Chapter 222. Other Topical Medications

This chapter reviews topical therapies not covered elsewhere in the text that are used to treat dermatologic diseases. The topic headings are those of the drug designation of the US Pharmacopeia and at times reflect clinical usage rather than specific pharmacologic mechanisms. All topicals when applied to large areas of skin, particularly in the presence of skin disease or to infants and children, have the potential for systemic side effects.

Capsaicin

Capsaicin is the molecule that confers the “hotness” to hot peppers of the genus Capsicum, including cayenne, jalapeno, and Tabasco peppers.1 Initial topical application results in itching, pricking, and burning as nociceptor activate. Repeated applications, however, are hypothesized to lead to degeneration of epidermal nerve fibers and nociceptor desensitization, thereby producing hypalgesia.1

Topical capsaicin has been used to treat postherpetic neuralgia, diabetic neuropathy, reflex sympathetic dystrophy, Raynaud phenomenon, nostalgia paresthetica, arthralgias, plantar warts, diabetic neuralgia, and hemodialysis-related pruritus.1 A recent placebo-controlled trial of a high-concentration capsaicin dermal patch showed that the patch significantly reduced postherpetic neuralgia pain with transient application site pain reactions managed effectively with analgesics.2 Other therapies for postherpetic neuralgia should also be considered.3

Topical Anesthetics

Numerous topical anesthetics are available.4 Eutectic mixture of local anesthetics (EMLA) cream contains the sodium-channel-blocking amide anesthetics lidocaine 2.5% and prilocaine 2.5%. Application under occlusion to intact skin or genital mucous membranes for at least 1 hour before performance of a painful procedure, including debridement of venous leg ulcers,5 can provide local anesthesia that may persist for up to 2 hours. The cream may cause transient local blanching followed by transient local erythema. Like all products containing lidocaine, it should not be used in patients with hypersensitivity to amide anesthetics. Additionally, the prilocaine component has been linked to cases of methemoglobinemia in patients for whom applications exceeded the recommended dose, application area, or application time.6 Those particularly susceptible to methemoglobinemia include patients who are very young, those with glucose-6-phosphate dehydrogenase deficiency, and those taking oxidizing drugs such as sulfonamides and antimalarials.

Caution regarding dosing should also be used in patients susceptible to systemic effects of lidocaine or prilocaine, including acutely ill, debilitated, and elderly patients. Finally, as EMLA is ototoxic, it should not be used if there is a concern that it could penetrate or migrate beyond the tympanic membrane to the middle ear.

Various topical anesthetic products contain only lidocaine, typically at concentrations of 4% or 5%, which may be applied with or without occlusion. Systemic toxicity from topical lidocaine prepared in a 30% concentration has been reported.7 In 2007, FDA reported that two women, aged 22 and 25, experienced seizure, coma, and death after using compounded topical formulations of lidocaine and tetracaine, under occlusion, prior to laser hair removal procedures. Cases of arrhythmia and apnea were also reported. Those adverse events prompted FDA to warn the public about potential hazards of use of topical numbing products for cosmetic procedures,8 and pharmacies against violating regulations in compounding such products.9

Coal Tar

Coal tar has been used to treat inflammatory dermatoses for up to 2 millennia, although currently it is used primarily to treat psoriasis.10 Coal tar has been shown to inhibit DNA synthesis and mitosis in epidermal cells, an effect potentiated by ultraviolet A exposure.11 Coal tar also has anti-infective, antipruritic, photosensitizing, and vasoconstrictive effects and, with repeated applications, causes epidermal atrophy. The precise mechanism by which it treats inflammatory skin diseases has not been fully described.

In 1925, Goekerman pioneered the concomitant use of coal tar and ultraviolet B therapy for psoriasis.

Coal tar has historically been messy to use, has an unpleasant odor, and can stain clothing, making its use challenging for some. Newer formulations, however, might be better tolerated.12,13 Systemic adverse effects are uncommon, whereas local adverse effects can include tar folliculitis, acneiform eruptions, irritant dermatitis, burning, and stinging, allergic contact dermatitis, atrophy, telangiectases, pigmentation, exfoliative dermatitis, and keratoacanthomas.10 Although occupational exposure to coal tar has been associated with increased risk of developing skin cancer, epidemiologic studies of coal tar-treated psoriasis have not demonstrated an increased risk of skin cancer due to coal tar.14

Wood Tar

Produced by distillation of wood under controlled conditions, wood tar can be added to arachis oil (peanut oil) or other bases. The preparation is then typically used to treat scalp psoriasis. Most commonly derived from juniper (oil of cade), wood tar may also be derived from beech, birch, and pine. Contact sensitivity to wood tar has been reported.15

Shale Oil

Shale oil (also referred to as ammonium bituminosulphonate, ichthyol, ichthammol, or black salve) is derived from oil shale, a sulfur-rich sedimentary rock. Further processing of extracted shale oil yields light- and dark-colored components. The light component is also referred to as pale sulfonated shale oil (PSSO) or ichthyol pale.16 Shale oil decreases inflammation by inhibiting lipoxygenase.17 A recent trial of PSSO cream for atopic dermatitis showed that it was more effective than vehicle in treating atopic dermatitis.18 A study of PSSO to treat venous leg ulcers showed that the size of ulcers treated with PSSO gel, compared with vehicle, significantly decreased, although there was no difference in complete epithelialization of granulation of ulcers.19 PSSO has also been used to treat acne, psoriasis, seborrhea, eczema, rosacea, and pruritus.16,20

(Table 222-1)

Chlorhexidine

Chlorhexidine gluconate is a bisbiguanide that binds to the stratum corneum, providing sustained bactericidal and fungicidal activity for over 6 hours, even when wiped from the field. Although it does not kill bacterial spores or mycobacteria, it does inhibit their growth. Because it does not lose its effectiveness in the presence of organic material, such as whole blood, it is an important antiseptic, disinfectant, antibacterial dental rinse, and preservative. Due to ototoxicity and the risk of conjunctivitis and corneal ulceration, chlorhexidine is not recommended for preoperative preparation of the face or head.

Dyes

Dyes are useful topical treatments because they are inexpensive and chemically and physically stable. The topical antiseptic dyes used in dermatology, gentian violet (methylrosaniline chloride), brilliant green (p-diethylamine triphenylmethanol), malachite green, and fuchsine, are all derivatives of triphenylmethane. The dyes are effective against Candida species and several aerobic Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. Gentian violet is a known contact sensitizer and may cause skin necrosis in concentrations greater than 2% aqueous solution or when used undiluted in skin folds.21

Hydrogen Peroxide

Hydrogen peroxide has been used for a number of years as a cleansing agent and for the removal of debris. It has antibacterial properties against both Gram-positive and -negative bacteria, and its effervescent quality helps débride wounds.

Iodinated Compounds

Iodine solution is bactericidal, sporicidal, and viricidal. Iodophors are complexes of iodine with a carrier that slowly liberates inorganic iodine on contact with reducing substances. This preserves the antimicrobial activities of iodine without the irritant effects of the free tincture. Iodophors must be applied to dry skin as they are inactivated by contact with blood, serum proteins, and sputum.

Povidone-Iodine

Povidone iodine has a wide spectrum of in-vitro activity against Gram-negative and -positive bacteria, fungi, and viruses. Systemic absorption can occur with resultant renal and thyroid dysfunction if large or prolonged quantities are used.

Clioquinol

Clioquinol, 5-chloro-8-hydroxy-7-iodoquinolinol, is weakly antifungal and antibacterial. It is effective alone or combined with a topical steroid to treat inflammatory dermatoses, especially in intertriginous areas. Adverse reactions include a yellowish discoloration on clothing or skin, delayed contact hypersensitivity, and contact dermatitis. In the early 1970s, it was linked to subacute myelo-optic neuropathy in Japan22 and was banned in many countries, including the United States. This link was questioned by subsequent epidemiologic studies,23 but product labeling still warns of possible irreversible optic atrophy and peripheral neuromuscular disease.

Metronidazole

Metronidazole is an imidazole with activity against anaerobic bacteria and protozoa that is most often used in dermatology for rosacea. In addition to its antibiotic properties, its mode of action in rosacea may involve the impedance of leukocyte chemotaxis and selective suppression of cellular immunity.

Mupirocin

Mupirocin, also known as pseudomonic acid, is bactericidal at the concentration achieved with topical application to the skin and mucous membranes. As mupirocin has a unique mechanism of action, in which it prevents the incorporation of isoleucine into proteins by inhibiting bacterial isoleucyl-t-RNA synthetase, there is no cross-resistance with other antimicrobials.25 It has activity against staphylococci, streptococci, and certain Gram-negative bacteria, but is inactive against much of the normal skin flora. It is the treatment of choice for nonbullous impetigo and the most effective topical antibiotic for the elimination of S. aureus nasal colonization.24

Retapamulin

Retapamulin is a member of the pleuromatilin class of antibiotics prescribed as a 1% topical ointment. It is bacteriostatic and inhibits the elongation phase of protein synthesis through selective binding to the 50S subunit of prokaryotic ribosomes. It is FDA approved for treatment of methicillin sensitive S. aureus and Streptococcus pyogenes, but is effective in vitro against isolates resistant to B-lactams, macrolides, quinolones, fusidic acid, and mupirocin.25

Azelaic Acid

Azelaic acid is a naturally occurring aliphatic dicarboxylic acid that is a competitive inhibitor of tyrosinase. Azelaic acid is a reversible inhibitor of cytochrome P450 reductase and 5α-reductase in microsomes and a reversible inhibitor of some enzymes in the respiratory chain. In-vitro azelaic acid has antimicrobial affects against Propionibacterium acnes and Staphylococcus epidermidis. Its efficacy against acne and rosacea is attributed to activity against P. acnes, normalization of keratinization, and a direct anti-inflammatory effect.26

Benzoyl Peroxide

Benzoyl peroxide is a nonspecific bactericidal agent that derives its biologic function through decomposition into benzoyloxy and phenyl radicals that react with numerous constituents of microbial cells. This effect may be enhanced by the addition of antibiotics or other molecules containing tertiary amines or transitional metals. As a topical therapy, benzoyl peroxide is mainly used for acne, although it is also occasionally used to speed healing of chronic wounds. When used for acne, it is frequently combined with topical antibiotics, as such combination therapy may reduce the development of antibiotic resistance by P. acnes.27

(See Chapter 208; Table 222-2)

Crotamiton

Crotamiton (crotonyl-N-ethyl-O-toluidine) is a colorless or pale yellow oil used in the treatment of scabies, pediculosis capitis, and pruritus. Its mode of action is unknown. Other antiparasitic formulations, such as lindane (see next section) 1% and permethrin cream (see later) 5%, are more effective than crotamiton,28 which is rarely a sensitizer. It is approved for use in infants and children, but is pregnancy category C.

γ-Benzene Hexachloride

γ-Benzene hexachloride, also known as hexachlorocyclohexane or lindane, is a chlorinated hydrocarbon pesticide that is effective against lice, scabies, and fleas as a 1% lotion or shampoo. Scabies and lice resistant to γ-benzene hexachloride have been reported.28 Furthermore, multiple side effects of topical application including central nervous system toxicity, seizures, and aplastic anemia have been reported leading to the US Food and Drug Administration recommendation that γ benzene hexachloride only be used as a second-line agent.29 Patients with seizure disorders, children weighing less than 50 kg, and patients with acutely inflamed or raw skin should avoid γ benzene hexachloride.

Malathion

Malathion is an organophosphate insecticide that acts by irreversibly binding to acetylcholinesterase.30 It is approved in the United States as a 0.5% lotion for the treatment of head lice. The lotion, containing 78% isopropyl alcohol, is flammable. Safety for children younger than 6 years of age has not been established, and it is pregnancy category B.

Permethrin

Permethrin is a synthetic pyrethroid modeled after the natural insecticide found in the pyrethrum flower, Chrysanthemum cinerariaefolium. It acts on parasitic nerve cell membranes, causing paralysis and death. It is available over-the-counter as a 1% cream rinse, which is left on dry hair for 10 minutes. A single application is often effective against head lice and nits. Due to increasing resistance, however, two applications, 7–10 days apart, are generally recommended. There is a lack of safety data for its use in children younger than 2 months of age, and in pregnant and breastfeeding women. Prescription strength permethrin 5% cream is also effective against pediculosis capitis resistant to the 1% cream, pediculosis pubis, scabies, and mite infestations including cheyletiella.31 The 5% cream is applied to dry skin and hair overnight (8–14 hours).

Pyrethrins

Pyrethrins are the naturally occurring esters of chrysanthemumic acid. In combination with piperonyl butoxide, it is available as a liquid, gel, oil, aerosol spray, foam, and shampoo. Pyrethrins are neurotoxins, and piperonyl butoxide inhibits pyrethrin metabolism, potentiating the effects of pyrethrins. It is also effective against fleas, mosquitoes, and houseflies. As it is derived from the extract of chrysanthemums, the American Academy of Pediatrics suggests that individuals who are sensitive to chrysanthemums or ragweed should avoid this medication.32 However, this recommendation is controversial as patch and prick testing of commercially available synergized pyrethrins fail to elicit a response in ragweed-allergic patients.33 The aerosol spray should never be prescribed to patients with a history of asthma.

Spinosad

Spinosad is a fermentation product of the soil bacterium Saccharopolyspora spinosa that causes widespread excitation of the insect central nervous system resulting in paralysis. It is being developed as a 0.9% cream rinse for the treatment of head lice. It is both pediculocidal and ovicidal with a 10-minute application.34

Aluminum Compounds

Aluminum chloride solutions are typically used as a first-line therapy for hyperhidrosis in 15% to 20% solutions in the axilla and up to 30% on the palms and soles.35 The solution is applied for a week at night, when eccrine glands are less active, and if tolerated up to twice daily. After control is achived, it can be applied every 1–3 weeks as maintenance therapy. Use may lead to irritation.35

Iontophoresis

Iontophoresis is a procedure in which current is used to transport ions through the skin.36 The mechanism by which iontophoresis acts to decrease sweating is not fully understood,37 although it is hypothesized that ion channels in eccrine glands are reversibly disrupted. In an iontophoretic treatment, a hyperhidrotic area of skin to be treated is covered with lukewarm tap water. Electrodes are then inserted into the water and a direct current delivered, usually at 8–20 amperages. The amperage is increased until a tingling sensation is experienced and applied for 10–20 minutes three to four times weekly. Improvement is typically noted in approximately 2 weeks and full improvement within 1 month. Maintenance treatments once or twice weekly can be helpful thereafter. Anticholinergic agents such as glycopyrronium bromide may be added to the tap water for refractory patients. Adverse effects may include irritation, hyperesthesia, and blisters.36 Iontophoresis using botulinum toxin type A for treatment of palmar hyperhidrosis has also been reported.38,39

(Table 222-3)

Antihistamines

(See Chapter 229.)

Doxepin

(See Chapter 229.)

Menthol

Menthol is a highly lipid-soluble cyclic terpene alcohol, often used with camphor. It is derived from naturally occurring plant oils or prepared synthetically. Menthol is a counterirritant that, by induction of a cool sensation, “crowds out” the sensation of itch. The cooling sensation may be the result of a direct interaction of menthol with cold receptors and/or nerve fibers.40,41

Phenol

Phenol in low concentrations (0.5% to 2.0%) acts as an antipruritic agent through its anesthetic effect. It is percutaneously absorbed and should be avoided in pregnant women and infants.41 In higher concentrations, it is caustic and is used for deep chemical peels (see Chapter 251).

Pramoxine Hydrochloride

Pramoxine hydrochloride is effective in cases of mild to moderate pruritus. As with other local anesthetics, it inhibits conduction of nerve impulses by altering the cell membrane permeability to ions. The onset of action of pramoxine products is 2–5 minutes.

In medical practice, astringents are agents that cause contraction of the tissues, arrest of secretion, or control of bleeding. The US Food and Drug Administration more strictly defines astringent drugs as “a drug product that is applied to the skin or mucous membranes for a local and limited protein coagulant effect.”42

Aluminum Salts

Aluminum acetate tablets diluted 1:10 to 1:40 (Burow solution) are an effective astringent and germicidal agent. Over-the-counter aluminum sulfate and calcium acetate (Domeboro) are available and, when dissolved in water, a chemical reaction occurs forming aluminum acetate and a precipitate of calcium sulfate (modified Burow solution). These solutions may be used as wet dressings, compresses, or soaks.

Potassium Permanganate

Potassium permanganate is an oxidizing agent, astringent, antiseptic, and antifungal that may be used to clean or deodorize wounds. Solutions of 1:4,000 to 1:16,000 may be used as wet compresses to reduce weeping or at 1:25,000 as a medicated bath. This agent may cause permanent staining of clothing and ceramics and temporary brown or bright purple staining of the skin, which may be removed with a weak solution of oxalic acid or sodium thiosulfate.

Silver Nitrate

Silver nitrate in 0.5% aqueous solution is an astringent and antimicrobial that is applied as a wet dressing in the treatment of infected eczema, gravitational ulcers, and other weeping and/or infected skin lesions caused by Gram-positive or Gram-negative bacteria. It is also available in a solid form that may be used as a hemostat. At low concentration (0.5% formulation, used clinically), it is bacteriostatic, while bactericidal at higher concentrations (10%). As methemoglobinemia has been noted secondary to topical treatment, methemoglobin levels should be followed with prolonged use.43

Hydroquinone

Usually used in concentrations of 2% to 5%, hydroquinone decreases pigmentation by inhibiting tyrosinase, thereby blocking the conversion of dopa to melanin.44 It may also act by inhibiting DNA and RNA synthesis, degrading melanosomes, and destroying melanocytes. Hydroquinone 4% in combination with tretinoin 0.05%, and fluocinolone acetonide 0.01% has been shown to be effective in the treatment of melasma.45 Adverse effects include irritant dermatitis, contact dermatitis, postinflammatory pigmentation, and cutaneous ochronosis. In 2006, FDA announced that it was considering new rules on marketing of hydroquinone, based on safety concerns.46 The American Academy of Dermatology and others have argued that stricter rules are not necessary.47,48

Tretinoin (Retinoic Acid)

(See also Chapter 217.)

Tretinoin is thought to inhibit transcription of tyrosinase, leading to decreased pigmentation.44 It is typically used in concentrations of 0.05% to 0.1% to treat melasma.44 Local adverse effects include erythema and desquamation, and postinflammatory hyperpigmentation has been reported. Concerns about systemic toxicity of topical tretinoin, including mortality resulting from lung and cardiovascular disease seen in a randomized controlled trial, have also been raised,49,50 although others have defended tretinoin's safety.51,52

Azelaic Acid

Azelaic acid is hypothesized to mediate decreased pigmentation by inhibition of mitochondrial oxidoreductase activity, DNA synthesis, and tyrosinase. Treatment of melasma is typically with concentrations of 15% to 20%. Side effects include burning, itching, and erythema.

Monobenzyl Ether of Hydroquinone

Occasionally used to depigment skin in individuals with widespread vitiligo, monobenzyl ether of hydroquinone typically causes irreversible depigmentation by causing melanocyte necrosis.53

(Table 222-4)

Keratolytics are agents that cause keratolysis, or peeling, of the epidermis. At low concentrations, most keratolytics act as humectants, or moisturizing agents.

α-Hydroxy Acids

(See Chapter 251.)

α-Hydroxy acids (lactic acid, glycolic acid, citric acid, glucuronic acid, and pyruvic acid) reduce the thickness of hyperkeratotic stratum corneum by an incompletely understood mechanism wherein the acids may directly solubilize the protein components of desmosomes or activate endogenous hydrolytic enzymes by changing the pH of the stratum corneum, resulting in keratolysis. Also, by diffusing into the stratum corneum and binding water, the acids act as humectants increasing the water content of the stratum corneum. This decreases the formation of dry scales on the skin surface and allows gentle rubbing of the skin during bathing to mechanically remove cornified tissue. The concentration of α-hydroxy acid, pH of the preparation, and composition of the base in which they are compounded are important in determining their efficacy. In general, more anhydrous preparations are less irritating, allowing higher concentrations of acid to be tolerated.

Propylene Glycol

Propylene glycol is a humectant, occlusive, and keratolytic agent. It is often combined with other medications to enhance their penetration. A combination of 20% propylene glycol with 5% lactic acid in a semiocclusive cream base is used as a highly effective and well-tolerated keratolytic in patients with lamellar ichthyosis and may be used in various other hyperkeratotic diseases.54

Salicylic Acid

Salicylic acid has been used in concentrations ranging from 0.5% to 60% in almost any base. In concentrations of 3% to 6%, it causes shedding of scales by softening the stratum corneum, dissolving the intracellular matrix, and loosening connections between corneocytes.55 In concentrations higher than 6%, salicylic acid is destructive to tissue. Salicylism has been reported with widespread and prolonged use, especially in children who should apply no more than 2 g (33 mL of a 6% solution) to their skin in a 24-hour period. Sensitization is rare, and irritation can be minimized if introduced at lower concentrations.

Urea

Urea is a humectant that is proteolytic at high concentrations. Urea has been added to some topical glucocorticoid preparations to possibly increase their penetration.56 It is in preparations for dry skin and nail plate destruction.

Lactic Acid

Lactic acid is a humectant and keratolytic that is available at concentrations up to 12%. In addition to being a keratolytic, lactic acid increases ceramide production by keratinocytes improving water barrier function.57

(See Chapter 18.)

Anthralin

(See Chapter 18.)

Calcipotriene

(See Chapter 18.)

A vitamin D analog, calcipotriol inhibits epidermal proliferation, induces epidermal differentiation, and exerts anti-inflammatory effects. Its effectiveness in psoriasis has been demonstrated in systematic reviews.58,59 Hypercalcemia may occur if more than 100 g is used per week. It is applied initially twice daily, and maximal improvement can be expected within 6–8 weeks. Cutaneous irritation may occur in up to 20% of patients, particularly when used on the face or in intertriginous areas. Calcipotriene is currently marketed in the United States only as a combination product with betamethasone dipropionate for treatment of psoriasis.60,61 Other Vitamin D analogs, including calcitriol and tacalcitol, are available and used to treat psoriasis outside of the United States.61

Diphenylcyclopropenone

Diphenylcyclopropenone (DPCP), also known as diphencyprone, is a potent contact allergen used in the treatment of viral warts and alopecia areata. It is not available in pharmaceutic quality. Theories for its mechanism of action include alterations in cytokine levels, nonspecific inflammation causing wart regression, and binding of DPCP to wart protein inducing a specific immune response.62 Cross-sensitivity to other chemicals, apart from its precursor, α,α-dibromodibenzyl ketone, has not been reported.62 Many clinics recommend avoiding DPCP in children younger than 12 years of age, although children with alopecia areata less than 12 years of age have been successfully treated with DPCP.62

Squaric Acid Dibutyl Ester

Squaric acid dibutyl ester is a potent topical sensitizer with a similar mechanism of action and use as DPCP. It requires refrigeration to maintain its potency.

Dinitrochlorobenzene

Dinitrochlorobenzene is a potent sensitizer with a similar mechanism of action and use as DPCP. Although dinitrochlorobenzene is mutagenic in vitro, there is no evidence of carcinogenicity in clinical practice.62

5-Fluorouracil

(See Chapter 220.)

Formaldehyde

Formaldehyde is a powerful disinfectant that causes anhidrosis, desiccation, and sometimes, hypersensitivity when applied to skin. It can cause hardening and fissuring of the skin, so normal surrounding skin should be protected from it by petrolatum, zinc paste, or meticulous application. Individuals with eczema or allergies should avoid formaldehyde as sensitization is problematic being that it is a ubiquitous component of many personal products.

Glutaraldehyde

Glutaraldehyde is viricidal. It also combines chemically with keratin producing polymers that harden the wart surface thereby facilitating paring.

Mono-, Di-, and Trichloroacetic Acids

Monochloroacetic acid, dichloroacetic acid, and trichloroacetic acid in concentrations of 50% to 90% are all effective in the management of warts.59 Trichloroacetic acid is also commonly used at lower concentrations (10% to 35%) for facial peels (see Chapter 252). Anal and vaginal lesions are occasionally treated with trichloroacetic acid, whereas monochloroacetic acid is most commonly used on plantar warts under salicylic acid plaster occlusion. The application needs to be repeated at 1- to 2-week intervals until complete resolution.

Podophyllin Resin

(See Chapter 196.)

Podofilox

Podofilox is podophyllotoxin, the active ingredient of podophyllin. It does not contain any of the ingredients responsible for the toxicity of podophyllin. It should not be used during pregnancy unless the potential benefit justifies the potential risk for the fetus.

Salicylic Acid

The effectiveness of salicylic acid in treating warts is thought to be related to keratolysis and local irritation of the skin in which the virus is present. Salicylic acid is the most established agent in terms of efficacy and safety in the treatment of viral warts.63

Sinecatechins

Sincatechins ointment is an extract of green tea leaves from Camellia sinensis used in the treatment of external genital warts. It is available as a 15% ointment applied three times daily until all warts have cleared up to a maximum of 16 weeks. The mechanism of clearance may be related to the immunostimulatory, antiproliferative, and antitumor properties of catechins within sinecatechins ointment. It appears to have a clinical efficacy comparable to the other currently available topical therapies for external genital warts.64,65