The risks of PTU

Summary

ResearchBlogging.orgThere are two main drugs used to treat Graves’ Disease medically – MMI (methimazole or it’s nearly identical relative carbimazole) and PTU (propylthiouracil).

As with all drugs, there are risks and side effects.  As a patient, I’ve often been frustrated when trying to understand exactly how risky these drugs are.  The listed risks (liver failure, loss of white blood cells) are terrifying, and yet, very few people ever experience these.  What do we know about the risks and what can we patients do to avoid them?  Dr. David Cooper at Johns Hopkins has published several papers about these risks and I’m going to review them over the next few weeks.

The paper today is a recent (2009) summary of two scientific meetings that were held to discuss the risks involved with the use of PTU.  Currently in the US, about 25% of Graves’ patients are on PTU.  Doctors prescribe PTU rather than MMI for several reasons.  PTU is considered better for pregnant women, especially during the first trimester, as MMI can sometimes cause birth defects.  Some people have an allergic reaction or other mild side effects from MMI and so take PTU instead.

Because of this, the general trend is to prescribe MMI first, and if that doesn’t work for some reason (pregnancy or adverse reaction), then switch to PTU.  MMI is also considered “better” than PTU in that in is more effective when people are severely hyperthyroid, people adhere to it better, and it causes less toxicity, especially at low doses.


So, how risky is PTU?

There are approximately 600,000 60,000 new cases of Graves’ diagnosed in the US each year.  Of these, 25% get put on PTU for one of the above reasons, so there are 15,000 people who start taking PTU each year.  Of these people, approximately 1 in 1000, or 15 people total, develop severe liver damage, and 1 or 2 die.

Various organizations keep different sorts of records on PTU-related liver failure.  For instance, there are 42 cases reported in the scientific literature since 1947, while the FDA knows of 47 cases.  UNOS (the organ transplant association) reported 23 liver transplants over a 17-year period related to PTU, but none related to MMI.  The FDA-AERS database lists 34 cases of liver failure in the last 20 years.

Who gets these nasty reactions?

The average dose of PTU in the people who had these reactions was 300 mg per day.  The victims had been taking PTU for 6-450 days.  About half had been taking PTU for less than 120 days, and half for more than that.  About a third of the victims were children, and there were two reports of fetal liver damage.  Because children make up only about 6% of Graves’ disease patients, but nearly 33% of the patients experiencing liver damage, PTU may affect children more negatively than it does adults.

Can you tell if you are having these reactions?

Because liver toxicity happens so rapidly, routine monitoring of liver values is not helpful.  Monitoring does not reduce the risk of liver injury because of the unpredictable nature of the drug reaction.  Signs of liver failure include:

  • jaundice (yellowish skin or eyes)
  • fatigue or malaise (tiredness)
  • nausea
  • anorexia (no appetite)
  • pharyngitis (sore throat)

If you have any of these signs, stop taking PTU and go get your liver enzymes checked immediately.

 

What about pregnancy?

I’ll quote here from the paper:

Considering the intricacies of care and risks involved for a woman with active [Graves’ disease] during pregnancy, treatment with radioactive iodine or surgery before pregnancy should be strongly considered for those who desire future pregnancy. Doing so can avoid the dilemma of choosing between a drug associated with a small risk of fetal birth defects [MMI] and another drug associated with a similarly small but finite risk of serious liver injury in the mother [PTU].

For women who choose not to take the risks of surgery (anesthesia, mistakes) or radioactive iodine (radioactivity, hypothyroidism), the current recommendation is to take:

  • PTU for the first trimester (to prevent birth defects)
  • MMI (if needed) for the second two trimesters

The upshot?

Stick to MMI if possible.  If you choose PTU, you will more than likely be one of the 999/1000 people who has no problems whatsoever.  Hooray!

But, be aware of the symptoms mentioned above and seek help immediately if you experience them.

If you are thinking about getting pregnant, have a good look over the risks of all of these options and talk with your doctor.

Reference
Cooper, D., & Rivkees, S. (2009). Putting Propylthiouracil in Perspective Journal of Clinical Endocrinology & Metabolism, 94 (6), 1881-1882 DOI: 10.1210/jc.2009-0850

Abstract

This paper had no abstract

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8 Responses to The risks of PTU

  1. Simon says:

    25% of 600,000 is 150,000 not 15,000, or did I miss something?

    If there are 47 cases since 1947, you need the number of people receiving PTU since 1947, which is presumably of the order of 150,000 (new people getting PTU in a year x 64 years).

    It is possible the figures are higher than that, as PTU was licensed in 1947, but I think the methimazole & Carbimazole drugs were licensed later as they were created to overcome shortcoming in PTU, so in the early years I suspect it was far more receiving PTU.

    So that is 47 reported cases of liver problems in about 10 million people, or of the order of 1 in 200,000 patients not 1 in a 1,000. It is likely that the incidence of ill effects are under reported, the “rule of thumb” is that only 1 in 10 bad outcomes are reported but that still means it is at least an order of magnitude safer than your article suggests (1 in 20,000 versus 1 in 1000).

    In practice the liver damage from PTU is substantially rarer than the other severe side effects of antithyroid drugs (agranulocytosis), but the evidence does support the FDA position that Methimazole and Carbimazole are safer than PTU so should be preferred. Last I looked the PTU preference in pregnancy was based on limited data, and all the common antithyroid drugs are believe to cause birth defects including PTU, which the quote you give doesn’t seem to acknowledge.

    I’m not a doctor, pharmacist, toxicologist or epidemiologist, just someone who thinks the current “panic” about PTU and liver damage is probably overstated.

  2. gravity says:

    Whoops – You are correct, the number from the paper is 60,000 new cases each year, and 25% of that is 15,000. The 1:1000 number is from the paper, which stated that 0.1% of adult PTU patients experienced liver damage.

    Thanks a bunch for your input – I wasn’t even aware there was a PTU “panic”. I’m planning on reviewing what I can find on MMI safety after I get through the PTU papers.

  3. Jen says:

    I just went to a new endo today because my insurance is no longer accepted at the practice which I’ve been at since the start of my diagnosis.

    From what I can recall, I’ve only ever been on PTU (diagnosed in 2004 or 2005 with Graves after a miscarriage, with remission periods), but this new endo has told me that I need to stop taking PTU as it’s dangerous outside of being pregnant (taken only in the 1st trimester).

    I have been on 50mg twice a day of PTUn (for the past year), and she is wanting me to go to 10mg a day of Methimazole, and I have to say, I’m scared of starting this drug.

    At this low dose, should I try it? Or, should I be steadfast in keeping to my PTU since I have no side effects.

    My current blood test levels as of last week while on PTU are: TSH: 0.03 & T4: 1.3

    Questions
    #1 – Is Methimozole safer than PTU as far as liver damage and side effects?
    #2 – Since I’ve had no side effects (liver tests fine, etc) am I going to be more prone to side effects from Methimazole?

    Any input would be greatly appreciated — I am not only dealing with a new endo, she is now telling me to try something new!

    God Bless all of you who are going through Graves <3

    • gravity says:

      Jen,

      If you look around on this website, you’ll find some more info about the relative pros and cons of MMT vs. PTU. Specifically, check out the category “anti-thyroid drugs”: http://graves.pandapoop.net/category/anti-thyroid-drugs/.

      I’ve never taken PTU, so I can’t speak for the side effects that I’ve experienced. Nor do I know about any studies that looked specifically at switching from one drug to the other, although I don’t think anything about PTU would make you MORE prone to side effects from MMT. As a non-medical person, I’d lean towards “if it ain’t broke, don’t fix it” and talk with your doctor about staying with what you know works for you, but that’s just my $0.02. Whichever drug you take, take it regularly at the same time each day and don’t skip doses. Certainly neither drug is outrageously “dangerous” or neither would be as common as they are. However, as you’ve heard, there are small, but significant risks with both drugs (and small, but significant risks with surgery and RAI too, and of course, the risks involved with not treating your GD at all – no easy options here).

      I’d encourage you to talk to your doctor about your fears (take an outgoing friend with you to your appointment if that makes you uncomfortable), and if needed, get a second opinion.

      Good luck,
      Gravity

  4. Joe Burnitt says:

    I’ve been on ptu for six months. How often should I have my liver checked ? My lft was last check 5 months ago and I had a liver ultrasound 2 months ago should I be worried.

    • gravity says:

      This is an excellent question for your doctor. My understanding is that the liver problems that are sometimes seen in people taking PTU come on really suddenly, so routine monitoring is not helpful. You might also work with your doctor to get on the lowest dose possible that still treats your GD. Higher doses have more risk than lower doses. Good luck!

  5. Shine says:

    A friend of mine, had skip a dose for the day because of lack of stocks she has. She been experienced a day after of drowsiness and unusualites. Is it possible effect of skipping the ptu dose??? Thank you for the response.

    • gravity says:

      Shine – have your friend read the article posted here about why your friend might be having those swings. PTU has a very short half-life in the body compared to MMI, so it is more important to take it multiple times per day. I know that when I bought MMI (generic) on my own without insurance, a month’s prescription was $15-20. I don’t know the price of PTU, but perhaps if MMI is cheaper, and your friend needs to save $, her doctor could prescribe the cheaper generics or maybe MMI (if that is cheaper – I don’t know).

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