Table 2.
Summary of interfering drugs, proposed mechanisms, and recommendations
| Mechanism | Drugs | Recommendations for clinicians (in case of drug interactions) |
|---|---|---|
| Direct complexing | Calcium carbonatea | (a) Switch to other drugs of the same class |
| Calcium acetate | (b) Address concomitant diseases | |
| Calcium citrate | (c) Separate the times of ingestion (2-8 hours) | |
| Ferrous sulfatea | (d) Switch to liquid LT4 or capsule | |
| Aluminum hydroxidea | (e) Adjust LT4 doses | |
| Magnesium oxidea | (f) Discontinue interfering medications | |
| Sucralfate | (g) Close monitoring | |
| Cholestyramine | ||
| Colesevelam hydrochloride | ||
| Orlistat | ||
| Simethicone | ||
| Sodium polystyrene sulphonate | ||
| Sevelamer hydrochloridea | ||
| Sevelamer carbonate | ||
| Lanthanum carbonate | ||
| Raloxifene | ||
| Colestipol | ||
| Drug-induced alterations in mucosal transport processes | Chromium picolinate | (a) Adjust LT4 doses |
| Ciprofloxacin | (b) Close monitoring | |
| Rifampin | (c) Address concomitant diseases | |
| Grapefruit juice | (d) Discontinue interfering medications | |
| (e) Switch to other drugs of the same class | ||
| Alkalization | Esomeprazole | (a) Switch to other antacids |
| Pantoprazolea | (b) Address concomitant diseases | |
| Omeprazolea | (c) Switch to liquid LT4 or capsule | |
| Lansoprazole | (d) Adjust LT4 doses | |
| Other proton pump inhibitors | (e) Discontinue interfering medications | |
| Cimetidine | (f) Close monitoring | |
| Papaya | ||
| Acidification | Vitamin C | Of no clinical importance in most cases |
| (a) Discontinue vitamin C | ||
| (b) Adjust LT4 doses Vitamin C can be used in those with LT4 malabsorption |
||
| Acceleration of catabolism of LT4 in the liver (not specific) | Lovastatin | (a) Switch to other drug of the same class |
| Simvastatin | (b) Address concomitant diseases | |
| Lopinavir | (c) Adjust LT4 doses | |
| Ritonavir | (d) Discontinue interfering medications | |
| Nelfinavir | (e) Close monitoring | |
| Phenobarbital | ||
| Nicardipine | ||
| Chloroquine | ||
| Proguanil | ||
| Inhibited hepatic T4 uptake and catabolism | Rifampin | Same as the recommendations for lovastatin and simvastatin |
| Indinavir | ||
| Increased inactivation of T4 via deiodinases | Mifepristone | Same as the recommendations for lovastatin and simvastatin |
| Rifampin | ||
| Carbamazepine | ||
| Sertraline | ||
| Fluoxetine | ||
| Capecitabine | ||
| Sorafenib | ||
| Motesanib | ||
| Selpercatinib | ||
| Increased inactivation of T4 via nondeiodinases | Rifampin | Same as the recommendations for lovastatin and simvastatin |
| Phenytoin | ||
| Imatinib | ||
| Sunitinib | ||
| Inhibition of the mono-deiodination of T4 to T3 | Amiodarone | Same as the recommendations for lovastatin and simvastatin |
| Propranolol | ||
| Propylthiouracil | ||
| Dexamethasone | ||
| Flavonoids | ||
| Iodinated contrast | ||
| Competing for hormone binding sites | Nonsteroidal anti-inflammatory drugs | Same as the recommendations for lovastatin and simvastatin |
| Furosemide | ||
| Dicoumarin | ||
| Clofibrate | ||
| Increasing the serum T4-binding globulin concentration | Estrogen | Same as the recommendations for lovastatin and simvastatin |
| Rifampin | ||
| Capecitabine | ||
| Raloxifene | ||
| Tamoxifen | ||
| Mitotane | ||
| Fluorouracil | ||
| Heroin | ||
| Methadone | ||
| Decreasing the serum T4-binding globulin concentration | Androgen | Similar to the recommendations for vitamin C |
| Enhancing the inhibitory modulation of thyroid hormones on central TSH secretion | Metformin | Similar to the recommendations for vitamin C |
Drugs in italics have not been reported to interact with LT4 in human study. These drugs may affect serum thyroid hormone levels in some observational studies without LT4 dosing. Some other studies revealed the drug interaction by in vitro or animal experiments, or just hypothesis. Notably, most food and beverages impair the absorption of LT4 by direct complexing.
Abbreviations: LT4, levothyroxine; TSH, thyrotropin.
Malabsorption induced by drugs with asterisks have been reported to relieved by novel formulations (liquid solution and/or soft gel capsule).