PENLAC
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PENLAC (PENLAC).
Ciclopirox, a hydroxypyridone antifungal, inhibits the uptake of essential elements and disrupts fungal cell membrane integrity by chelating polyvalent cations (Fe3+, Al3+). It also inhibits fungal enzymes involved in energy production and detoxification processes.
| Metabolism | Ciclopirox is metabolized via glucuronidation and oxidation. Approximately 96% of the absorbed dose is excreted in urine as metabolites, with less than 0.1% excreted unchanged. |
| Excretion | Primarily excreted renally as unchanged drug; approximately 90% of absorbed dose recovered in urine within 24 hours; minimal biliary/fecal elimination (<5%) |
| Half-life | Terminal elimination half-life is 17–21 hours in patients with normal renal function; prolonged in renal impairment (up to 40-50 hours in severe renal failure) |
| Protein binding | Concentration-dependent; at therapeutic concentrations, approximately 30-40% bound to plasma proteins (mainly albumin) |
| Volume of Distribution | Approximately 1.6 L/kg in healthy adults; distributes widely into tissues, including skin and nails; high affinity for keratin leading to extensive accumulation in nail plate |
| Bioavailability | Topical: Systemic bioavailability is <5% of the applied dose due to poor percutaneous absorption; oral bioavailability of ciolopirox is approximately 70-80% (but not used orally for onychomycosis) |
| Onset of Action | Topical: Therapeutic effect on onychomycosis typically observed after 2-3 months of daily application; systemic absorption is negligible so no systemic onset |
| Duration of Action | Prolonged due to high affinity for keratin and slow clearance from nail plate; drug remains in nail for weeks to months after discontinuation of therapy; clinical cure requires 48 weeks of treatment for fingernails and up to 72 weeks for toenails |
Apply a thin layer to affected nails once daily, preferably at bedtime or 8 hours before washing. Use the provided applicator to apply to the entire nail plate and under the nail tip. Treatment duration is up to 48 weeks.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for renal impairment because systemic absorption after topical application is negligible. |
| Liver impairment | No dose adjustment required for hepatic impairment because systemic absorption after topical application is negligible. |
| Pediatric use | Safety and effectiveness in pediatric patients have not been established; use is not recommended. |
| Geriatric use | No specific dose adjustment is required; use the same dosing as adults because systemic absorption is negligible. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PENLAC (PENLAC).
| Breastfeeding | It is unknown whether ciclopirox is excreted in human milk after topical application. Due to minimal systemic absorption, the amount likely to be ingested by a nursing infant is negligible. Caution is advised when used in breastfeeding women. M/P ratio is not available. |
| Teratogenic Risk | PENLAC (ciclopirox 8% topical solution) is classified as FDA Pregnancy Category B. Animal reproduction studies at topical doses up to 10 times the human dose showed no fetal harm. There are no adequate and well-controlled studies in pregnant women. Systemic absorption is minimal (approximately 1.3% of applied dose) after topical application to toenails. Therefore, risk is considered low; however, use during pregnancy only if clearly needed. No specific trimester risks have been identified. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to ciclopirox or any component of the formulation"]
| Precautions | ["Avoid use in immunocompromised patients due to risk of infection spread.","Monitor for signs of local irritation or sensitization.","Not for ophthalmic, oral, or intravaginal use.","Effectiveness in immunocompromised patients has not been established."] |
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| Fetal Monitoring | No specific maternal or fetal monitoring required beyond standard prenatal care. Monitor for local skin reactions at application site. No evidence of fetal effects expected. |
| Fertility Effects | No studies have been conducted on fertility in humans. Animal studies with oral ciclopirox showed no impairment of fertility at doses up to 10 times the maximum human topical dose. Based on minimal systemic absorption, no significant effect on fertility is anticipated. |