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standards of non-Merck sources.
ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section and/or refer to product labeling for additional detail.
Medication Safety Issues
Sound-alike/look-alike issues:
Soriatane® may be confused with Loxitane®
Pronunciation
(a si TRE tin)
U.S. Brand Names
Generic Available
No
Canadian Brand Names
Pharmacologic Category
Use: Labeled Indications
Treatment of severe psoriasis
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.
Pregnancy Risk Factor
X
Pregnancy Considerations
Acitretin is teratogenic in humans. Severe birth defects have been reported when conception occurred during treatment or after therapy was complete. [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. 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.
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 tetracyclines
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 have pregnancy test repeated monthly during therapy. After discontinuation of therapy, a pregnancy test must be repeated every 3 months for at least 3 years.
4) Patient must commit to using two effective forms of birth control starting 1 month prior to acitretin treatment and for 3 years after discontinuation. Prescriber must counsel patient about contraception every month during therapy and every 3 months following discontinuation for at least 3 years.
5) Patient is reliable in understanding and carrying out instructions.
6) 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.
7) All patients (male and female) should not donate blood during and for 3 years following treatment with acitretin.
Warnings/Precautions
Boxed warnings:
• Blood donation: See “Other warnings/precautions” below.
• Ethanol use: See “Concurrent drug therapy issues” below.
• Hepatotoxicity: See “Concerns related to adverse effects” below.
• Medication guide: See “Other warnings/precautions” below.
• Pregnancy/Do Your P.A.R.T. program: See “Special populations” below.
Concerns related to adverse effects:
• Depression: Depression, including thoughts of self-harm have been reported; use with caution in patients with a history of mental illness.
• Hepatotoxicity: [U.S. Boxed Warning]: Changes in transaminases occur in up to 1/3 of patients. Monitor for hepatotoxicity; discontinue if significant elevations of liver enzymes occur. Use with caution in patients at risk of hypertriglyceridemias.
• Hyperostosis: Patients receiving long-term treatment should be periodically examined for bony abnormalities; if occur risk vs. benefit of therapy should be considered.
• Lipid effects: Lipid changes including, increased triglycerides, increased cholesterol, and decreased HDL are common (up to 66%); increased triglycerides may lead to pancreatitis.
• Photosensitivity: May be photosensitizing; minimize sun or other UV exposure to treated areas.
• 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.
• Tetracyclines: Pseudotumor cerebri (benign intracranial hypertension) has been reported with use of tetracyclines and acitretin independently; concomitant use is contraindicated.
Special populations:
• Pediatrics: Safety and efficacy have not been established in children; growth potential may be affected.
• Pregnancy/Do Your P.A.R.T. program: [U.S. Boxed Warning]: Not for use by women who are pregnant or want to become pregnant; patient should not get pregnant for at least 3 years after discontinuation. 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.
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.
Adverse Reactions
>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%: Abnormal gait, acne, anal disorder, anxiety, bleeding time increased, bone disorder, bursitis, chalazion, chest pain, cirrhosis, conjunctival hemorrhage, constipation, corneal ulceration, cough, cyanosis, deafness, diplopia, dizziness, dyspepsia, dysphonia, dysuria, ectropion, eczema, esophagitis, ethanol intolerance, fever, flu-like syndrome, fungal infection, furunculosis, gastritis, gastroenteritis, glossitis, gum hyperplasia, hair discoloration, healing impaired, hemorrhage, hemorrhoids, hepatic dysfunction, hepatitis, hyperkeratosis, hypertrichosis, hypoesthesia, intermittent claudication, itchy eyes, jaundice, lacrimation abnormal, leukorrhea, libido decreased, malaise, melena, migraine, moniliasis, muscle weakness, nervousness, neuritis, olecranon bursitis, papilledema, peripheral ischemia, pharyngitis, photosensitivity, pseudotumor cerebri, recurrent sties, scleroderma, skin hypertrophy, spinal hyperostosis (new lesion), taste loss, tendonitis, tenesmus, tongue ulceration, urticaria, vaginitis, weight gain
Postmarketing and/or case reports: Aggression, MI, myopathy with peripheral neuropathy, nail fragility, pancreatitis, skin fragility or thinning, stroke, suicidal thoughts, thromboembolism, vulvovaginitis
Drug Interactions
Alcohol (Ethyl): May enhance the teratogenic effect of Acitretin. Risk X: Avoid combination
Contraceptive (Progestins): Acitretin may diminish the therapeutic effect of Contraceptive (Progestins). Contraceptive failure is possible. Risk X: Avoid combination
Methotrexate: Acitretin may enhance the hepatotoxic effect of Methotrexate. Risk X: Avoid combination
Oral Contraceptive (Estrogens): Retinoic Acid Derivatives may diminish the therapeutic effect of Oral Contraceptive (Estrogens). Two forms of contraception are recommended in females of child-bearing potential during retinoic acid derivative therapy. Risk C: Monitor therapy
Oral Contraceptive (Progestins): Retinoic Acid Derivatives may diminish the therapeutic effect of Oral Contraceptive (Progestins). Two forms of contraception are recommended in females of child-bearing potential during retinoic acid derivative therapy. Risk C: Monitor therapy
Tetracycline Derivatives: May enhance the adverse/toxic effect of Retinoic Acid Derivatives. The development of pseudotumor cerebri is of particular concern. Risk X: Avoid combination
Vitamin A: May enhance the adverse/toxic effect of Retinoid-like Compounds. Risk D: Consider therapy modification
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.
Storage
Store between 15°C to 25°C (59°F to 77°F). Avoid high temperatures and humidity. Protect from light.
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%)
Dosage
Oral: Adults: 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
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)
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.
Additional Information
Female patients are required to use two forms of birth control, at least one of which is a primary form, unless they have undergone a hysterectomy or are postmenopausal. Both forms of birth control must be used simultaneously for at least 1 month prior to therapy and for at least 3 years after discontinuation. Primary forms of birth control include tubal ligation, partner's vasectomy, IUD, or hormonal birth control products. Microdosed progestin products, referred to as “mini-pills,” have been shown to be less effective when used with acitretin, and are not recommended. Secondary forms of contraception include diaphragms, latex condoms and cervical caps, all if used with a spermicide.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
None reported
Mental Health: Effects on Psychiatric Treatment
None reported
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule:
Soriatane®: 10 mg [DSC], 25 mg [DSC]
Soriatane® CK Convenience Kit™: 10 mg, 25 mg [packaged with VersaFoam-EF™]
Pricing: U.S. (www.drugstore.com)
Capsules (Soriatane)
25 mg (30): $607.90
International Brand Names
Lexi-Comp.com
Last full review/revision August 2008
Content last modified August 2008
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