As a humectant, urea is used in concentrations of 2–20% in creams and lotions. As a keratolytic agent, it is used in 20% concentration in diseases such as ichthyosis vulgaris, hyperkeratosis of palms and soles, xerosis, and keratosis pilaris. Concentrations of 30–50% applied to the nail plate have been useful in softening the nail prior to avulsion.
Podophyllum resin, an alcoholic extract of Podophyllum peltatum, commonly known as mandrake root or May apple, is used in the treatment of condyloma acuminatum and other verrucae. It is a mixture of podophyllotoxin, α and β peltatin, desoxypodophyllotoxin, dehydropodophyllotoxin, and other compounds. It is soluble in alcohol, ether, chloroform, and compound tincture of benzoin.
Percutaneous absorption of podophyllum resin occurs, particularly in intertriginous areas and from applications to large moist condylomas. It is soluble in lipids and therefore is distributed widely throughout the body, including the central nervous system.
The major use of podophyllum resin is in the treatment of condyloma acuminatum. Podophyllotoxin and its derivatives are active cytotoxic agents with specific affinity for the micro-tubule protein of the mitotic spindle. Normal assembly of the spindle is prevented, and epidermal mitoses are arrested in metaphase. A 25% concentration of podophyllum resin in compound tincture of benzoin is recommended for the treatment of condyloma acuminatum. Application should be restricted to wart tissue only, to limit the total amount of medication used and to prevent severe erosive changes in adjacent tissue. In treating cases of large condylomas, it is advisable to limit application to sections of the affected area to minimize systemic absorption. The patient is instructed to wash off the preparation 2–3 hours after the initial application, because the irritant reaction is variable. Depending on the individual patient’s reaction, this period can be extended to 6–8 hours on subsequent applications. If three to five applications have not resulted in significant resolution, other methods of treatment should be considered.
Toxic symptoms associated with excessively large applications include nausea, vomiting, alterations in sensorium, muscle weakness, neuropathy with diminished tendon reflexes, coma, and even death. Local irritation is common, and inadvertent contact with the eye may cause severe conjunctivitis. Use during pregnancy is contraindicated in view of possible cytotoxic effects on the fetus.
Pure podophyllotoxin (podofilox) is approved for use as either a 0.5% solution or gel (Condylox) for application by the patient in the treatment of genital condylomas. The low concentration of podofilox significantly reduces the potential for systemic toxicity. Most men with penile warts may be treated with less than 70 μL per application. At this dose, podofilox is not routinely detected in the serum. Treatment is self-administered in treatment cycles of twice-daily application for 3 consecutive days followed by a 4-day drug-free period. Local adverse effects include inflammation, erosions, burning pain, and itching.
Sinecatechins 15% ointment (Veregen) is a prescription botanical drug product of a partially purified fraction of the water extract of green tea leaves from Camellia sinensis containing a mixture of catechins. Sinecatechins ointment is indicated for the topical treatment of external genital and perianal warts in immunocompetent patients 18 years and older. The mechanism of action is unknown. Sinecatechins ointment should be applied three times daily to the warts until complete clearance, not to exceed 16 weeks of therapy.