A shortage of a drug used to treat pregnant women with hyperthyroidism is putting some women at significant risk, says a Toronto endocrinologist.
Propylthiouracil (PTU), used mainly to treat younger pregnant women who have an overactive thyroid gland due to Grave’s disease, was discontinued in December 2019 due to “manufacturing issues,” according to Drug Shortages Canada.
Grave’s disease generally affects people between the ages of 30 to 50 but can occur at any age. The disease affects as many as one in 100 people in Canada, says the Thyroid Foundation of Canada. It can be treated by surgically removing the thyroid gland or by taking radioactive iodine (RAI) pills but many patients opt to take antithyroid drugs, such as PTU or methimazole, to preserve the thyroid gland and avoid lifelong thyroid replacement afterwards.
While methimazole is still widely available, it is associated with double the risk of birth defects compared to PTU.
In 2018, there were about 36,000 prescriptions for PTU, according to Health Canada’s Marketed Health Products Directorate.
Now, with the drug in short supply and no manufacturing on the horizon, pregnant patients have to scour neighbourhoods in search, sometimes calling as many as 10 different pharmacies to find a supply.
Omar Saeed, an endocrinologist and assistant professor at the University of Toronto, says that the situation is rare.
“From my experience, I have not seen a situation where a medication has been outright discontinued. I would have to think that it is very uncommon for a medication, especially one that has been around for decades with no new safety concerns, to suddenly go out of production completely.”
The Canadian Society of Endocrinology and Metabolism (CSEM) wrote to Canadian Health Minister Patty Hajdu outlining its concerns in April and is in discussions with Health Canada to resolve the situation. Among the steps being taken are an assessment of the PTU supply across Canada, discussions with Paladin Labs and other manufacturers to restart PTU manufacturing, and exploring the availability of PTU in other countries to review whether it could be imported under the Interim Order Respecting Drugs, Medical Devices and Foods for a Special Dietary Purpose in Relation to COVID-19.
Steve Morgan, a professor at UBC’S School of Population and Public Health, says shortages like this generally are rare.
“There is no single reason for shortages. Shortages or temporary outages occur in pharmaceutical markets around the world for a variety of reasons and manufacturers also sometimes cease to produce drugs for a variety of reasons.”
He argues that the Canadian medical system is not as good as it seems, which can lead to some shortages.
“Canadians are lulled into believing that our system is good just because it is better than possibly the worst system in the world, and that is the United States … Canada is the only wealthy country in the world that has a universal system of health insurance without universal coverage of medicines as a part of it.”
Heather Zoumas Lubeski, vice-president of corporate affairs at Endo International, the parent company of Paladin Labs that makes PTU, said the discontinuation was not due to “safety or efficacy concerns.”
“The product was manufactured by a partner who stopped production and we do not have another option available,” says Zoumas Lubeski.
For Saeed, the response does not help.
“My first reaction is of disappointment because we’ve known this drug to be safe and effective for the indications that we use it for … This medication has been around for a long time and has a clear set of indications for use in a small subset of patients such as those with hyperthyroidism in early pregnancy. It is unfortunate that these patients can no longer count on this medication being available.”
Without PTU, there are few other options. RAI is contraindicated in pregnancy and surgical removal of the thyroid while pregnant is invasive and comes with higher complication rates.
According to Saeed, the choice is to take methimazole or get no medication. Without medication, “a mother could potentially have early labour and get a potentially dangerous condition associated with high blood pressure called preeclampsia. Without treatment, consequences for the baby include fetal tachycardia, small size for gestational age at birth, premature birth, stillbirth, and congenital malformations,” says Saeed.
But taking methimazole carries its own risk of birth defects.
“As an example, methimazole causes an increased risk of abnormal connections between the windpipe/trachea and the esophagus … It can also cause abnormalities in the development of the nasal passage,” he says.
Seema Marwaha, an internal medicine physician, was diagnosed with Grave’s disease postpartum and faces a difficult choice if she wants to have another child.
“All of my choices sort of suck. I want to have a second baby. I don’t want to have my thyroid removed. I don’t want to destroy my thyroid gland with radioactive iodine pills. I also don’t want to take the risk of being on a medication with birth defects or going hyperthyroid during my pregnancy, which can be associated with miscarriage,” says Marwaha. “So without PTU, I’m stuck with all of these options that have an increased personal risk to me or potentially my baby should I get pregnant.”
Saeed tells patients considering pregnancy of the shortage of PTU to give them time to consider their options.
“I’m actually telling them that this is very important for you to know because I don’t want you to get caught in a situation where we can’t get you the best treatment.
“We want to make sure that they don’t get caught in a situation where there is no good alternative. To me, that is sort of the crux of the issue.”