boxed CONTRAINDICATIONS AND WARNINGS
CONTRAINDICATIONS AND WARNINGS: SORIATANE Capsules must not be used by females who are pregnant, or who intend to become pregnant during therapy or at any time for at least 3 years following discontinuation of therapy. SORIATANE Capsules also must not be used by females who may not use reliable contraception while undergoing treatment and for at least 3 years following discontinuation of treatment. Acitretin is a metabolite of etretinate (Tegison®), and major human fetal abnormalities have been reported with the administration of acitretin and etretinate. Potentially, any fetus exposed can be affected.
Clinical evidence has shown that concurrent ingestion of acitretin and ethanol has been associated with the formation of etretinate, which has a significantly longer elimination half-life than acitretin. Because the longer elimination half-life of etretinate would increase the duration of teratogenic potential for female patients, ethanol must not be ingested by female patients either during treatment with SORIATANE Capsules or for 2 months after cessation of therapy. This allows for elimination of acitretin, thus removing the substrate for transesterification to etretinate. The mechanism of the metabolic process for conversion of acitretin to etretinate has not been fully defined. It is not known whether substances other than ethanol are associated with transesterification.
Acitretin has been shown to be embryotoxic and/or teratogenic in rabbits, mice, and rats at oral doses of 0.6, 3 and 15 mg/kg, respectively. These doses are approximately 0.2, 0.3 and 3 times the maximum recommended therapeutic dose, respectively, based on a mg/m2 comparison.
Major human fetal abnormalities associated with acitretin and/or etretinate administration have been reported including meningomyelocele, meningoencephalocele, multiple synostoses, facial dysmorphia, syndactyly, absence of terminal phalanges, malformations of hip, ankle and forearm, low-set ears, high palate, decreased cranial volume, cardiovascular malformation and alterations of the skull and cervical vertebrae.
SORIATANE Capsules should be prescribed only by those who have special competence in the diagnosis and treatment of severe psoriasis, are experienced in the use of systemic retinoids, and understand the risk of teratogenicity.
Because of the teratogenicity of SORIATANE Capsules, a program called the Do Your P.A.R.T program, P regnancy Prevention A ctively R equired During and After T reatment, has been developed to educate women of childbearing potential and their healthcare providers about the serious risks associated with acitretin and to help prevent pregnancies from occurring with the use of this drug and for 3 years after its discontinuation. The Do Your P.A.R.T. program requirements are described below (see also PRECAUTIONS section).
Important Information for Women of Childbearing Potential:
SORIATANE Capsules should be considered only for women with severe psoriasis unresponsive to other therapies or whose clinical condition contraindicates the use of other treatments.
Females of reproductive potential must not be given a prescription for SORIATANE Capsules until pregnancy is excluded. SORIATANE Capsules are contraindicated in females of reproductive potential unless the patient meets ALL of the following conditions:
• Must have had 2 negative urine or serum pregnancy tests with a sensitivity of at least 25 mIU/mL before receiving the initial SORIATANE Capsules prescription. The first test (a screening test) is obtained by the prescriber when the decision is made to pursue SORIATANE Capsules therapy. The second pregnancy test (a confirmation test) should be done during the first 5 days of the menstrual period immediately preceding the beginning of SORIATANE Capsules therapy. For patients with amenorrhea, the second test should be done at least 11 days after the last act of unprotected sexual intercourse (without using 2 effective forms of contraception [birth control] simultaneously).
• Must have a pregnancy test repeated every month during SORIATANE Capsules treatment. The patient must have a negative result from a urine or serum pregnancy test before receiving a SORIATANE Capsules prescription. To encourage compliance with this recommendation, a limited supply of the drug should be prescribed. For at least 3 years after discontinuing SORIATANE Capsules therapy, a pregnancy test must be repeated every 3 months.
• Must have selected and have committed to use 2 effective forms of contraception (birth control) simultaneously, at least 1 of which must be a primary form, unless absolute abstinence is the chosen method, or the patient has undergone a hysterectomy or is clearly postmenopausal.
• Patients must use 2 effective forms of contraception (birth control) simultaneously for at least 1 month prior to initiation of SORIATANE Capsules therapy, during SORIATANE Capsules therapy, and for at least 3 years after discontinuing SORIATANE Capsules therapy. A SORIATANE Capsules Patient Referral Form is available so that patients can receive an initial free contraceptive counseling session and pregnancy testing. Counseling about contraception and behaviors associated with an increased risk of pregnancy must be repeated on a monthly basis by the prescriber during SORIATANE Capsules therapy and every 3 months for at least 3 years following discontinuation of SORIATANE Capsules therapy.
Effective forms of contraception include both primary and secondary forms of contraception. Primary forms of contraception include: tubal ligation, partner’s vasectomy, intrauterine devices, birth control pills, and injectable/implantable/insertable/topical hormonal birth control products. Secondary forms of contraception include latex condoms (with or without spermicide), diaphragms and cervical caps (which must be used with a spermicide).
Any birth control method can fail. Therefore, it is critically important that women of childbearing potential use 2 effective forms of contraception (birth control) simultaneously. It has not been established if there is a pharmacokinetic interaction between acitretin and combined oral contraceptives. However, it has been established that acitretin interferes with the contraceptive effect of microdosed progestin preparations.1 Microdosed “minipill” progestin preparations are not recommended for use with SORIATANE Capsules. It is not known whether other progestational contraceptives, such as implants and injectables, are adequate methods of contraception during acitretin therapy.
Prescribers are advised to consult the package insert of any medication administered concomitantly with hormonal contraceptives, since some medications may decrease the effectiveness of these birth control products. Patients should be prospectively cautioned not to self-medicate with the herbal supplement St. John’s Wort because a possible interaction has been suggested with hormonal contraceptives based on reports of breakthrough bleeding on oral contraceptives shortly after starting St. John’s Wort. Pregnancies have been reported by users of combined hormonal contraceptives who also used some form of St. John’s Wort (see PRECAUTIONS).
• Must have signed a Patient Agreement/Informed Consent for Female Patients that contains warnings about the risk of potential birth defects if the fetus is exposed to SORIATANE Capsules, about contraceptive failure, about the fact that they must not ingest beverages or products containing ethanol while taking SORIATANE Capsules and for 2 months after SORIATANE Capsules treatment has been discontinued, and about preventing pregnancy while taking SORIATANE Capsules and for at least 3 years after discontinuing SORIATANE Capsules therapy.
If pregnancy does occur during SORIATANE Capsules therapy or at any time for at least 3 years following discontinuation of SORIATANE Capsules therapy, the prescriber and patient should discuss the possible effects on the pregnancy. The available information is as follows:
Acitretin, the active metabolite of etretinate, is teratogenic and is contraindicated during pregnancy. The risk of severe fetal malformations is well established when systemic retinoids are taken during pregnancy. Pregnancy must also be prevented after stopping acitretin therapy, while the drug is being eliminated to below a threshold blood concentration that would be associated with an increased incidence of birth defects. Because this threshold has not been established for acitretin in humans and because elimination rates vary among patients, the duration of posttherapy contraception to achieve adequate elimination cannot be calculated precisely. It is strongly recommended that contraception be continued for at least 3 years after stopping treatment with acitretin, based on th following considerations:
• In the absence of transesterification to form etretinate, greater than 98% of the acitretin would be eliminated within 2 months, assuming a mean elimination half-life of 49 hours.
• In cases where etretinate is formed, as has been demonstrated with concomitant administration of acitretin and ethanol,
- greater than 98% of the etretinate formed would be eliminated in 2 years, assuming a mean elimination half-life of 120 days.
- greater than 98% of the etretinate formed would be eliminated in 3 years, based on the longest demonstrated elimination half-life of 168 days.
However, etretinate was found in plasma and subcutaneous fat in one patient reported to have had sporadic alcohol intake, 52 months after she stopped acitretin therapy.2
• Severe birth defects have been reported where conception occurred during the time interval when the patient was being treated with acitretin and/or etretinate. In addition, severe birth defects have also been reported when conception occurred after the mother completed therapy. These cases have been reported both prospectively (before the outcome was known) and retrospectively (after the outcome was known). The events below are listed without distinction as to whether the reported birth defects are consistent with retinoid-induced embryopathy or not.
- There have been 318 prospectively reported cases involving pregnancies and the use of etretinate, acitretin or both. In 238 of these cases, the conception occurred after the last dose of etretinate (103 cases), acitretin (126) or both (9). Fetal outcome remained unknown in approximately one-half of these cases, of which 62 were terminated and 14 were spontaneous abortions. Fetal outcome is known for the other 118 cases and 15 of the outcomes were abnormal (including cases of absent hand/wrist, clubfoot, GI malformation, hypocalcemia, hypotonia, limb malformation, neonatal apnea/anemia, neonatal ichthyosis, placental disorder/death, undescended testicle and 5 cases of premature birth). In the 126 prospectively reported cases where conception occurred after the last dose of acitretin only, 43 cases involved conception at least 1 year but less than 2 years after the last dose. There were 3 reports of abnormal outcomes out of these 43 cases (involving limb malformation, GI tract malformations and premature birth). There were only 4 cases where conception occurred at least 2 years after the last dose but there were no reports of birth defects in these cases.
- There is also a total of 35 retrospectively reported cases where conception occurred at least one year after the last dose of etretinate, acitretin or both. From these cases there are 3 reports of birth defects when the conception occurred at least 1 year but less than 2 years after the last dose of acitretin (including heart malformations, Turner’s Syndrome, and unspecified congenital malformations) and 4 reports of birth defects when conception occurred 2 or more years after the last dose of acitretin (including foot malformation, cardiac malformations [2 cases] and unspecified neonatal and infancy disorder). There were 3 additional abnormal outcomes in cases where conception occurred 2 or more years after the last dose of etretinate (including chromosome disorder, forearm aplasia, and stillbirth).
- Females who have taken Tegison (etretinate) must continue to follow the contraceptive recommendations for Tegison. Tegison is no longer marketed in the US; for information, call Stiefel at 1-888-500-DERM (3376).
- Patients should not donate blood during and for at least 3 years following the completion of SORIATANE Capsules therapy because women of childbearing potential must not receive blood from patients being treated with SORIATANE Capsules.
Important Information For Males Taking SORIATANE Capsules:
• Patients should not donate blood during and for at least 3 years following SORIATANE Capsules therapy because women of childbearing potential must not receive blood from patients being treated with SORIATANE Capsules.
• Samples of seminal fluid from 3 male patients treated with acitretin and 6 male patients treated with etretinate have been assayed for the presence of acitretin. The maximum concentration of acitretin observed in the seminal fluid of these men was 12.5 ng/mL. Assuming an ejaculate volume of 10 mL, the amount of drug transferred in semen would be 125 ng, which is 1/200,000 of a single 25 mg capsule. Thus, although it appears that residual acitretin in seminal fluid poses little, if any, risk to a fetus while a male patient is taking the drug or after it is discontinued, the no-effect limit for teratogenicity is unknown and there is no registry for birth defects associated with acitretin. The available data are as follows:
There have been 25 cases of reported conception when the male partner was taking acitretin. The pregnancy outcome is known in 13 of these 25 cases. Of these, 9 reports were retrospective and 4 were prospective (meaning the pregnancy was reported prior to knowledge of the outcome)3.
Media Articles Related to Soriatane (Acitretin)
FDA Panel Backs Approval of Psoriasis Drug Brodalumab
Source: Medscape Allergy & Clinical Immunology Headlines [2016.07.20]
The panelists said that patients should be given proper informed consent about the risk for suicide.
Medscape Medical News
FDA Panel Backs Psoriasis Drug With Caveats
Source: MedPage Today Dermatology [2016.07.20]
(MedPage Today) -- Says suicide risk means brodalumab needs careful management
Valeant Psoriasis Drug's Suicide Risk Hard to Assess -FDA Staff
Source: Medscape Dermatology Headlines [2016.07.18]
Valeant Pharmaceuticals International Inc's experimental drug to treat psoriasis carries a potential risk of suicide that is challenging to assess due to limited data, a preliminary review by the U.S. Food and Drug Administration said on Friday.
Reuters Health Information
Suicide Risk Jeopardizes Promising New Psoriasis Drug
Source: MedPage Today Dermatology [2016.07.16]
(MedPage Today) -- Six completed suicides among brodalumab trial participants
Psoriasis Rashes, Symptoms, Treatments
Source: MedicineNet Psoriasis Specialty [2016.07.15]
Title: Psoriasis Rashes, Symptoms, Treatments
Created: 8/17/2012 12:00:00 AM
Last Editorial Review: 7/15/2016 12:00:00 AM
Published Studies Related to Soriatane (Acitretin)
Randomized controlled trial of acitretin versus placebo in patients at high-risk for basal cell or squamous cell carcinoma of the skin (North Central Cancer Treatment Group Study 969251). [2011.08.31]
BACKGROUND: Chemoprevention with systemic retinoids has demonstrated promise in decreasing the incidence of new primary nonmelanoma skin cancers (NMSCs) in immunocompromised post-transplantation recipients. There is limited evidence for the use of systemic retinoids in the nontransplantation patient. To the authors' knowledge, this is the first randomized controlled trial to assess the efficacy of acitretin as a chemopreventive agent in nontransplantation patients at high-risk for NMSC... CONCLUSIONS: Although there was not a statistically significant benefit observed with the use of acitretin, this may have been the result of low statistical power. Cancer 2011;. (c) 2011 American Cancer Society. Copyright (c) 2011 American Cancer Society.
Development, evaluation and clinical studies of Acitretin loaded nanostructured lipid carriers for topical treatment of psoriasis. [2010.11.30]
The objective of the present study was to formulate and characterize Acitretin loaded Nanostructured Lipid Carriers (ActNLCs), to understand in vitro drug release and clinically evaluate the role of the developed gel in the topical treatment of psoriasis... Clinical studies demonstrated significant improvement in therapeutic response and reduction in local side effects with ActNLCs loaded gel indicated its effectiveness in the topical treatment of Psoriasis.
Acitretin for severe lichen sclerosus of male genitalia: a randomized, placebo controlled study. [2010.04]
PURPOSE: Genital lichen sclerosus is a chronic inflammatory and fibrosclerotic disease associated with substantial morbidity. Acitretin has been reported to be of benefit in many dermatological indications including lichen sclerosus. We evaluated the efficacy and tolerability of acitretin for biopsy confirmed, severe lichen sclerosus of the male genitalia... CONCLUSIONS: Acitretin is safe and effective for the management of severe, long-standing lichen sclerosus of the male genitalia. Study limitations included bias during clinical evaluation considering the expected side effects of acitretin. Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
Development, evaluation and clinical studies of Acitretin loaded nanostructured
lipid carriers for topical treatment of psoriasis. 
The objective of the present study was to formulate and characterize Acitretin
loaded Nanostructured Lipid Carriers (ActNLCs), to understand in vitro drug
release and clinically evaluate the role of the developed gel in the topical
treatment of psoriasis... Clinical studies demonstrated significant improvement in therapeutic response and
reduction in local side effects with ActNLCs loaded gel indicated its
effectiveness in the topical treatment of Psoriasis.
Acitretin for severe lichen sclerosus of male genitalia: a randomized, placebo
controlled study. 
lichen sclerosus of the male genitalia... CONCLUSIONS: Acitretin is safe and effective for the management of severe,
Clinical Trials Related to Soriatane (Acitretin)
Acitretin and Etanercept in Psoriasis [Completed]
To determine whether acitretin plus etanercept is more effective than etanercept alone in
clearing psoriasis plaques in adults.
Low-Dose (17.5 mg/Day) Acitretin: Comparable Efficacy Without the Side Effects? [Recruiting]
Psoriasis is a chronic skin disorder with a prevalence of approximately 1-3% worldwide. At
present, there is no curative therapy available and the clinical course is unpredictable,
but in the majority of cases psoriasis is a chronically remitting and relapsing disease.
Several clinical subtypes of psoriasis exist with differences in manifestations and skin
Chronic stable plaque psoriasis (Psoriasis Vulgaris) is the commonest form of the disease,
accounting for 85-90% of cases. The circumscribed infiltrated skin lesions are scaly and
erythematous and often symmetrically distributed over the body. Several types of palliative
therapies exist. The therapies are either topical or systemic. The severity of chronic
plaque psoriasis is often determined by the percentage of body surface area (BSA) involved.
For mild, moderate and severe chronic plaque psoriasis with BSA involvement of up to 20%,
initial therapy is topical. Phototherapy and numerous systemic therapies are usually
indicated when more than 20% of skin is affected.
Severe plaque-type psoriasis requires systemic and long-term therapy in order to induce and
maintain remission. Acitretin 25mg/day combined with a phototherapy regimen is a standard
treatment that provides clinically significant efficacy, however many patients experience
tolerability issues due to retinoid-related adverse events. Retinoid-related adverse events
include but are not limited to: alopecia, dry mucus membranes, pruritus, photosensitivity,
elevation of liver enzymes, elevation of serum triglycerides, cholesterol and decrease of
HDL, arthralgias, myalgias, eye irritation, blepharitis, photophobia, conjunctivitis,
headaches, nausea, anemia and leukemia. Reducing the acitretin dose from 25mg/day to
17. 5mg/day may provide improved tolerability without compromising efficacy.
The purpose of this study is to ascertain if reducing the acitretin dose from 25mg/day to
17. 5mg/day will provide improved tolerability without compromising efficacy.
Pilot Study on the Use of Acitretin for the Treatment of Severe Chronic Hand Dermatitis [Completed]
This pilot, phase II, 24-week study will recruit a total of 10 patients and will evaluate
the efficacy and safety of acitretin in patients with severe chronic hand dermatitis .
Dose Ranging Study to Assess the Efficacy and Safety of Acitretin in Severe Plaque Type Psoriasis [Completed]
In this study, the investigators will intend to compare the efficacy and safety of various
doses of acitretin in a randomized double blind manner in patients with severe plaque-type
psoriasis, by i) studying the change PASI score from baseline as a measure of efficacy ii)
determining the frequency of side effects at various doses. Sixty patients will be recruited
from Psoriasis Clinic of Department of Dermatology, Venerology and Leprology, PGIMER.
Patients will be randomly assigned to one of the three groups: Group A, consisting of 20
patients, will be administered acitretin 25 mg/ day ,Group B, consisting of 20 patients,
will be administered acitretin 35 mg/day and GROUP C consisting of 20 patients, will be
administered acitretin 50 mg/day This therapy will be continued until PSORIASIS AREA AND
SEVERITY INDEX (PASI) scores are reduced to < 25% of the original scores or 12 weeks,
whichever comes earlier. It is expected that acitretin at higher doses will be more
efficacious . As the exact etiopathogenesis of psoriasis is not fully known, it is difficult
to provide a definite cure to all patients, though the disease activity can be controlled to
a great extent with various treatment modalities. However the dosage of acitretin be
adjusted according to response of the patients and tolerability of side effects.
A Phase II Study of Vemurafenib Combined With Acitretin in Patients With Advanced Melanoma [Completed]
We propose to conduct a phase 2 study to assess whether the addition of acitretin to
vemurafenib therapy is able to decrease the rate of cutaneous squamous cell carcinoma (cSCC)
development, a known side effect of vemurafenib therapy, in patients with advanced melanoma.
Further, we seek a preliminary assessment as to whether the addition of acitretin to
vemurafenib enhances the clinical efficacy of this anti-melanoma agent.
Reports of Suspected Soriatane (Acitretin) Side Effects
Drug Ineffective (8),
Skin Exfoliation (6),
Chapped Lips (5),
Vision Blurred (5),
Visual Acuity Reduced (4), more >>