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Ciclopirox (Topical)


VA CLASSIFICATION
Primary: DE102{01}

Commonly used brand name(s): Loprox; Penlac Nail Lacquer.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antifungal (topical)—
Note: Ciclopirox is a broad-spectrum antifungal, which has an antifungal spectrum similar to that of the imidazoles.



Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Candidiasis, cutaneous (treatment)—Ciclopirox is indicated as a primary agent in the topical treatment of cutaneous candidiasis (moniliasis) caused by Candida albicans (Monilia albicans) .{02} {04}{16}

Tinea corporis (treatment)
Tinea cruris (treatment) or
Tinea pedis (treatment)—Ciclopirox cream or lotionis indicated as a primary agent in the topical treatment of tinea corporis (ringworm of the body), tinea cruris (ringworm of the groin; jock itch), or tinea pedis (ringworm of the foot; athlete's foot) caused by Trichophyton rubrum, T. mentagrophytes, Epidermophyton floccosum (Acrothesium floccosum), and Microsporum canis.{02}{04}{16}Ciclopirox gel is indicated as a primary agent in the topical treatment of tinea pedis or tinea corporis caused by Trichophyton rubrum, Trichophyton mentagrophytes, or epidermophyton floccosum .{11}

Tinea versicolor (treatment)—Ciclopirox is indicated as a primary agent in the topical treatment of tinea versicolor (pityriasis versicolor; “sun fungus”) caused by Pityrosporon orbiculare (Malassezia furfur). {02}{04}{16}

Seborrheic dermatitis—Ciclopirox gel is indicated for the topical treatment of seborrheic dermatitis of the scalp.{11}

Onychomycosis (treatment),—Ciclopirox topical solution is indicated as a primary agent in the topical treatment of mild to moderate onychomycosis of the nails (without lunula involvement) caused by Trichophyton rubrum.{12}

—Not all species or strains of a particular organism may be susceptible to ciclopirox.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—


• Ciclopirox: 207.27.


• Ciclopirox olamine: 268.36.


pH
    — Ciclopirox cream and lotion have a pH of 7.{02} {04}

Mechanism of action/Effect:

Exact mechanism unknown; fungicidal in vitro against Trichophyton rubrum, T. mentagrophytes, Epidermophyton floccosum (Acrothesium floccosum), Microsporum canis, and Candida albicans (Monilia albicans); may inhibit transport of certain essential substrates into fungal cells; may also interfere with the synthesis of proteins, RNA, and DNA in growing fungal cells; alterations in cell permeability, osmotic fragility, and endogenous respiration are affected only at high concentrations of ciclopirox. {02}{06}

Absorption:

1% Solution in polyethylene glycol 400—Rapid, but minimal; 1.3% of dose absorbed following topical application to 750 cm 2 of skin on the back, followed by occlusion for 6 hours. {02}{04}

0.77% Cream—In penetration studies of human cadaveric skin from the back, 0.8 to 1.6% of the dose was present in the stratum corneum 1.5 to 6 hours following application. {02} In addition, the levels in the dermis were still 10 to 15 times the minimum inhibitory concentrations (MICs).{02}

0.77% Lotion—Penetration studies have indicated that the penetration of the cream and the lotion are equivalent. {04}

Ciclopirox olamine also penetrates into hair and through the epidermis and hair follicles into sebaceous glands and dermis.{02} {04}

8% Solution—Mean absorption of ciclopirox after application to nails of all twenty digits and adjacent 5 millimeters of skin once daily for 6 months in patients with dermatophytic onychomycoses was < 5 % of the applied dose.{12}

Protein binding:

Very high (94-97%).{07}

Biotransformation:

The main metabolic pathway of absorbed ciclopirox is glucuronidation.{12}

Half-life:

1% Solution in polyethylene glycol 400—1.7 hours.{02} {04}

Elimination:


1% Solution in polyethylene glycol 400——
        Renal: Absorbed portion rapidly and almost completely excreted in urine; only 0.01% of dose remains in urine 2 days following topical application.{02}{04}
        Fecal: Negligible.{02} {04}



Precautions to Consider

Carcinogenicity/Tumorigenicity

A study in female mice given cutaneous doses of ciclopirox twice a week for 50 weeks, followed by a six-month drug-free period, has shown that ciclopirox is not carcinogenic or tumorigenic at the application site.{02}{04}{04}

Mutagenicity

Several studies have shown that ciclopirox is not mutagenic.{02} {04}{11}

Pregnancy/Reproduction
Fertility—
Studies in mice, rats, rabbits, and monkeys given ciclopirox by various routes at doses of 10 or more times the topical human dose have not shown that ciclopirox causes impaired fertility.{02}{04}{11}{12}

Pregnancy—
Adequate and well-controlled studies in humans have not been done.{02}{04}

Studies in rats have shown that ciclopirox crosses the placenta in very small amounts. {08} Studies in mice, rats, rabbits, and monkeys given ciclopirox by various routes at doses of 10 or more times the topical human dose have not shown that ciclopirox causes adverse effects in the fetus.{02}{04}{11}

FDA Pregnancy Category B.{02}{04}{11}{12}

Breast-feeding

It is not known whether ciclopirox is distributed into breast milk.{02}{04}{11}{12} However, problems in humans have not been documented.

Pediatrics

Appropriate studies on the relationship of age to the effects of ciclopirox lotion and creamhave not been performed in infants and children up to 10 years of age,{02}{04} ciclopirox gel in pediatric patients up to 16 years of age{11} and ciclopirox 8% solution in pediatric patients up to 18 years of age.{12} Safety and efficacy have not been established.{02}{04}{11}{12}


Geriatrics


Appropriate studies on the relationship of age to the effects of ciclopirox have not been performed in the geriatric population. However, no geriatrics-specific problems have been documented to date.

Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problem exists
Sensitivity to ciclopirox


Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence rare
    
Local irritation{13}{14} (burning, itching, redness, swelling, or other signs of irritation not present before therapy)





Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Ciclopirox (Topical).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to ciclopirox

Proper use of this medication
Applying sufficient medication to cover affected and surrounding areas, and rubbing in gently

Proper administration technique for topical solution

» Avoiding contact with the eyes and mucous membranes

» Not applying occlusive dressing over this medication unless directed to do so by physician

» Compliance with full course of therapy; fungal infections may require prolonged therapy

» Proper dosing
Missed dose: Applying as soon as possible; not applying if almost time for next dose

» Proper storage

Precautions while using this medication
Checking with physician if no improvement within 2 to 4 weeks {02}{08} {11}{12}

» Using hygienic measures to cure infection and prevent reinfection:

For tinea cruris
Avoiding underwear that is tight-fitting or made from synthetic materials; wearing loose-fitting cotton underwear instead

Using a bland, absorbent powder or an antifungal powder on the skin; using the powder between administration times for ciclopirox

For tinea pedis
Carefully drying feet, especially between toes, after bathing

Avoiding socks made from wool or synthetic materials; wearing clean, cotton socks and changing them daily or more often if feet perspire excessively

Wearing sandals or well-ventilated shoes

Using a bland, absorbent powder or an antifungal powder between toes, on feet, and in socks and shoes liberally once or twice daily; using the powder between administration times for ciclopirox


Side/adverse effects
Signs of potential side effects, especially local irritation


General Dosing Information
Use of topical antifungals may lead to skin sensitization, resulting in hypersensitivity reactions with subsequent topical use of the medication.

To reduce the possibility of recurrence, Candida infections, tinea cruris, tinea corporis, and tinea versicolor should be treated for at least 2 weeks to 1 month; tinea pedis should be treated for at least 1 month or longer.{09} If no improvement is observed after 4 weeks while using the cream, lotion, or gel, the diagnosis may need to be redetermined.{02}{04}{11}

When this medication is used in the treatment of candidiasis, occlusive dressings should be avoided, since they provide conditions that favor growth of yeast and release of its irritating endotoxin.

When using the ciclopirox cream, lotion, or gel, the medication should be gently massaged into the affected and surrounding skin or scalp areas.{02}{04}{11} Clinical improvement with relief of pruritus and other symptoms usually occurs within the first week of treatment.{02}{04}{11} Patients with tinea versicolor usually exhibit clinical and mycological clearing after two weeks of treatment.{02}{04} Patients with seborrheic dermatitis of the scalp usually show clinical improvement within the first week, and continuing resolution of signs and symptoms through the fourth week of treatment.{11}

When using the ciclopirox topical solution, apply evenly with applicator brush. When possible, nail lacquer should be also be applied to the underside of the nail and to the skin beneath it. Allow the solution to dry, which should take approximately 30 seconds. Loose nail material should be filed down and trimmed as required every 7 days after the solution is removed with alcohol. Daily applications should be made over the previous coat and removed with alcohol every 7 days. This cycle should be repeated throughout the duration of therapy.{12} Removal of the unattached, infected nail, trimming of the onycholytic nail, and filing of excess horny material should be performed by a health care professional, as frequently as monthly.{12} A completely clear or almost clear toenail may not be achieved with use of this medication.{12}


Topical Dosage Forms

CICLOPIROX OLAMINE CREAM USP

Usual adult and adolescent dose
Antifungal
Topical, to the skin and surrounding areas, two times a day, morning and evening. {02}{02}{18}


Usual pediatric dose
Antifungal
Infants and children up to 10 years of age: Safety and efficacy have not been established. {02}

Children 10 years of age and over: See Usual adult and adolescent dose.


Strength(s) usually available
U.S.—
{02}

0.77% (Rx) [Loprox]

Canada—
{05}{16}{18}

1% (Rx) [Loprox]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F).{02}

Auxiliary labeling:
   • For external use only. {02}
   • Continue medicine for full time of treatment.{02}


CICLOPIROX OLAMINE LOTION

Usual adult and adolescent dose
See Ciclopirox Olamine Cream USP. {11}

Usual pediatric dose
See Ciclopirox Olamine Cream USP. {14}

Strength(s) usually available
U.S.—


0.77% (Rx) [Loprox{04}]

Canada—


1% (Rx) [Loprox{16}{17}]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F). {04} Protect from freezing.

Auxiliary labeling:
   • Shake well. {04}
   • For external use only.{04}
   • Continue medicine for full time of treatment.{04}


CICLOPIROX GEL

Usual adult and adolescent dose
Antifungal
Topical, to the skin and surrounding areas, two times a day, morning and evening, immediately after cleaning or washing the areas to be treated.{11}

For seborrheic dermatitis of scalp
Topical, to affected scalp areas, two times a day, morning and evening.{11}


Usual pediatric dose
Children up to 16 years of age—Safety and efficacy have not been established{11}

Strength(s) usually available
U.S.—


0.77% (Rx) [Loprox{11}]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F). {11} Protect from freezing.

Auxiliary labeling:
   • For external use only. {11}
   • Continue medicine for full time of treatment. {11}


CICLOPIROX TOPICAL SOLUTION

Usual adult dose
Antifungal
Topical, to all affected nails and under the surface nail plate when it is free of the nail bed, once daily preferably at bedtime, or eight hours before washing. Apply with applicator brush. Patients should file away loose nail material and trim nails as required every 7 days after the solution is removed with alcohol. Daily applications should be made over the previous coat and removed with alcohol every 7 days. This cycle should be repeated throughout the duration of therapy.{12}


Usual pediatric dose
Safety and efficacy have not been established.{12}

Strength(s) usually available
U.S.—


8% (Rx) [Penlac Nail Lacquer{12}]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F). {12} Protect from light and from freezing.

Auxiliary labeling:
   • For external use only. {12}
   • Continue medicine for full time of treatment. {12}
   • Protect from light. {12}
   • Flammable—Keep away from heat and flame.{12}



Revised: 03/02/2000



References
  1. VA Medication Classification System, USP DI 1989: 2472.
  1. Product Information: Loprox (R) cream, ciclopirox. Hoechst-Roussel Pharmaceuticals, Kansas City, MO, (PI revised 12/1997) reviewed 1/2000.
  1. Canada JR, editor. USP dictionary of USAN and international drug names 1998. Rockville, MD: The United States Pharmacopeial Convention Inc; 1997. p. 163.
  1. Product Information: Loprox (R) lotion, ciclopirox. Hoechst-Roussel Pharmaceuticals, Kansas City, MO, (PI revised 12/1997) reviewed 1/2000.
  1. Loprox (Hoechst). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 23rd ed. Ottawa: Canadian Pharmaceutical Association, 1988: 502.
  1. Panel comment, 1/85.
  1. McEvoy GK, editor. AHFS Drug information 88. Bethesda, MD: American Society of Hospital Pharmacists, 1988: 1990.
  1. Ciclopirox olamine 1% cream. A preliminary review of its antimicrobial activity and therapeutic use. Drugs 1985; 29: 330-41.
  1. Panel comment, 10/84.
  1. Not used.
  1. Product Information: Loprox (R) gel, ciclopirox. Hoechst-Roussel Pharmaceuticals, Kansas City, MO, (PI revised 8/1997) reviewed 1/2000.
  1. Product Information: Penlac Nail Lacquer (R), ciclopirox topical solution. Hoechst-Roussel Pharmaceuticals, Kansas City, MO, (PI revised 12/1999) reviewed 1/2000.
  1. Not used.
  1. Not used.
  1. Not used.
  1. Loprox Lotion (Hoechst). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 28th ed. Ottawa: Canadian Pharmaceutical Association, 1993: 669.
  1. Loprox Lotion (Hoechst). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 26th ed. Ottawa: Canadian Pharmaceutical Association, 1991: 671.
  1. Loprox Cream (Hoechst). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 26th ed. Ottawa: Canadian Pharmaceutical Association, 1991: 671.
  1. Abramowicz M, editor. Some topical antifungal drugs. Med Lett Drugs Ther 1983: 99.
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