Acitretin

U.S. BRAND NAMES — Soriatane®
PHARMACOLOGIC CATEGORY Retinoid-Like Compound
DOSING: ADULTS Psoriasis: Oral: Individualization of dosage is required to achieve maximum therapeutic response while minimizing side effects Initial therapy: Therapy should be initiated at 25-50 mg/day, given as a single dose with the main meal Maintenance: Doses of 25-50 mg/day may be given after initial response to treatment; the maintenance dose should be based on clinical efficacy and tolerability
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule: 10 mg, 25 mg
DOSAGE FORMS: CONCISE Capsule: Soriatane®: 10 mg, 25 mg
GENERIC EQUIVALENT AVAILABLE — No
USE — Treatment of severe psoriasis
ADVERSE REACTIONS SIGNIFICANT >10%: Central nervous system: Hyperesthesia (10% to 25%) Dermatologic: Cheilitis (>75%), alopecia (50% to 75%), skin peeling (50% to 75%), dry skin (25% to 50%), nail disorder (25% to 50%), pruritus (25% to 50%), erythematous rash (10% to 25%), skin atrophy (10% to 25%), sticky skin (10% to 25%), paronychia (10% to 25%) Endocrine & metabolic: Hypercholesterolemia (25% to 50%), hypertriglyceridemia (50% to 75%), HDL decreased (25% to 50%), phosphorus increased (10% to 25%), potassium increased (10% to 25%), sodium increased (10% to 25%), magnesium increased/decreased (10% to 25%), fasting blood sugar increased (25% to 50%), fasting blood sugar decreased (10% to 25%) Gastrointestinal: Xerostomia (10% to 25%) Hematologic: Reticulocytes increased (25% to 50%), hematocrit decreased (10% to 25%), hemoglobin decreased (10% to 25%), WBC increased/decreased (10% to 25%), haptoglobin increased (10% to 25%), neutrophils increased (10% to 25%) Hepatic: Liver function tests increased (25% to 50%), alkaline phosphatase increased (10% to 25%), direct bilirubin increased (10% to 25%), GGTP increased (10% to 25%) Neuromuscular & skeletal: Paresthesia (10% to 25%), arthralgia (10% to 25%), rigors (10% to 25%), CPK increased (25% to 50%), spinal hyperostosis progression (10% to 25%) Ocular: Xerophthalmia (10% to 25%), Renal: Uric acid increased (10% to 25%), acetonuria (10% to 25%), hematuria (10% to 25%), RBC in urine (10% to 25%) Respiratory: Rhinitis (25% to 50%), epistaxis (10% to 25%)
1% to 10%: Cardiovascular: Flushing, edema Central nervous system: Headache, pain, depression, insomnia, somnolence, fatigue Dermatologic: Skin odor, hair texture change, bullous eruption, dermatitis, diaphoresis increased, psoriasiform rash, purpura, pyogenic granuloma, rash, seborrhea, ulcers, fissures, sunburn Endocrine & metabolic: Hot flashes, potassium decreased, phosphorus decreased, sodium decreased, calcium increased or decreased, chloride increased or decreased Gastrointestinal: Gingival bleeding, gingivitis, saliva increased, stomatitis, thirst, ulcerative stomatitis, abdominal pain, diarrhea, nausea, taste disturbance, anorexia, appetite increased, tongue disorder Hepatic: Total bilirubin increased Neuromuscular & skeletal: Arthritis, back pain, hypertonia, myalgia, osteodynia, peripheral joint hyperostosis, Bell's palsy Ocular: Blurred vision, blepharitis, conjunctivitis, night blindness, photophobia, corneal epithelial abnormality, eye pain, eyebrow or eyelash loss, diplopia, cataract Otic: Earache, tinnitus Renal: BUN increased, creatinine increased, glycosuria, proteinuria Respiratory: Sinusitis
<1% (Limited to important or life-threatening): Anxiety, bleeding time increased, chest pain, cirrhosis, conjunctival hemorrhage, constipation, corneal ulceration, cyanosis, deafness, diplopia, dizziness, dyspepsia, dysphonia, dysuria, eczema, esophagitis, fever, furunculosis, gastritis, glossitis, gum hyperplasia, hair discoloration, healing impaired, hemorrhage, hepatic dysfunction, hepatitis, hyperkeratosis, hypertrichosis, hypoesthesia, intermittent claudication, itchy eyes, jaundice, leukorrhea, malaise, melena, MI, moniliasis, myopathy, nervousness, neuritis, pancreatitis, papilledema, peripheral ischemia, photosensitivity, pseudotumor cerebri, scleroderma, skin fragility or thinning, spinal hyperostosis (new lesion), stroke, taste loss, tendonitis, thromboembolism
CONTRAINDICATIONS — Hypersensitivity to acitretin, other retinoids, or any component of the formulation; patients who are pregnant or intend on becoming pregnant; ethanol ingestion; severe hepatic or renal dysfunction; chronically-elevated blood lipid levels; concomitant use with methotrexate or tetracycline
Acitretin is contraindicated in females of childbearing potential unless all of the following conditions apply. 1) Patient has severe psoriasis unresponsive to other therapy or if clinical condition contraindicates other treatments. 2) Patient must have two negative urine or serum pregnancy tests prior to therapy. 3) Patient must commit to using two effective forms of birth control starting 1 month prior to acitretin treatment and for 3 years after discontinuation. 4) Patient is reliable in understanding and carrying out instructions. 5) Patient has received, and acknowledged, understanding of a careful oral and printed explanation of the hazards of fetal exposure to acitretin and the risk of possible contraception failure; this explanation may include showing a line drawing to the patient of an infant with the characteristic external deformities resulting from retinoid exposure during pregnancy. Patient must sign an agreement/informed consent document stating that she understands these risks and that she should not consume ethanol during therapy or for 2 months after discontinuation. 6) All patients (male and female) should not donate blood during and for 3 years following treatment with acitretin.
WARNINGS / PRECAUTIONS Box warnings: Blood donation: See "Other warnings/precautions" below. Ethanol use: See "Concurrent drug therapy issues" below. Medication guide: See "Other warnings/precautions" below. Pregnancy: See "Special populations" below.
Concerns related to adverse effects: Hepatotoxicity: Monitor for hepatotoxicity; discontinue if elevations of liver enzymes occur. Use with caution in patients at risk of hypertriglyceridemias. Pseudotumor cerebri: Rarely associated with pseudotumor cerebri. Visual disturbances: May cause a decrease in night vision or decreased tolerance to contact lenses; discontinue if visual changes occur.
Concurrent drug therapy issues: Ethanol use: [U.S. Boxed Warning]: All patients (male and female) should abstain from ethanol or ethanol-containing products during therapy and for 2 months after discontinuation.
Special populations: Pediatrics: Safety and efficacy have not been established in children; growth potential may be affected. Pregnancy: [U.S. Boxed Warning]: Not for use by women who want to become pregnant; patient should not get pregnant for at least 3 years after discontinuation.
Other warnings/precautions: Blood donation: [U.S. Boxed Warning]: All patients should be advised not to donate blood during therapy or for 3 years following completion of therapy. Medication guide: [U.S. Boxed Warning]: 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.
RESTRICTIONS — An FDA-approved medication guide must be distributed when dispensing an outpatient prescription (new or refill) where this medication is to be used without direct supervision of a healthcare provider. Medication guides are available at http://www.fda.gov/cder/Offices/ODS/medication_guides.htm.
DRUG INTERACTIONS Ethanol: Etretinate (a retinoid with a much longer half-life) can be formed with concurrent use; contraindicated.
Methotrexate: The concomitant administration of methotrexate and etretinate has been associated with hepatitis, a similar increased hepatitis risk may be expected with the combined use of acitretin and methotrexate; concomitant use is contraindicated.
Progestins: Decreased contraceptive effect with concurrent use; use of "mini-pill" preparations are not recommended. Interactions with other progestational agents or hormonal contraceptives have not been established.
Sulfonylureas: Glucose-lowering effect may be potentiated. Effect seen with glibenclamide.
Tetracycline: Acitretin and tetracyclines may both cause increased intracranial pressure; concomitant use is contraindicated.
Vitamin A: Concomitant administration of vitamin A and other systemic retinoids must be avoided due to the risk of possible additive toxic effects.
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Use leads to formation of etretinate, a teratogenic metabolite with a prolonged half-life; concomitant use of ethanol or ethanol-containing products is contraindicated.
PREGNANCY RISK FACTOR — X (show table)
PREGNANCY IMPLICATIONS — Acitretin is teratogenic in humans. Severe birth defects have been reported when conception occurred during treatment or after therapy was complete. Not for use by women who want to become pregnant; patient should not get pregnant for at least 3 years after discontinuation. 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. Limited amounts of acitretin are found in seminal fluid; although it appears this poses little risk to a fetus, the actual risk of teratogenicity is not known. Any pregnancy which occurs during treatment, or within 3 years after treatment is discontinued, should be reported to the manufacturer at 1-888-500-3376 or to the FDA at 1-800-FDA-1088.
LACTATION — Enters breast milk/not recommended
BREAST-FEEDING CONSIDERATIONS — Acitretin should not be given prior to or during nursing due to the potential for adverse effects in the nursing infant.
DIETARY CONSIDERATIONS — Administer with food. Avoid ingestion of additional sources of exogenous vitamin A (in excess of RDA); use of ethanol and ethanol-containing products is contraindicated.
PRICING — (data from drugstore.com)Capsules (Soriatane) 10 mg (30): $451.54 25 mg (30): $573.49
MONITORING PARAMETERS — Lipid profile (baseline and at 1- to 2-week intervals for 4-8 weeks); liver function tests (baseline, and at 1- to 2-week intervals until stable, then as clinically indicated); blood glucose in patients with diabetes; bone abnormalities (with long-term use)
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms of acute hypervitaminosis A (headache, vertigo) would be expected; vomiting has also been reported. Pregnancy test for women of childbearing age; counseling regarding potential for birth defects and appropriate contraceptive use.
CANADIAN BRAND NAMES — Soriatane®
INTERNATIONAL BRAND NAMES — Neo-Tigason (TH); Neotigason (AN, AR, AT, AU, BB, BE, BF, BG, BJ, BM, BR, BS, BZ, CH, CI, CL, CN, CO, CZ, DE, DK, EC, EE, EG, ES, ET, FI, GB, GH, GM, GN, GY, HU, IE, IL, IT, JM, KE, KR, LR, MA, ML, MR, MU, MW, MX, NE, NG, NL, NO, NZ, PE, PH, PL, PT, PY, SC, SD, SE, SL, SN, SR, TT, TW, TZ, UG, UY, VE, ZA, ZM, ZW); Soriatane (CA, FR)
PHARMACODYNAMICS / KINETICS — Etretinate has been detected in serum for up to 3 years following therapy, possibly due to storage in adipose tissue.
Onset: May take 2-3 months for full effect; improvement may be seen within 8 weeks.
Absorption: Oral: ~72% absorbed when given with food
Protein binding: >99% bound, primarily to albumin
Metabolism: Metabolized to cis-acitretin; both compounds are further metabolized. Concomitant ethanol use leads to the formation of etretinate (active).
Half-life elimination: Acitretin: 49 hours (range: 33-96); cis-acitretin: 63 hours (range: 28-157); etretinate: 120 days (range: 84-168 days)
Excretion: Feces (34% to 54%); urine (16% to 53%)
PATIENT INFORMATION — Take with food. Do not drink alcohol during therapy and for 2 months after discontinuation. Use contraception for 1 month before, during, and for 3 years after discontinuation. You may not be able to tolerate contact lenses during treatment. Do not donate blood during treatment and for 3 years after discontinuation (male and female patients). Avoid exposure to sunlight. Wear protective clothing and sunscreens. Avoid use of other vitamin A products. Females: Use two effective forms of birth control. If you have had your tubes tied, then use an additional form of birth control. If you become pregnant, contact your prescriber immediately.
(For additional information see "Acitretin: Patient drug information")