Levothyroxine is the thyroid hormone used to treat hypothyroidism (underactive thyroid). It replaces the hormone the body does not produce in sufficient amounts. It is taken daily on an empty stomach, and the dose is adjusted with blood tests (TSH).
Reduced Levothyroxine absorption with higher gastric pH.
The levothyroxine label states that gastric acidity is essential for adequate absorption and that proton pump inhibitors can cause hypochlorhydria, affect intragastric pH and reduce levothyroxine absorption, potentially raising dose requirements in some hypothyroid patients; appropriate patient monitoring is recommended. In practice, keep levothyroxine always on an empty stomach, 30–60 minutes before breakfast, separate it from the PPI as much as possible and monitor TSH, adjusting the dose if needed, especially when starting or stopping the PPI.
Levothyroxine + omeprazole: the PPI can reduce levothyroxine absorption (hypochlorhydria). Keep levothyroxine on an empty stomach, separate administration and monitor TSH.
Levothyroxine dissolution depends on gastric acid; the PPI reduces absorption.
TSH 6–8 weeks after starting the PPI.
Persistent fatigue, weight gain, cold intolerance — possible signs of hypothyroidism.
Give Levothyroxine 30–60 minutes before breakfast and monitor TSH.
DailyMed/FDA (NIH/NLM) — approved Levothyroxine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=55f4c679-86cb-b97f-e063-6294a90ad5ef ; approved Omeprazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=37291cab-e350-d8e3-e063-6294a90a9cb1
Orlistat reduces levothyroxine absorption and may compromise hypothyroidism control.
Orlistat inhibits pancreatic lipase and reduces absorption of fats and fat-soluble vitamins. Its label lists "thyroid medicine" among drugs whose absorption may be altered and recommends that patients "take a multivitamin daily at bedtime" — which includes levothyroxine, although the mechanism is not solely fat-solubility (levothyroxine is an iodinated amino acid, but its absorption occurs in the proximal small intestine and can be affected by dietary fat and intestinal transit). Cases of raised TSH after starting orlistat in stable levothyroxine patients are reported, with normalisation after separating the doses. Administer levothyroxine at least 4 hours before or after orlistat (preferably on waking, fasting, as usual); monitor TSH 4–8 weeks after starting or adjusting orlistat and readjust the levothyroxine dose if needed.
Levothyroxine + orlistat: orlistat reduces levothyroxine absorption (fat-soluble vitamins). Separate administration by 4+ hours; monitor TSH.
Interference with fat-soluble absorption / levothyroxine absorption window.
Monitor TSH and hypothyroidism symptoms.
Decompensated hypothyroidism.
Separate administration times (4 hours) and monitor TSH.
DailyMed (FDA) — approved Orlistat label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a2d3bd73-f3af-4ea5-a57c-66b0004cfe4f ; approved Levothyroxine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=55f4c679-86cb-b97f-e063-6294a90ad5ef — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Metoclopramide increases gastric motility and may reduce levothyroxine absorption, decreasing its effect.
Metoclopramide increases gastric peristalsis and accelerates gastric emptying, which may reduce the dissolution and absorption time of levothyroxine in the proximal duodenum. The metoclopramide label documents that "increased GI motility by metoclopramide may impact absorption of other drugs, leading to a decrease" thereof. Although levothyroxine is not explicitly listed, the mechanism is applicable to drugs absorbed in the proximal duodenum that depend on adequate contact time. This interaction is mild and variable between patients, but may be clinically relevant in patients with borderline hypothyroidism or who have recently had their levothyroxine dose adjusted. Separate the doses (metoclopramide after meals, levothyroxine on an empty stomach) and monitor TSH if malabsorption or worsening of hypothyroidism is suspected.
Metoclopramide + levothyroxine: accelerated gastric emptying by metoclopramide shortens the contact time of levothyroxine with the absorptive mucosa. Monitor TSH.
Accelerated gastric emptying shortens levothyroxine contact time with the absorptive mucosa.
Monitor TSH and hypothyroidism symptoms (fatigue, weight gain).
Decompensated hypothyroidism.
Separate administration times and monitor TSH when starting or stopping metoclopramide.
DailyMed (FDA) — approved Metoclopramide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5d31d815-50fa-4e78-8ebd-affc2514ce78 ; approved Levothyroxine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=55f4c679-86cb-b97f-e063-6294a90ad5ef — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Antacids (aluminium and magnesium) reduce levothyroxine absorption when taken at the same time.
Levothyroxine has gastrointestinal absorption that is reduced by several drugs and foods; antacids containing aluminium, magnesium or calcium chelate or adsorb the hormone, decreasing its absorption and potentially destabilising the hypothyroid patient (signs of hypothyroidism, raised TSH). The levothyroxine label recommends separating antacid administration by at least 4 hours. Levothyroxine should always be kept on an empty stomach, 30–60 minutes before breakfast, and the antacid schedule adjusted accordingly, with TSH reassessment if needed.
Antacids + levothyroxine: cations (Al, Mg, Ca) reduce levothyroxine absorption. Separate administration by at least 4 hours.
Chelation/adsorption of levothyroxine by antacid cations.
Monitor TSH and hypothyroidism symptoms.
Decompensated hypothyroidism.
Separate administration times (4 hours) and monitor TSH.
DailyMed (FDA) — approved Antacids label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5e346dc0-69ce-4cc5-bb5d-bfa833e11c1f ; approved Levothyroxine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=55f4c679-86cb-b97f-e063-6294a90ad5ef — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Levothyroxine + calcium: calcium reduces levothyroxine absorption.
Calcium carbonate (and other calcium salts) binds levothyroxine in the gastrointestinal tract and reduces its absorption, potentially decreasing the effect of therapy and raising TSH in patients with hypothyroidism. The levothyroxine label recommends separating calcium supplements by at least 4 hours. Levothyroxine should continue to be taken fasting, preferably 30–60 minutes before breakfast, with calcium at another time of day; when calcium is started or stopped, monitor TSH and adjust the dose if needed.
Levothyroxine + calcium: calcium reduces levothyroxine absorption. Separate by ≥ 4 h.
Calcium salts bind levothyroxine in the gut lumen.
TSH after 6-8 weeks of any dosing change.
Fatigue, weight gain, bradycardia (hypothyroidism).
Separate levothyroxine and calcium dosing by at least 4 hours.
DailyMed (FDA) — approved Levothyroxine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c8ae9dc4-836f-4912-80d7-684fd374f40a ; approved Calcium carbonate label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=348d3dfa-6a52-4583-96e3-83c4bf2df45b — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Sucralfate reduces levothyroxine absorption, compromising hypothyroidism control.
The sucralfate label documents that simultaneous administration "reduced the extent of absorption (bioavailability) of single doses of... l-thyroxine" and that "dosing the concomitant medication 2 hours before sucralfate eliminated the interaction". Sucralfate forms an adherent barrier on the gastric and duodenal mucosa and may chemically adsorb levothyroxine, preventing its absorption in the proximal duodenum. This interaction is relevant in hypothyroid patients starting sucralfate for peptic ulcer or GERD (especially in the context of critical illness or polypharmacy). Administer levothyroxine on an empty stomach (30–60 minutes before breakfast) and sucralfate at least 2 hours later (ideally a 4-hour interval); monitor TSH 6–8 weeks after starting, adjusting or stopping sucralfate.
Levothyroxine + sucralfate: sucralfate adsorbs levothyroxine and reduces its absorption. Separate administration by 4+ hours (sucralfate 2h after levothyroxine).
Chelation/adsorption of levothyroxine by sucralfate in the gut.
Monitor TSH and hypothyroidism symptoms.
Decompensated hypothyroidism.
Separate administration times (4 hours) and monitor TSH.
DailyMed (FDA) — approved Sucralfate label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1e781cc0-24ec-4028-8262-dcef9873ea1f ; approved Levothyroxine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=55f4c679-86cb-b97f-e063-6294a90ad5ef — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Levothyroxine + zinc: zinc may reduce levothyroxine absorption.
Zinc, like calcium and iron, can bind levothyroxine in the gastrointestinal tract and reduce its absorption, potentially raising TSH in patients with hypothyroidism. Administration should be separated by at least 4 hours: levothyroxine fasting 30–60 minutes before breakfast, and the zinc supplement at another time of day. When zinc supplementation is started or stopped, monitor TSH and adjust the levothyroxine dose if needed.
Levothyroxine + zinc: zinc may reduce levothyroxine absorption. Separate by ≥ 4 h.
Zinc supplements may bind levothyroxine in the gut.
TSH after regimen changes.
Signs of hypothyroidism.
Separate dosing by at least 4 hours.
DailyMed (FDA) — approved Levothyroxine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c8ae9dc4-836f-4912-80d7-684fd374f40a ; approved Zinc (zinc sulfate) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2bd646d2-2a2a-4376-8da0-c7f08b0511ac — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Soybean flour (including soy-based infant formulas) and other foods can reduce gastrointestinal absorption of levothyroxine, lowering thyroid hormone exposure.
Give levothyroxine on an empty stomach, separated from soy-based foods or formulas; in infants, disperse the tablet in water or a soy-free formula.
Health Canada — Eltroxin (levothyroxine) Product Monograph: https://pdf.hres.ca/dpd_pm/00071854.PDF
Dietary fibre reduces gastrointestinal absorption of levothyroxine, potentially lowering serum hormone levels and requiring dose adjustment.
Keep a consistent empty-stomach routine, separating the dose from high-fibre meals to avoid thyroid function fluctuations.
Health Canada — Eltroxin (levothyroxine) Product Monograph: https://pdf.hres.ca/dpd_pm/00071854.PDF
Food and drink significantly alter levothyroxine absorption; empty-stomach intake reduces variability in absorption and hormone levels.
Give a single daily dose on an empty stomach, about 30 to 60 minutes before breakfast, at the same time, and separate by at least 4 hours from drugs that interfere with absorption.
EMC-UK (MHRA) — approved Levothyroxine SmPC: https://www.medicines.org.uk/emc/product/12781/smpc — corroborated by Health Canada Product Monograph: https://pdf.hres.ca/dpd_pm/00071854.PDF
Levothyroxine is contraindicated in untreated thyrotoxicosis, as it can worsen the hypermetabolic state.
Do not start therapy in patients with untreated suppressed TSH; confirm thyroid status before starting.
EMC-UK (MHRA) — approved Levothyroxine SmPC: https://www.medicines.org.uk/emc/product/12781/smpc
Thyroid hormones increase the metabolic clearance of glucocorticoids and may precipitate adrenal crisis in uncorrected adrenal insufficiency.
Correct adrenal insufficiency and start corticosteroid before levothyroxine, especially in hypopituitarism.
EMC-UK (MHRA) — approved Levothyroxine SmPC: https://www.medicines.org.uk/emc/product/12781/smpc
Thyroid hormone increases cardiac work; levothyroxine is contraindicated during acute myocardial infarction, myocarditis and acute pancarditis.
Do not start during the acute phase of these conditions; stabilise cardiac status before treatment.
EMC-UK (MHRA) — approved Levothyroxine SmPC: https://www.medicines.org.uk/emc/product/12781/smpc
Overtreatment can worsen angina or arrhythmias; occult cardiac disease is more likely in the elderly.
Start at low doses and titrate gradually, with ECG in at-risk patients and TSH monitoring.
EMC-UK (MHRA) — approved Levothyroxine SmPC: https://www.medicines.org.uk/emc/product/12781/smpc
Studies have not shown an increased risk of fetal malformations; untreated maternal hypothyroidism is associated with miscarriage, pre-eclampsia and preterm delivery.
Do not discontinue treatment during pregnancy; monitor TSH every 4 weeks in the first half and at least once between 26 and 32 weeks, adjusting the dose.
Levothyroxine at adequate doses is generally compatible with breastfeeding; minimal amounts are excreted into milk.
No specific data; keep routine thyroid function monitoring in women of child-bearing age.
EMC-UK (MHRA) — approved Levothyroxine SmPC: https://www.medicines.org.uk/emc/product/12781/smpc — corroborated by Health Canada Product Monograph: https://pdf.hres.ca/dpd_pm/00071854.PDF
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Synthetic thyroid hormone (T4) that exerts the same physiological effect as endogenous T4, maintaining normal levels when a deficiency exists. The onset and duration of effect depend on the long half-life of T4, with dose adjustments based on TSH.
Thyroid hormones exert their physiological actions through control of DNA transcription and protein synthesis: T3 and T4 diffuse into the cell nucleus and bind to thyroid receptor proteins attached to DNA, activating gene transcription. Most of the action is produced by T3, about 80% of which is derived from T4 by peripheral deiodination.
Oral absorption of T4 ranges from 40 to 80%, occurring mainly in the jejunum and upper ileum. Fasting increases absorption; dietary fibre, soybeans and malabsorption syndromes decrease it. More than 99% of circulating hormones are bound to plasma proteins (TBG, TBPA and albumin).
The major metabolic pathway is sequential deiodination; the hormones are also conjugated with glucuronides and sulfates and excreted in bile, with enterohepatic recirculation. Thyroid hormones are eliminated mainly by the kidneys; about 20% of T4 is eliminated in faeces.
The half-life of T4 is 6 to 7 days in euthyroid patients (3 to 4 days in hyperthyroidism and 9 to 10 days in hypothyroidism), which justifies once-daily dosing and slow dose titration.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
