Synthroid and Anesthesia: Perioperative Interaction Guide

What the label says that applies to surgery

Two sentences in the Warnings and Precautions section of the levothyroxine sodium tablets label address the operating room directly:

• 'Monitor for cardiac arrhythmias during surgical procedures in patients with coronary artery disease receiving suppressive levothyroxine sodium therapy.'
• 'Monitor patients receiving concomitant levothyroxine sodium and sympathomimetic agents for signs and symptoms of coronary insufficiency.' [1]

These sentences come from a generic levothyroxine sodium tablets label and are not presented as Synthroid-specific wording. The same section says that if cardiac symptoms develop or worsen, the dose can be reduced or withheld for one week and restarted at a lower dose [1].

The boxed warning says thyroid hormones should not be used to treat obesity or for weight loss. It adds that larger doses may produce serious or even life-threatening toxicity, particularly when given with sympathomimetic amines such as those used for their anorectic effects [1].

Ketamine and sympathomimetic drugs

Ketamine is the anesthetic named as having additive cardiovascular effects with levothyroxine [1].

The label describes in detail the over-replaced state. Over-treatment with levothyroxine may increase heart rate, cardiac wall thickness and cardiac contractility, and may precipitate angina or arrhythmias, particularly in patients with cardiovascular disease and in elderly patients [1]. For sympathomimetic agents used alongside levothyroxine, the instruction is to monitor for signs and symptoms of coronary insufficiency [1].

Under-replacement and the adrenal gland

Myxedema coma is the under-treated extreme. The label calls it a life-threatening emergency characterised by poor circulation and hypometabolism, notes that absorption of levothyroxine from the gut may be unpredictable in that state, and states that oral thyroid hormone products are not recommended to treat it; it names thyroid hormone formulated for intravenous administration instead [1].

Uncorrected adrenal insufficiency is a contraindication to levothyroxine [1]. Thyroid hormone increases the metabolic clearance of glucocorticoids. The label directs that patients with adrenal insufficiency be treated with replacement glucocorticoids before levothyroxine is started, because starting thyroid hormone first may precipitate an acute adrenal crisis [1].

Medicines given around surgery that affect absorption

Some medicines used around a procedure, including PPIs, sucralfate and antacids, may reduce levothyroxine absorption. The tablet label calls for monitoring but gives no fixed spacing for those medicines [1].

Calcium carbonate, ferrous sulfate, sevelamer and lanthanum are grouped as phosphate binders, and the label says to give levothyroxine sodium tablets at least 4 hours apart from these agents [1]. Bile acid sequestrants (colesevelam, cholestyramine, colestipol) and the ion-exchange resin Kayexalate are handled differently: levothyroxine is given at least 4 hours before them, or TSH is monitored [1].

One 2023 open-label study switched 47 thyroidectomized patients on levothyroxine tablets and a PPI to the same dose as Tirosint soft gelatin capsules for 12 weeks; 45 completed, and mean TSH fell by 0.32 mIU/L at 6 weeks and 0.68 mIU/L at 12 weeks [3]. The study had no control group and was sponsor-linked, so it does not establish that PPIs cannot affect capsule absorption [3].

Anticoagulants, digoxin, amiodarone and steroids

Levothyroxine increases the response to oral anticoagulant therapy. The label says a decrease in anticoagulant dose may be warranted when the hypothyroid state is corrected or when the levothyroxine dose is increased, and that coagulation tests should be monitored closely to allow timely adjustment [1].

Levothyroxine may also reduce the therapeutic effect of digitalis glycosides, and serum digitalis levels may fall as a hypothyroid patient becomes euthyroid, requiring a higher digitalis dose [1].

Amiodarone inhibits peripheral conversion of T4 to T3 and can produce isolated biochemical changes, such as higher free T4 with low or normal free T3, in patients who remain clinically euthyroid [1]. Glucocorticoids act at the same step: short-term large doses may lower serum T3 concentrations by 30% with minimal change in T4, and long-term use can lower T3 and T4 slightly through reduced thyroid-binding globulin production [1]. Propranolol at doses above 160 mg/day changes T3 and T4 levels while TSH stays normal [1].

For monitoring after any dose change, two label points matter. The peak effect of a given dose may not be attained for 4 to 6 weeks, and in secondary or tertiary hypothyroidism TSH is not a reliable measure of dose adequacy; free T4 is used instead [1].

The morning dose

The label's administration instruction is a single daily dose on an empty stomach, one-half to one hour before breakfast with a full glass of water, and at least 4 hours before or after drugs known to interfere with absorption [1].

Suppressive therapy in thyroid cancer

TSH suppression is one of the drug's labelled indications: levothyroxine is used as an adjunct to surgery and radioiodine in thyrotropin-dependent well-differentiated thyroid cancer [1]. This is the setting the label has in mind when it refers to suppressive levothyroxine therapy and arrhythmia monitoring during surgical procedures [1].