Have you taken time to read the prescribing information (“PI”) for your thyroid hormone replacement medication? If not, you should. Because as Francis Bacon said: “Knowledge is power”. You can ask your pharmacist for the information (if it doesn’t come with your medication) or you can find it online here: http://www.rxabbvie.com/pdf/synthroid.pdf
Recently, I spent some time reviewing the over 20 page PI for Synthroid (levothyroxine sodium tablets) and found many interesting things I wanted to share and discuss. Below I have highlighted the items that caught my attention. These are the things that interest me the most, but not a replacment for reading the PI for your medication and discussing it with your doctor.
SOY AND IRON
The first item that I found of interest in the Prescribing Information was under CLINICAL PHARMACOLOGY – Pharmacokinetics – Absorption. It states: “T4 absorption is increased by fasting, and decreased malabsorption syndromes and by certain foods such as soybean infant formula.” In other words, infant formula made from soy can interfere with your child’s absorption of the medication. Our pediatric endocrinologist mentioned this to us, but I am always shocked at the number of parents of children with congenital hypothyroidism that I talk with who have never heard this information. Here is an article in the US News about the importance of avoiding soy, not just in infants, but also in children and adults (see the discussion about soy milk). http://health.usnews.com/health-news/news/articles/2012/08/21/soy-formula-may-harm-babies-with-underactive-thyroid-report
Another thing I found under PRECAUTIONS – Information for Patients – item 13 was reference to iron and calcium supplements and antacids, which can decrease the absorption of levothyroxine sodium tablets. The PI states that the medicine “should not be administered within 4 hours of these agents”. So, parents of infants with congenital hypothyroidism need to talk to their doctors about infant formula with iron. Also, it was recommended that I give my boys iron drops when they were infants, because they were breast fed. I gave them the drops later in the day to avoid potential interference with the absorption of their medication. I also take my vitamins and minerals at lunch and dinner for the same reason.
To me, this highlights the importance of limiting soy intake, but also of having regular blood tests for infants and children so that any dietary changes that maybe affecting absorption will be caught and can be changed.
Absorption of T4 is increased by fasting, which is why your doctor and pharmacists advise you to take your medication on an empty stomach and wait 30 minutes to an hour before eating breakfast. See the explanation under the section of the PI entitled “CLINICAL PHARMACOLOGY – Pharmacokinetics – Absorption”. This is also noted under “PRECAUTIONS – Information for Patients – Item 5”. Our pediatric endocrinologist advised us to give the kids their medication first thing in the morning and then wait 45 minutes to an hour (if we could) before letting our children eat. It was challenging when they were very young and woke up hungry. Now, they are content with cartoons until it’s time to eat – and an occasional stick of gum to assuage those hunger pains.
PRECAUTIONS – General: “Levothyroxine has a narrow therapeutic index. Regardless of the indication for use, careful dosage titration is necessary to avoid the consequences of over – or under-treatment. These consequences include, among others, effects on growth and development, cardiovascular function, bone metabolism, reproductive function, cognitive function, emotional state, gastrointestinal function, and on glucose and lipid metabolism.” Wikipedia defines therapeutic index as the comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes death (in animal studies) or toxicity (in human studies). http://en.wikipedia.org/wiki/Therapeutic_index. Drugs with a narrow therapeutic index have little difference between toxic and therapeutic doses. So, with Synthroid having a narrow therapeutic index, it means that even if your dosage is off just a bit, it can throw off your TSH and cause side effects. (See http://www.synthroid.com/prescription/rightdose.aspx)
Under PRECAUTIONS – Congenital Hypothyroidism, it states: “During the first 2 weeks of Synthroid therapy, infants should be closely monitored for cardiac overload, arrhythmias, and aspiration from avid suckling. The patient should be monitored closely to avoid undertreatment or overtreatment.” The PI references the link between overtreatment and crainiosynostosis (skull closing too soon), which is something we went through with my youngest son (to read more about how what symptoms to watch for read this post http://www.thyroidmom.com/blog/the-hyper-hypo-roller-coast.html).
This matter is again addressed under PRECAUTIONS – Pediatrics. It states: “The recommended frequency of monitoring of TSH and total or free T4 in children is as follows: at 2 and 4 weeks after the initiation of treatment; every 1-2 months during the first year of life; every 2-3 months between 1 and 3 years of age; and every 3-12 months thereafter until growth is completed. More frequent intervals of monitoring may be necessary if poor compliance is suspected or abnormal values are obtained. It is recommended that TSH and T4 levels, and a physical examination, if indicated be performed 2 weeks after any change in SYNTHROID dosage.” I found this particularly interesting given a recent discussion among parents of children with congenital hypothyroidism from around the world in which many of us had been told varying information by our pediatric endocrinologists about how often thyroid levels need to be checked at each age. If there is any question or concern, take this information to your doctor and discuss it with them.
For children with acquired hypothyroidism (diagnosed when older than an infant), the PI again emphasizes close monitoring and discusses symptoms. It states: “Undertreatment may result in poor school performance due to impaired concentration and slowed mentation and in reduced adult height.” Poor school performance!! Slowed mentation!! Reduced adult height!! These can be the results of not treating hypothyroidism in children!! It is important to read and understand this information so you know what symptoms to be on the look-out for, particularly in children. The PI talks about catch-up growth, which is something we observed in both children, but more so with our oldest son.
Overall, these sections of the PI remind me of the importance of having thyroid levels closely monitored, especially in children with congenital hypothyroidism, hypothyroidism, or Hashimoto’s Thyroiditis.
Another thing that jumped out at me was what I found under the section labeled “Inactive Ingredients” – namely the food dyes. I know that this is life saving medication for my children and some of you may think I’m being over-reactive regarding this, but it’s something that bothers me. Food dyes are not necessary in medicine or food. My children are now taking the generic form of Synthroid (Levothyroxine) and are on 50 mcg, so there is no dye in their current medications. I am taking an alternating dose of 112 mcg and 125 mcg, so there is D&C Red No.27 & 30 Aluminum Lake and FD&C Yellow No.6 Aluminum Lake, FD&C Red No.40 Aluminum Lake, FD&C Blue No.1 Aluminum Lake in mine. I’m guessing the food dyes were added so that we can tell the doses apart (particularly for those of us that are taking alternating doses). I think I’m smart enough to figure that out and would prefer that the food dyes be eliminated, as they don’t appear to have any medicinal qualities. If we really need the different colors, I wish they could add them on the bottle with different stickers or different colored lids. An article on Synthroid by Physician’s Desk Reference suggests taking 50 mcg to make your dose, if you are sensitive to dyes: http://www.pdrhealth.com/drugs/synthroid
There is an entire section of the PI devoted to pediatric dosage (congenital or acquired). It talks about how to administer the medication and what dose to start newborns on, etc. It’s worth reading just for information.
TRIAL OFF MEDS
The PI suggests a trial off Synthroid for children who have not been diagnosed with “permanent hypothyroidism”, in other words children who have thyroid glands that appear to be normal but aren’t functioning. The PI states that this should not be done until after age 3. We did a trial off Synthroid with my oldest son, but test results after the 30 day trial period indicated high levels of TSH. So, he will be on Synthroid for the rest of his life. We have not done the trial off meds with my youngest son, but did have an ultrasound done confirming that he has a thyroid gland. Not sure that it’s worth having him do the trial off considering his brother, mother, father and grandmother all have thyroid disorders. If you have a child with hypothyroidism who is under the age of 3, you need to read this section of the PI as it outlines the testing protocols for the trial off the medication.
BONE MINERAL DENSITY
Particularly of interest to women would be the section entitled PRECAUTIONS – Effects on Bone Mineral Density. It states: “In women, long-term levothyroxine sodium therapy has been associated with increased bone resorption, thereby decreasing bone mineral density, especially in post-menopausal women on greater than replacement doses or in women who are receiving suppressive doses of levothyroxine sodium.” It goes on to say “Therefore, it is recommended that patients receiving levothyroxine sodium be given the minimum dose necessary to achieve the desired clinical and biochemical response.” My endocrinologist highlighted this to me, particularly because my mother has already been diagnosed with osteopenia (lower than normal bone mineral density). I was told to be sure that I’m getting enough calcium, but to also be sure that I’m taking it at least 4 hours AFTER taking Synthroid. I’m also wondering what effect Armour (natural thyroid hormone) has on bone density (something I’ll be asking and writing about soon). Being the mother of children with congenital hypothyroidism, I’m wondering about the effects on children. I’m guessing this hasn’t been studied yet, but I wonder about children who take Synthroid for their entire life and what effects Synthroid has on their bone mineral density. I need to discuss this more with my children’s pediatric endocrinologist. My boys love milk, so I think they are probably fine, but it bears asking if they need more than the daily average of calcium normally recommended for children.
OTHER CONGENITAL ABNORMALITIES
Another interesting find was about other congenital abnormalities. I’m not sure why it’s in the PI for Synthroid, but it states: “Infants with congenital hypothyroidism appear to be at increased risk for other congenital anomalies, with cardiovascular anomalies (pulmonary stenosis, atrial septal defect, and ventricular septal defect) being the most common association.” I have been dealing with congenital hypothyroidism for nearly 8 years now, and I have never heard of this association between congenital hypothyroidism and cardiovascular anomalies. Neither of my children have any other congenital defects, so perhaps this is why it was never brought up. I did find this interesting study in the International Journal of Pediatric Endocrinology discussing the link between congenital hypothyroidism and other congenital abnormalities: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2864451/#
Make sure to read the section entitled “PRECAUTIONS – Drug Interactions”. You will find additional references to the troubles with Iron, Calcium and Antacids, but also many other things that may affect your ability to take Synthroid.
BLACK BOX WARNINGS
Finally – the black box warning – my husband used to be in pharmaceutical sales. He says it’s a big deal for a drug to have black box warning in their PI. Synthroid has one, and you should read it. It talks about how Synthroid should NOT be used for the treatment of obesity or for weight loss.
Well, that’s my summary of the most interesting things I found in the Prescribing Information for Synthroid. I hope it helps you. Again, knowledge is power. Just from re-reading this fine print, I’ve found many new things that I want to discuss with my endocrinologist and my children’s pediatric endocrinologist.
By Blythe Clifford