Acitretin

Trade Names:Soriatane- Capsules 10 mg- Capsules 25 mg

Pharmacology

Unknown.

Pharmacokinetics

Absorption

Absorption is linear and proportional with increasing doses; approximately 72% is absorbed following a 50 mg dose. C _max (mean 416 ng/mL) is achieved in 2 to 5 h.

Distribution

Plasma protein binding is 99.9%, primarily to albumin.

Metabolism

Undergoes extensive metabolism to cis-acitretin.

Elimination

Excreted in the feces (34% to 54%) and urine (16% to 53%). Terminal t _½ of acitretin is 49 h; t _½ of cis-acitretin is 63 h.

Special Populations

Higher plasma concentrations are seen; however, no changes occur in the t _½ .

Plasma concentrations are lower in end-stage renal failure. Acitretin is not removed by dialysis.

Indications and Usage

Treatment of severe psoriasis.

Contraindications

Pregnancy; severe liver or kidney function impairment; chronic abnormal elevation in blood lipid values; concurrent use of methotrexate or tetracyclines; hypersensitivity to other retinoids or any component of the product.

Dosage and Administration

PO Start with 25 to 50 mg/day given as a single dose with the main meal. Maintenance doses of 25 to 50 mg/day may be given dependent upon the patient's response to initial treatment.

PO Relapses may be treated as outlined for initial treatment.

PO When used with phototherapy, the phototherapy dose should be decreased by the prescriber based upon the patient's individual response.

Storage/Stability

Store capsules at controlled room temperature (59° to 77°F). Protect from light. Avoid exposure to high temperatures and humidity after bottle is opened.

Drug Interactions

Concurrent use of alcohol and acitretin may lead to the formation of etretinate, which increases the duration of teratogenic potential in women.

The glucose-lowering effect of glyburide may be potentiated.

Because the risk of hepatitis may be increased, concurrent use is contraindicated.

Protein binding of phenytoin may be reduced.

Acitretin may interfere with the contraceptive effect.

Because acitretin and tetracyclines can cause increased intracranial pressure, concurrent use is contraindicated.

Because the risk of hypervitaminosis A is increased, concurrent use is contraindicated.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Acute MI, thromboembolism, stroke (postmarketing).

CNS

Rigors (10% to 25%); headache, pain, depression, insomnia, somnolence (1% to 10%); myopathy with peripheral neuropathy, aggressive feelings and/or suicidal thoughts (postmarketing).

Dermatologic

Alopecia, skin peeling (60% to 75%); dry skin, nail disorder, pruritus (25% to 50%); erythematous rash, hyperesthesia, paresthesia, paronychia, skin atrophy, sticky skin (10% to 25%); abnormal skin odor, abnormal hair texture, bullous eruption, cold/clammy skin, dermatitis, increased sweating, psoriasiform rash, purpura, pyogenic granuloma, rash, seborrhea, skin fissures, skin ulceration, sunburn, infection (1% to 10%); skin thinning, skin fragility and scaling (postmarketing).

EENT

Rhinitis (25% to 50%); dry eyes (23%); xerophthalmia, epistaxis (10% to 25%); eye irritation (9%); brow and lash loss (5%); Bell palsy, blepharitis, crusting of eye lids, blurred vision, conjunctivitis, corneal epithelial abnormality, cortical cataract, decreased night vision/night blindness, diplopia, itchy eyes or eyelids, nuclear cataract, pannus, papilledema, photophobia, posterior subcapsular cataract, recurrent sties, subepithelial corneal lesions (less than 5%); eye pain, sinusitis, earache, taste perversion, tinnitus (1% to 10%).

Electrolytes

Increased phosphorus, potassium, sodium, magnesium, decreased magnesium (10% to 25%); increased calcium, chloride, decreased calcium, chloride, phosphorus, potassium, sodium (1% to 10%).

GI

Cheilitis (greater than 75%); dry mouth (10% to 25%); abdominal pain, diarrhea, nausea, tongue disorder, stomatitis, ulcerative stomatitis (1% to 10%).

Genitourinary

White blood cells in urine (25% to 50%); acetonuria, hematuria, red blood cells in urine (10% to 25%); glycosuria, proteinuria (1% to 10%); vulvo-vaginitis from Candida albicans (postmarketing).

Hematologic

Increased reticulocytes (25% to 50%); decreased hematocrit, hemoglobin, WBC (10% to 25%); increased haptoglobin, neutrophils, WBC (10% to 25%); increased bands, basophils, eosinophils, hematocrit, hemoglobin, lymphocytes, monocytes, platelets, red blood cells, decreased haptoglobin, lymphocytes, neutrophils, reticulocytes, platelets, RBC (1% to 10%).

Hepatic

Increased cholesterol, LDH, AST, ALT, decreased HDL (25% to 50%); increased alkaline phosphatase, direct bilirubin, gamma-glutamyl transpeptidase (10% to 25%); increased globulin, total bilirubin, total protein, serum albumin, decreased serum albumin (1% to 10%).

Musculoskeletal

Arthralgia, spinal hyperostosis (10% to 25%); arthritis, arthrosis, back pain, hypertonia, myalgia, osteodynia, peripheral joint hyperostosis (1% to 10%).

Renal

Increased uric acid (10% to 25%); increased BUN, creatinine (1% to 10%).

Miscellaneous

Increased triglycerides (50% to 75%); increased CPK, fasting blood glucose (25% to 50%); decreased fasting blood sugar, high occult blood (10% to 25%); anorexia, edema, fatigue, hot flashes, increased appetite, gingival bleeding, gingivitis, increased salivation, thirst, infection, decreased and increased iron, flushing (1% to 10%).

Precautions

Pregnancy

Category X .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established.

Photosensitivity

May occur; avoid excessive use of sunlamps, exposure to sunlight, and ultraviolet light.

Blood donation

Patients should not donate blood during and for at least 3 yr following completion of acitretin therapy.

Hyperostosis

Examine patient for possible ossification abnormalities.

Lipid effects and CV risk

Elevation in triglycerides and cholesterol may occur; decreased HDL may occur. CV risk status may be increased.

Pancreatitis

Pancreatitis (including fatal fulminant pancreatitis) with or without elevated triglyceride levels may occur.

Pseudotumor cerebri

May occur.

Psychiatric disorder

Depression and other psychiatric symptoms such as aggressive feeling or thought of self-harm may occur.

Vision

Night vision and tolerance to contact lenses may be decreased.

Overdosage

Symptoms

Identical to acute hypervitaminosis A (headache, vertigo).

Patient Information

• Advise patient to review the Medication Guide before starting therapy and with each refill.
• Advise patient that dose may be adjusted based on tolerance and effectiveness.
• Instruct patient to take prescribed dose every day with main meal. Advise patient that food increases absorption and beneficial effects.
• Advise patient that if a dose is missed to skip the missed dose and resume the normal schedule. Caution patient not to double the dose to try to catch up.
• Advise patient that psoriasis may worsen during the initial treatment period but that gradual improvement should follow and max benefit may not be noted for 2 to 3 mo. Advise patient to notify health care provider if symptoms do not improve as expected or continue to worsen.
• Caution women of childbearing potential not to consume alcohol or products containing alcohol during and for 2 mo following cessation of therapy.
• Instruct sexually active women who are not clearly menopausal or have undergone a hysterectomy to use 2 reliable forms of contraception beginning 1 mo before starting therapy, during therapy, and for 3 yr following cessation of therapy. Caution patient that micro-dosed progestin “minipills” are not recommended during therapy with acitretin.
• Advise women of childbearing potential to notify health care provider immediately if pregnant, miss a period, or have sex without using 2 effective forms of birth control either while taking acitretin or for 3 yr following cessation of therapy.
• Caution both men and women not to donate blood during and for at least 3 yr following cessation of therapy because women of childbearing potential must not receive blood from patients being treated with acitretin.
• Advise patient, family, or caregiver to inform health care provider of the following: persistent severe headache; persistent nausea and/or vomiting; yellowing of the skin or eyes; dark urine; persistent appetite loss; frequent urination; great thirst or unexplained hunger; sudden vision changes; severe skin or mucus membrane dryness; depression or other mental symptoms; shortness of breath; dizziness; chest pain; sudden weakness; trouble speaking; swelling of a leg.
• Advise patient that medication can cause chapped lips, peeling of the fingertips, palms, and soles, itching or scaly skin, runny or dry nose, or nosebleeds and to inform health care provider if any of these occur and are bothersome. Advise patient that health care provider or pharmacist can recommend a lotion or cream to help treat drying or chapping.
• Advise patient that drug may cause decreased night vision and to avoid driving at night if any sudden vision problems occur.
• Advise diabetic patient to monitor blood sugars more frequently when medication is started or after a dose adjustment and to inform health care provider if significant changes in blood sugar are noted.
• Caution patient that medication can increase sensitivity to UV light and to avoid use of sun lamps and unnecessary exposure to sunlight while undergoing treatment.
• Advise patient wearing contact lenses that decreased tolerance to lenses may be experienced during treatment and after therapy has been stopped.
• Caution patient against taking vitamin A supplements in excess of recommended daily allowances.

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