Anthralin (Topical)



INN:

Dithranol

BAN:
Dithranol

VA CLASSIFICATION
Primary: DE802
Secondary: DE900

Commonly used brand name(s): Anthraforte 1; Anthraforte 2; Anthranol 0.1; Anthranol 0.2; Anthranol 0.4; Anthrascalp; Dritho-Scalp; Drithocreme; Drithocreme HP; Micanol.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antipsoriatic (topical)—

hair growth stimulant, alopecia areata (topical)—

Indications

Accepted

Psoriasis (treatment)—Anthralin is indicated in the topical treatment of quiescent or chronic psoriasis of the skin and scalp {01} {02} {03} {04} {05} {06}.

Acceptance not established
Anthralin has been used in patients for the topical treatment of alopecia areata after other treatments were unsuccessful. The best results were achieved in patients who recently had acquired alopecia areata; 0.5% anthralin cream produced a low rate of cosmetically acceptable results {12} {13} {14} {15} {16}. Study results evaluating the use of anthralin are preliminary and larger studies are required. (Evidence rating: C-3.)

Unaccepted
Anthralin should not be used on acutely inflamed psoriatic eruptions {01} {02} {03} {05} {06}.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    226.23

Mechanism of action/Effect:

Antipsoriatic—The mechanism of action of anthralin is not known. Anthralin restores the normal rate of epidermal cell proliferation and keratinization by reducing the mitotic activity of the hyperplastic epidermis of psoriasis. In vitro studies show that anthralin prolongs the prophase of mitosis for keratinocytes and leukocytes; in vivo studies show that anthralin inhibits DNA synthesis and may increase the release of reactive oxygen species, upsetting oxidative metabolic processes. {09} {10} {11}

Hair growth stimulant—Although its mechanism is not known, anthralin does not have direct follicular stimulating effects. Anthralin's hair growth properties may be due to its irritant properties and its ability to cause a nonallergenic inflammatory dermatitis. {12} {13} {14} {15} {16}

Absorption:

The amount of anthralin absorbed through the skin has not been fully determined {05}; however, absorption appears to be low. {21}. Anthralin penetrates damaged skin and psoriatic lesions faster and to a greater extent than normal skin {22} {25}, possibly because of greater blood flow to the lesions or a poor barrier junction of psoriatic skin. {23} {24} {31}

Elimination:
    Two studies found evidence of anthralin metabolites (mainly danthron) in the urine {24}. However, a later study using a detection limit of 20 mcg per mL found no evidence of excretion of anthraquinones in the urine {21}. In addition, other studies have found no evidence of systemic toxicity, even in patients with renal disease {24}.


Precautions to Consider

Carcinogenicity/Tumorigenicity

Some long-term studies in mice have shown anthralin to be tumorigenic to mouse skin; the carcinogenic potential has not been evaluated {05}. Tumorigenic and carcinogenic effects of anthralin have not been reported in humans {05}.

Pregnancy/Reproduction

Pregnancy—
Anthralin may be systemically absorbed {22}.

Studies have not been done in humans {05}.

Studies have not been done in animals {05}.

FDA Pregnancy Category C {04} {05}.

Breast-feeding

It is not known whether anthralin is distributed into breast milk {05} {06}, and problems in humans have not been documented. However, anthralin may be systemically absorbed {22}.

Pediatrics

Appropriate studies on the relationship of age to the effects of anthralin have not been performed in the pediatric population. Safety and efficacy have not been established {05} {06} {19} {20}.


Geriatrics


Appropriate studies on the relationship of age to the effects of anthralin have not been performed in the geriatric population. However, no geriatrics-specific problems have been documented to date. {26} {27}

Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
» Acute eruptions or presence of inflammation of skin{04}{05}{06} , including folliculitis
Allergy to components of formulation, such as parabens
Sensitivity to anthralin or to components of formulation, such as salicylic acid    (transient irritation of uninvolved skin surrounding the psoriatic lesions occurs frequently and may be occasionally severe; medication should be discontinued if a sensitivity skin reaction or excessive irritation occurs {04} {05}. Some formulations contain 2 to 3% salicylic acid, a keratolytic, to serve as an antioxidant {29}. Rarely, anthralin may cause allergic contact dermatitis {04} {05} {17})




Side/Adverse Effects

Note: Severe conjunctivitis may occur if this medication comes into contact with the eye. {01}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
    
Redness or other skin irritation not present before therapy —including treated and uninvolved skin{01}{05}

Incidence rare
    
Allergic reaction (skin rash){17}





Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Anthralin (Topical) .
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to anthralin or to components of formulation, such as salicylic acid, or allergy to components of formulation, such as parabens
Other medical problems, especially acute eruptions or presence of inflammation of skin, including folliculitis

Proper use of this medication
» Avoiding contact with the eyes and mucous membranes

» Not applying medication to blistered, raw, or oozing areas of skin or scalp

» Not using medication on face or sex organs or in the folds and creases of the skin; checking with physician if necessary

» Using medication only as directed; importance of not using more medication than the amount prescribed

Knowing correct method of administration; checking with physician if necessary

Proper administration
If irritation of normal skin occurs, applying petrolatum around affected areas before applying anthralin

Applying a thin layer to only the affected areas; rubbing in well

Washing hands immediately after application

For short contact anthralin therapy
Allowing medication to remain on affected area for 10 to 30 minutes or as prescribed by physician; then bathing, if applied to the skin, or shampooing, if applied to the scalp, to remove medication

For patients using the cream for overnight treatment
If the skin is being treated—Removing cream from skin by bathing the next morning

If the scalp is being treated—Shampooing to remove scales and any previous application, then drying and parting hair before application; checking with physician to see when cream should be removed

For patients using the ointment for overnight treatment
If the skin is being treated—Removing ointment from skin with warm liquid petrolatum the next morning, then bathing

If the scalp is being treated—Removing from scalp by shampooing the next morning

» Proper dosing
Missed dose: Applying as soon as possible; not applying if almost time for next dose; not doubling doses

» Proper storage

Precautions while using this medication
» Staining may occur on contact with this medication, especially to skin, hair, fingernails, clothing, bed linens, or bathtub or shower; staining of skin or hair wears off several weeks after medication is discontinued

Minimizing or preventing possible staining from anthralin by:    • Wearing plastic gloves to prevent staining of hands
   • Checking with physician to see if plastic cap may be worn to prevent staining of pillow if medication is applied to scalp at night
   • Removing any medication on surface of bathtub or shower by rinsing with cool to lukewarm water immediately after bathing or showering, then washing with a household cleanser to remove any remaining deposit of medication on bathtub or shower stall



Side/adverse effects
Anthralin has been shown to cause tumors in animals. However, there have been no reports of anthralin causing tumors in humans

Signs of potential side effects, especially redness or other skin irritation not present before therapy (for both treated and uninvolved skin) or allergic reaction


General Dosing Information
Anthralin's skin-irritating properties increase with its concentration. The optimal period of contact will vary according to the strength used and the patient's response or tolerance to anthralin therapy. A short contact time and the initial use of a low concentration are recommended, with subsequent increase in contact time and/or concentration only as necessary. {04} {05}

One criterion for determining the optimal concentration for use is the occurrence of erythema on normal skin adjacent to the lesions. When erythema occurs, the dosage, frequency of application, and/or duration of treatment should be reduced. {05} {06} Anytime severe skin irritation or edema of treated or untreated skin occurs, patients should notify their physicians, and anthralin dosage adjustment or treatment discontinuation should be considered {04} {05}.

Anthralin should be carefully applied directly to psoriatic skin lesions to avoid exposing uninvolved skin. Unintentionally applied medication should be washed off, especially residue collected behind ears when anthralin is applied to the scalp. Contact with the eyes and mucous membranes should be avoided. {04} {05} It is recommended that anthralin not be applied to:    • acute psoriatic lesions;
   • blistered, raw, or oozing areas of skin or scalp;
   • genitalia;
   • facial skin, for most formulations;
   • intertriginous skin areas; or
   • folds or creases of skin. {04} {05}


In the treatment of psoriasis, two types of anthralin therapy are being used:    #149; Conventional therapy—Anthralin cream or ointment is applied once (sometimes twice) a day to dry skin or scalp, preferably at night, and allowed to remain on the affected area overnight, then removed by bathing or shampooing the next morning or before the next application. {02} {04} {05} {06}
   #149; Short contact anthralin therapy (S.C.A.T.)—Anthralin 0.1 to 1% cream or ointment is applied once a day to dry skin or scalp and allowed to remain on the affected area for only 10 to 30 minutes or as prescribed by physician, then removed by bathing, if applied to skin, or by shampooing, if applied to scalp. {01} {04} {05} {06}


Some products require that a metal cover on tube be pierced at initial use by inverting the cap. Formulations used on the scalp may contain a black applicator that can be screwed onto the tube. {03} {04}

Many surfaces stain on contact with anthralin, including skin, hair, fingernails, clothing, bed linens, bathtubs, and showers. It may take several weeks after medication is discontinued to remove the stains from treated skin or hair. {04} {05} Patients can be instructed in ways to limit the contact of medication from unintended surfaces or areas. Suggestions include:    • using plastic gloves for application {04} {05}; otherwise, washing hands thoroughly after using the medication {01}.
   • pretreating the uninvolved skin around psoriatic lesions with a protective film of petrolatum or other suitable emollient {04} {05}.
   • immediately removing medication from inanimate surfaces, such as bathtubs or shower stalls, by rinsing surfaces with cool to lukewarm water and then washing with household cleansers {04} {05}.
   • wearing plastic caps during sleep, if appropriate, to protect bed linens for patients applying anthralin to scalp before bedtime {04} {05}.


Long-term use of topical corticosteroids may destabilize psoriasis and, on their withdrawal, result in a rebound effect; it is recommended by the manufacturer that corticosteroids be discontinued for 1 week before initiating treatment with anthralin. Using petrolatum or another appropriate emollient during this 1-week interval may be useful for the patient. Some clinicians have not found a rebound effect in such treated patients. {04} {31}


Topical Dosage Forms

ANTHRALIN CREAM USP

Usual adult and adolescent dose
Psoriasis
Conventional therapy: Topical, to dry, affected skin, once a day, preferably at night. Wash medication off at the end of the contact time. {02} {04} {05} {06}

Short contact therapy: Topical, to dry, affected skin, once a day for ten to thirty minutes or as prescribed by physician {04}. Wash medication off at the end of the contact time. {02} {04} {05} {06} Strengths of 1% or higher are generally used for short contact therapy {31} and cream may be preferred for scalp administration {31}.


Usual pediatric dose
Safety and efficacy have not been established.

Usual geriatric dose
See Usual adult and adolescent dose .

Strength(s) usually available
U.S.—


0.1% (Rx) [Drithocreme (ascorbic acid) (cetostearyl alcohol) (chlorocresol) (petrolatum) (salicylic acid) (sodium lauryl sulfate) (water){05}]


0.25% (Rx) [Drithocreme (ascorbic acid) (cetostearyl alcohol) (chlorocresol) (petrolatum) (salicylic acid) (sodium lauryl sulfate) (water){05}] [Dritho-Scalp (ascorbic acid) (cetostearyl alcohol) (chlorocresol) (petrolatum) (salicylic acid) (sodium lauryl sulfate) (water){04}]


0.5% (Rx) [Drithocreme (ascorbic acid) (cetostearyl alcohol) (chlorocresol) (petrolatum) (salicylic acid) (sodium lauryl sulfate) (water){05}] [Dritho-Scalp (ascorbic acid) (cetostearyl alcohol) (chlorocresol) (petrolatum) (salicylic acid) (sodium lauryl sulfate) (water){04}]


1% (Rx) [Drithocreme HP (ascorbic acid) (cetostearyl alcohol) (chlorocresol) (petrolatum) (salicylic acid) (sodium lauryl sulfate) (water){05}] [Micanol (citric acid) (glyceryl monolaurate) (glyceryl monomyristate) (sodium hydroxide) (water){06}]

Canada—


0.1% (Rx) [Anthranol 0.1 (vanishing cream base){02}]


0.2% (Rx) [Anthranol 0.2 (vanishing cream base){02}]


0.4% (Rx) [Anthranol 0.4 (vanishing cream base){02}] [Anthrascalp (bisulfite) (parabens) (vanishing cream base){02}]

Packaging and storage:
Store between 8 and 15 °C (46 and 59 °F), unless otherwise specified by manufacturer. Store in a tight container. Protect from light. Protect from freezing. {08}

Auxiliary labeling:
   • For external use only {04}.


ANTHRALIN OINTMENT USP

Usual adult and adolescent dose
Psoriasis
Conventional therapy: Topical, to the dry, affected skin, once a day or as directed by physician. Wash medication off at the end of the contact time. {09} {10} {11}

Short contact therapy: See Anthralin Cream USP {01}. Strengths of 1% or higher are generally used for short contact therapy {31}.


Usual pediatric dose
See Anthralin Cream USP .

Usual geriatric dose
See Usual adult and adolescent dose .

Strength(s) usually available
U.S.—
Not commercially available.

Canada—


1% (Rx) [Anthraforte 1 (petrolatum){01}]


2% (Rx) [Anthraforte 2 (petrolatum){01}]

Packaging and storage:
Store between 8 and 15 °C (46 and 59 °F), unless otherwise specified by manufacturer. Store in a tight container. Protect from light. Protect from freezing. {08}

Auxiliary labeling:
   • For external use only {01}.



Revised: 06/30/1998



References
  1. Anthraforte ointment package insert (Medican Pharma—Canada), Rev 11/92, Rec 9/93.
  1. Anthranol cream package insert (Medican Pharma—Canada), Rev 1/92, Rec 9/93.
  1. Anthrascalp lotion package insert (Medican Pharma—Canada), Rev 3/87, Rec 9/93.
  1. Dritho-Scalp cream package insert (Dermik—US), Rev 1/97, Rec 12/98.
  1. Drithocreme and Drithocreme HP package insert (Dermik—US), Rev 1/97, Rec 12/98.
  1. Micanol cream package insert (Bioglan Pharma—US), Rev 3/96, Rec 10/97.
  1. Canada JR, editor. USP dictionary of USAN and international drug names 1998. Rockville, MD: The United States Pharmacopeial Convention, Inc.; 1997. p. 58.
  1. The United States pharmacopeia. The national formulary. USP 23rd revision (January 1, 1995). NF 18th ed (January 1, 1995). Rockville, MD: The United States Pharmacopeial Convention, Inc.; 1995. p. 118-9.
  1. Silverman A, Menter A, Hairston JL. Tars and anthralins. Dermatol Clin 1995 Oct; 13(4): 817-33.
  1. Naldi L, Carrel CF, Parazzini F, et al. Development of anthralin short-contact therapy in psoriasis: survey of published clinical trials. Int J Dermatol 1992 Feb; 31(2): 126-30.
  1. Fiore M. Practical aspects of anthralin therapy. Cutis 1990 Oct; 46(4): 351-4.
  1. Fiedler VC, Wendrow A, Szpunar GJ, et al. Treatment-resistant alopecia areata. Response to combination therapy with minoxidil plus anthralin. Arch Dermatol 1990 Jun; 126(6): 756-9.
  1. Fielder-Weiss VC, Buys CM. Evaluation of anthralin in the treatment of alopecia areata. Arch Dermatol 1987 Nov; 123(11): 1491-3.
  1. Nelson DA, Spielvogel RL. Anthralin therapy for alopecia areata. Int J Dermatol 1985 Nov; 24(9): 606-7.
  1. de Groot AC, Nater JP, Bleumink E, et al. Does DNCB therapy potentiate epicutaneous sensitization to non-related contact allergens? Clin Exp Dermatol 1981 Mar; 6(2): 139-44.
  1. Schmoeckel C, Weissmann I, Plewig G, et al. Treatment of alopecia areata by anthralin-induced dermatitis. Arch Dermatol 1979 Oct; 115(10): 1254-5.
  1. Burden AD, Stapleton M, Beck MH. Dithranol allergy: fact or fiction? Contact Dermatitis 1992 Nov; 27(5): 291-3.
  1. Richards C. Topical and systemic treatment of psoriasis: Part 2. Nurs Times 1995 Jun 21-7; 91(25): 38-9.
  1. Zvulunov A, Anisfeld A, Metzker A. Efficacy of short-contact therapy with dithranol in childhood. Int J Dermatol 1994 Nov; 33(11): 808-10.
  1. Verbov J. Psoriasis in childhood. Arch Dis Child 1992 Jan; 67(1): 75-6.
  1. Letter from American Dermal Corp, manufacturer of Dritho products, 4/2/87.
  1. Goodfield MJ, Hull SM, Cunliffe WJ. The systemic effect of dithranol treatment in psoriasis. Acta Derm Venereol 1994 Jul; 74(4): 295-7.
  1. Goransson A. Irritation and staining by dithranol (anthralin) and butantrone (10-butyryl dithranol): further short contact and tape stripping experiments. Acta Derm Venereol 1987; 67(1): 72-6.
  1. Neill S, Bugrein A, Coulson IH, et al. Toxicologic study of anthralin in an aqueous cream formulation. Cutis 1984; 34: 563.
  1. Hardman JG, Limbird LE, editors. Goodman and Gilman's the pharmacological basis of therapeutics. 9th ed. New York: McGraw Hill; 1996. p. 1608.
  1. Christensen OB, Entrom Y, Juhlin L, et al. A novel dithranol formulation in the overnight treatment of psoriasis at home. Acta Derm Venerol Suppl (Stockh) 1992; 172: 25-7.
  1. Jekler J, Swanbeck G. One-minute dithranol therapy in psoriasis: a placebo-controlled comparative study. Acta Derm Venereol 1992 Nov; 72(6): 449-50.
  1. Storbeck K, Holzle E, Schurer N, et al. Narrow-band UVB (311 nm) versus conventional broad-band UVB with and without dithranol in phototherapy for psoriasis. J Am Acad Dermatol 1993 Feb; 28(2 Pt 1): 227-31.
  1. Young LY, Koda-Kimble MA. Applied therapeutics. The clinical use of drugs. 6th ed. Vancouver, WA: Applied Therapeutics, Inc.; 1995. p. 38-2.
  1. Manufacturer comment, 3/3/98.
  1. Panel comments, 3/3/98.
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