Acitretin
Indications
Acitretin is indicated in severe extensive
psoriasis which is resistant to other forms of therapy, palmo-plantar
pustular psoriasis, severe congenital ichthyosis, severe Darier’s
disease (keratosis follicularis).
Pharmacology
Acitretin is a retinoid, an aromatic
analogue of vitamin A. The mechanism of action of acitretin is unknown,
however, evidence exists for a wide range of actions at various cellular
and subcellular levels. These include regulation of RNA/DNA synthesis,
modulation of factors which influence epidermal proliferation,
modification of glycoprotein synthesis and modulation of the immune
response. Whatever the exact mechanism of action, the most prominent
effect of acitretin is a modulation of cellular differentiation in the
epidermis which re-establishes a more normal pattern of cell growth.
Dosage & Administration
Adult and elderly: Initial
daily dose should be 25 mg or 30 mg for 2 to 4 weeks. After this
initial treatment period the involved areas of the skin should show a
marked response and/or side-effects should be apparent. In general, a
daily dosage of 25-50 mg taken for a further 6 to 8 weeks to achieve
optimal therapeutic results. However, it may be necessary in some cases
to increase the dose up to a maximum of 75 mg/day.
In patients with Darier’s disease a starting dose of 10 mg may be appropriate. The dose should be increased cautiously as isomorphic reactions may occur. Patients with severe congenital ichthyosis and severe Darier’s disease may require therapy beyond 3 months. The lowest effective dosage, not exceeding 50mg/day, should be given. Continuous use beyond 6 months is contra-indicated as only limited clinical data are available on patients treated beyond this length of time.
Children: The daily dosage is about 0.5mg/kg. Higher doses (up to 1mg/kg daily) may be necessary in some cases for limited periods, but only up to a maximum of 35 mg/day.
In patients with Darier’s disease a starting dose of 10 mg may be appropriate. The dose should be increased cautiously as isomorphic reactions may occur. Patients with severe congenital ichthyosis and severe Darier’s disease may require therapy beyond 3 months. The lowest effective dosage, not exceeding 50mg/day, should be given. Continuous use beyond 6 months is contra-indicated as only limited clinical data are available on patients treated beyond this length of time.
Children: The daily dosage is about 0.5mg/kg. Higher doses (up to 1mg/kg daily) may be necessary in some cases for limited periods, but only up to a maximum of 35 mg/day.
Interaction
Existing data suggests that concurrent
intake of acitretin with ethanol led to the formation of etretinate.
Concomitant administration of methotrexate, tetracyclines or vitamin A
and other retinoids with acitretin is contraindicated. In concurrent
treatment with phenytoin, it must be remembered that Acitretin partially
reduces the protein binding of phenytoin. Low dose progesterone-only
products (minipills) may be an inadequate method of contraception during
acitretin therapy, Investigations into the effect of acitretin on the
protein binding of anticoagulants of the coumarin type (warfarin)
revealed no interaction.
Contraindications
Acitretin is highly teratogenic and must
not be used by women who are pregnant. The same applies to women of
childbearing potential unless strict contraception is practiced 4 weeks
before, during and for 2 years after treatment. The use of Acitretin is
contra-indicated in women who are breast feeding.Acitretin is
contraindicated in patients with severe hepatic or renal impairment and
in patients with chronic abnormally elevated blood lipid values.
Concomitant administration of Acitretin with other retinoids or Vitamin A
is contra-indicated due to the risk of hypervitaminosis A. Acitretin is
contra-indicated in cases of hypersensitivity to the preparation
(acitretin or excipients) or to other retinoids. Patients with rare
glucose-galactosemalabsorption should not take this medicine.
Side Effects
Adverse effects are seen in most patients
receiving acitretin. Most of the clinical side-effects of Acitretin are
dose-related and are usually well-tolerated at the recommended dosages.
However, the toxic dose of Acitretin is close to the therapeutic dose
and most patients experience some side-effects during theinitial period
whilst dosage is being adjusted. The skin and mucous membranes are most
commonly affected. An initial worsening of psoriasis symptoms
issometimes seen at the beginning of the treatment period.
Pregnancy & Lactation
Acitretin is contraindicated in pregnant
women or nursing mother. It is highly teratogenic. Its use is
contraindicated in women who might become pregnant during or within 2
years of the cessation of treatment.
Precautions & Warnings
The risk of giving birth to a deformed
child is exceptionally high if Acitretin is taken before or during
pregnancy, no matter for how long or at what dosage. Women of
childbearing potential must not receive blood from patients being
treated with acitretin. Donation of blood by a patient being treated
with acitretin is prohibited during and for two years after completion
of treatment with acitretin. The effects of UV light are enhanced by
retinoid therapy; therefore patients should avoid excessive exposure to
sunlight. Hepatic function should be checked before starting treatment
with Acitretin, every 1-2 weeks for the first 2 months after
commencement and then every 3 months during treatment. Serum cholesterol
and serum triglycerides (fasting values) must be monitored before
starting treatment, one month after the commencement and then every 3
months during treatment, especially in high-risk patients and during
long-term treatment. Retinoids can alter glucose tolerance, blood sugar
levels should therefore be checked. Patients should be warned of the
possibility of alopecia. Decreased night vision has been reported with
acitretin therapy. Patients with severe headache, nausea, vomiting, and
visual disturbances should discontinue acitretin immediately.
Overdose Effects
Manifestations of acute Vitamin A toxicity
include severe headache, vertigo, nausea or vomiting, drowsiness,
irritability and pruritus. Signs and symptoms of accidental or
deliberate overdosage with Acitretin would probably be similar. Specific
treatment is unnecessary because of the low acute toxicity of the
preparation.
Therapeutic Class
Oral Retinoid preparations
Storage Conditions
Store in a cool & dry place, protected from light. Do not store above 25°C.
Showing 1 to 4 of 4 (1 Pages)