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.

[Willy50]

I think it has been 6 years since Prove 1.  Time flies.
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http://www.aidsmeds.com/articles/Incivek_Deaths_1667_23316.shtml

One of two FDA-approved protease inhibitors available for use in triple combination therapy with interferon and ribavirin to cure hepatitis C virus (HCV), Incivek caused skin reactions in less than 1 percent of those taking the antiviral in Phase III clinical trials. Some of those study participants were subsequently hospitalized, but there were no fatalities. This is the first report of deaths from the drug. Vertex urges anyone who has a skin reaction to stop treatment immediately, as the two who have died continued therapy after identifying the reaction.
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http://investors.vrtx.com/releases.cfm?hdr02=press

"INCIVEK® (telaprevir) tablets is an oral medicine that acts directly on the hepatitis C virus protease, an enzyme essential for viral replication. INCIVEK has been prescribed to more than 50,000 patients in the United States. Approximately three out of four U.S. patients who are prescribed a direct-acting antiviral for the treatment of genotype 1 chronic hepatitis C (HCV) receive INCIVEK combination therapy. "
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http://en.wikipedia.org/wiki/Telaprevir

On December 19, 2012, Vertex announced it would add a “Black Box” warning of possible side effects on the US labels of Telaprevir, following "reports of a small number of fatal skin reactions in patients who continued to receive Incivek combination therapy after a serious skin reaction was identified.”. The FDA reported that two people had died from serious skin reactions caused by the Incivek combination treatment and that a total of 112 patients had developed serious skin reactions of two different types.[8]
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willy

[dointime]

I was in a phase 2 trial of incivek 5 years ago and got the dreaded rash bad.  So how come I am only finding out NOW that the rash can be FATAL.  I wonder how information as important as this could have been suppressed for 5 years?  

Would it have made any difference to my determination to tough it out with incivek?  He!! yes!  So just as well that I, and now several thousand other people didn't know, isn't it.

dointime          

[coeric]

during my end of treatment visit in August the doc volunteered that i had one of worst rashes seen in the clinic.  at the time the clinic was treating about 120 with incivek and had also conducted stage 2 and 3 clinical trials.  i hope the images posted on my profile don't freak anyone to the point of not using this drug.  my experience like mremeet's represents less than 1 percent of all those that have used the drug. i feel very fortunate to have had the opportunity to use this drug.  and to have been treated by a hepatologist that knows enough to discontinue the drug before the patient is in danger.
blessing and happy holidays to all
eric

[mremeet]

A lot of new faces around here. I was in the first cohort to take Telaprevir (called VX-950 at the time) way back in 2006. I got a horrible rash (coming on strong at about week 6) and experienced all sorts of troubles dealing with it as it progressed. Nothing was known at the time of Telaprevir's propensity to trigger severe rash in some people or how best to handle it. So my situation devolved into a comedy of errors trying to deal with it while still pushing forward with my treatment. It got REALLY bad before it was under control. Even then it was just managed in a crippled, hobbled way for the remaining 2/3rd year until EOT and final RELIEF from it all.

I'm not surprised that a few people have died - probably out of many thousands who have taken the drug by now - as a result of the rash. It's too bad, because I'm confident if doctors were educated and attentive to the potential side effects of this drug, the death toll could approach zero. I'm sure there are some HCV+ people that are in pretty bad shape before treatment and they aren't robust enough to tolerate a serious stressor like THE RASH without an astute and quick acting doctor on their side.

Bottom line is that Telaprevir is a very effective drug, I probably owe my life to it. Even with all the hardships I went through with it, I'm glad I took it. It was an imperfect vehicle that brought me to the promised land: SVR! At a time when there was only a ~40% chance of being cured with the only other two FDA approved drugs complete with their own horrible side effects.

I hope Telaprevir isn't yanked and I hope anyone pondering treatment isn't scared off from treatment because of these stories. People with HCV in slowly declining health (as I was) need all the arrows they can get in their quiver. Telaprevir is a golden arrow and it drives at the very heart of the beast. Sometimes it can fly back at you, but only rarely. And even if it does, it can still strike a fatal blow against the dragon (as it did for me). You just have to be educated and wary. You have to know when to turn it off and walk away. And you need to know the side effect treatment strategies to give you the best chance for dealing with whatever level of side  effects you're experiencing. EDUCATION is the key along with working with and even prompting and guiding your doctor based on your education. Especially if he/she is not a highly experienced hepatologist.

That's how it should be done. Hopefully Teleprevir won't get shut down. HCV+ people need this imperfect drug until better drugs come along.

[Willy50]

A few things....  

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"Could Hector please inform us as to the exact source of his information so that we may read it ourselves"
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First you complain that a link is not provided.  
I copied the first 2 lines into the browser and had the result in less than a second.  It was more work to complain than to just do the work.  

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

That is because you haven't looked.  Vertex has it right in their site and it has been provided in this thread;

http://investors.vrtx.com/releases.cfm?hdr02=press

I got my notification by e-mail from vertex.     : )

You seem to be diminishing the importance of this 1%.  First off to be clear.....it's less than 1%.  Second, if 1% of the people died during trials the drug would not have been approved.  It is a big deal.

The reason that this is being "hyped"..... publicly announced and discussed is that often, the lesser experienced doctors may monitor people as well as the more experienced trial doctors.  The intention of this thread is probably not to scare people away from treatment, but to better educate the patients so that they will get a higher level of care.

I know a patient who got very very sick from the rash.  People in weakened conditions can get very sick, very fast.  

willy

[orphanedhawk]

Thanks for the link.
I had no idea.
Personally I avoid antibiotics and have had allergic reactions to some, including immediately after my transplant while in the hospital.
My hepatologist has all his post transplant patients use them whenever they have dental work. The reason, is to avoid a very rare though horrible, possible infection.

I copied this from the link you provided:

"Patients at risk are mainly those with previous experience of hepatotoxic reaction to antibiotics, the aged or those with impaired hepatic function in the absence of close monitoring, making it important to carefully balance potential risks with expected benefits in primary care."