Soriatane (acitretin) Capsules
Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
Soriatane is an oral retinoid, which is a synthetic form of vitamin A. Acitretin is the only oral retinoid approved by the FDA specifically for treating psoriasis.
- angioedema, urticarial hypersensitivity
- added Capillary Leak Syndrome, Exfoliative Dermatitis/Erythroderma
- Added Immune System Disorders, Madarosis and exfoliative dermatitis, and Vascular Disorders
Pregnancy SORIATANE 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 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 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.
Source FDA (May 2014)
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Two cases of progressive multifocal leukoencephalopathy (PML) in Europe with Fumarate
Two cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients treated with oral dimethyl fumarate, a form of which won FDA approval last month for multiple sclerosis.
One patient in the Netherlands and another in Germany developed PML after several years of treatment with European formulations of the drug, long available as psoriasis treatments, according to two separate case reports in the April 25 issue of the New England Journal of Medicine.
Both patients had psoriasis, although the Dutch patient had developed neurological symptoms leading to a diagnosis of "possible" MS 6 months before PML was detected.
In a response also published in the NEJM, researchers from dimethyl fumarate's U.S. manufacturer, Biogen Idec, said they were aware of two other cases of PML in patients taking drugs containing dimethyl fumarate, both involving its European product sold as Fumaderm.
But they also pointed out that Fumaderm, as well as a compounded product known as Psorinovo -- involved in one of the NEJM reports -- contained other active ingredients, and the patients had additional "significant confounding factors" as well.
PML has been a significant issue for the MS drug natalizumab (Tysabri), with more than 300 PML cases reported worldwide since the drug was approved in 2004. PML has also been reported with rituximab (Rituxan), but in much smaller numbers.
The condition develops when latent JC virus infections become reactivated in patients with certain patterns of immunosuppression. It was first seen in the context of cancer chemotherapy and later in patients with AIDS.
However, PML had not been reported in conjunction with any of the newer oral drugs used in MS until now. In addition to the new FDA-approved formulation of dimethyl fumarate (BG-12, Tecfidera), others include fingolimod (Gilenya) and teriflunomide (Aubagio).
The first of the two PML cases reported in the NEJM involved a 74-year-old man in Germany who had received Fumaderm, which consists of dimethyl fumarate plus monoethyl fumarate, for 3 years before neurological symptoms consistent with PML developed in 2010.
In the second case, a 42-year-old Dutch woman with psoriasis had been treated for 5 years with Psorinovo from a compounding pharmacy when PML was detected in November 2012. Beginning in May of that year, the woman had developed progressive right-side hemiparesis that had been diagnosed as possible MS.
In both cases, PML was diagnosed on the basis of MRI scans and detection of JC virus in cerebrospinal fluid, following long periods of serious lymphopenia. Other causes such as HIV infection were ruled out. Both patients recovered after the fumarate drugs were stopped.
Jörg Schultz, MD, of Rheinisch-Westfälisch Technische Hochschule Aachen in Germany, and colleagues, noted that their patient had received a variety of other drugs including acitretin and methotrexate prior to initiating Fumaderm therapy.
The Dutch woman had not received other immunosuppressive drugs, according to Bob W. van Oosten, MD, PhD, of VU University Medical Center in Amsterdam, and colleagues. But Psorinovo contained copper gluconate as an additive until 2010.
Biogen Idec researchers led by Marianne Sweetser, MD, PhD, argued in their response that the other compounds administered along with dimethyl fumarate complicate the interpretation of these cases.
That was also true in the other two cases of PML seen previously in conjunction with Fumaderm. One of those patients was also on methotrexate and steroids, while the other had been taking efalizumab, another drug connected to PML.
Sweetser and colleagues commented that, overall, PML has been rare in patients receiving dimethyl fumarate-containing drugs, "on the basis of more than 180,000 patient-years of experience with Fumaderm."
They also pointed to the fact that both cases in the NEJM reports involved long periods of lymphopenia prior to development of PML.
"Severe lymphopenia is a [known] risk factor for PML and can be mitigated through the periodic monitoring of lymphocytes," they wrote.
Finally, Sweetser and colleagues noted that no cases of PML have been seen with the U.S.-approved formulation, which has no active ingredients other than dimethyl fumarate. "More than 2,600 patients with MS have been treated for periods of up to 4 years or more, with a median follow-up of approximately 2 years," they wrote, with lymphocyte reductions of about 30% from baseline typically seen.
Source : MedPage Today
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