Wednesday, March 14, 2012

Incivek-Help Recognizing Rash Severity:Photos and grading system

HCV therapy has always been challenging, a few side effects include fatigue, nausea, fever, headaches and anemia. Enter. Incivek-telaprevir. According to clinical trials over 5o percent of people suffer with a rash and about 20 percent deal with itchiness or inflammation in the rectum.

Clinical data has showen the Incivek rash is often mild and not serious in most cases, although, in a small amount of people during the Phase II and III clinical trials some serious skin reactions were reported.(see Severe Cutaneous Eruptions on Telaprevir-An Update below)

The information and links provided on the blog today will help you recognize the severity of a rash, although the first course of action is to contact your physician immediately if you have any concerns.

Help Recognizing Rash Severity
To better understand the grading system used by physicians to determine how serious a rash is, a grading system is included below with grades 1-3, along with photos to assist readers with recognizing rash severity. 
  Severe Cutaneous Eruptions on Telaprevir-An Update
This month in the Journal Of Hepatology, correspondence (In Press Accepted Manuscript) - Steven T. Chen, Peggy A. Wu from "The Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, MA" report on Severe Cutaneous Eruptions on Telaprevir.

Noted @ The Journal Of Hepatology
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Steven T. Chen, Peggy A. Wu -The Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, MA

PII: S0168-8278(12)00160-2
DOI: 10.1016/j.jhep.2012.02.004
Reference: JHEPAT 4136

 Severe Cutaneous Eruptions on Telaprevir
To the editor:
 Since its approval by the Food and Drug Administration in May 2011, telaprevir, a novel  serine protease inhibitor, in combination with peginterferon and ribavirin has been increasingly used as an effective treatment for hepatitis C virus (HCV)[1]. In Phase II and  III clinical trials involving over 3,800 patients, a cutaneous eruption, usually eczematous, occurred in 56% of patients compared to 34% taking peginterferon and ribavirin alone[2]. Furthermore, 3.7% of telaprevir-treated patients developed severe cutaneous adverse  events. These events included 11 patients considered to have drug reaction with  eosinophilia and systemic symptoms (DRESS), but of these, only one was definite, two were probable, and the remainder were possible, according to diagnostic criteria proposed by Kardaun et al[2,3]. Herein we report three patients out of 56 patients at risk (5%)  taking telaprevir, peginterferon, and ribavirin at our institution who developed probable  and definite DRESS.
Photos and case studies included - Download PDF Here

Telaprevir - Protocol-Specified Rash Severity Grading 

Grade 1- Localized skin eruption
Grade 2-Diffuse skin eruption up to 50% of the body surface area (BSA)
Grade 3-Generalized skin eruption involving > 50% BSA, or–Rash with bullae, vesicles, mucous membrane ulceration, target lesions, purpura, or with epidermal detachment
Excerpt From: Dermatological side effects of hepatitis C and its treatment: Patient management in the era of direct-acting antivirals:
The telaprevir prescribing information does not require telaprevir discontinuation for Grade 1 or 2 (mild/moderate) rash, which can be treated using emollients/moisturizers and topical corticosteroids.

For Grade 3 rash, the prescribing information mandates immediate telaprevir discontinuation, with ribavirin interruption (with or without peginterferon) within 7 days of stopping telaprevir if there is no improvement, or sooner if it worsens. In case of suspicion or confirmed diagnosis of SCAR, all study medication must be discontinued.  

Related Links
Updated Dec 2012-
HCV Drug Incivek (telaprevir) - View Rash Grade 1 and 2
FDA Podcast: Serious skin reactions with Hepatitis C drug Incivek (telaprevir)
INCIVEK® (telaprevir)-Updates label after reports of a ‘small number of fatal skin reactions’

Of Interest

Hepatitis C Drug Incivek (telaprevir); What are the side effects ?

FDA Package Insert: Vertex -Telaprevir-Incivek,

Serious Skin Reactions
Serious skin reactions, including Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) and Stevens-Johnson Syndrome (SJS) were reported in less than 1% of subjects who received INCIVEK combination treatment compared to none who received peginterferon alfa and ribavirin alone. These serious skin reactions required hospitalization, and all patients recovered. The presenting signs of DRESS may include rash, fever, facial edema, and evidence of internal organ involvement (e.g., hepatitis, nephritis). Eosinophilia may or may not be present. The presenting signs of SJS may include fever, target lesions, and mucosal erosions or ulcerations (e.g., conjunctivae, lips). If a serious skin reaction occurs, all components of INCIVEK combination treatment must be discontinued immediately and the patient should be promptly referred for urgent medical care.

Rash developed in 56% of subjects who received INCIVEK combination treatment [see Adverse Reactions (6.1)]. Severe rash (e.g., a generalized rash or rash with vesicles or bullae or ulcerations other than SJS) was reported in 4% of subjects who received INCIVEK combination treatment compared to less than 1% who received peginterferon alfa and ribavirin alone. The severe rash may have a prominent eczematous component. Patients with mild to moderate rashes should be followed for progression of rash or development of systemic symptoms. If rash progresses and becomes
severe or if systemic symptoms develop, INCIVEK should be discontinued. Peginterferon alfa and ribavirin may be continued. If improvement is not observed within 7 days of INCIVEK discontinuation, sequential or simultaneous interruption or discontinuation of ribavirin and/or peginterferon alfaribavirin and peginterferon alfa should be considered. Patients should be monitored until the rash has resolved. INCIVEK must not be reduced or restarted if discontinued due to rash. Treatment of rash with oral antihistamines and/or topical corticosteroids may provide symptomatic relief but effectiveness of these measures has not been established. Treatment of rash with systemic corticosteroids is not recommended [see Drug Interactions (7)].

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