Interactions : אינטראקציות

4.5 Interaction with other medicinal products and other forms of interaction

Interactions reducing the absorption of thyroxine.
Cholestyramine, colestipol
Concomitant administration of cholestyramine or colestipol reduces the absorption of levothyroxine.

Calcium, aluminium, magnesium, iron supplements, polystyrene sulfonates, bile acid binding agents, anion / cation exchangers, sucralfate, lanthanum, and proton pump inhibitors.

Proton pump inhibitors (PPI):

Concomitant administration of PPI may cause a decrease in uptake of thyroid hormones due to the increase in intragastric pH caused by PPI.

Regular monitoring of thyroid function and clinical monitoring are recommended during concomitant therapy. It may be necessary to increase the dose of thyroid hormones.

Caution should also be exercised when terminating treatment with PPI.

These medicinal products reduce the absorption of levothyroxine. Therefore, it is necessary to increase the dose of levothyroxine with concomitant administration. To avoid interaction between the medicinal products in the stomach or in the small intestine it should be attempted to separate the dosages of levothyroxine and the above medicinal products as much as possible (see section 4.2).

Sevelamer may decrease levothyroxine absorption. Therefore, it is recommended that patients are monitored for changes in thyroid function at the start or end of concomitant treatment. If necessary, the levothyroxine dose has to be adjusted.

Ciprofloxacin:
Ciprofloxacin may reduce serum concentrations of levothyroxine.

Products containing soy and a diet with a high fibre content
Products containing soy and a diet with a high fibre content may reduce the intestinal absorption of levothyroxine. Therefore, a dose adjustment of Eltroxin may be warranted, especially in the initial phase or after supplementation with soy containing products has been discontinued.

Weight loss medicinal products
Orlistat may reduce the absorption of levothyroxine, which may lead to hypothyroidism. To avoid this, orlistat and levothyroxine should be administered at least 4 hours apart.
Regular monitoring of changes in the thyroid function is necessary.

Interactions affecting thyroxine

Carbamezapine, phenytoin
Anticonvulsants such as e.g. carbamezapine and phenytoin enhance the metabolism of thyroid hormones and may displace them from plasma proteins. Initiation or discontinuation of anticonvulsant therapy may therefore require adjustment of levothyroxine dose.

Barbiturates, rifampicin
Effects of medicinal products that induce cytochrome P-450: Enzyme-inducing medicinal products such as barbiturates, other substances such as rifampicin and products containing St. John's wort (Hypericum perforatum L.) may increase the hepatic clearance of levothyroxine, resulting in decreased serum thyroid hormone concentrations.

Therefore, it may be necessary to simultaneously increase the dose of thyroid hormone in patients receiving thyroid replacement therapy.

Propylthiouracil, glucocorticoids, beta-sympatholytics, amiodarone , lithium and iodine as well as contrast agents containing iodine
These substances inhibit the peripheral conversion of T4 to T3. Due to the high content of iodine amiodarone may trigger hyperthyroidism as well as hypothyroidism.
Should be used with special caution in case of nodular goitre with possible not known autonomy.

Amiodarone
Treatment with amiodarone in patients with hypothyroidism leads tomultiple effects on thyroid function including an increased need for levothyroxine.

Tyrosine kinase inhibitors
In patients with hypothyroidism, treatment with imatinib and sunitinib is associated with a need for an increased levothyroxine dose. Patients treated with sunitinib may need an increased levothyroxine dose.

Sertraline, chloroquine /proguanil
These substances reduce the effect of levothyroxine and increase the level of serum TSH.

Oestrogens
Women taking contraceptive agents containing oestrogen or postmenopausal women treated with hormone replacement therapy may have an increased need for levothyroxine.

Administration of other medicinal products such as tamoxifen, clofibrate, methadone and 5-fluorouracil may increase the serum concentration of thyroxine-binding globulin, and therefore increase the need for levothyroxine.

Simvastatin, lovastatin
Reports have shown that some HMG-CoA reductase inhibitors (statins), such as simvastatin and lovastatin, may increase the need for thyroid hormone in patients treated with levothyroxine. It is unknown if this applies to all statins. Close monitoring of thyroid function and appropriate levothyroxine dose adjustment may be necessary when levothyroxine and statins are co-administered.

Protease inhibitors
Post-marketing cases have been reported, suggesting possible interactions between medicinal products containing ritonavir and levothyroxine. Thyroid stimulating hormone (TSH) should be monitored in patients treated with levothyroxine, for at least the first month after initiation and/or discontinuation of treatment with ritonavir, indinavir, lopinavir.

A number of medicinal products may affect the results of tests of thyroid function, and this should be considered when monitoring patients treated with levothyroxine.

Interaction with other medicinal products

Antidiabetics
Levothyroxine may increase the need for antidiabetic medicinal products in patients with diabetes. A reduction of the levothyroxine dose may cause hypoglycaemia if the dose of antidiabetics remain unchanged.

Salicylates, furosemide, clofibrate
Salicylates, dicumarol, furosemide in high dose (250 mg) and other substances may displace levothyroxine sodium from plasma proteins. This leads to an increased fT4-fraction.

Coumarin derivatives
The effect of anticoagulants may be intensified as levothyroxine displaces anticoagulants from plasma proteins. It is therefore necessary to monitor coagulation parameters regularly when initiating, during and discontinuing treatment with thyroid hormone. The anticoagulant dose may have to be adjusted.

Phenytoin
Levothyroxine may increase the phenytoin concentration.

Cardiac glycosides
With concomitant administration of levothyroxine and cardiac glycosides it may be necessary to adjust the dose of cardiac glycosides.


Tricyclic antidepressants
The receptor sensitivity to catecholamines is increased, and the effect of tricyclic antidepressants is hereby enhanced. The effects of sympathomimetics are also enhanced.

Interactions in laboratory tests

Androgens, anabolic steroids
A number of medicinal products, such as androgens and anabolic steroids, may reduce the serum concentration of thyroxine-binding globulin, and would therefore require a reduction of levothyroxine dose.

With concomitant treatment with levothyroxine and anti-inflammatory substances such as phenylbutazone or acetylsalicylic acid, falsely low plasma concentrations of thyroid hormones have been observed. Concomitant administration of acetylsalicylic acid and levothyroxine results in an initial transient increase of free T4 in serum. Continued administration leads to normal concentrations of free T4 and TSH, and the patients will therefore become clinically euthyroid.

Interference with laboratory tests:

Biotin may interfere with thyroid immunoassays based on interaction between biotin and streptavidin, resulting in leading to either falsely low or falsely high test results (see section 4.4).