ACTION AND MECHANISM

- Antifungal. Clotrimazole is an antifungal with an imidazole structure and essentially fungistatic activity (fungicidal at 5 MIC). It inhibits ergosterol production by binding to the heme site of cytochrome P450, a cofactor of the enzyme lanosterol-14α-demethylase. The decrease in ergosterol levels, along with the accumulation of lanosterol, causes structural and functional alterations of the cell membrane, increasing its permeability and promoting cell lysis.

Resistance mechanisms: Isolated cases of clotrimazole resistance, both primary and secondary, have been reported. Generally, the following resistance mechanisms to azole antifungals have been described:

- Alterations in membrane permeability.

- Appearance of expulsion bombs.

- Alterations of the target, due to overproduction of the enzyme or due to the appearance of mutations in the ER11 gene that codes for lanosterol-14alpha-demethylase.

- Increased fungal cytochrome P450 activity, requiring a higher dose of antifungal.

Microbial sensitivity/resistance: It has a broad spectrum, with an MIC between 0.062-4 mcg/ml, being effective against the following fungi:

- Susceptible microorganisms:

* Dermatophytes: Trychophyton spp., Ephidermophyton spp., Microsporum spp.

* Yeasts: Candida spp., Malassezia furfur, Histoplasma capsulatum.

* Dysmorphic fungi: Coccidioides immitis, Blastomyces dermatitidis, Paracoccidioides brasiliensis, Sporothrix schenckii.

* Other fungi: Cryptococcus neoformans.

* Other microorganisms: Naegleria fowleri, Nocardia spp.

- Resistant microorganisms: Haemophilus vaginalis, Trichomonas vaginalis.

Reduced sensitivity to azole antifungals has been described in certain Candida spp. species other than C. albicans, which can lead to infections in immunocompromised or diabetic patients.

SPECIAL WARNINGS

- Re-evaluate the diagnosis and consider therapeutic alternatives if symptoms continue or worsen after 4 weeks of treatment (or 10 days in the case of athlete's foot).

PATIENT ADVICE

- The treatment does not exclude the need to follow basic hygiene measures and body care to prevent the risk of reinfection.

In the case of foot infections, it is recommended to change socks after each application and wear well-ventilated shoes. It is advisable to avoid synthetic socks or shoes with rubber soles.

In addition, extra precautions should be taken to avoid infecting other people, such as avoiding sharing socks, shoes or towels, and not walking barefoot.

- Remember to apply clotrimazole every day, and for the entire period of time prescribed by your doctor, even if your symptoms have disappeared. Stopping treatment prematurely could lead to a return of symptoms and the development of antibiotic resistance.

- Do not cover the application area with occlusive dressings.

CONTRAINDICATIONS

- [ALLERGY TO AZOLE ANTIFUNGALS] or to any other component of the medication.

ADVANCED AGE

No specific problems have been described in the elderly that would require a dosage adjustment.

EFFECTS ON DRIVING

It is not expected to have a significant impact.

PREGNANCY

Animal safety: no teratogenic or embryotoxic effects have been observed.

Safety in humans: No harmful effects on the mother and child are expected if this preparation is used during pregnancy. Clotrimazole can be used during pregnancy, always under the supervision of a healthcare professional.

Effects on fertility: Clotrimazole did not adversely affect fertility in animals. No specific studies have been conducted in humans.

PHARMACOKINETICS

- Absorption: It exhibits good dermal penetration, reaching concentrations between 50-100 mcg/ml (stratum corneum) and 1.53-3 mcg/ml (capillary layer). Systemic absorption is low (0.5% topical; 3-10% vaginal), reaching concentrations below the limit of detection (cp < 1 ng/ml). Absorption may be greater under occlusive conditions.

- Metabolism: undergoes hepatic metabolism.

- Elimination: After parenteral administration, it is excreted in feces, via biliary secretion, with minimal renal elimination (< 0.5%). Its t1/2 is 3.5-5 h.

INDICATIONS

- Treatment of [ATHLETE'S FOOT].

Official recommendations regarding the proper use of antifungals should be taken into account, especially those related to resistance problems.

INTERACTIONS

Specific studies of interactions with other topically administered medications have not been conducted, so it is recommended to avoid applying other drugs where clotrimazole has been applied.

LACTATION

Animal safety: Clotrimazole is excreted in rat milk at levels higher than maternal plasma concentrations. There are no data regarding the consequences of this excretion in offspring.

Safety in humans: It is unknown whether it is excreted in breast milk. Systemic absorption is minimal after topical administration and systemic effects are unlikely. Therefore, it can be used during breastfeeding.

CHILDREN

Clotrimazole has been used to treat athlete's foot in children and adolescents, with the same dosages recommended as for adults. However, its use in children under 12 years of age should be restricted to medical advice.

Select the presentations specifically indicated for children (see information regarding the different presentations available).

GUIDELINES FOR PROPER ADMINISTRATION

- Cream, topical solution: apply and massage to promote absorption.

POSOLOGY

"CANESPIE CLOTRIMAZOLE"

- Adults: apply a thin layer 2-3 times a day.

- Children and adolescents < 18 years: no dosage adjustment required. Use in children < 12 years should be under medical supervision.

- Elderly: no dosage adjustment required.

Treatment duration: usually 3-4 weeks. Consult your doctor and/or pharmacist if symptoms persist or worsen after 10 days of treatment.

If necessary, and once the 4-week period has ended, the treatment could be extended for an additional 2 weeks.

Missed dose: Take the missed dose as soon as possible, unless it is almost time for the next dose. Take the next dose at the usual time. Do not double the next dose.

DOSAGE IN HEPATIC INSUFFICIENCY

No specific dosage recommendations have been made.

DOSAGE IN RENAL INSUFFICIENCY

No specific dosage recommendations have been made.

PRECAUTIONS

- Occlusive dressings. Avoid occlusive dressings as they may promote systemic absorption.

- Do not apply to eyes. In case of accidental contact with eyes, rinse thoroughly with water and consult an ophthalmologist.

PRECAUTIONS RELATING TO EXCIPIENTS

- Because it contains benzyl alcohol, it should not be administered to premature infants or newborns.

Doses of benzyl alcohol exceeding 90 mg/kg/day can produce fatal toxic reactions in children under 3 years of age, so it is recommended to avoid exceeding these doses.

Doses of benzyl alcohol below 90 mg/kg/day can cause anaphylactoid and toxic reactions in children under three years of age.

ADVERSE REACTIONS

Adverse reactions are usually limited to local symptoms at the injection site. These typically appear during the first few days of treatment and do not usually require discontinuation of clotrimazole.

Adverse reactions are described according to each frequency interval, being considered very common (>10%), common (1-10%), uncommon (0.1-1%), rare (0.01-0.1%), very rare (<0.01%) or of unknown frequency (cannot be estimated from the available data).

- Dermatological: frequency unknown [ERYTHEMA], [PRURITUS], [SKIN ERUPTIONS], [EXFOLIATIVE DERMATITIS], [SKIN IRRITATION], [BLISTERS], [EDEMA] or burning, itching, stinging or painful sensation.

- Allergic: frequency unknown [HYPERSENSITIVITY REACTIONS], with [URTICARIA], [DYSPNEA], [HYPOTENSION] or [SYNCOPE].

ADVERSE REACTIONS RELATED TO EXCIPIENTS

- Because it contains cetostearyl alcohol, it may cause local skin reactions, such as [CONTACT DERMATITIS].

OVERDOSE

Symptoms: Significant poisoning is unlikely with topical application. Accidental ingestion has resulted in vomiting and gastrointestinal discomfort.

Measures to be taken:

- Antidote: there is no specific antidote.

- General disposal measures: In case of over-application, washing the area and temporarily suspending treatment may suffice. If symptomatic poisoning occurs due to accidental ingestion, gastric lavage with airway protection may be necessary.

- Treatment: symptomatic.