Hep C Drug Linked to Fatal Skin Reactions - less than 1% of patients

[HectorSF]

Hep C Drug Linked to Fatal Skin Reactions
By John Gever, Senior Editor, MedPage Today
Published: December 19, 2012
The oral hepatitis C drug telaprevir (Incivek) will now carry a boxed warning about potentially fatal skin reactions in the wake of multiple deaths, its manufacturer said Wednesday.

According to a statement from Vertex Pharmaceuticals, "Fatal cases of serious skin reactions have been reported in patients with progressive rash and systemic symptoms who continued to receive Incivek combination treatment after a serious skin reaction was identified."

The new warning stresses that combination treatment with telaprevir should be stopped immediately in patients with serious skin reactions, such as rashes with systemic symptoms or progressive severe rashes. Discontinuation of other drugs with the potential for skin reactions also should be considered.

Serious skin reactions were seen during the drug's clinical trials prior to approval, including some requiring hospitalization and considered life-threatening. The risk was noted on telaprevir's original label.

But these events were rare -- affecting less than 1% of patients -- and all patients eventually recovered, Vertex said.

The reports of deaths associated with skin reactions emerged during postmarketing surveillance. The company did not indicate how many fatalities were reported.

"Given the severity of the events reported in the postmarketing setting, and the importance of discontinuing Incivek combination treatment in the event of one of these reactions, the information has been given greater prominence through a boxed warning," Vertex said.

It also said the telaprevir label had been modified with new information on the time to onset of anemia and on its management.

The drug, a hepatitis C virus protease inhibitor, was approved in May 2011.

[frijole]

WARNING: SERIOUS SKIN REACTIONS
Fatal and non-fatal serious skin reactions, including Stevens Johnson Syndrome (SJS), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), and Toxic Epidermal Necrolysis (TEN), have been reported in patients treated with INCIVEK combination treatment [see Warnings and Precautions (5.1)]. Fatal cases have been reported in patients with progressive rash and systemic symptoms who continued to receive INCIVEK combination treatment after a serious skin reaction was identified. For serious skin reactions, including rash with systemic symptoms or a progressive severe rash, INCIVEK, peginterferon alfa, and ribavirin must be discontinued immediately. Discontinuing other medications known to be associated with serious skin reactions should be considered. Patients should be promptly referred for urgent medical care.


...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).

THis is from the letter to physicians on Vertex' website

[frijole]

Also from this letter, an update on anemia

[frijole]

hit the post button too soon...

The prescribing information was also updated to include additional information on the time to onset and monitoring for anemia.

WARNINGS AND PRECAUTIONS5.2       Anemia
In clinical trials, the median time to onset of hemoglobin less than or equal to 10 g/dL was faster among subjects treated with INCIVEK combination treatment compared to those who received peginterferon alfa and ribavirin: 56 days (range 8-365 days) versus 63 days (range 13-341 days), respectively.
Anemia requiring ribavirin dose reduction, blood transfusion, and/or erythropoiesis stimulating agent (ESA) has been reported to occur as soon as 10 days following initiation of INCIVEK combination treatment.
Hemoglobin should be monitored prior to and at least at weeks 2, 4, 8 and 12 during INCIVEK combination treatment and as clinically appropriate. Earlier and more frequent monitoring for some patients should be considered.

[frijole]

I am very glad to see Vertex presenting this because I think it will make an impact on treating physicians who, in many cases, have not paid enough attention to the severity of the rash.    I had listened to a CCO panel presentation a few weeks ago and the panel moderator was a treating physician and the other members of the panel were PA's and a pharmacist.  The moderator asked a question about how the patients were treated for the rash and the PA said with a topical steroid 1% ointment, an over the counter product.  He asked her a second time, and she repeated the same thing.  I was stunned that this was all that was being done by a lot of so-called informed PA's.  I didn't even do Incevik and the rash I had from Victrelis was at times, unbearable, and I may have developed some lifetime excema issues from it.  -- and Victrelis was the lesser of the rash evils.  

I am glad Vertex is stepping up the anemia warnings too. Trying to make the physicians aware that anemia can happen within the first 10 days after Incevik is administered.   They are indicating that more bloodwork must be done to monitor this.

In my 48 weeks, and, as I said, I did Vic, not Inc -- these were the worse side effects - rash and anemia.

Hector, thanks for posting this.
bean

[BoceprevirGal]

  My hemolytic anemia began, 3 weeks after I began my Boceprevir, it had
a very early on-set, and like Frijole mentioned, although I was on Victrelis, my anemia was my worst symptom.
  I also got a rash, which felt systemic, but it was after being in the sun, and presented as hives on my torso, front and back, but my face felt swollen and I itched from my torso, to the top of my head.
   Since it felt like my rash was coming form the inside of my body (systemic) I didn't think putting a topical ointment on it would do anything at all, and I stuck with taking the(prescription) anti-itch pill, Atarax,  immediately after the rash began, very regularly, every 6 hrs, for 5 days, and my rash went away, luckily.
   The Incivek rash is much worse, and tends to present with blistered skin,(I've observed from forum members on here posting pics) and once it covers 90% of the body is very dangerous, I imagine

[pooh55811]

Thanks, Hector, for posting that.

I agree with Frijole that many Hep C treating docs and PAs do not take the rash seriously and have no clue how to treat it. The over the counter meds and creams may work for a bump or two, but they won't work for most of the mild, moderate, or severe rashes that these drugs cause.

While I am very glad that Vertex took this step, someone also needs to educate these treating docs on how to assess, recognize, and treat the rash effectively and immediately.

I fear that these docs, because they know so little about the rash and the treatment for it, will just start discontinuing the drug treatment, and that is not necessary in most cases if they would just recognize, assess, and treat the rash immediately.

Rash was my second worse side effect after nausea and its related complications. Maybe they were tied for first place, LOL.

[Idyllic]

I guess it is a step in the right direction for Vertex but to me it is the naivete of treating physicians - and patients who put faith in them rather doing independent research. I wish it were not like that but with Hepatitis C and Triple it seems to be the case. I cannot speak for any area other than my own (Southwest Texas - San Antonio) but there are many doctors trying to treat triple who in the past did not even accept Hepatitis C patients in the past. Some of the things I have been seeing and hearing have been alarming to say the least.

[1swimmer]

I am the first boceprevir patient for my doctor. Toward the end of my tx, he mentioned that one of his telaprevir patients had to stop tx due to rash, after one week. I know he was prepared to give me a script for any rash, so I was surprised. As Pooh mentions, it seems important for docs to get aggressive about the rash. I did learn before treating that some people have extreme reactions. Managing the patient closely early on is muy important.

Thanx Hector,
C

[dooklebug]

This is all very frightening for someone who hasn't begun treatment yet.  When the time comes, what questions should I ask my doctor related to this?  I have pretty much come to terms with the fact that I'm going to experience side effects such as nausea, fatigue, irritability, depression, etc.  But now this?  I'm beginning to wonder which is worse:  the disease or the treatment.  
#scaredoftheunknown

[copyman]

This is very scary news. For a pharm company to admit this is even scarier! I have a feeling it may be a little more serious then 1%

I remember a few MH members during telaprevir trials with the rash from hell ! From what they described it was horrible.
I felt very fortunate only to have severe itching when I treated during a trial.

Even Riba has been known to cause nasty rashes. This was a hot topic on this forum way before telaprevir was in the picture

As for the anemia with telaprevir, my riba dose was reduced at 13 weeks because of anemia. After a few weeks I went back to full dose.

At this point I still think the risk is worth the reward

[1swimmer]

Hey there,
Everything about hep c is scary at first.
And then we start to learn, on our own, w/ forums like this, thru our health providers. People like Hector and others post new information so that you can make an informed decision, about your tx.

As pooh pointed out, the doctors need to be informed too. Make sure you have a doc that is on the same page as you. If side effects hit you right away, is your doc going to treat you aggressively or quit on you.  

I learned that the incivek carried the risk of serious rash, so I treated with boceprevir , knowing that anemia was likely to occur. And it did.

Yes, triple tx is serious. Learn everything you can before you start.
I'd like to borrow Poohs phrase "it's doable". Treatment may be very difficult, or for some, not so bad.

I made it thru tx. I worked. It was hard mentally and physically. Now 2 months post, I'm gradually getting my life back.
Good luck,
C

[pooh55811]

If I was you, I would get an experienced hepatologist as my doctor. I had a GI to begin with and that GI and the treating team, while getting the blood work correct, most of the time, were completely ignorant and useless when it came to side effects. If I had not been a registered nurse with a critical care background, I would have been lost down the pipes. It took me awhile to realize how totally inept they were, but once I did, I put my medical background to work and demanded side effect relief (which they were very reluctant to give). I went along with me basically managing my own care for months. Eventually, when it became clear that they may reduce my Riba by half for anemia instead of giving me Procrit (contrary to what they told me when I started), I switched doctors and got a hepatologist (who does give Procrit). I had to drive 70 miles to the hepatologist but it was worth it to have a doctor who knew what he was doing and who knew how to assess and treat side effects (and was more than willing to do so). Get a good doctor from the outset. If your side effects are mild, great. But if you have side effects that need immediate treatment you need a doctor who can recognize them, assess them, and treat them appropriately and immediately.

Best of luck.

[coeric]

I experienced the telaprevir rash.  i was fortunate to have a caring dermatologist prescribe clobetasol at week 9.  at week 10 the hepatologist discontinued telaprevir and reduced the pegasys and ribavirin..  at week 11 prednisone was started, and i remained on prednisone for 5 weeks. I posted a photographic time-series of the effects of prednisone on the rash. after the rash calmed down i experience stasis dermatitis.  i made it through 48 weeks of treatment albeit on reduced doses. if i experienced SVR, it will all be worth it.  without an experienced hepatologist i would have had to end treatment at week 10.

[coeric]

the photos of the rash are on my profile page.  the docs asked me to email them weekly photos.
eric

[desrt]

"The new warning stresses that combination treatment with telaprevir should be stopped immediately in patients with serious skin reactions, such as rashes with systemic symptoms or progressive severe rashes"

"For serious skin reactions, including rash with systemic symptoms or a progressive severe rash, INCIVEK, peginterferon alfa, and ribavirin must be discontinued immediately."


Less than 1% is comparable to the black box warning for fatal psych events from IFN alpha. The problem I see is doctors not experienced with what constitutes "systemic symptoms" or "progressive severe rash" being quick to pull patients off tx and creating resistant strains of the virus. For safe, effective tx, you now need another specialist, since occurance of non-fatal rash is way higher than 1%.

So:

gastro or hepatologist
hematologist
dermatologist
psychiatrist

The likelihood of all patients having the full support of all the specialists they need is low, so, once again it falls to the patient to educate themselves in order to make informed decisions.

[can-do-man]

"The likelihood of all patients having the full support of all the specialists they need is low, so, once again it falls to the patient to educate themselves in order to make informed decisions."

So true!

[quayle]

Could Hector please inform us as to the exact source of his information so that we may read it ourselves to make our own determination,please inform us of links articles research and such.

[hrsepwrguy]

WARNING: SERIOUS SKIN REACTIONS See full prescribing information for complete boxed warning. Fatal and non-fatal serious skin reactions, including Stevens Johnson Syndrome (SJS), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), and Toxic Epidermal Necrolysis (TEN), have been reported in patients treated with INCIVEK combination treatment [see Warnings and Precautions (5.1)]. Fatal cases have been reported in patients with progressive rash and systemic symptoms who continued to receive INCIVEK combination treatment after a serious skin reaction was identified. For serious skin reactions, including rash with systemic symptoms or a progressive severe rash, INCIVEK, peginterferon alfa, and ribavirin must be discontinued immediately. Discontinuing other medications known to be associated with serious skin reactions should be considered. Patients should be promptly referred for urgent medical care.

http://pi.vrtx.com/files/uspi_telaprevir.pdf

[hrsepwrguy]

Hep C Drug Linked to Fatal Skin Reactions

By John Gever, Senior Editor, MedPage Today
Published: December 19, 2012

http://www.medpagetoday.com/InfectiousDisease/Hepatitis/36528

[quayle]

I should clarify my statement the article was a newspaper article,by a journalist and to terrify people with less than 1% danger is like saying look both ways before crossing the road there has been no official statement made by the manufacturer that I've seen,just a journo hyping a fact that was pretty much already realized.And if anyone taking  any new drug for Hep C there are many things yet to know from all of them,I don't know about anyone else on tx but I've disclaimed all effects including Death from the clinic that is treating me,so If you don't want to do the time don,t do the crime,and as soon as you have clinical scientific research that,is more than a journalists hyp let me Know.

[hrsepwrguy]

"there has been no official statement made by the manufacturer that I've seen"

They changed the package warning is that not enough, I don't think it was meant to scare people but to warn them that the drug has the potential to cause death in some cases

WARNING: SERIOUS SKIN REACTIONS See full prescribing information for complete boxed warning. Fatal and non-fatal serious skin reactions, including Stevens Johnson Syndrome (SJS), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), and Toxic Epidermal Necrolysis (TEN), have been reported in patients treated with INCIVEK combination treatment [see Warnings and Precautions (5.1)]. Fatal cases have been reported in patients with progressive rash and systemic symptoms who continued to receive INCIVEK combination treatment after a serious skin reaction was identified. For serious skin reactions, including rash with systemic symptoms or a progressive severe rash, INCIVEK, peginterferon alfa, and ribavirin must be discontinued immediately. Discontinuing other medications known to be associated with serious skin reactions should be considered. Patients should be promptly referred for urgent medical care.

5 WARNINGS AND PRECAUTIONS
5.1 Serious Skin Reactions/Rash  Fatal and non-fatal serious skin reactions, including Stevens Johnson Syndrome (SJS), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), and Toxic Epidermal Necrolysis (TEN), have been reported in patients treated with INCIVEK combination treatment. Fatal cases have been reported in patients with progressive rash and systemic symptoms who continued to receive INCIVEK combination treatment after a serious skin reaction was identified.  
For serious skin reactions, including rash with systemic symptoms or a progressive severe rash, INCIVEK, peginterferon alfa, and ribavirin must be discontinued immediately. Discontinuing other medications known to be associated with serious skin reactions should be considered. Patients should be promptly referred for urgent medical care.  
In clinical trials, serious skin reactions, including DRESS and 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 subjects 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).     TEN and Erythema Multiforme (EM) have been observed in post-marketing experience [see also Boxed Warning and Adverse Reactions (6.2)].

6.2   Post-marketing Experience The following adverse reactions have been identified during post-approval use of INCIVEK. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.  
Skin and Subcutaneous Tissue Disorders: Toxic Epidermal Necrolysis (TEN) and Erythema Multiforme (EM) [see also Boxed Warning and Warnings and Precautions (5.1)]

http://pi.vrtx.com/files/uspi_telaprevir.pdf

[can-do-man]

"Could Hector please inform us as to the exact source of his information so that we may read it ourselves to make our own determination,please inform us of links articles research and such."

I have always been told from Medhelp that a link must be provided when you copy from another site. not sure why it's not enforced...

[quayle]

In less than 1%! that's hardly earth shattering and incase you have not read the side of thousands of Drugs they cover everything from discomfort to death,and most all drug disclaimers say and other effects not listed hear your being very melodramatic my friend,I'm willing to bet there will be more to come.

[quayle]

Antibiotics can cause hepatic failure!