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Podophyllum Resin

Class: Skin and Mucous Membrane Agents, Miscellaneous
- Antimitotic Agents
VA Class: DE500
CAS Number: 8050-60-0
Brands: Podocon-25

Medically reviewed by Last updated on Aug 24, 2020.


Antimitotic; caustic agent.100 117 118

Uses for Podophyllum Resin

Human Papillomavirus (HPV) Infections

Topical treatment of external genital and perianal exophytic warts (condylomata acuminata) caused by HPV.100 101 102 103 104 105 106 107 111 112 116

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).101 111 112 116 Alternative therapies include intralesional interferon alfa or laser surgery.101

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%).120 An alternative treatment for external genital HPV warts in HIV-infected children; topical therapies often are ineffective in such children, and a surgical technique (cryotherapy, electrosurgery) may be preferred.121

Primary goal is destruction or clearance of visible, symptomatic warts.101 110 111 112 No regimen has been shown to eradicate HPV or affect natural history of HPV infection; effect on transmission of HPV unknown.101 110 112 114

Do not use to treat subclinical genital HPV infection (without exophytic warts).101

Topical treatment of urethral meatus HPV warts.101 CDC recommends cryotherapy or topical podophyllum resin (10–25% solution in benzoin tincture).101

Not included in CDC recommendations for treatment of intravaginal, cervical, rectal, or anal HPV warts.101

Podophyllum Resin Dosage and Administration


Topical Administration

Apply topically as a solution containing 10–25% podophyllum resin in benzoin tincture.100 101 109 120 121

Solutions containing 10–25% podophyllum resin in benzoin tincture should only be applied by a health-care provider100 101 109 120 121 and should not be dispensed to the patient.100 Solutions containing lower concentrations of podophyllum resin (e.g., 0.5–2% ethanolic solutions) have been prepared extemporaneously for self-administration by patients,103 106 but safety and efficacy not established.103 104

For external use only; avoid contact with eyes.100 (See Administration Precautions under Cautions.)

Prior to application, wash affected area.100 Shake solution well prior to each use.100

Apply solution sparingly to intact HPV warts and allow to air dry.100 101 Do not apply to bleeding warts, moles, birthmarks, unusual warts with hair growing from them, or warts that have recently been biopsied.100 101 109 Do not apply to normal tissue or mucous membranes.100 101 109

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

Immediately following prescribed period of treatment, thoroughly remove dried drug from application site using alcohol or soap and water.100

To determine patient sensitivity to the drug, remove the drug 30–40 minutes after the first application.100 For subsequent applications, remove drug after the minimum time period required to produce the desired result (usually 1–4 hours).100 120 121

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.a


Pediatric Patients

HPV Infections
External Genital and Perianal HPV Warts

HIV-infected children: Apply 10–25% solution of podophyllum resin in benzoin tincture sparingly to each HPV wart once weekly for up to 3–6 weeks.101 121


HPV Infections
External Genital and Perianal HPV Warts

Apply 10–25% solution of podophyllum resin in benzoin tincture sparingly to each HPV wart100 101 120 once weekly for up to 3–6 weeks.101 120

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.101 120

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.a

Urethral Meatus HPV Warts†

Apply 10–25% solution of podophyllum resin in benzoin tincture; may be repeated once weekly if necessary.101 Ensure treatment area has dried completely before making contact with surrounding normal mucosa.101

Prescribing Limits


HPV Infections
External Genital and Perianal HPV Warts

Maximum recommended treatment area is 10 cm2.101 120 Maximum volume of solution for each treatment session is <0.5 mL.101

Avoid excessive amounts because of risk of systemic toxicity.101 a (See Systemic Effects under Cautions.)

Special Populations

No special population dosage recommendations.100

Cautions for Podophyllum Resin


  • Diabetes mellitus or poor circulation.100 a

  • Corticosteroid therapy.100 a

  • Application to bleeding warts, moles, birthmarks, or unusual warts with hair growing from them.100 a (See Systemic Effects under Cautions.)

  • Pregnancy.100 101 120 (See Pregnancy under Cautions.)

  • Breast-feeding.100 (See Lactation under Cautions.)



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.100 a (See Contraindications under Cautions.)

Systemic Effects

Potentially serious adverse systemic effects (GI, hematologic, CNS) reported.100 101 108 109 112 At least one fatality occurred because of systemic toxicity following topical application to extensive areas of exophytic HPV warts.109

Use only under close medical supervision.100 101 108 109 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.109 Use caution to ensure drug is applied as recommended.100 101 108 109 (See Administration Precautions under Cautions.)

Initial manifestations of systemic toxicity include dizziness, lethargy, nausea, vomiting, abdominal pain, and diarrhea (sometimes severe and protracted).108 109

Adverse CNS effects may be delayed in onset and prolonged in duration.a 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.a

Delayed nervous system toxicity involving peripheral nervous system may occur.a 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.a

Electrodiagnostic determinations (i.e., nerve conduction studies and electromyelography) indicate an axonal neuropathy.a 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.a

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

Adverse hematologic effects (e.g., leukopenia, thrombocytopenia) reported,100 108 109 especially after application to extensive areas.108 109

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

Administration Precautions

Should only be applied by a health-care provider.100 101 109 120 121 Close medical supervision required because of the risk of systemic effects.100 101 108 109

Use caution to ensure drug is not applied to extensive areas or in excessive amounts100 101 108 109 and is removed from the treatment area within the prescribed period of time.100 101 108 109 (See Administration under Dosage and Administration.)

A powerful caustic and severe irritant.100 Avoid contact with eyes.100 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).100

Do not use if wart or surrounding tissue is inflamed or irritated.100 Do not apply to bleeding warts, moles, birthmarks, unusual warts with hair growing from them, or warts that have recently been biopsied.100 101 109

Do not apply to normal tissue or mucous membranes.100 101 109

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.101

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.101 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.101

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.101 120 121

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.101 120

Women with genital HPV warts should be advised to undergo regular Papanicolaou (Pap) tests as recommended for women without genital HPV warts.101

Specific Populations


Category X.100 Contraindicated in pregnant women.100 101 120 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)


Not known whether topically applied podophyllum resin is distributed into milk.100 Contraindicated in breast-feeding women.100

Pediatric Use

Safety and efficacy not established in pediatric patients.b

Common Adverse Effects

Local reactions (erythema, tenderness, pruritus, burning, pain, swelling).104 112

Interactions for Podophyllum Resin

Specific Drugs





Concomitant use contraindicated100 a

Podophyllum Resin Pharmacokinetics



Absorbed systemically following topical application.100 (See Systemic Effects under Cautions.)





Tight, light-resistant container at 15–30°C.100 Darkens when exposed to light or temperatures >25°C.118


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

  • 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).100 117 118 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.117 118

  • 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.117

  • 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.117

  • Has cathartic effects.109 117 (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.100 101 109 (See Administration under Dosage and Administration.)

  • Importance of avoiding contact with eyes.100 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).100

  • Advise patients that podophyllum resin is not a cure for HPV; new HPV warts may develop during or after therapy with the drug.101 110 112 114 Importance of patients watching for recurrences, particularly during the first 3 months.101

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.100 (See Contraindications under Cautions.)

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.100

  • Importance of informing patients of other important precautionary information.100 (See Cautions.)


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

Podophyllum Resin


Dosage Forms


Brand Names







Podocon-25 (in compound benzoin tincture)


AHFS DI Essentials™. © Copyright 2021, Selected Revisions September 1, 2007. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.


Only references cited for selected revisions after 1984 are available electronically.

100. Paddock Laboratories. Podocon-25 (25% podophyllin in benzoin tincture) prescribing information. Minneapolis. MN; 2005 Aug.

101. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2006. MMWR Recomm Rep. 2006; 55(RR-11):1-94.

102. Stone KM, Becker TM, Hadgu A et al. Treatment of external genital warts: a randomised clinical trial comparing podophyllin, cryotherapy, and electrodisiccation. Genitourin Med. 1990; 66:16-9.

103. White DJ, Billingham C, Chapman S et al. Podophyllin 0.5% or 2.0% v podophyllotoxin 0.5% for the self treatment of penile warts: a double blind randomised study. Genitourin Med. 1997; 73:184-7.

104. Edwards A, Atma-Rm A, Thin RN. Podophyllotoxin 0.5% v podophyllin 20% to treat penile warts. Genitourin Med. 1988; 64:263-5.

105. Lassus A. Comparison of podophyllotoxin and podophyllin in treatment of genital warts. Lancet. 1987; 1:512-3.

106. Maiti H, Haye KR. Topical podophyllin for genital warts. Lancet. 1987; 1:795- 6.

107. Jensen SL. Comparison of podophyllin application with simple surgical excision in clearance and recurrence of perianal condylomata acuminata. Lancet. 1985; 2:1146-7.

108. Stoehr GP, Peterson AL, Taylor WJ. Systemic complications of local podophyllin therapy. Ann Intern Med. 1978; 89:362-3.

109. Slater GE, Rumack BH, Peterson RG. Podophyllin poisoning: systemic toxicity following cutaneous application. Obstet Gynecol. 1978; 52:94-5.

110. Phelps WC, Alexander KA. Antiviral therapy for human papillomaviruses: rationale and prospects. Ann Intern Med. 1995; 123:368-382.

111. Drake LA, Ceilley RI, Cornelison RL et al. Guidelines of care for warts: human papillomavirus. J Am Acad Dermatol. 1995; 32:98-103.

112. Beutner KR, Ferenczy A. Therapeutic approaches to genital warts. Am J Med. 1997; 102:28-37.

113. Beutner KR. Bridging the gap. Arch Dermatol. 1990; 126:1432-34.

114. Stone KM. Human papillomavirus infection and genital warts: update on epidemiology and treatment. Clin Infect Dis. 1995; 20(Suppl 1):S91-7.

115. Syrjanen KJ. Epidemiology of human papillomavirus (HPV) infections and their associations with genital squamous cell cancer. APMIS. 1989; 97:957-70.

116. Baker GE, Tyring SK. Therapeutic approaches to papillomavirus infections. Dermatol Clin. 1997; 15:331-40.

117. Sackett DL. Podophyllotoxin, steganacin and combretastatin: natural products that bind at the colchicine site of tubulin. Pharmacol Ther. 1993; 59:163-228.

118. Reynolds JEF, ed. Martindale: the extra pharmacopoeia. 30th ed. London: The Pharmaceutical Press; 1993:765-6.

119. The United States pharmacopeia, 23rd rev, and The national formulary, 18th ed. Rockville, MD: The United States Pharmacopeial Convention, Inc; 1995: 1238-9.

120. Centers for Disease Control and Prevention. Treating opportunistic infections among HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association/Infectious Diseases Society of America. MMWR Recomm Rep. 2004; 53(RR-15):1-112.

121. Centers for Disease Control and Prevention. Treating opportunistic infections among HIV-exposed and infected children: recommendations from CDC, the National Institutes of Health, and the Infectious Diseases Society of America. MMWR Recomm Rep. 2004; 53(RR-14):1-92.

a. AHFS drug information 2007. McEvoy GK, ed. Podophyllum Resin. Bethesda, MD: American Society of Health-System Pharmacists; 2007: 3592–3594.

b. Paddock Laboratories. Personal Communication. 13 Jun 2007.

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