Podophyllotoxin

(BAN)
Podophyllotoxin Chemical formula
Synonyms: Podofilotoxina; Podofilox (USAN); Podofyllotoksiini; Podofyllotoxin; Podophyllotoxinum. (5R,5aR,8aR,9R)-5,5a,6,8,8a,9-Hexahydro-9-hydroxy-5-(3,4,5-trimethoxyphenyl)furo[3′4′:6,7]naphtho[2,3d]-1,3-dioxol-6-one.
Cyrillic synonym: Подофиллотоксин.

💊 Chemical information

Chemical formula: C22H22O8 = 414.4.
CAS — 518-28-5.
ATC — D06BB04.
ATC Vet — QD06BB04.

💊 Adverse Effects

Podophyllum is very irritant, especially to the eyes and mucous membranes. It can also cause severe systemic toxicity after ingestion or topical application, which is usually reversible but has been fatal. Symptoms of toxicity include nausea, vomiting, abdominal pain, and diarrhoea; there may be thrombocytopenia, leucopenia, renal failure, and hepatotoxicity. Central effects are delayed in onset and prolonged in duration and include acute psychotic reactions, hallucinations, confusion, dizziness, stupor, ataxia, hypotonia, seizures, and coma. EEG changes may persist for several days. Peripheral and autonomic neuropathies develop later and may result in paraesthesias, reduced reflexes, muscle weakness, tachycardia, apnoea, orthostatic hypotension, paralytic ileus, and urinary retention. Neuropathy may persist for several months.

Poisoning.

Reports and reviews of podophyllum toxicity.1-7 A few of the cases followed consumption of herbal preparations containing podophyllum or the related plant bajiaolian (Dysosma pleianthum). Death has occurred after ingestion of 10 g of podophyllum.
1. Cassidy DE, et al. Podophyllum toxicity: a report of a fatal case and a review of the literature. J Toxicol Clin Toxicol 1982; 19: 35–44
2. Dobb GJ, Edis RH. Coma and neuropathy after ingestion of herbal laxative containing podophyllin. Med J Aust 1984; 140: 495–6
3. Holdright DR, Jahangiri M. Accidental poisoning with podophyllin. Hum Exp Toxicol 1990; 9: 55–6
4. Tomczak RL, Hake DH. Near fatal systemic toxicity from local injection of podophyllin for pedal verrucae treatment. J Foot Surg 1992; 31: 36–42
5. Kao W-F, et al. Podophyllotoxin intoxication: toxic effect of bajiaolian in herbal therapeutics. Hum Exp Toxicol 1992; 11: 480–7
6. Chan TYK, Critchley JAJH. Usage and adverse effects of Chinese herbal medicines. Hum Exp Toxicol 1996; 15: 5–12
7. Chu CC, et al. Sensory neuropathy due to bajiaolian (podophyllotoxin) intoxication. Eur Neurol 2000; 44: 121–3.

💊 Precautions

The risk of systemic toxicity after topical application of podophyllum is increased by the treatment of large areas with excessive amounts for prolonged periods, by the treatment of friable, bleeding, or recently biopsied warts, and by inadvertent application to normal skin or mucous membranes. Podophyllum should not be used during pregnancy or breast feeding. There are few reports of use during pregnancy and a teratogenic risk cannot be ruled out. Adverse systemic effects in the mother would also be undesirable during pregnancy, and there are other nondrug treatments available for the treatment of anogenital warts. It is not known whether podophyllum is distributed into breast milk.

Handling.

Podophyllum resin is strongly irritant to the skin, eyes, and mucous membranes and requires careful handling.

💊 Uses and Administration

Podophyllum resin and podophyllotoxin have an antimitotic action and are used principally as topical treatments for anogenital warts (condylomata acuminata). Podophyllum resin and podophyllotoxin may be used on external genital and perianal warts; podophyllum resin may also be used on urethral meatus warts. However, neither of these compounds should be used to treat warts on mucous membranes, including vaginal, cervical, intra-urethral, intra-anal, and rectal warts. Podophyllum resin is usually formulated in compound benzoin tincture in strengths of 15% Indian podophyllum resin or 10 to 25% American podophyllum resin. Lower concentrations of American podophyllum resin in alcoholic solutions have been used. The solution is left on the warts for 1 to 6 hours, and then washed off. Only a small area or number of warts should be treated at any one time and care must be taken to avoid application to healthy tissue. This procedure is carried out once a week for up to 3 to 6 weeks. Preparations containing podophyllotoxin 0.5% in alcohol or alcoholic gel or podophyllotoxin 0.15% cream are used similarly. They are applied twice daily for 3 days but not washed off. Treatment may be repeated at weekly intervals for up to a total of 4 or 5 weeks of treatment. Podophyllum resin is also used with other keratolytics for the removal of plantar warts. Although podophyllum resin and podophyllotoxin preparations are generally not used in children, see below. When taken orally podophyllum resin is highly irritant to the intestinal mucosa and produces violent peristalsis resulting in a drastic purging action. It has been superseded by less toxic laxatives. Podophyllum has been used in homoeopathic medicine.

Administration in children.

The use of podophyllum resin and podophyllotoxin preparations in children is generally avoided because of the potential for severe local irritation and systemic toxicity. Nonetheless, podophyllotoxin has been used for the treatment of symptomatic, persistent anogenital warts in children.1 The BNFC suggests that, although not licensed for use in children, podophyllum resin and podophyllotoxin preparations may be used in regimens similar to those used in adults (see above) in children 2 years of age and older who are able to cooperate with treatment.
1. Bellew SG, et al. Childhood warts: an update. Cutis 2004; 73: 379–84.

Anogenital warts.

Podophyllum preparations are one of the treatment choices for anogenital warts caused by human papillomavirus infection (condylomata acuminata). Podophyllum resin preparations have traditionally been applied by a healthcare provider because of the potential local and systemic toxicity associated with inappropriate or excessive use.1 However, podophyllotoxin may be more effective2,3 and less toxic2 than podophyllum resin, and is suitable for self-treatment by the patient.1,4
1. CDC. Sexually transmitted diseases treatment guidelines, 2006. MMWR 2006; 55 (RR-11): 1–94. Correction. ibid.; 997. Also available at: http://www.cdc.gov/mmwr/PDF/rr/rr5511.pdf (accessed 27/09/07
2. von Krogh G, Longstaff E. Podophyllin office therapy against condyloma should be abandoned. Sex Transm Infect 2001; 77: 409–12
3. Lacey CJN, et al. Randomised controlled trial and economic evaluation of podophyllotoxin solution, podophyllotoxin cream, and podophyllin in the treatment of genital warts. Sex Transm Infect 2003; 79: 270–5
4. von Krogh G, et al. European Course on HPV Associated Pathology (ECHPV). European guideline for the management of anogenital warts. Int J STD AIDS 2001; 12 (suppl 3): 40–7. Also available at: http://www.iusti.org/sti-information/pdf/ guidelines.pdf (accessed 27/09/07)

💊 Preparations

BP 2008: Compound Podophyllin Paint; USP 31: Podophyllum Resin Topical Solution.

Proprietary Preparations

Arg.: Podoxin; Austral.: Condyline; Wartec; Austria: Condylox; Belg.: Wartec; Braz.: War tec; Canad.: Condyline; Podofilm; Wartec; Chile: War tec†; Cz.: Wartec; Denm.: Condyline; Wartec; Fin.: Condyline; Wartec; Fr.: Condyline; Wartec†; Ger.: Condylox; Wartec; Gr.: Podofilox†; Wartec; Hong Kong: Podofilm; Wartec; Hung.: Condyline; Wartec; Irl.: Condyline; Warticon; Israel: Condylox; Ital.: Condyline; Wartec; Mex.: Podofilia; Vipodo; Wartec; Neth.: Condyline; Wartec; Norw.: Condyline; Wartec; NZ: Condyline; Wartec; Pol.: Condyline; Wartec; Port.: Condyline; Rus.: Condyline (Кондилин); S.Afr.: Wartec; Singapore: Wartec; Spain: War tec; Swed.: Condyline; Wartec; Switz.: Condyline; Warix; UK: Condyline; Warticon; USA: Condylox; Pod-Ben-25; Podocon; Podofin. Multi-ingredient: Arg.: Calculina†; Austral.: Posalfilin; Canad.: Canthacur-PS; Cantharone Plus; Ger.: Unguentum lymphaticum; Hong Kong: Posalfilin†; Irl.: Posalfilin; Malaysia: Posalfilin†; NZ: Posalfilin; Port.: Cholagutt†; S.Afr.: Posalfilin; Singapore: Posalfilin†; Spain: Alofedina; UK: Posalfilin; Venez.: Linfoderm; Podoben†.
Published January 09, 2019.