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 |
| Molecular Weight | 268.35 |
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 | Avoid use; limited data suggest potential risk; consider alternative therapy. |
| 2nd trimester | Avoid use; no adequate studies; potential harm to fetus. |
| 3rd trimester | Avoid use; theoretical risk of premature ductus arteriosus closure with systemic absorption; topical application may have minimal systemic absorption but safety not established. |
Clinical note
Comprehensive clinical and safety monograph for PENLAC (PENLAC).
| Placental transfer | Unknown; ciclopirox olamine has low molecular weight and may cross placenta, but systemic absorption from topical application is less than 1%. |
| Breastfeeding | PENLAC (ciclopirox olamine) topical solution is minimally absorbed systemically; however, due to lack of data in breastfeeding women, caution is advised. Apply on smallest area possible and avoid contact with infant. |
■ 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. |
| Food/Dietary | No known food interactions. Avoid applying immediately after hand washing to ensure nail remains dry. No dietary restrictions required. |
| Clinical Pearls |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
| PENLAC (ciclopirox) 8% topical solution is indicated for mild to moderate onychomycosis of fingernails and toenails without lunula involvement. It is a synthetic antifungal agent that inhibits key metabolic pathways. Clinical efficacy is modest; complete cure rates are low (~5-12%). Therapy requires daily application over 48 weeks for toenails. Nail debridement and removal of loose nail material enhance penetration. Not recommended for severe cases or patients with immunosuppression. Avoid concomitant use with nail polish or artificial nails. |
| Patient Advice | Apply PENLAC once daily to the affected nail(s) using the supplied brush applicator. · Avoid nail polish or artificial nails during treatment as they may reduce drug penetration. · Do not use on open wounds or near eyes; if contact occurs, rinse with water. · Expect treatment duration of up to 48 weeks for toenail infection; consistency is key. · Missed doses should be applied as soon as remembered, but skip if next dose is due. · May cause mild local irritation; discontinue if severe reaction occurs. · Continue for the full prescribed period even if nails appear improving. · Keep bottle tightly closed and store at room temperature away from heat and flame. |