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Soriatane (Acitretin) - Summary

 
 



BOX WARNING

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.

 

SORIATANE SUMMARY

What is the most important information I should know about SORIATANE Capsules?

Soriatane (acitretin), a retinoid, is available in 10 mg and 25 mg gelatin capsules for oral administration.

Soriatane is indicated for the treatment of severe psoriasis in adults. Because of significant adverse effects associated with its use, Soriatane should be prescribed only by those knowledgeable in the systemic use of retinoids. In females of reproductive potential, Soriatane should be reserved for non-pregnant patients who are unresponsive to other therapies or whose clinical condition contraindicates the use of other treatments (see boxed CONTRAINDICATIONS AND WARNINGS -- Soriatane can cause severe birth defects).

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


See all Soriatane indications & dosage >>

NEWS HIGHLIGHTS

Media Articles Related to Soriatane (Acitretin)

Oral Ponesimod Relieves Chronic Plaque Psoriasis
Source: Medscape Medical News Headlines [2014.08.22]
Ponesimod, an oral selective modulator of the sphingosine 1-phosphate receptor, yielded significant clinical benefit in a phase 2 trial of patients with moderate to severe chronic plaque psoriasis.
Reuters Health Information

Lilly Psoriasis Drug Succeeds in Late-Stage Studies
Source: Medscape Today Headlines [2014.08.21]
Eli Lilly and Co said its experimental psoriasis drug was found to be more effective in clearing skin than a generic treatment and a placebo in late-stage studies.
Reuters Health Information

Health Tip: Soothing Psoriasis on the Feet
Source: MedicineNet Psoriasis Specialty [2014.08.20]
Title: Health Tip: Soothing Psoriasis on the Feet
Category: Health News
Created: 8/20/2014 7:35:00 AM
Last Editorial Review: 8/20/2014 12:00:00 AM

Psoriasis Ups Risk of Cancer, Serious Infection
Source: MedPage Today Dermatology [2014.08.08]
CHICAGO (MedPage Today) -- Rates of malignancy and infection-related hospitalization among patients with psoriasis outpaced national averages, irrespective of therapy in most cases.

Psoriasis: Screen for Fatty Liver Before MTX?
Source: MedPage Today Dermatology [2014.08.08]
CHICAGO (MedPage Today) -- What began as a case of chronic plaque psoriasis has evolved into consideration of routine testing for nonalcoholic steatohepatitis before initiating methotrexate, according to a British study.

more news >>

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. [2010]
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]
lichen sclerosus of the male genitalia... CONCLUSIONS: Acitretin is safe and effective for the management of severe,

more studies >>

Clinical Trials Related to Soriatane (Acitretin)

Study Evaluating the Efficacy and Safety of Etanercept and Acitretin in Korean Patient With Moderate to Severe Psoriasis [Recruiting]
To compare the efficacy of ETN 50mg twice weekly for 12 weeks followed by reduction to a maintenance dose of 25mg twice weekly at week 24 with that of combination of ETN 25 mg Twice Weekly plus Acitretin 10mg BID at week 24 in subjects with moderate to severe psoriasis.

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 areas involved.

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 [Recruiting]
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 .

Acitretin Plasma Levels Under Hemodialysis [Recruiting]
Acitretin is given to hemodialysis patients who have developed in-situ or invasive squamous cell carcinoma of the skin in increasing doses up to 25 mg daily for one year.

Acitretin or Tazarotene Gel and Excimer Laser for Treatment of Psoriasis [Recruiting]
The hypothesis of this study is that excimer (308-nm UVB) laser added to either tazarotene 0. 1% gel or acitretin 25 mg daily will lead to improved efficacy of these treatments alone.

The primary objective of this study is to compare the improvement of psoriatic plaques with and without excimer laser (308-nm UVB) treatment, applied in a randomized and blinded fashion, in subjects on acitretin 25 mg or tazarotene gel 0. 1% QD. The primary endpoint will be the comparison between the change in NPF score of plaques treated with excimer laser and those treated with sham treatment.

The secondary objectives are to compare the number of excimer light treatments and time necessary to achieve an average lesion assessment score of 0 to 1 in subjects treated with acitretin 25 mg PO or tazarotene gel 0. 1% QD, and to evaluate adverse events related to combinations of the study treatments.

more trials >>

Reports of Suspected Soriatane (Acitretin) Side Effects

Drug Ineffective (8)Alopecia (8)Pruritus (6)Skin Exfoliation (6)Erythema (6)Chapped Lips (5)Acne (5)Vision Blurred (5)Chills (4)Visual Acuity Reduced (4)more >>


Page last updated: 2014-08-22

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