February 4th, 2010

Non-Cirrhotic Portal Hypertension: A Rare but Serious Side Effect of ddI

videx_old formulation.The FDA has issued a warning about an association between use of ddI (didanosine) and the development of non-cirrhotic portal hypertension:

Non-cirrhotic portal hypertension (portal hypertension that is not caused by cirrhosis of the liver) is rare in the United States. It occurs when blood flow in the major vein in the liver (the portal vein) slows down.
Because of the potential severity of portal hypertension, including death from hemorrhaging esophageal varices, FDA has revised the Warning and Precautions section of the didanosine drug label to assure safe use of the medication.

Yes, this is a bad one — of the 42 reported cases, 4 patients died; several others required aggressive interventions to reduce the risk of variceal bleeding, including banding/ligation of esophageal varices, transjugular intrahepatic portosystemic shunts (TIPPS),  and liver transplantation.

ddI was our second approved antiretroviral, way back in 1991.

Over the years, it has improved — we’ve reduced the dose, now can give it once daily, and have gotten rid of the original bizarre formulation (pictured).

And while it does have reasonable antiviral potency (at least for an NRTI), its myriad potentially severe side effects — neuropathy, pancreatitis, lactic acidosis, to name a few — and the availability of numerous other options mean that there is little reason for a person to be receiving it today.

6 Responses to “Non-Cirrhotic Portal Hypertension: A Rare but Serious Side Effect of ddI”

  1. Just curious–When would you still use ddI and why?

    • Paul Sax says:

      Two situations come to mind:
      1) patient has been on it for years, stable and no side effects
      2) no other options for NRTIs (resource-limited setting)

      Won’t comment on the latter — not my area of expertise — but for the former, I’d carefully scrutinize the regimen to try and figure out if it’s really needed. Most of the time there are enough background active agents (especially these days) to make older NRTIs not necessary.


  2. Clint says:

    Thank you for bringing this information to light. Until now I was not aware of any drug which could possibly cause non-Cirrhotic portal hypertension.

  3. Robert Boulanger says:

    Hello,I am one of these patients. Bleeding occurred last year in April for the first time. My Liver enzymes had been slightly elevated for years. I was told by Doctors not to worry about this. Bleeding occurred again this year,nearly one year after first bleed.Now my Liver is getting worse.I was at the time in SF and I am now living in Montreal where I was born. I am a long term survivor,living with HIV since 1978. I refused to take AZT,and started to take Meds only 1994. Anyone who would like more info do not hesitate to contact me.

  4. Marcos Augusto says:

    I have been suffering from Non-Cirrhotic Portal Hypertension for about 7 years now thanks to Videx, which i took from 1999 to 2002; I’ve had Variceal Bandings performed several times thanks to Videx; I’ve had severe intestinal bleeding quite a few times thanks to Videx, and let’s not forget my spleen that’s so swelled up with back-up blood that it is twice its normal size and my liver, whose extremities look “shredded and fatty”, as described by a gastroenterologist, again, all thanks to Videx.
    To help with the dangers of Non-Cirrhotic Portal Hypertension i now have to take daily a beta blocker with side effects that i hate (how about feeling literally tortured by coldness every year from October to May, even at 72 degrees indoors, to the point of crying ? Doesn’t that sound fun ?), but, to give the med some credit, it seems to be working in my case.
    Considering all we now know about the dangers of using this med, why is it still being prescribed by HIV specialists or even allowed by the FDA to be sold in the USA is beyond my comprehension…

  5. Marcus Aurelius says:

    I have just recently been diagnosed with Non-Cirrhotic Portal Hypertension, my liver has been enlarged for 7 years past chemotherapy on Folfox 5. I am not even 30 y.o. yet, not a habitual drinker, not HIV positive, nor user of any street drugs. If anyone knows what to do in my case, please let me know…

HIV Information: Author Paul Sax, M.D.

Paul E. Sax, MD

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NEJM Journal Watch
Infectious Diseases

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