Ciclopirox

Ciclopirox is an Antifungal, Antibacterial and Anti Inflammatory agent belonging to the pharmacological class of Pyridine

Ciclopirox has been approved to relieve symptoms and also for the treatment and maintenance of Cutaneous candidiasis, Onychomycosis, mild to moderate, Seborrheic dermatitis of the scalp, Tinea infections.

After being taken orally, Ciclopirox is quickly absorbed. In patients with dermatophytic onychomycoses, applying it once daily to all twenty digits' nails and the adjacent 5 millimeters of skin for 6 months resulted in an average absorption rate of less than 5% of the applied dose.Ciclopirox olamine is also capable of penetrating into hair and traversing the epidermis and hair follicles, reaching sebaceous glands and dermis.

The volume of distribution of ciclopirox is not available, but it exhibits a high protein binding rate of 94-97% following topical administration.

The primary metabolic pathway of ciclopirox involves glucuronidation. After oral administration of 10 mg of radiolabeled drug (14C-ciclopirox) to healthy volunteers, a study found that about 96% of the radioactivity was excreted through the kidneys within 12 hours. Most of this excretion (94%) was in the form of glucuronides.

The common side effects involved in using Ciclopirox are Skin irritation (redness, itching, burning, or stinging at the application site), Allergic reactions (swelling, rash, or hives), Dry skin, Skin discoloration, Peeling or scaling of the skin, Contact dermatitis (rash or irritation due to contact with the medication), Nail changes (temporary changes in nail color or texture).

Ciclopirox is available in the form of Nail lacquer, Cream/Lotion/Gel, Shampoo.

Ciclopirox is approved in Germany, Japan, Malaysia, India, the U.K., the U.S., and China.

Ciclopirox, belonging to the pharmacological class of Triazoles, acts as an Antifungal, Antibacterial and Anti Inflammatory agent.

The mechanism of action of ciclopirox has been extensively studied using different in vitro and in vivo infection models. One particular in vitro study proposed that ciclopirox exerts its effects through chelation of polyvalent cations (Fe+3 or Al+3), which subsequently inhibits the metal-dependent enzymes responsible for breaking down peroxides within the fungal cell. However, the clinical significance of this finding remains uncertain.

Ciclopirox has been approved to relieve symptoms and also for the treatment and maintenance of Cutaneous candidiasis, Onychomycosis, mild to moderate, Seborrheic dermatitis of the scalp, Tinea infections.

Ciclopirox is found to be available in the form of Nail lacquer, Cream/Lotion/Gel, Shampoo.

Ciclopirox can be used in the following treatment:

• Cutaneous candidiasis
• Onychomycosis, mild to moderate
• Seborrheic dermatitis of the scalp
• Tinea infections

Ciclopirox can help to relieve symptoms and also for the treatment and maintenance of Cutaneous candidiasis, Onychomycosis, mild to moderate, Seborrheic dermatitis of the scalp, Tinea infections.

Ciclopirox is approved for use in the following clinical indications:

• Cutaneous candidiasis
• Onychomycosis, mild to moderate
• Seborrheic dermatitis of the scalp
• Tinea infections

Cutaneous candidiasis:

• Topical: Cream 0.77%, suspension 0.77%:
• Apply twice daily, gently massaging into affected areas and surrounding skin. If there is no improvement after 4 weeks of treatment, the diagnosis should be re-evaluated.

Onychomycosis, mild to moderate:

• Note: For patients with distal subungual onychomycosis involving ≤50% of the nail and sparing the matrix/lunula.
• Topical: Lacquer (solution):
• Apply to affected fingernail(s) and/or toenail(s) and adjacent skin once daily in combination with weekly nail trimming and periodic nail debridement. Remove with alcohol every 7 days; continue therapy until nail clearance (maximum duration: 48 weeks).

Seborrheic dermatitis of the scalp:

• Topical:
• Gel 0.77%: Apply twice daily, gently massaging into the affected area. If there is no improvement after 4 weeks of treatment, the diagnosis should be re-evaluated.
• Shampoo 1%: Apply approximately 5 mL to wet hair; lather, and leave on hair and scalp for about 3 minutes; rinse. For longer hair, up to 10 mL may be used. Repeat twice weekly for 4 weeks; allow a minimum of 3 days between applications. If there is no improvement after 4 weeks of treatment, the diagnosis should be re-evaluated.

Tinea infections:

• Tinea corporis/tinea cruris:
• Topical: Cream 0.77%, gel 0.77% (gel is for tinea corporis only), lotion 1% [Canadian product], suspension 0.77%:
• Apply to affected and surrounding area(s) twice daily until clinical resolution, typically 1 to 4 weeks.
• Tinea pedis (labeled use)/tinea manuum (off-label use):
• Topical: Cream 0.77%, gel 0.77%, lotion 1% [Canadian product], suspension 0.77%:
• Apply to affected and surrounding area(s) once or twice daily until 1 week after clinical resolution, typically for 4 weeks total.
• Tinea versicolor:
• Topical: Cream 0.77%, suspension 0.77%:
• Apply to affected area(s) and immediate surrounding skin twice daily for 2 weeks.

Ciclopirox is available in the following dosage forms and strengths:

• Cream/lotion/gel: 0.77%
• Shampoo: 1%
• Nail lacquer: 8%

Nail lacquer, Cream/Lotion/Gel, Shampoo.

Dosage Adjustments in Pediatric Patients:

Cutaneous candidiasis, tinea cruris, and tinea versicolor:

• Cream and suspension (lotion):
• For Children ≥10 years and Adolescents: Apply twice daily (morning and evening) to the affected area. If there is no improvement after 4 weeks, the treatment should be reevaluated.

Tinea corporis and tinea pedis:

• Cream and suspension (lotion):
• For Children ≥10 years and Adolescents: Apply twice daily (morning and evening) to the affected area. If there is no improvement after 4 weeks, the treatment should be reevaluated.
• Gel:
• For Adolescents ≥16 years: Apply twice daily (morning and evening) to affected areas and surrounding skin. If there is no improvement after 4 weeks of treatment, the diagnosis should be reevaluated.

Onychomycosis of the fingernails and toenails:

• Lacquer (solution):
• For Children ≥12 years and Adolescents: Apply to adjacent skin and affected nails once daily, preferably at bedtime, or 8 hours before washing, as part of a comprehensive management program for onychomycosis. Remove with alcohol every 7 days.

Seborrheic dermatitis of the scalp:

• Gel:
• For Adolescents ≥16 years: Apply twice daily, gently massaging into affected areas and surrounding skin. If there is no improvement after 4 weeks of treatment, the diagnosis should be reevaluated.
• Shampoo:

• Apply approximately 5 mL to wet hair, lather, and leave in place for about 3 minutes, then rinse. For longer hair, up to 10 mL may be used. Repeat twice weekly for 4 weeks, allowing a minimum of 3 days between applications. If there is no improvement after 4 weeks of treatment, the diagnosis should be reevaluated.

When taking Ciclopirox, there are certain dietary restrictions that should be followed to ensure the medication's effectiveness and safety:

• Ciclopirox is a topical medication primarily used for treating fungal infections of the skin and nails. Since it is applied externally, there are generally no dietary restrictions related to its use. However, to ensure the safety and efficacy of the treatment.

The dietary restriction should be individualized as per patient requirements.

Ciclopirox may be contraindicated under the following conditions:

• Ciclopirox (ciclopirox topical solution, 8% w/w) NAIL LACQUER should not be used in individuals who have demonstrated hypersensitivity to any of its ingredients.

The treating physician must closely monitor the patient and keep pharmacovigilance as follows:

WARNINGS

• Ciclopirox (ciclopirox topical solution, 8% w/w) NAIL LACQUER is intended for use on nails and immediately adjacent skin only. It should not be used in the eyes, mouth, or vagina.

PRECAUTIONS

• It is not recommended to use Ciclopirox in combination with systemic antifungal agents for onychomycosis as no studies have been conducted to
• determine if it reduces their effectiveness. The effectiveness and safety of Ciclopirox have not been studied in specific populations such as pregnant or nursing women, patients with a history of immunosuppression or HIV seropositive, organ transplant recipients, those requiring medication for epilepsy, or those with severe plantar (moccasin) tinea pedis.
• There is currently no relevant clinical experience for patients with insulin-dependent diabetes or diabetic neuropathy, and prescribing Ciclopirox to such patients should be done with careful consideration of the risks. If there is a reaction suggesting sensitivity or chemical irritation while using Ciclopirox, treatment should be stopped, and appropriate therapy should be initiated.

It is advisable to avoid alcohol consumption during Ciclopirox treatment, as it may increase the risk of liver toxicity and other adverse effects.

The excretion of this drug in human milk is unknown. As many medications are excreted in human milk, caution should be exercised when administering Ciclopirox to a nursing woman.

Pregnancy:

Pregnancy Category B

Teratology studies were conducted on mice, rats, rabbits, and monkeys, administering oral doses of up to 77 mg/kg/day, 23 mg/kg/day, 23 mg/kg/day, and 38.5 mg/kg/day of ciclopirox as ciclopirox olamine, respectively. Additionally, rats and rabbits received topical doses of up to 92.4 mg/kg/day and 77 mg/kg/day, respectively. In all these studies, there were no significant fetal malformations observed.

Furthermore, teratology studies were carried out with ciclopirox free acid in rats receiving oral doses of 20 mg/kg/day, 50 mg/kg/day, or 125 mg/kg/day and in rabbits receiving oral doses of 12.5 mg/kg/day, 32 mg/kg/day, or 80 mg/kg/day. Again, no significant fetal malformations were noted in these studies.

However, it is important to note that there are no sufficient or well-controlled studies of topically applied ciclopirox in pregnant women. Therefore, Ciclopirox should only be used during pregnancy if the potential benefits are deemed to outweigh the potential risks to the fetus.

There are certain food-related warnings and precautions to consider when using Ciclopirox:

• Ciclopirox is a topical medication primarily used for treating fungal infections of the skin and nails. Since it is applied externally, there are generally no dietary restrictions related to its use. However, to ensure the safety and efficacy of the treatment.

The adverse reactions related to Ciclopirox can be categorized as follows:

Common :

• Skin irritation (redness, itching, burning, or stinging at the application site)

Less common :

• Dry skin
• Peeling or scaling of the skin

Rare :

• Allergic reactions (swelling, rash, or hives)
• Skin discoloration
• Contact dermatitis (rash or irritation due to contact with the medication)
• Nail changes (temporary changes in nail color or texture)

The clinically relevant drug interactions of Ciclopirox are briefly summarized here:

Ciclopirox products do not have any associated drug interactions.

The following are the side effects involving Ciclopirox:

• Skin irritation (redness, itching, burning, or stinging at the application site)
• Allergic reactions (swelling, rash, or hives)
• Dry skin
• Skin discoloration
• Peeling or scaling of the skin
• Contact dermatitis (rash or irritation due to contact with the medication)
• Nail changes (temporary changes in nail color or texture).

The use of Ciclopirox should be prudent in the following group of special populations:

Pregnancy:

Pregnancy Category B

Teratology studies were conducted on mice, rats, rabbits, and monkeys, administering oral doses of up to 77 mg/kg/day, 23 mg/kg/day, 23 mg/kg/day, and 38.5 mg/kg/day of ciclopirox as ciclopirox olamine, respectively. Additionally, rats and rabbits received topical doses of up to 92.4 mg/kg/day and 77 mg/kg/day, respectively. In all these studies, there were no significant fetal malformations observed.

Furthermore, teratology studies were carried out with ciclopirox free acid in rats receiving oral doses of 20 mg/kg/day, 50 mg/kg/day, or 125 mg/kg/day and in rabbits receiving oral doses of 12.5 mg/kg/day, 32 mg/kg/day, or 80 mg/kg/day. Again, no significant fetal malformations were noted in these studies.

However, it is important to note that there are no sufficient or well-controlled studies of topically applied ciclopirox in pregnant women. Therefore, Ciclopirox should only be used during pregnancy if the potential benefits are deemed to outweigh the potential risks to the fetus.

Lactation:

The excretion of this drug in human milk is unknown. As many medications are excreted in human milk, caution should be exercised when administering Ciclopirox to a nursing woman.

Pediatric:

The safety and efficacy in pediatric patients have not been verified.

Geriatric Use:

In the US, vehicle-controlled clinical trials of ciclopirox topical solution, 8% w/w, did not involve an adequate number of patients aged 65 and over, making it challenging to ascertain if they exhibit different responses compared to younger patients. However, based on other reported clinical experiences, no notable differences in responses have been identified between elderly and younger patients.

The physician should be vigilant about the knowledge pertaining to the identification and treatment of overdosage of Ciclopirox.

The probability of overdosing from applying ciclopirox nail lacquer, 8%, topically is exceedingly low. In a rat study assessing acute oral toxicity, the LD50 (lethal dose for 50% of the subjects) was found to be greater than 10 mL/kg of the nail lacquer. For an adult weighing 60 kg or more, this would equate to 600 mL, which means over 1000 vials of 3 mL each. Moreover, the possibility of overdosing through oral ingestion of the nail lacquer is improbable due to its unappealing taste, which discourages excessive consumption.

Pharmacodynamics:

Ciclopirox is a versatile antifungal medication that offers additional antibacterial and anti-inflammatory properties. Its primary mode of action involves its strong binding affinity for trivalent cations, which hinders essential co-factors in enzymes. In laboratory settings, Ciclopirox has shown either fungistatic or fungicidal effects against a wide range of fungal organisms, including dermatophytes, yeasts, dimorphic fungi, eumycetes, and actinomycetes. Notably, it also possesses antibacterial activity against both Gram-positive and Gram-negative bacteria. Moreover, in human polymorphonuclear cells, Ciclopirox has demonstrated anti-inflammatory effects by inhibiting the synthesis of prostaglandin and leukotriene. Additionally, its ability to suppress 5-lipoxygenase and cyclooxygenase formation contributes to its anti-inflammatory properties.

Pharmacokinetics:

In pharmacokinetic studies conducted on both animals and humans, it was observed that ciclopirox olamine, when administered orally, is rapidly absorbed and entirely eliminated through feces and urine in all species. The majority of the compound is excreted either unchanged or as glucuronide. In a study involving healthy volunteers who were given 10 mg of radiolabelled drug (14C-ciclopirox) orally, approximately 96% of the radioactivity was excreted via the kidneys within 12 hours of administration, with 94% of the renally excreted radioactivity present as glucuronides. This indicates that glucuronidation is the primary metabolic pathway for this compound.

To investigate systemic absorption, 5 patients with dermatophytic onychomycoses were treated with ciclopirox topical solution, 8% w/w, on all 20 digits and adjacent 5 mm of skin once daily for six months. Serum concentrations and urinary excretion of ciclopirox were measured at various intervals. The results showed that serum levels ranged from 12-80 ng/mL, and the mean absorption of ciclopirox from the topical dosage form was less than 5% of the applied dose. One month after treatment cessation, ciclopirox levels in both serum and urine were below the limit of detection.

In two vehicle-controlled trials, patients with toenail and affected fingernail issues applied ciclopirox topical solution, 8% w/w. Out of 66 patients on active treatment, 24 had detectable serum ciclopirox concentrations during the dosing interval, with concentrations ranging from 10.0-24.6 ng/mL. It's worth noting that eleven of these 24 patients were also using concomitant medication containing ciclopirox as ciclopirox olamine (Loprox® Cream).

An in vitro investigation was conducted to assess the penetration of ciclopirox topical solution, 8% w/w. Radiolabelled ciclopirox was applied once to avulsed onychomycotic toenails, demonstrating penetration up to a depth of about 0.4 mm. Concentrations of ciclopirox in the nail plate decreased with nail depth. However, the clinical significance of these findings in the nail plates remains uncertain as nail bed concentrations were not determined.

1. https://reference.medscape.com/drug/loprox-penlac-ciclopirox-topical-343484
2. https://go.drugbank.com/drugs/DB01188
3. https://pdf.hres.ca/dpd_pm/00010842.PDF
4. https://www.webmd.com/drugs/2/drug-18039-3262/ciclopirox-topical/ciclopirox-lacquer-topical/details
5. https://www.clinicalkey.com/#!/content/drug_monograph/6-s2.0-1259