Dosing thyroid replacement therapy correctly to achieve a euthyroid state can be challenging at times. If hypothyroidism is not appropriately treated, it can make a person feel rather tired and weak, potentially raise cholesterol levels and place a person at risk of a heart attack and/or stroke. Conversely, hyperthyroidism can result in symptoms including nervousness, increased heart rate and an intolerance to heat. Thus, it is useful to understand some of the medication related reasons why we can go from having stable control with thyroid medications to becoming hyper or hypothyroid.
One of the ways that a patient can become unstable is by beginning (or ceasing) a medication which can affect the absorption of thyroxine. The mechanism for this is usually that the causative medication binds to thyroxine in the gastrointestinal tract, thereby preventing its absorption. The most common examples are iron salts such as ferrous sulphate, antacids that contain aluminium hydroxide, calcium supplements, cholestyramine, ciprofloxacin (potentially other quinolone antibiotics), lanthanum, orlistat, polystyrene sulfonate resins, raloxifene, sevelamer, regular use of simethicone, soy preparations and sucralfate. Fibre supplements have been known to interfere with the absorption of thyroxine.
Studies have also shown that proton pump inhibitors such as omeprazole, rabeprazole or pantoprazole can inhibit the absorption of thyroxine due to the change in the gastric acidity. A hypochlorhydric gastric environment can prevent thyroxine from dissociating from the sodium salt, and thereby reduce the absorption of thyroxine. In most of these cases, a separation of administration times of approximately 4-5 hours is recommended, however a time separation of 10 hours is the suggested administration gap for polystyrene sulfonate resins. This point becomes particularly important for older patients where poly-pharmacy is more common, thus we should be thinking more carefully about how we allocate drug administration times.
If the metabolism rate of thyroxine changes significantly, we again need to alter (increase) the thyroxine dosage to compensate. This can happen when commencing medications which induce enzymes involved in the metabolism of thyroxine. Examples of this include sunitinib, phenytoin, barbiturates, carbamazepine, oxcarbazepine, primidone, St John’s Wort and rifampicin. There are also reports that propranolol and amiodarone can affect conversion of thyroxine (T4) to tri-iodothyronine (T3) which can have unpredictable effects. Therefore it is prudent, when any of these medications are commenced in combination with thyroxine, that we monitor for both symptom changes and check thyroid function tests.
Protein in the bloodstream assists with the transportation of thyroid hormones through the blood. If the levels of this protein, thyroid-binding globulin (TBG), are increased then this will decrease the amount of thyroid hormone that can reach tissues, resulting in apparent hypothyroidism. An example of this can occur with combined oral contraceptives, or other hormone replacement therapy, which would subsequently require blood monitoring of thyroxine and potentially an increase in the dose. This can also occur during pregnancy, as the body increases oestrogen production, thus it is necessary to monitor and most likely increase the thyroxine dose early in pregnancy. In contrast to this, androgens such as testosterone can reduce TBG, and therefore cause hyperthyroidism, requiring a dose reduction of thyroxine.
There are many drugs that can interrupt or interfere with thyroid hormone treatment and as we age, and increase the number of medications we take, the risk of taking a combination of medications that interact with thyroxine increases. The risky part of drug interactions is that, due to the long half-life of thyroxine, we may not know for weeks or months after such changes that there is a problem; or until symptoms of hyper or hypothyroidism have started to become apparent. We need to remain aware of the existence of potential interactions, and take remedial action by adjusting drug doses and administration times appropriately, and ensure that we regularly monitor symptoms and pathology after changes in drug regimens.
- De Luise M A. Thyroid Disease in the Elderly. JPPR 2003; 33 (3): 228-30.
- Endocrinology Expert Group. Drugs that influence thyroid hormones and function. In: Therapeutic guidelines: endocrinology. Version 5 (1). Melbourne: Therapeutic Guidelines Limited; 2013.
- Hughes G, Donnelly R, James-Chatgilou G, editors. Clinical pharmacy: a practical approach. 2nd ed. Melbourne: The Society of Hospital Pharmacists of Australia, 2001.
- Rossi S, editor. Australian Medicines Handbook 2013. Adelaide: Australian Medicines Handbook Pty Ltd; 2013.
- Sweetman SC, editor. Martindale: The Complete Drug Reference. 36th ed. London: Pharmaceutical Press, 2008. p. 2172-4.