Podofilox is a topical mitotic agent for the treatment of external genital and perianal warts (i.e., condylomata acuminata) caused by human papillomavirus (HPV). The 0.5% topical solution is used to treat external genital warts; the solution is not suitable for use in the perianal area. Podofilox 0.5% gel may be used to treat external genital or perianal warts. Podofilox is derived from the plant families Coniferae and Berberidaceae (e.g., species of Juniperus and Podophyllum). Like imiquimod, podofilox can be self-administered by the patient, whereas other treatments for condylomata acuminata (e.g., intralesional interferon alfa, podophyllum resin, trichloroacetic acid) must be administered by a health-care provider. Podofilox, like other currently available therapies for exophytic genital and perianal warts, does not eradicate HPV or affect the natural history of HPV infection. Despite destruction of HPV warts, latent or subclinical HPV infection can persist and recurrence of visible warts is common. Condylox topical solution was approved in December 1990. Condylox gel formulation was approved in March 1997.
General Administration Information
For storage information, see the specific product information within the How supplied section.
Route-Specific Administration
Topical Administration
-Podofilox is for external topical use to the affected skin only; do not ingest and do not get in the eyes.
Other Topical Formulations:
-Topical gel: Apply gel using the applicator supplied or by fingertip. May be used in the genital or perianal area.
-Topical solution: Apply solution using the applicator supplied or a cotton-tipped applicator. Touch the drug-dampened applicator to the wart to be treated, applying the minimum amount of solution necessary to cover the lesion. Allow the solution to dry before allowing the return of opposing skin surfaces to their normal positions. After each treatment, dispose of the used applicator and wash hands. Podofilox solution is not suitable for use in the perianal area.
The most common adverse events reported following topical podofilox gel or solution application are primarily local reactions at the treated skin site. Frequent adverse reactions include: burning (64-78% with solution, 12-37% with gel), skin pain (50-72% with solution, 12-24% with gel), inflammation (63-71% with solution, 9-32% with gel), skin erosion (67% with solution, 9-27% with gel), pruritus (50-65% with solution, 8-32% with gel), and bleeding (< 5% with solution, 1-19% with gel). The burning and pain reported with the topical solution are more frequent and of greater severity in women than in men. Other local effects reported with podofilox solution and gel include crusting, edema, dryness (xerosis), peeling, skin ulcer, and skin irritation (tingling and tenderness). Less common (< 5%) adverse effects reported with podofilox solution include: painful intercourse (dyspareunia), chafing, malodor, scarring, vesicle formation, phimosis, and hematuria. For the gel formulation, other adverse reactions include stinging (7%) and erythema (5%). Less common (< 5%) adverse events with the gel formulation include: scabbing, skin discoloration, fissures, rash (unspecified), skin soreness, and swelling.
The most common systemic adverse event reported during clinical studies with podofilox gel is headache (7%). Systemic events reported in < 5% of patients using the solution include dizziness, nausea, vomiting, and insomnia.
Safety and efficacy of podofilox have not been established in adolescents and children < 18 years of age.
Podofilox is contraindicated in patients who have a podophyllum hypersensitivity or intolerance to podofilox or any components contained in the topical gel or solution. Podofilox should only be used for external warts; it has not been evaluated for the treatment of warts occurring inside the mucous membranes of the genital area (i.e., urethral, intravaginal, cervical, or rectal). Podofilox solution has not been evaluated for use in the treatment of warts occurring in the perianal area. Avoid accidental exposure to healthy skin areas, avoid ocular exposure, and do not administer internally.
Guidelines recommend against use of podofilox during pregnancy. The manufacturer recommends use only if the potential benefits justify the potential risks to the fetus. No adequate and well-controlled studies have been conducted in pregnant women. In animal studies, use of systemic podofilox was found to be embryotoxic in rats at doses 19-times the maximum recommended human dose (RHD); however, the drugs was not teratogenic when given topically to pregnant rabbits at doses 2-times the RHD for 13 days. Because genital warts can proliferate and become friable during pregnancy, consideration can be given to their removal during pregnancy. HPV types 6 and 11 can cause respiratory papillomatosis in infants and children. The route of transmission (i.e., transplacental, perinatal, or postnatal) is not completely understood. In rats, podofilox did not appear to impair fertility when administered topically at doses corresponding to the recommended human daily dose.
According to the manufacturer, a decision should be made whether to discontinue podofilox or to discontinue nursing, taking into account the importance of the drug to the mother. It is not known if podofilox is distributed into the human milk. However, in pharmacokinetic studies, topical application of podofilox to external genitalia did not result in detectable serum levels and the drug did not accumulate after multiple treatments. Therefore, it is unlikely that a clinically significant amount of drug would be present in breast-milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: human papillomavirus (HPV)
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
For the treatment of external genital and perianal warts (condylomata acuminata) due to human papillomavirus (HPV) infection:
NOTE: The 0.5% gel may be used to treat external genital or perianal warts. The 0.5% topical solution may be used to treat external genital warts; however, it is not indicated for use in the perianal area.
-for the treatment of external genital warts (condylomata acuminata):
Topical dosage (0.5% topical solution):
Adults: Apply a thin layer topically to wart(s) twice daily for 3 consecutive days, followed by 4 days of no therapy. May repeat this 1-week cycle until there is no visible wart tissue or for a maximum of 4 cycles. Max: 0.5 mL/day. Limit treatment area to 10 cm2 or less of wart tissue. If there is incomplete response after 4 treatment cycles, discontinue treatment and consider alternative treatment.
Infants*, Children* and Adolescents*: Apply a thin layer topically to wart(s) twice daily for 3 consecutive days, followed by 4 days of no therapy. May repeat this 1-week cycle until there is no visible wart tissue or for a maximum of 4 cycles. Max: 0.5 mL/day. Limit treatment area to 10 cm2 or less of wart tissue. If there is incomplete response after 4 treatment cycles, discontinue treatment and consider alternative treatment.
Topical dosage (0.5% topical gel):
Adults: Apply a thin layer topically to wart(s) twice daily for 3 consecutive days, followed by 4 days of no therapy. May repeat this 1-week cycle until there is no visible wart tissue or for a maximum of 4 cycles. Max: 0.5 g/day. Limit treatment area to 10 cm2 or less of wart tissue. If there is incomplete response after 4 treatment cycles, discontinue treatment and consider alternative treatment.
Infants*, Children* and Adolescents*: Apply a thin layer topically to wart(s) twice daily for 3 consecutive days, followed by 4 days of no therapy. May repeat this 1-week cycle until there is no visible wart tissue or for a maximum of 4 cycles. Max: 0.5 g/day. Limit treatment area to 10 cm2 or less of wart tissue. If there is incomplete response after 4 treatment cycles, discontinue treatment and consider alternative treatment.
-for the treatment of external perianal warts (condylomata acuminata):
Topical dosage (0.5% topical gel):
Adults: Apply a thin layer topically to wart(s) twice daily for 3 consecutive days, followed by 4 days of no therapy. May repeat this 1-week cycle until there is no visible wart tissue or for a maximum of 4 cycles. Max: 0.5 g/day. Limit treatment area to 10 cm2 or less of wart tissue. If there is incomplete response after 4 treatment cycles, discontinue treatment and consider alternative treatment.
Infants*, Children* and Adolescents*: Apply a thin layer topically to wart(s) twice daily for 3 consecutive days, followed by 4 days of no therapy. May repeat this 1-week cycle until there is no visible wart tissue or for a maximum of 4 cycles. Max: 0.5 g/day. Limit treatment area to 10 cm2 or less of wart tissue. If there is incomplete response after 4 treatment cycles, discontinue treatment and consider alternative treatment.
For the treatment of molluscum contagiosum*:
Topical dosage:
Adults: Apply topically to molluscum lesions twice daily for 3 consecutive days, then discontinue for 4 consecutive days; repeat this 1-week cycle as necessary until clearance for up to 4 weeks.
Infants, Children, and Adolescents: Apply topically to molluscum lesions twice daily for 3 consecutive days, then discontinue for 4 consecutive days; repeat this 1-week cycle as necessary until clearance for up to 4 weeks.
Maximum Dosage Limits:
-Adults
0.5 g/day for topical gel or 0.5 ml/day for topical solution; limit treatment area to <= 10 cm2 of wart tissue (gel or solution).
-Elderly
0.5 g/day for topical gel or 0.5 ml/day for topical solution; limit treatment area to <= 10 cm2 of wart tissue (gel or solution).
-Adolescents
Safety and efficacy have not been established; 0.5 g/day for topical gel or 0.5 ml/day for topical solution has been used off-label.
-Children
Safety and efficacy have not been established; 0.5 g/day for topical gel or 0.5 ml/day for topical solution has been used off-label.
Patients with Hepatic Impairment Dosing
No dosage adjustment is needed.
Patients with Renal Impairment Dosing
No dosage adjustment is needed.
*non-FDA-approved indication
Imiquimod: (Minor) While no drug interactions have been reported with imiquimod, there is no clinical experience with imiquimod cream therapy immediately following the treatment of genital/perianal warts with other cutaneously applied drugs, such as podofilox. Therefore, imiquimod cream administration is not recommended until skin is healed from any previous topical drug treatments or surgery.
Podophyllum: (Minor) No drug interactions of clinical significance have been noted for podofilox. While no drug interactions have been reported, there is no clinical experience with podofilox immediately following the treatment of genital/perianal warts with other cutaneously applied drugs like podophyllum resin. Therefore, podofilox administration is not recommended until genital and/or perianal tissue is healed from any previous topical drug treatment or surgery.
The exact mechanism of action of podofilox in treating condylomata acuminata is not known, but it causes visible necrosis of the wart tissue. Podofilox potently inhibits cell mitosis. It acts by binding to tubulin to prevent the formation of microtubules, which results in mitotic arrest. It exerts a variety of biological effects including attenuation of nucleoside transport damage to the endothelium of small blood vessels, reduction of the lymphocyte response to mitogens, induction of interleukin-1 and interleukin-2, enhancement of macrophage growth, stifling of immune responses, and inhibition of macrophage metabolism.
Podofilox is for external topical use only. The elimination half-life of podofilox ranges from 1.0 to 4.5 hours. Podofilox does not accumulate after multiple treatments.
-Route-Specific Pharmacokinetics
Topical Route
When applied topically at a dosage of 0.1-1.5 ml of the 0.5% solution, peak serum concentrations of 1-17 ng/ml occur within 1-2 hours after application. Topical application of 0.5 ml of the 0.5% solution to the external genitalia does not result in detectable podofilox serum concentrations.