Zydelig: The Black Box Warnings for use in CLL (Chronic Lymphocytic Leukemia), SLL (Small Lymphocytic Lymphoma), and Follicular Lymphoma
Before you get very far into the Zydelig (CAL 101 or GS 1101 or idelasilib) label, you come across a big bold black box warning.
WARNING: FATAL AND SERIOUS TOXICITIES: HEPATIC, SEVERE DIARRHEA, COLITIS, PNEUMONITIS, and INTESTINAL PERFORATION
See full prescribing information for complete boxed warning.
While black box warnings are the strongest language that the FDA can put on a label, it is focused on the worst of the worst and not necessarily on common problems.
Our old friend, the rather gentle giant in the CLL world, rituximab has multiple black box warnings (as it should):
From the Rituxan label:
Each one of those problems can kill us (PML has a 90% mortality rate, worse than Ebola) and if it doesn't cause our demise, leave us badly shaken and permanently damaged. But those concerns are thankfully relatively rare and it hasn't stop me or many others from enjoying the real benefits of rituximab.
Black boxes are found on many labels. Even common antidepressant medications come with a black box warning for the rare but obviously critically important issue of increased risk of suicide in those patients younger than 24.
For Zydelig, the serious liver issues and severe diarrhea and colitis occurred in one out of every seven patients in their trials. Not so rare. Colitis is miserable and can be fatal. Fortunately, the other, generally more life threatening, adverse events are less common.
Gilead have instituted a FDA mandated REMS (Risk Evaluation and Mitigation Strategy) program. Using this link and further links found on that webpage, you can see how serious the FDA and Gilead are about staying ahead of these potential problems for us patients.
They are being proactive. The fine print in the package insert gives strict guidelines on monitoring and what do based on what the patient's conditions and the lab test are telling the doctor. And most problems can be reversed if the patient and clinician are on their game and respond quickly and appropriately when there's a signal of an emerging problem. After a period off the drug, many of us can safely restart it at a reduced dose and continue to do get the benefits.
This is yet another reason to be choosy about who is managing your CLL. Please pick a doctor who is experienced with CLL and with the new medications so that he or she is on top of all the good and all the possible bad associated with them.
CLL is itself risky. Doing nothing is not an option for many of us.
FCR is no cakewalk. BR is not much better. Lenalidomide comes with a host of its own unique nasty issues.
But all of these drugs and and other drug combinations have saved lives. We can not afford to be therapeutic nihilists because we have no guaranteed safe choices.
Carefully read the label. Ask your doctor. Insist on the correct monitoring. Report any and all problems promptly.
Odds are heavily in our favor. Have perspective.
One place I do see as an advantage for idelalisib at this time is that there it has no warning on the label about bleeding in association with anticoagulants as there is with ibrutinib. By the way, Imbruvica has no black box warnings. The bleeding issues with Imbruvica are being studied more as they are not presently fully understood. Time will tell, but there is reason to believe that most of the bleeding/bruising problems may be simply increased bruising that is more a cosmetic than a health issue. Still, at this time, Zydelig has no such caution and Imbruvica does.
As I said in my last post, we are so lucky to have this choice of two new potent oral medicines that are targeted at our cancer.
To borrow from my dear friend and patient advocate, WWW: May our paths be well chosen.
WARNING: FATAL AND SERIOUS TOXICITIES: HEPATIC, SEVERE DIARRHEA, COLITIS, PNEUMONITIS, and INTESTINAL PERFORATION
See full prescribing information for complete boxed warning.
- Fatal and/or serious hepatotoxicity occurred in 14% of Zydelig- treated patients. Monitor hepatic function prior to and during treatment. Interrupt and then reduce or discontinue Zydelig. (5.1)
- Fatal and/or serious and severe diarrhea or colitis occurred in 14% of Zydelig-treated patients. Monitor for the development of severe diarrhea or colitis. Interrupt and then reduce or discontinue Zydelig. (5.2)
- Fatal and serious pneumonitis can occur in Zydelig-treated patients. Monitor for pulmonary symptoms and bilateral interstitial infiltrates. Interrupt or discontinue Zydelig. (5.3)
- Fatal and serious intestinal perforation can occur in Zydelig- treated patients across clinical trials. Discontinue Zydelig if intestinal perforation is suspected. (5.4)
While black box warnings are the strongest language that the FDA can put on a label, it is focused on the worst of the worst and not necessarily on common problems.
Our old friend, the rather gentle giant in the CLL world, rituximab has multiple black box warnings (as it should):
From the Rituxan label:
WARNING: FATAL INFUSION REACTIONS, SEVERE
MUCOCUTANEOUS REACTIONS, HEPATITIS B VIRUS
REACTIVATION and PROGRESSIVE MULTIFOCAL
LEUKOENCEPHALOPATHY
See full prescribing information for complete boxed warning.
See full prescribing information for complete boxed warning.
-
Fatal infusion reactions within 24 hours of Rituxan infusion; approximately 80% of fatal reactions occurred with first infusion.
Monitor patients and discontinue Rituxan infusion for severe
reactions (5.1).
-
Severe mucocutaneous reactions, some with fatal outcomes (5.2).
-
Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death (5.3).
- Progressive multifocal leukoencephalopathy (PML) resulting in death (5.4).
Black boxes are found on many labels. Even common antidepressant medications come with a black box warning for the rare but obviously critically important issue of increased risk of suicide in those patients younger than 24.
For Zydelig, the serious liver issues and severe diarrhea and colitis occurred in one out of every seven patients in their trials. Not so rare. Colitis is miserable and can be fatal. Fortunately, the other, generally more life threatening, adverse events are less common.
Gilead have instituted a FDA mandated REMS (Risk Evaluation and Mitigation Strategy) program. Using this link and further links found on that webpage, you can see how serious the FDA and Gilead are about staying ahead of these potential problems for us patients.
They are being proactive. The fine print in the package insert gives strict guidelines on monitoring and what do based on what the patient's conditions and the lab test are telling the doctor. And most problems can be reversed if the patient and clinician are on their game and respond quickly and appropriately when there's a signal of an emerging problem. After a period off the drug, many of us can safely restart it at a reduced dose and continue to do get the benefits.
This is yet another reason to be choosy about who is managing your CLL. Please pick a doctor who is experienced with CLL and with the new medications so that he or she is on top of all the good and all the possible bad associated with them.
CLL is itself risky. Doing nothing is not an option for many of us.
FCR is no cakewalk. BR is not much better. Lenalidomide comes with a host of its own unique nasty issues.
But all of these drugs and and other drug combinations have saved lives. We can not afford to be therapeutic nihilists because we have no guaranteed safe choices.
Carefully read the label. Ask your doctor. Insist on the correct monitoring. Report any and all problems promptly.
Odds are heavily in our favor. Have perspective.
One place I do see as an advantage for idelalisib at this time is that there it has no warning on the label about bleeding in association with anticoagulants as there is with ibrutinib. By the way, Imbruvica has no black box warnings. The bleeding issues with Imbruvica are being studied more as they are not presently fully understood. Time will tell, but there is reason to believe that most of the bleeding/bruising problems may be simply increased bruising that is more a cosmetic than a health issue. Still, at this time, Zydelig has no such caution and Imbruvica does.
As I said in my last post, we are so lucky to have this choice of two new potent oral medicines that are targeted at our cancer.
To borrow from my dear friend and patient advocate, WWW: May our paths be well chosen.
Labels: black box warning, bruising, CA-101, Chronic lymphocytic leukemia, CLL, diarrhea, FDA approval, GS-1101, ibrutinib, Idelalisib, Imbruvica, Rituximab, side effects, SLL, targeted therapy, TKI, Zydelig
posted by Brian Koffman at
12:21 AM
1 Comments:
Nice balance Brian. As our former "Catcher in the Rye" Chaya Venkat often said "There is no free lunch" but if one is unlucky enough to get CLL/SLL the "Lunches" are indeed getting more tasty;-)
WWW
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