Interaction of Liothyronine (T3) with other drugs

Liothyronine changes the rate of metabolism throughout the body, so it affects the action of many other drugs - and itself depends on some of them. Some interactions concern the absorption of tablets in the intestine, others the sensitivity of the heart and other organs. The editorial team has systematized the interactions described in official package inserts and clinical reviews and explains which of them are the most significant.

Two types of interactions of thyroid hormones

The interactions of liothyronine are conveniently divided into two large groups. The first is pharmacokinetic: other agents change the absorption, binding to blood proteins, or metabolism of T3. The second is pharmacodynamic: T3 changes how the body responds to other drugs, accelerating their elimination or increasing receptor sensitivity.

For thyroid hormones the second group is especially important. Since T3 accelerates the basal metabolism and increases the heart's sensitivity to catecholamines, any drug that affects heart rhythm, blood clotting or glucose levels potentially interacts with it.

Much of the data on interactions was obtained for levothyroxine, and for liothyronine they are transferred by analogy, since the active form of the hormone in both cases is T3. However, it is worth considering that liothyronine is absorbed faster and more completely, so some of the 'intestinal' interactions may be less pronounced for it.

A practical rule: when prescribing, discontinuing or changing the dose of a thyroid hormone, the doctor reviews the patient's other drugs. And vice versa - when adding a new drug to thyroid hormone treatment, it is worth checking whether a correction is needed.

The heart and nervous system: additive stimulation

Sympathomimetics - adrenaline, ephedrine, pseudoephedrine, phenylephrine, amphetamines, as well as clenbuterol - in combination with thyroid hormones enhance cardiovascular effects. Package inserts for thyroid drugs directly warn that combination with sympathomimetic amines during attempts at weight loss can cause serious or life-threatening toxicity.

Tricyclic antidepressants in combination with thyroid hormones can mutually enhance effects: the risk of arrhythmias and stimulation of the central nervous system increases. In psychiatry T3 is sometimes used as an addition to antidepressants, but precisely for that reason such therapy is conducted under careful monitoring.

Ketamine, when used in patients receiving thyroid hormones, can cause pronounced hypertension and tachycardia. The anesthesiologist must know about hormone use before any intervention.

Beta-blockers partially neutralize the cardiac effects of excess T3, which is why they are used in thyrotoxicosis. At the same time, a change in thyroid status can change the clearance of some beta-blockers, and the dose may require correction.

Warfarin, digoxin and antidiabetic agents

One of the most important interactions is with oral anticoagulants, in particular warfarin. Thyroid hormones accelerate the breakdown of blood clotting factors, so they enhance the action of warfarin. When starting T3 treatment or increasing the dose, the risk of bleeding rises, and the patient needs more frequent INR monitoring.

Digoxin and other cardiac glycosides act more weakly in hyperthyroidism or with thyroid hormone use: the volume of distribution and clearance of the drug increase, and its blood concentration decreases. On the other hand, an excess of hormones provokes arrhythmias that digoxin is meant to control.

Insulin and oral antidiabetic agents may be less effective under the influence of thyroid hormones, since T3 increases glucose production by the liver. At the start of thyroid hormone treatment the need for glucose-lowering therapy may rise, and after reducing their dose - decrease, which creates a risk of hypoglycemia.

These interactions are also important in the reverse direction: if a patient suddenly stops taking T3, the effect of warfarin may weaken and that of digoxin may strengthen. Therefore any changes in therapy are coordinated with a doctor.

Agents affecting absorption and transport

Bile acid sequestrants (cholestyramine, colestipol, colesevelam) bind thyroid hormones in the intestine and reduce their absorption. Package inserts recommend separating the intake of these drugs in time by several hours.

• iron and calcium preparations, antacids with aluminum and magnesium;
• bile acid sequestrants;
• sevelamer, orlistat;
• proton pump inhibitors (they reduce acidity, which may worsen the absorption of T4 tablets);
• soy products, dietary fiber, coffee, taken simultaneously with the tablet.

Estrogens, in particular as part of oral contraceptives and hormone replacement therapy, increase the level of thyroxine-binding globulin (TBG). This increases the bound fraction of hormones, and in patients with hypothyroidism a dose correction may be needed. Androgens, on the contrary, lower the level of TBG.

Amiodarone, which contains a large amount of iodine, can cause both hypothyroidism and thyrotoxicosis, and also suppresses the conversion of T4 into T3. Patients on amiodarone need regular monitoring of thyroid function.

Inducers of liver enzymes - rifampicin, carbamazepine, phenytoin, phenobarbital - accelerate the metabolism of thyroid hormones and may increase the need for them.

Interactions in the sports context

In the sports environment T3 is often combined with clenbuterol, caffeine, yohimbine, synephrine and other components of 'fat burners'. Each of them separately accelerates the pulse, and together they create a cumulative burden on the heart. It is precisely such combinations that appear in the warnings of thyroid hormone package inserts.

Combination with anabolic steroids changes hormone transport: androgens lower the level of TBG, which changes the readings of total T4 and T3. This complicates the interpretation of tests and may mask the real thyroid status.

Insulin outside of medical indications in combination with T3 creates an unpredictable situation: the thyroid hormone changes the need for insulin, and incorrect insulin dosing threatens severe hypoglycemia and death.

Diuretics against the background of thyrotoxicosis intensify dehydration and the loss of electrolytes, which additionally increases the risk of arrhythmias. Therefore any 'cutting schemes' with several drugs pose a particular danger.

Editorial conclusions

Liothyronine interacts with many drugs: it enhances the action of warfarin, weakens the action of digoxin and glucose-lowering agents, and enhances the cardiac effects of sympathomimetics and tricyclic antidepressants.

The absorption of thyroid hormones can be reduced by iron and calcium preparations, bile acid sequestrants and some other agents, while estrogens, androgens and amiodarone change the transport and metabolism of the hormones.

The most dangerous are combinations of T3 with stimulants and with insulin outside of medical indications, so any combinations should be assessed by a doctor.

We also recommend our materials on overdose of liothyronine (T3), on the interaction of clenbuterol with other drugs, and on the effect of liothyronine on the liver and kidneys.

References

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