatophytes and yeasts do not develop one-stage or oligo-stage secondary resistance.

Topically applied clotrimazole has shown efficacy in the treatment of experimental skin infections in guinea pigs caused by T.mentagrophytes and T.quinckeanum . Mycologically controlled double-blind clinical studies have shown that clotrimazole is effective in the treatment of tinea groin, mycosis of the smooth skin of the trunk, dermatophytosis of the feet, pityriasis versicolor (multicolor) and cutaneous candidiasis. Mycological studies have proven its effectiveness against Trichophyton rubrum, T.mentagrophytes, Malassezia furfur and Candida albicans . Dermatophytes resistant to griseofulvin do not show cross-resistance to clotrimazole. Therefore, it can be assumed that the site of action of this drug differs from the site of action of other antimycotics. Therefore, there is no cross-resistance between these drugs.

Antifungal activity in vitro. The MIC of clotrimazole was determined by serial dilution in broth (liquid nutrient medium) or agar and in agar diffusion tests using the hole punching method. Usual substrates for cultivation, time and temperature of incubation were used. At a concentration of less than 2 µg/ml, clotrimazole had a fungicidal effect on many isolates C.albicans, Trichophyton sp., Microsporum sp. and Epidermophyton sp. and at a concentration of less than 5 µg / ml – a fungistatic effect on other isolates of these species. The addition of bovine serum to the culture medium at a final concentration of 30% resulted in a slightly higher MIC of clotrimazole.

The antifungal activity of clotrimazole in vitro”> in vitro was comparable to that of pyrrolnitrin, any of these compounds at a concentration of 0.78 μg / ml had a fungicidal effect against most strains Trichophyton sp., Microsporum sp. and Epidermophyton sp. tested.

The type of action of clotrimazole was determined in the Warburg apparatus by measuring the oxygen consumption of breeding organisms exposed to various concentrations of the substance. Additional studies were carried out using the classical subculture technique with microorganism counts 16, 24 and 48 hours after exposure to clotrimazole. These studies have shown that the main effect of clotrimazole at concentrations up to 20 µg/ml is fungistatic and affects only proliferating organisms. At concentrations of more than 20 μg / ml, clotrimazole has a fungicidal effect on some organisms.

It has been shown that the determination of the MIC of clotrimazole for budding fungi and for biphasic fungi in the yeast phase depends on the size of the inoculum and the length of the incubation time. MICs for some Candida albicans and Torulopsis glabrata isolates were higher with increasing inoculum size, incubation time, or both.

The effect of inoculum size is due to the binding of clotrimazole to the surface of fungal cells. This was established during a study of cultures C.albicans using rotating nozzles. After 24 hours, the amount of clotrimazole in the nutrient substrate decreased from 1 to 0.7 μg/ml due to the inoculum from 1 to 5×10 ⁵ cells/ml.

The larger inoculum, 1 x 10 ⁸ cells/mL, reduced the concentration of clotrimazole from 1 to 0.3 µg/mL. When the cultures were centrifuged and the cell pellet was washed with saline, the washings contained clotrimazole at concentrations of 0.2 to 0.4 μg/ml.

Presumably, the effect of incubation time on the determination of MIC values ​​is related to the mechanism of action of clotrimazole. Initial studies showed that clotrimazole acts as an antimetabolite on the metabolism of amino acids and fungal proteins, causing a gradual inhibition of their growth.

However, recent studies using C.albicans as a test microorganism have shown that the main mechanism of action of clotrimazole is a violation of the permeability of the cell membrane. The effect of clotrimazole on C.albicans promotes the release of intracellular phosphorus compounds from the cell with concomitant destruction of cellular nucleic acids. After application of clotrimazole, its effect on C. albicans was rapid and extensive and caused a time- and concentration-dependent inhibition of fungal growth.

Pharmacokinetics

Metabolic studies conducted after oral or intravenous administration showed that in most of the species studied, the concentrations of clotrimazole in tissues and blood serum are low. Most of clotrimazole was excreted as metabolites in the feces, and a small amount in the urine. Human studies have shown slow elimination after oral administration of ¹⁴ C-labeled clotrimazole (greater than 6 days). After intraperitoneal and s / c administration, very low concentrations of clotrimazole were observed in the urine. When administered parenterally, the absorption and distribution of clotrimazole throughout the organs is very low.

When applied externally and topically in humans, the penetration of radioactively labeled clotrimazole in the form of a 1% cream and 1% solution into intact and acutely inflamed skin has been reported. Six hours after application, the concentration of clotrimazole in the skin layers varied from 100 µg/cm ³ in the stratum corneum to 0.5-1 µg/cm ³ in the reticular dermis and to <0.1 µg/cm ³ in the subcutaneous tissue. Within 48 hours after application of 0.5 ml of solution or 0.8 g of cream, no measurable amount of radioactivity (0.001 µg/ml) was detected in the blood serum. Serum radioactivity levels of about 3 µg/mL have been reported in neonates and premature infants and about 2.7 µg/mL in schoolchildren. Preterm and neonates still had values ​​of 0. 4 to 1.2 µg/mL at 24 hours due to delayed clearance from the body, with older children declining more rapidly to zero at 12 hours.

In animal studies, clotrimazole produced in vitro”> in vitro and in vivo”> ​​ in vivo a dose-dependent stimulatory effect on certain microsomal enzyme systems, which in its inductive potential can be equated to the action of phenobarbital. However, this stimulating effect rapidly subsided after discontinuation of the use. In adrenalectomized animals, the enzyme-inductive effect of clotrimazole did not change.

Results of 22 double-blind, 1 single-blind and 4 open mycological studies showed that clotrimazole in the form of 1% solution and 1% cream is effective in the treatment of tinea groin, fungal infections of the smooth skin of the trunk, tinea pedis, pityriasis versicolor and cutaneous candidiasis . For clotrimazole 1% cream, the mycological cure rate was 80% for tinea groin/mycosis of the smooth skin of the trunk, 67% for tinea pedis, 88% for pityriasis versicolor, and 92% for cutaneous candidiasis compared to 4. 7; 0; 37.5 and 0%, respectively, compared with the control excipient (total 238 patients).

Toxicology

Preclinical data from routine studies of safety, genotoxicity, and carcinogenic potential have not shown any particular hazard to humans. Effects such as effects on the liver (increased levels of transaminases and alkaline phosphatase, hypertrophy of liver cells) in preclinical toxicity studies with repeated doses, effects on survival in a rat fertility study, species-specific indirect effects on fetal growth/survival in a teratological study in rats, were observed when administered orally, but only at exposures in excess of the maximum human exposure, indicating little relevance to clinical use. Given the limited absorption of clotrimazole after topical application, the potential for toxicity from accidental application of clotrimazole 1% cream is even more limited.

In 679 of 721 patients with ringworm treated for several months, clotrimazole 1% solution and 1% cream was well tolerated. In 12 cases, mild irritation was observed during treatment, which did not require interruption of therapy or any other therapeutic measures. In 17 cases, poor tolerance was observed, which led to interruption of treatment. In 3 of these 17 patients, the patch test with clotrimazole 1% solution was positive.

3 out of 200 patients suffering mainly from allergies and eczema received a positive patch test result.

In 133 healthy patients, clotrimazole 1% solution was evaluated in a continuous exposure test lasting 14 to 25 days. None of the subjects showed irritation.

No reactions were observed in 453 cases with treatments evaluated for photosensitivity and phototoxicity.

20 healthy patients tested in a controlled study for sensitivity to UV radiation. Skin areas treated with clotrimazole were irradiated for 30 s on day 1 and 30 s longer on every second day thereafter. 1 out of 20 patients was irradiated only 1 time; 9patients – 3 times and 10 patients – 4 times. In 1 patient, after the first exposure to UV radiation, papules formed.

Allergy and skin irritation after topical application of clotrimazole 1% cream could not be determined even after extensive testing. It has also been noted that adverse reactions in children are less pronounced than in adults. This was explained by the fact that clotrimazole does not affect liver enzymes in children, as is observed in adults.

Reproductive function and teratology . At doses up to 100 mg/kg (oral), clotrimazole was well tolerated in pregnant mice, rats and rabbits and did not cause embryotoxic or teratogenic effects.

When administered orally to pregnant rats at a dose of 100 mg/kg from days 6 to 15 of gestation, the number of resorptions was higher and the fetal weight was lower than in the control group, but the number of fetal malformations did not differ significantly from the control group.

Rats treated with clotrimazole for 10 weeks at doses up to 50 mg/kg/day did not differ from the control group in terms of estrus duration, fertility, gestational age, number of implantations and resorptions.