Acitretin

Capillary leak syndrome, a potential manifestation of retinoic acid syndrome (differentiation syndrome) has been reported with acitretin use. Capillary leak syndrome features may include localized or generalized edema with secondary weight gain, fever, and hypotension; rhabdomyolysis and myalgias have also been reported. Laboratory tests may show neutrophilia, hypoalbuminemia, and an elevated hematocrit. Discontinue use if capillary leak syndrome develops during therapy.

Depression, including aggressive behavior and thoughts of self-harm have been reported; use with caution in patients with a history of mental illness.

Exfoliative dermatitis has been reported with acitretin use; discontinue use if exfoliative dermatitis occurs during therapy.

[US Boxed Warnings]: Hepatitis has been reported (including fatalities); some patients received etretinate for ≤1 month before presenting with hepatic signs or symptoms. Changes in transaminases have occurred in up to 1/3 of patients, which generally returned to normal after discontinuation of treatment. Monitor for hepatotoxicity; discontinue if hepatotoxicity is suspected.

Lipid changes, including increased triglycerides, increased cholesterol, and decreased HDL, are common (up to 66%), which were reversible upon discontinuation of treatment; increased triglycerides may lead to pancreatitis. Fatal fulminant pancreatitis has been reported. Use with caution in patients at risk of hypertriglyceridemia (eg, patients with lipid metabolism disturbances, diabetes mellitus, obesity, increased alcohol intake, or a familial history of these conditions). Consider discontinuation if hypertriglyceridemia and decreased HDL persist. Use is contraindicated in patients with chronic abnormally elevated blood lipid values.

Tinnitus and impaired hearing have been reported with use; consider therapy discontinuation and further evaluation if clinically indicated.

May be photosensitizing; minimize sun or other UV exposure to treated areas. The risk of burning is increased with phototherapy; decreased doses are required.

Retinoids, including acitretin, have been associated with pseudotumor cerebri (benign intracranial hypertension). Concurrent use of other drugs associated with this effect (eg, tetracyclines) may increase risk. Early signs and symptoms include papilledema, headache, nausea, vomiting, and visual disturbances. Discontinue use in patients experiencing papilledema.

Patients receiving long-term treatment should be periodically examined for bony abnormalities; risk vs benefit of therapy should be considered if abnormalities occur.

May cause adverse effects to the eyes and vision, including a decrease in night vision or decreased tolerance to contact lenses. Use caution when operating vehicles at night; discontinue if visual changes occur. Disease-related concerns:

Impaired glucose control has been reported with retinoid use. Use with caution in patients with diabetes mellitus; new cases of diabetes have been diagnosed. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Female patients should abstain from ethanol or ethanol-containing products during therapy and for 2 months after discontinuation. Special populations:

Females of childbearing potential must be able to fulfill all conditions for use prior to initiating therapy, including a Patient Agreement/Informed Consent (consult manufacturer's labeling for further detail). Prescriptions should be written for a monthly supply. The Do Your P.A.R.T. (Pregnancy Prevention Actively Required During and After Treatment) program explains teratogenic risks and requirements expected of females of childbearing potential to prevent pregnancies from occurring during use and 3 years following discontinuation; this should be used to educate patients and healthcare providers. Information for the Do Your P.A.R.T. program is available at www.soriatane.com/doyour-part-Program.html or by calling 1-888-784-3335.

Growth potential may be affected. Long-term use of high-dose oral retinoids within this population has been associated with decreased bone mineral density, skeletal hyperostosis, and ossification of interosseous tendons and ligaments of the extremities (Menter, 2009).

Acitretin is a known teratogen and contraindicated in females who are or may become pregnant. Birth defects (including facial, ear, central nervous system, cardiovascular, limb, bone, and joint) have been noted following acitretin exposure during pregnancy. Use only in women with severe psoriasis that is unresponsive to other therapies or with contraindications to the use of alternative treatments. Pregnancy must be avoided for at least 3 years after treatment discontinuation. Two reliable forms of contraception must be used simultaneously for 1 month prior to initiating therapy, during therapy, and for 3 years after discontinuation. Two negative pregnancy tests (sensitivity at least 25 milliunits/mL) are required prior to initiating therapy; pregnancy tests must be repeated every month during treatment. In addition, because ethanol forms a teratogenic metabolite and would increase the duration of teratogenic potential, ethanol should not be consumed during treatment or for 2 months after discontinuation. Any pregnancy which occurs during treatment, or within 3 years after treatment is discontinued, should be reported to the manufacturer at 1-888-784-3335 or to the FDA at 1-800-FDA-1088. Other warnings/precautions:

All patients should be advised not to donate blood during therapy or for 3 years following completion of therapy.

Only physicians experienced with the diagnosis and treatment of severe psoriasis, including the use of retinoid treatment, and physicians who understand the risk of teratogenicity should prescribe acitretin.

All patients must be provided with a medication guide each time acitretin is dispensed. Female patients must also sign an informed consent prior to therapy.

Most patients experience relapse of psoriasis after discontinuing therapy. Subsequent courses, when clinically indicated, have produced results similar to the initial course of therapy.

Transient worsening of psoriasis may initially occur; patients should be advised that it may take 2-3 months to achieve the full benefits of treatment.