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Podophyllum derivatives


See also Topoisomerase inhibitors

General information

Podophyllum is a powerful skin irritant and antimitotic agent, widely used in the topical treatment of condylomata acuminata.

Etoposide and teniposide are semisynthetic derivatives of podophyllin, which was originally isolated from the root of the Indian podophyllum plant. They inhibit topoisomerase II and are dealt with in a separate monograph.

The signs and symptoms of systemic toxicity [ , ] include:

  • cyanosis, tachycardia, electrocardiographic changes;

  • stertorous respiration;

  • polyneuritis, ataxia, coma, agitation, delirium, confusion, lethargy, muscular weakness, paresthesia;

  • leukopenia, leukocytosis, thrombocytopenia, anemia;

  • nausea, vomiting, abdominal pain, paralytic ileus;

  • raised liver enzymes;

  • oliguria, anuria, hematuria;

  • urticaria;

  • fever.

Intrauterine death and teratogenicity have not been demonstrated convincingly.

Podophyllum emodi (Indian podophyllum)

Proresid (mitopodozide), a mixture of more than 20 derivatives of Podophyllum emodi , has been used for many years in some countries as a disease-modifying agent in rheumatoid arthritis. A microtubulin antagonist, it is comparable with colchicine and griseofulvin. Its use has been limited because treatment is often complicated by severe diarrhea, abdominal pain, nausea, and vomiting. Leukopenia and thrombocytopenia have been reported [ , ].

Podophyllum peltatum (American mandrake)

The resin prepared from the dried rhizome and roots of Podophyllum peltatum contains podophyllotoxin, α-peltatin, and β-peltatin. When applied topically, it is a strong irritant to the skin and mucous membranes and can lead to poisoning because of systemic absorption. When taken by mouth, it has a drastic laxative action and produces violent peristalsis. Ingestion of large doses can result in severe neuropathic toxicity [ ]. The oral and local use of the resin should be avoided during pregnancy, as this has been associated with teratogenicity and fetal death.

  • A 31-year-old man took an unknown amount of Podophyllum peltatum , thinking it to be Mandragora officinarum ; he developed severe nausea and vomiting and recovered uneventfully [ ].

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