Podofilox

Podofilox gel is indicated for the topical treatment of anogenital warts (external genital warts and perianal warts). This product is not indicated in the treatment of mucous membrane warts (see PRECAUTIONS). Diagnosis Although anogenital warts have a characteristic appearance, histopathologic confirmation should be obtained if there is any doubt of the diagnosis. Differentiating warts from squamous cell carcinoma and "Bowenoid papulosis" is of particular concern. Squamous cell carcinoma may also be associated with human papillomavirus which should not be treated with podofilox gel.

The prescriber should ensure that the patient is fully aware of the correct method of therapy and identify which specific warts should be treated. Apply twice daily for 3 consecutive days, then discontinue for 4 consecutive days. This one-week cycle of treatment may be repeated until there is no visible wart tissue or for a maximum of four cycles. If there is incomplete response after four treatment cycles, discontinue treatment and consider alternative treatment. Safety and effectiveness of more than four treatment cycles has not been established. There is no evidence to suggest that more frequent application will increase efficacy, but additional applications would be expected to increase the rate of local adverse reactions and systemic absorption. Podofilox gel should be applied to the warts with the applicator tip or finger. Application on the surrounding normal tissue should be minimized. Treatment should be limited to 10 cm 2 or less of wart tissue and to no more than 0.5 gram of the gel per day. Care should be taken to allow the gel to dry before allowing the return of opposing skin surfaces to their normal positions. Patients should be instructed to wash their hands thoroughly before and after each application.

Podofilox gel is contraindicated for patients who develop hypersensitivity or intolerance to any components of the formulation.

Correct diagnosis of the lesions to be treated is essential. See the Diagnosis subsection of the INDICATIONS AND USAGE section. Podofilox gel is intended for cutaneous use only. Avoid contact with the eyes. If contact with the eyes occurs, patients should immediately flush the eyes with copious quantities of water and seek medical advice. Drug Product is Flammable. Keep Away from Open Flame.

In clinical trials with podofilox gel, the following local adverse reactions were reported during the treatment of anogenital warts. The severity of local adverse reactions were predominantly mild or moderate and did not increase during the treatment period. Severe reactions were most frequent within the first 2 weeks of treatment. Adverse Reaction Mild Moderate Severe Inflammation 32.2% 30.4% 9.3% Burning 37.1% 25.9% 11.5% Erosion 27.0% 20.8% 8.9% Pain 23.7% 20.4% 11.5% Itching 32.2% 16.0% 7.8% Bleeding 19.2% 3.0% 0.7% Other local adverse reactions reported included stinging (7%), and erythema (5%); less commonly reported local adverse events included desquamation, scabbing, discoloration, tenderness, dryness, crusting, fissures, soreness, ulceration, swelling/edema, tingling, rash, and blisters. The most common systemic adverse event reported during the clinical studies was headache (7%). To report SUSPECTED ADVERSE REACTIONS, contact Padagis at 1-866-634-9120 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

0.5% podofilox solution was not teratogenic in the rabbit following topical application of up to 0.21 mg/kg (2.85 mg/m 2, approximately 2 times the maximum human dose) once daily for 13 days. The scientific literature contains references that podofilox is embryotoxic in rats when administered intraperitoneally at a dose of 5 mg/kg (29.5 mg/m 2, approximately 19 times the recommended maximum human dose.) 9 Teratogenicity and embryotoxicity have not been studied with intravaginal application. Many antimitotic drug products are known to be embryotoxic. There are no adequate and well-controlled studies in pregnant women. Podofilox gel should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

It is not known whether this drug is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from podofilox, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Safety and effectiveness in pediatric patients have not been established.

Topically applied podofilox may be absorbed systemically (see CLINICAL PHARMACOLOGY section). Toxicity reported following systemic administration of podofilox in investigational use for cancer treatment included: nausea, vomiting, fever, diarrhea, bone marrow depression, and oral ulcers. Following 5 to 10 daily intravenous doses of 0.5 to 1 mg/kg/day, significant hematological toxicity occurred but was reversible. 10 Other toxicities occurred at lower doses. Toxicity reported following systemic administration of podophyllum resin included: nausea, vomiting, fever, diarrhea, peripheral neuropathy, altered mental status, lethargy, coma, tachypnea, respiratory failure, leukocytosis, pancytosis, hematuria, renal failure and seizures. 11 Treatment of topical overdosage should include washing the skin free of any remaining drug and symptomatic and supportive therapy.

Podofilox is an antimitotic drug which can be chemically synthesized or purified from the plant families Coniferae and Berberidaceae (e.g. species of Juniperus and Podophyllum). Podofilox gel is formulated for topical administration. Each gram of gel contains 5 mg of podofilox in a buffered alcoholic gel containing alcohol (81% v/v), butylated hydroxytoluene, glycerin, hydroxypropyl cellulose, lactic acid, and sodium lactate. Podofilox has a molecular weight of 414.4 daltons, and is soluble in alcohol and sparingly soluble in water. Its chemical name is [5R,-(5α, 5aβ, 8aα, 9α]-5,8,8a,9-tetrahydro-9-hydroxy- 5-(3,4,5-trimethoxyphenyl) furo[3',4':6,7]naphtho-[2,3,-d]-1,3-dioxol-6(5aH)-one. Podofilox has the following structural formula: podofilox-structure-07-19

Podofilox Gel 0.5% is supplied as 3.5 grams of clear gel in aluminum tubes with an applicator tip. NDC 0574-0621-05. Store at 20-25°C (68-77°F). [See USP controlled room temperature.] Avoid excessive heat. Do not freeze. Keep out of reach of children. Rx only