Podophyllum Resin (Monograph)

Brand name: Podocon-25
Drug class: Skin and Mucous Membrane Agents, Miscellaneous
- Antimitotic Agents
VA class: DE500
CAS number: 8050-60-0

Introduction

Antimitotic; caustic agent.

Uses for Podophyllum Resin

Human Papillomavirus (HPV) Infections

Topical treatment of external genital and perianal exophytic warts (condylomata acuminata) caused by HPV.

CDC and others recommend that external HPV warts be treated with a self-administered topical therapy (podofilox, imiquimod), a topical therapy administered by a health-care provider (podophyllum resin, trichloroacetic acid [TCA], bichloroacetic acid [BCA]), or a surgical technique (cryotherapy, electrosurgery, surgical excision). Alternative therapies include intralesional interferon alfa or laser surgery.

A preferred treatment for external genital HPV warts in adults and adolescents with HIV infection when complex or multicentric lesions are present or lesions are inaccessible to patient-applied treatments (e.g., podofilox 0.5%, imiquimod 5%). An alternative treatment for external genital HPV warts in HIV-infected children^{† [off-label]}; topical therapies often are ineffective in such children, and a surgical technique (cryotherapy, electrosurgery) may be preferred.

Primary goal is destruction or clearance of visible, symptomatic warts. No regimen has been shown to eradicate HPV or affect natural history of HPV infection; effect on transmission of HPV unknown.

Do not use to treat subclinical genital HPV infection (without exophytic warts).

Topical treatment of urethral meatus HPV warts^{† [off-label]}. CDC recommends cryotherapy or topical podophyllum resin (10–25% solution in benzoin tincture).

Not included in CDC recommendations for treatment of intravaginal, cervical, rectal, or anal HPV warts.

Related/similar drugs

cimetidine, imiquimod topical, Aldara, Podocon, resorcinol topical

Podophyllum Resin Dosage and Administration

Administration

Topical Administration

Apply topically as a solution containing 10–25% podophyllum resin in benzoin tincture.

Solutions containing 10–25% podophyllum resin in benzoin tincture should only be applied by a health-care provider and should not be dispensed to the patient. Solutions containing lower concentrations of podophyllum resin (e.g., 0.5–2% ethanolic solutions) have been prepared extemporaneously for self-administration by patients, but safety and efficacy not established.

For external use only; avoid contact with eyes. (See Administration Precautions under Cautions.)

Prior to application, wash affected area. Shake solution well prior to each use.

Apply solution sparingly to intact HPV warts and allow to air dry. Do not apply to bleeding warts, moles, birthmarks, unusual warts with hair growing from them, or warts that have recently been biopsied. Do not apply to normal tissue or mucous membranes.

Adjacent skin may be protected by applying petrolatum or flexible collodion prior to application of the drug.

Immediately following prescribed period of treatment, thoroughly remove dried drug from application site using alcohol or soap and water.

To determine patient sensitivity to the drug, remove the drug 30–40 minutes after the first application. For subsequent applications, remove drug after the minimum time period required to produce the desired result (usually 1–4 hours).

Warts generally become blanched within a few hours after application, become necrotic within 24–48 hours, and begin to slough and gradually disappear without scarring after about 72 hours.

Dosage

Pediatric Patients

HPV Infections

External Genital and Perianal HPV Warts

Topical

HIV-infected children^{† [off-label]}: Apply 10–25% solution of podophyllum resin in benzoin tincture sparingly to each HPV wart once weekly for up to 3–6 weeks.

Adults

HPV Infections

External Genital and Perianal HPV Warts

Topical

Apply 10–25% solution of podophyllum resin in benzoin tincture sparingly to each HPV wart once weekly for up to 3–6 weeks.

For each treatment session, CDC and others recommend a maximum treatment area of 10 cm² and a total of <0.5 mL of the solution.

Although safety and efficacy not established, some clinicians recommend lower concentrations (e.g., 5% solution) for treatment of large (i.e., >10–20 cm²) genital and perianal warts.

Urethral Meatus HPV Warts† [off-label]

Topical

Apply 10–25% solution of podophyllum resin in benzoin tincture; may be repeated once weekly if necessary. Ensure treatment area has dried completely before making contact with surrounding normal mucosa.

Prescribing Limits

Adults

HPV Infections

External Genital and Perianal HPV Warts

Topical

Maximum recommended treatment area is 10 cm². Maximum volume of solution for each treatment session is <0.5 mL.

Avoid excessive amounts because of risk of systemic toxicity. (See Systemic Effects under Cautions.)

Special Populations

No special population dosage recommendations.

Cautions for Podophyllum Resin

Contraindications

• Diabetes mellitus or poor circulation.

• Corticosteroid therapy.

• Application to bleeding warts, moles, birthmarks, or unusual warts with hair growing from them. (See Systemic Effects under Cautions.)

• Pregnancy. (See Pregnancy under Cautions.)

• Breast-feeding. (See Lactation under Cautions.)

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

Birth defects, fetal death, and stillbirths reported when topical podophyllum resin used to treat external genital HPV warts in pregnant women. (See Contraindications under Cautions.)

Systemic Effects

Potentially serious adverse systemic effects (GI, hematologic, CNS) reported. At least one fatality occurred because of systemic toxicity following topical application to extensive areas of exophytic HPV warts.

Use only under close medical supervision. Risk of systemic toxicity may be increased if applied to friable, bleeding, or recently biopsied skin or inadvertently applied to normal skin and mucous membranes surrounding a wart being treated. Use caution to ensure drug is applied as recommended. (See Administration Precautions under Cautions.)

Initial manifestations of systemic toxicity include dizziness, lethargy, nausea, vomiting, abdominal pain, and diarrhea (sometimes severe and protracted).

Adverse CNS effects may be delayed in onset and prolonged in duration. Cerebral toxicity (altered sensorium ranging from mild confusion to coma) may persist for 7–10 days; ataxia, hypotonia, and areflexia can occur and generally improve more slowly than effects on sensorium.

Delayed nervous system toxicity involving peripheral nervous system may occur. If sensorimotor polyneuropathy occurs, it usually appears about 2 weeks after application of the drug, may progressively worsen for up to 3 months, and may persist for up to ≥9 months.

Electrodiagnostic determinations (i.e., nerve conduction studies and electromyelography) indicate an axonal neuropathy. Signs and symptoms of peripheral neuropathy including autonomic neuropathy, include paralytic ileus, urinary retention, sinus tachycardia, symptomatic orthostatic hypotension, paresthesias of the extremities, absent ankle reflexes, stocking-and-glove sensory loss, weakness of the extremities, and decreased response to painful stimuli.

Other adverse nervous system effects include stupor, increased CSF protein, hyperventilation, decreased respiration and apnea, agitation, lethargy, and seizures.

Adverse hematologic effects (e.g., leukopenia, thrombocytopenia) reported, especially after application to extensive areas.

Renal failure and hepatotoxicity (increased serum concentrations of LDH, AST, and alkaline phosphatase) reported.

Administration Precautions

Should only be applied by a health-care provider. Close medical supervision required because of the risk of systemic effects.

Use caution to ensure drug is not applied to extensive areas or in excessive amounts and is removed from the treatment area within the prescribed period of time. (See Administration under Dosage and Administration.)

A powerful caustic and severe irritant. Avoid contact with eyes. If eye contact occurs, wash affected eye(s) with large amounts of warm water and consult a clinician or regional poison control center (800-222-1222).

Do not use if wart or surrounding tissue is inflamed or irritated. Do not apply to bleeding warts, moles, birthmarks, unusual warts with hair growing from them, or warts that have recently been biopsied.

Do not apply to normal tissue or mucous membranes.

General Precautions

Precautions Related to Treatment of External Genital and Perianal HPV Warts

Follow-up examinations not mandatory if visible genital and perianal warts have cleared after treatment, but may be beneficial 3 months after treatment is completed since identification of external genital warts may be difficult.

Examination of sexual partners is not necessary for the management of genital HPV warts because data do not indicate that reinfection plays a role in recurrences and, in the absence of curative therapy, treatment to reduce transmission is not realistic. However, sexual partners of patients with genital HPV warts may benefit from examination to assess the presence of HPV warts or other sexually transmitted diseases and also may benefit from counseling about the implications of having a partner who has HPV warts.

Immunosuppressed individuals (including patients with HIV) may not respond as well and may have more frequent recurrences of genital HPV warts after treatment compared with immunocompetent individuals.

Because HPV genital warts have a characteristic appearance, biopsy generally is necessary only if the diagnosis is uncertain, warts do not respond to standard therapies, the disease worsens during therapy, the patient is immunocompromised (e.g., HIV infection), and/or warts are pigmented, indurated, fixed, and ulcerated.

Women with genital HPV warts should be advised to undergo regular Papanicolaou (Pap) tests as recommended for women without genital HPV warts.

Specific Populations

Pregnancy

Category X. Contraindicated in pregnant women. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether topically applied podophyllum resin is distributed into milk. Contraindicated in breast-feeding women.

Pediatric Use

Safety and efficacy not established in pediatric patients.

Common Adverse Effects

Local reactions (erythema, tenderness, pruritus, burning, pain, swelling).

Drug Interactions

Specific Drugs

Podophyllum Resin Pharmacokinetics

Absorption

Bioavailability

Absorbed systemically following topical application. (See Systemic Effects under Cautions.)

Stability

Storage

Topical

Solution

Tight, light-resistant container at 15–30°C. Darkens when exposed to light or temperatures >25°C.

Actions

• Topical application to external genital and perianal exophytic HPV warts generally results in necrosis of visible wart tissue.

• Podophyllum resin is prepared from rhizomes and roots of certain plants, including Podophyllum peltatum (known as American mandrake, May apple, Duck's foot, Indian apple). It is a crude mixture containing a nonstandardized amount of podofilox (also known as podophyllotoxin), other lignans (e.g., α-peltatin, β-peltatin), and various known and unknown caustic and cytotoxic materials.

• Exact mechanism(s) of action of podophyllum resin in the topical treatment of HPV warts has not been elucidated, but may be related to the antimitotic effects of podofilox, the major biologically active lignan contained in the resin.

• Podofilox has antimitotic activity and arrests mitosis in metaphase in a manner similar to colchicine; it reversibly binds to tubulin, the protein subunit of the spindle microtubules, thereby preventing polymerization of tubulin into microtubules.

• Has cathartic effects. (See Systemic Effects under Cautions.)

Advice to Patients

• Advise patients of the importance of the administration precautions related to the drug, including instructions regarding immediate removal from application sites using alcohol or soap and water following the prescribed period of treatment. (See Administration under Dosage and Administration.)

• Importance of avoiding contact with eyes. If eye contact occurs, importance of washing affected eye(s) with large amounts of warm water and consulting a clinician or regional poison control center (800-222-1222).

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

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. (See Contraindications under Cautions.)

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.

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

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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