Monograph: |
Dithranol
A yellow to yellowish-brown, odourless, crystalline powder.
Practically insoluble in water, slightly soluble in alcohol, in
ether, and in glacial acetic acid: soluble in chloroform and in
dichloromethane; soluble to sparingly soluble in acetone; dis-
solves in dilute solutions of alkali hydroxides. The filtrate
from a suspension in water is neutral to litmus. Store at a tem-
perature of 8Β° to 15Β° in airtight containers. Protect from
light.
CAUTION. Dithranol is a powerful irritant and should be kept
Away from the eyes and tender parts of the skin.
Stability. The stability of dithranol has been studied in a
number of bases and vehicles. The weaker preparations of
dithranol may be the least stable. Salicylic acid is included in
dithranol preparations as an antoxidant and its inclusion in
pastes also containing zinc oxide prevents their discoloration
due to the inactivation of dithranol by zinc oxide. However
zinc oxide or starch can be omitted from dithranol pastes
without loss of effectiveness provided stiffness is main-
tained.~ Addition of ascorbic or oxalic acid may improve di-
thranol's stability in 'Unguentum Merck' but salicylic acid
appears to be ineffective. The effect of salicylic acid on the
instability of dithranol in yellow soft paraffin is variable
and its inclusion has been questioned as it can be irritant and
percutaneous absorption can be significant. Dithranol is rel-
atively stable in white soft paraffin.
The application of any type of heat and contact with metal
spatulas should be avoided during the manufacture of dithra-
nol pastes and if milling facilities are not available dithranol
can be incorporated in lassar's paste by dissolving it first in
chloroform.
Adverse Effects and Precautions
Dithranol may cause a burning sensation especially
on perilesional skin. Patients with fair skin may be
more sensitive than those with dark skin. It is irritant
to the eyes and mucous membranes. Use on the face.
skin flexures, and genitals should be avoided. Hands
should be washed after use.
Dithranol should not be used for acute or pustular
psoriasis or on inflamed skin. It stains skin. Hair,
some fabrics, plastics, and enamel. Staining of bath-
room ware may be less of a problem with creams
than ointments. Stains on skin and hair disappear on
cessation of treatment although such disappearance
may be slow.
Uses and Administration
Dithranol is used in the treatment of subacute and
chronic psoriasis usually in one of two ways. Con-
ventional treatment is commonly started with an
ointment or paste containing 0.1% dithranol (0.05%
in very fair patients) applied for a few hours; the
strength is gradually increased as necessary to 0.5%,
occasionally to 1%. and the duration of contact ex-
tended to overnight periods or longer. The prepara-
tion is sparingly and accurately applied to the
lesions only. If, on initial treatment, lesions spread
or excessive irritation occurs, the concentration of
dithranol or the frequency of application should be
reduced; if necessary, treatment should be stopped.
After each treatment period the patient should bathe
or shower to remove any residual dithranol.
For short-contact therapy dithranol is usually ap-
plied in a soft basis to the lesions for up to 60 min-
utes daily, before being washed off. As with
conventional treatment the strength used is gradual-
ly increased from 0.1 % to 2% but strengths up to 5%
have been used. Surrounding unaffected skin may
be protected by white soft paraffin.
Treatment for psoriasis should be continued until
the skin is entirely clear. Intermittent courses may be
needed to maintain the response. Treatment sched-
ules often involve coal tar and UV irradiation (pref-
erably UVB) before the application of dithranol (see
below). Salicylic acid is included in many topical
preparations of dithranol.
A cream containing dithranol triacetate 1% has been
used similarly to dithranol in conventional treatment
of psoriasis.
Psoriasis. Dithranol used alone or with coal tar with or with-
out ultraviolet light continues to be one of the drugs of first-
line treatment for psoriasis (p. 1075). It is particularly suited
to the treatment of stable chronic plaque psoriasis but unlike
coal tar. is irritant to healthy skin and care is required to en-
sure that it is only applied to lesions. Treatment with dithranol
is therefore more feasible when the plaques are large or few
in number. Concomitant use of coal tar may help to reduce the
irritant effects of dithranol without affecting efficacy. Tradi-
tional treatment with dithranol is time consuming and more
suitable for use on hospital inpatients. Dithranol formulated
in stiff preparations such as Lassar's paste to minimise
spreading to perilesional skin is left on overnight covered
with a suitable dressing and washed off the next day. Treat-
ment is usually initiated with a concentration of 0.1% (0.05%
in fair-skinned patients) and gradually increased according to
the response and irritation produced. Cream formulations
may be less effective but are more suitable for domestic use.
Dithranol is also used with UVB phototherapy and there have
been many modifications of the original Ingram's regimen in
which dithranol is applied after bathing in a tar bath and ex-
posure to ultraviolet light. Inpatient stays of up to 3 weeks
may be required but long periods of remission can be ob-
tained. However, short-contact therapy in which concentra-
tions of up to 5% of dithranol are applied daily for up to I
hour are more suitable for use on an outpatient basis and there
appears to be little reduction in efficacy; irritation and stain-
ing may also be reduced.
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