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)
- 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
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.
Cooper, D., & Rivkees, S. (2009). Putting Propylthiouracil in Perspective Journal of Clinical Endocrinology & Metabolism, 94 (6), 1881-1882 DOI: 10.1210/jc.2009-0850
This paper had no abstract