Podofilox

3.5 mL Podofilox (podofilox) Topical Solution 0.5% is supplied as a clear liquid in amber glass bottles with child-resistant screw caps. NDC 0574-0611-05. Store at controlled room temperature between 15° and 30°C (59° and 86°F). Avoid excessive heat. Do not freeze.

REFERENCES
1. Berenblum,1951.J.Natl.Cancer Inst.11:839-841
2. H.A.Kaminetsky and M.Swerdlow,1965.Am.J.Obst.Gyn.93 :486-490
3. E.A.McGrew and H.A.Kaminetsky,1961.Am.J.Clin.Pathol.35:538-545
4. F.J.C.Roe and M.H.Salaman,1955.Brit.J.Cancer.9:177-203
5. H.S.Taper,1977.Z.Krebsforsch.90:197-210
6. H.A.Kaminetsky E.A.McGrew,and R.L.Phillips,1959.Am.J.Obst.Gyn.
14:1-3
7. H.A.Kaminetsky and E.A.McGrew,1963.Arch.Path.73:481-485
8. K.Didcock,D.Jackson,and J.M.Robson,1956.Brit.J.Pharmacol.
11:437-441
9. J.Thiersch,1963.Soc.Exptl.Biol.Med.Proc.113:124-127

Paddock Laboratories,Inc.
Minneapolis,MN 55427                                                                 124159 (04-01)
www.paddocklabs.com                                                                  0611-01-0101

Topically applied podofilox (podofilox) may be absorbed systemically (see CLINICAL PHARMACOLOGY section). Toxicity reported following systemic administration of podofilox (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 1mg/kg/day, significant hematological toxicity occurred but was reversible. 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, leukocy-tosis, pancytosis, hematuria, renal failure, and seizures. Treatment of topical overdosage should include washing the skin free of any remaining drug and symptomatic and supportive therapy.

In clinical trials, the following local adverse reactions were reported at some point during treatment.

Reports of burning and pain were more frequent and of greater severity in women than in men.

Adverse effects reported in less than 5% of the patients included pain with intercourse, insomnia, tingling, bleeding, tenderness, chafing, malodor, dizzi-ness, scarring, vesicle formation, crusting edema, dryness/peeling, foreskin irretraction, hematuria, vomiting and ulceration.

Read the entire FDA prescribing information for Podofilox Topical Solution (Podofilox)

• Sexually Transmitted Diseases in Women (STD)

© Podofilox Topical Solution Patient Information is supplied by Cerner Multum, Inc. and Podofilox Topical Solution Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

• Topical application to external genital and perianal HPV warts generally results in necrosis of visible wart tissue.1 2 10 44 The effect on HPV warts may be related to interference with microtubular function of the keratinocytes contained in the warts and local vascular structures and also may be related to local immunomodulating effects.10 32 40

• Arrests mitosis in metaphase in a manner similar to that of colchicine.10 31 Podofilox reversibly binds to tubulin, thereby preventing polymerization of tubulin into microtubules.9 31 As a result of inhibition of microtubule formation, podofilox has a variety of biologic effects and, depending on the cell system, can stimulate or arrest cell proliferation and affect cell differentiation.31

• Reportedly inhibits the mitogen response of human lymphocytes, inhibits growth factor-stimulated macrophage proliferation, and induces production of interleukin-1 (IL-1) and interleukin-2 (IL-2).10 31

• May have anti-inflammatory activity related to a decrease in tumor necrosis factor receptors.31

• Importance of providing patient a copy of the manufacturer’s patient information.2 44

• Advise patients that podofilox is not a cure for HPV infection; new HPV warts may develop during or after therapy with the drug.1 2 22 Importance of patient watching for recurrences, particularly during the first 3 months.22

• Importance of not exceeding the recommended dosage or duration of therapy.42 43 44 Do not use more than twice daily, do not use >3 days in a row, and discontinue use and informing clinician if no improvement occurs after 4 weeks of treatment..42 43 44

• Importance of reporting adverse reactions to the clinician.1 2 If a severe adverse reaction (e.g., bleeding, swelling, excessive pain, burning, or itching) occurs, wash podofilox from the treatment area, discontinue the drug, and contact clinician.32 40 42 43 44 47

• Importance of carefully instructing the patient regarding proper techniques for application, including washing hands after each use.1 2 22 44 (See Topical Administration under Dosage and Administration.)

• Importance of not engaging in sexual intercourse on days when podofilox is applied.42 43 47

• Importance of not using the drug for any disorder other than that for which it was prescribed.1 44 47

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1 2 44

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 2 44

• Importance of informing patients of other important precautionary information. (See Cautions.)

Treatment of genital warts with Podofilox results in necrosis of visible wart tissue. The exact mechanism of action is unknown.

Although genital warts have a characteristic appearance, histopathologic confirmation should be obtained if there is any doubt of the diagnosis. Differentiating warts from squamous cell carcinoma (so-called “Bowenoid papulosis”) is of particular concern. Squamous cell carcinoma may also be associated with human papillomavirus but should not be treated with Podofilox Topical Solution 0.5%.

Exact mechanism of action is unknown; causes necrosis of visible wart tissue

Absorption

No detectable serum levels