Special warnings and special precautions for use

Replacement therapy needs to be commenced all the more cautiously the longer the hypothyroidism has existed and the older the patient is (elderly patients require less thyroxin) because in isolated cases there may be an increase in anginal symptoms in coronary heart disease or cardiac arrhythmias may be caused.

Even slight drug-induced hyperthyroidism must be avoided in patients with coronary failure, cardiac insufficiency or tachycardiac arrhythmias. Hence frequent checks of thyroid hormone parameters must be made in these cases.

Where thyroid autonomy is suspected a TRH test should be carried out or a suppression scintigram obtained before treatment.

Blood glucose levels should be checked frequently at the start of thyroid hormone therapy.

In the case of secondary hypothyroidism the cause must be determined before replacement therapy is given and if necessary replacement treatment of a compensated adrenal insufficiency must be commenced.

Interactions with other medicaments or other forms of interaction

Ingestion of cholestyramine inhibits the absorption of levothyroxine sodium. Levothyroxine sodium should therefore be taken 4-5 hours before administration of colestyramine.

Phenytoin, dicoumarol, salicylates, furosemide in high doses (250 mg), clofibrate and other substances can displace levothyroxine sodium from plasma proteins. Rapid intravenous administration of phenytoin may lead to elevated plasma levels of free levothyroxine and also liothyronine and in isolated cases may enhance the development of cardiac arrhythmias. The effect of anticoagulant therapy is intensified for the same reason and it is therefore necessary for coagulation parameters to be checked regularly at the start of thyroid hormone therapy.

Levothyroxine may increase the effect of certain drugs which inhibit blood clotting (coumarin derivatives) and reduce the effect of drugs which lower the blood sugar.

Pregnancy and lactation

Treatment with thyroid hormones should be given consistently during pregnancy and breast-feeding in particular. So far there have been no reports of any risk to the fetus despite extensive use during pregnancy. Even in high-dosed levothyroxine therapy the thyroid hormone quantity secreted into breast milk during lactation is not sufficient to cause development of hyperthyroidism or suppression of TSH secretion in the infant.

Use of levothyroxine as concomitant therapy in the treatment of hyperthyroidism with antithyroid drugs is contraindicated in pregnancy since the latter - in contrast to thyroid hormones - can cross the placenta in effective quantities. concomitant therapy with levothyroxine automatically necessitates a higher dosage of the antithyroid drug, which could induce hypothyroidism in the fetus. Consequently in hyperthyroid pregnant women monotherapy with antithyroid drugs in as low a dose as possible should be given.

Effects on ability to drive and use machines

There are no indications that levothyroxine interferes with driving a vehicle, operating machinery, or working without a firm hold.

Undesirable effects

Side effects need not to be anticipated in therapy with levothyroxine sodium when the preparation is used as prescribed and if clinical and laboratory chemical parameters are monitored. Where the individual tolerance limit for levothyroxine sodium is exceeded or after overdosage it is possible for the following clinical symptoms typical of hyperthyroidism to occur, especially if the dose is increased too quickly at the start of treatment: trembling of the fingers, tachycardia, excessive perspiration, diarrhea, weight loss, restlessness, etc.

Overdosage

After overdosage the symptoms of a sharp increase in the metabolic rate occur.

Depending on the extent of the overdosage it is recommended that treatment with the tablets is interrupted and that tests are carried out. Symptoms consisting of intense beta-sympathomimetic effects such as tachycardia, anxiety, agitation and hyperkinesia can be relieved by betablockers. After extreme doses plasmapheresis may be of help.