levothyroxine (Rx)

Mild Hypothyroidism

1.7 mcg/kg or 100-125 mcg PO qDay; not to exceed 300 mcg/day  

>50 years (or <50 yr with CV disease)

• Usual initial dose: 25-50 mcg/day
• May adjust dose by 12.5-25 mcg q6-8Week

>50 years with CV disease

• Usual initial dose: 12.5-25 mcg PO qDay
• May adjust dose by 12.5-25 mcg q4-6weeks until patient becomes euthyroid and serum TSH concentration normalized; adjustments q6-8weeks also used
• Dose range: 100-125 mcg PO qDay

Severe Hypothyroidism

Initial: 12.5-25 mcg PO qDay

Adjust dose by 25 mcg/day q2-4Week PRN

Subclinical Hypothyroidism

Initial: 1 mcg/kg PO qDay may be adequate, OR  

If replacement therapy not initiated, monitor patient annually for clinical status

Myxedema Coma

300-500 mcg IV once, THEN 50-100 mcg qDay until patient is able to tolerate oral administration; may consider smaller doses in patients with cardiovascular disease

Organ Preservation (Orphan)

Preservation of organ function in brain-dead organ donors

Orphan indication sponsor

• Fera Pharmaceuticals, LLC; 134 Birch Hill Road; Locust Valley, NY 11560

Dosing Considerations

Lower dose of Tirosint capsules may be required compared with standard T4 tablets for hypothyroidism in patients with impaired gastric acid secretion to reach their target TSH levels; Tirosint has shown improved absorption compared with conventional T4 tablets

Check for bioequivalence if switching brands/generics, OR every week after switching from one levothyroxine sodium preparation to another

Monitor serum thyroid levels; patient may be asymptomatic

Monitoring

• Initially evaluate patients q6-8Week
• Once normalization of thyroid function and serum TSH conc achieved, evaluate q6-12mo

Limitations of use

• IV: Relative bioavailability has not been established; use caution when converting patients from PO to IV

• PO

  • Not indicated for suppression of benign thyroid nodules and nontoxic diffuse goiter in iodine-sufficient patients, as there are no clinical benefits and overtreatment with levothyroxine may induce hyperthyroidism
  • Not indicated for treatment of hypothyroidism during recovery phase of subacute thyroiditis

Hypothyroidism

Indicated in patients from birth to <17 years of age:

• As a replacement therapy in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism
• As an adjunct to surgery and radioiodine therapy in management of thyrotropin-dependent well-differentiated thyroid cancer

Age 1-3 months

• 10-15 mcg/kg/day PO  
• 5-7.5 mcg/kg/day IV/IM
• Use lower starting dose (25 mcg/day) if patient at risk of cardiac failure; if initial serum T4 lower than 5 mcg/dL begin treatment at higher dose (50 mcg/day)

Age 3-6 months

• 8-10 mcg/kg/day PO, OR  
• 25-50 mcg/day PO
• 4-7.5 mcg/kg/day IV/IM

Age 6-12 months

• 6-8 mcg/kg/day PO, OR  
• 50-75 mcg/day PO
• 3-6 mcg/kg/day IV/IM

Age 1-5 years

• 5-6 mcg/kg/day PO, OR  
• 75-100 mcg/day PO
• 2.5-4.5 mcg/kg/day IV/IM

Age 6-12 years

• 4-5 mcg/kg/day PO, OR  
• 100-125 mcg/day PO
• 2-3.75 mcg/kg/day IV/IM

>12 years

• 2-3 mcg/kg/day PO, OR  
• 150 mcg/day PO
• 1-2.25 mcg/kg/day IV/IM

Dosing considerations

• Check for bioequivalence if switching brands/generics
• May minimize hyperactivity in older children by initiating dose at 1/4 of recommended dose; increase by that amount each week until full dose achieved
• Start children with severe or chronic hypothyroidism at 25 mcg/day; adjust dose by 25 mcg qweek

Because of increased prevalence of cardiovascular disease among the elderly, initiate therapy at less than full replacement dose; atrial arrhythmias can occur in elderly patients; atrial fibrillation is the most common of arrhythmias observed with levothyroxine overtreatment in the elderly

Contraindicated (2)

• sodium iodide I-131

  levothyroxine will decrease the level or effect of sodium iodide I-131 by Other (see comment). Contraindicated. Use of thyroid products or iodine before and during treatment with sodium iodide I-131 decreases uptake of sodium iodide I-131 by the thyroid gland

• sucroferric oxyhydroxide

  sucroferric oxyhydroxide decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Contraindicated. No interaction anticipated with parenteral levothyroxine.

Serious - Use Alternative (11)

• antithrombin alfa

  levothyroxine increases effects of antithrombin alfa by pharmacodynamic synergism. Avoid or Use Alternate Drug.

• antithrombin III

  levothyroxine increases effects of antithrombin III by pharmacodynamic synergism. Avoid or Use Alternate Drug.

• argatroban

  levothyroxine increases effects of argatroban by pharmacodynamic synergism. Avoid or Use Alternate Drug.

• bemiparin

  levothyroxine increases effects of bemiparin by pharmacodynamic synergism. Avoid or Use Alternate Drug.

• bivalirudin

  levothyroxine increases effects of bivalirudin by pharmacodynamic synergism. Avoid or Use Alternate Drug.

• bremelanotide

  bremelanotide will decrease the level or effect of levothyroxine by Other (see comment). Avoid or Use Alternate Drug. Bremelanotide may slow gastric emptying and potentially reduces the rate and extent of absorption of concomitantly administered oral medications. Avoid use when taking any oral drug that is dependent on threshold concentrations for efficacy. Interactions listed are representative examples and do not include all possible clinical examples.

• fondaparinux

  levothyroxine increases effects of fondaparinux by pharmacodynamic synergism. Avoid or Use Alternate Drug.

• heparin

  levothyroxine increases effects of heparin by pharmacodynamic synergism. Avoid or Use Alternate Drug.

• lycopus

  lycopus decreases effects of levothyroxine by pharmacodynamic antagonism. Contraindicated. Lycopus blocks peripheral conversion of T4 to T3.

• phenindione

  levothyroxine increases effects of phenindione by pharmacodynamic synergism. Avoid or Use Alternate Drug.

• protamine

  levothyroxine increases effects of protamine by pharmacodynamic synergism. Avoid or Use Alternate Drug.

Monitor Closely (55)

• amitriptyline

  levothyroxine increases effects of amitriptyline by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• amoxapine

  levothyroxine increases effects of amoxapine by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• apalutamide

  apalutamide will decrease the level or effect of levothyroxine by increasing elimination. Use Caution/Monitor. Apalutamide induces UGT and may decrease systemic exposure of drugs that are UGT substrates.

• caffeine

  caffeine decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. COFFEE binds levothyroxine in the GI tract. Separate by 2 hours.

• calcium acetate

  calcium acetate decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate administration by 4 hours.

• calcium carbonate

  calcium carbonate decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

• calcium chloride

  calcium chloride decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

• calcium citrate

  calcium citrate decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

• calcium gluconate

  calcium gluconate decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

• carbonyl iron

  carbonyl iron decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• cholestyramine

  cholestyramine decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• clomipramine

  levothyroxine increases effects of clomipramine by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• colesevelam

  colesevelam decreases levels of levothyroxine by drug binding in GI tract. Use Caution/Monitor. Concomitant administration decreases levothyroxine absorption; however, absorption is not reduced when levothyroxine is administered 4 hr before colesevelam.

• crofelemer

  crofelemer increases levels of levothyroxine by Other (see comment). Use Caution/Monitor. Comment: Crofelemer has the potential to inhibit transporters MRP2 and OATP1A2 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

• desipramine

  levothyroxine increases effects of desipramine by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• didanosine

  didanosine will decrease the level or effect of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Applies to didanosine chewable tablets and powder for oral solution; administer 2 hr before or several hours after didanosine oral solution or chewable tablet administration

• digoxin

  levothyroxine decreases effects of digoxin by unknown mechanism. Use Caution/Monitor.

• doxepin

  levothyroxine increases effects of doxepin by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• doxepin cream

  levothyroxine increases effects of doxepin cream by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• dulaglutide

  dulaglutide, levothyroxine. Other (see comment). Use Caution/Monitor. Comment: Dulaglutide slows gastric emptying and may impact absorption of concomitantly administered oral medications; be particularly cautious when coadministered with drugs that have a narrow therapeutic index.

• eluxadoline

  eluxadoline increases levels of levothyroxine by decreasing metabolism. Use Caution/Monitor. Eluxadoline may increase the systemic exposure of coadministered OATP1B1 substrates.

• epinephrine

  levothyroxine will increase the level or effect of epinephrine by unspecified interaction mechanism. Use Caution/Monitor.

• ferric maltol

  ferric maltol decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  ferric maltol, levothyroxine. Either increases effects of the other by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Coadministration of ferric maltol with certain oral medications may decrease the bioavailability of either ferric maltol and some oral drugs. For oral drugs where reductions in bioavailability may cause clinically significant effects on its safety or efficacy, separate administration of ferric maltol from these drugs. Duration of separation may depend on the absorption of the medication concomitantly administered (eg, time to peak concentration, whether the drug is an immediate or extended release product).

• ferrous fumarate

  ferrous fumarate decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• ferrous gluconate

  ferrous gluconate decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• ferrous sulfate

  ferrous sulfate decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• food

  food decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. COFFEE binds levothyroxine in the GI tract. Separate by 2 hours.

• imipramine

  levothyroxine increases effects of imipramine by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• insulin degludec

  levothyroxine decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Thyroid hormones regulate carbohydrate metabolism, gluconeogenesis, and glycogen stores mobilization; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

• insulin degludec/insulin aspart

  levothyroxine decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Thyroid hormones regulate carbohydrate metabolism, gluconeogenesis, and glycogen stores mobilization; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

• insulin inhaled

  levothyroxine decreases effects of insulin inhaled by pharmacodynamic antagonism. Use Caution/Monitor. Thyroid hormones regulate carbohydrate metabolism, gluconeogenesis, and glycogen stores mobilization; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

• iron dextran complex

  iron dextran complex decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• iron sucrose

  iron sucrose decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• ketamine

  levothyroxine increases toxicity of ketamine by unspecified interaction mechanism. Use Caution/Monitor. Coadministration may cause marked hypertension and tachycardia.

• lanthanum carbonate

  lanthanum carbonate decreases levels of levothyroxine by cation binding in GI tract. Use Caution/Monitor. Administer oral thyroid products at least 2 hr before or after lanthanum. Interaction applies only to oral thyroid products only. .

• letermovir

  letermovir increases levels of levothyroxine by Other (see comment). Use Caution/Monitor. Comment: Letermovir, an OATP1B1/3 inhibitor may increase plasma concentrations of coadministered OATP1B1/3 substrates.

• levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

  levonorgestrel oral/ethinylestradiol/ferrous bisglycinate will decrease the level or effect of levothyroxine by unknown mechanism. Modify Therapy/Monitor Closely. The estrogen component of combined hormonal contraceptives (CHCs) may raise the serum concentrations of thyroxine-binding globulin. Women on thyroid hormone replacement therapy may need increased doses of thyroid hormone with use of CHCs.

• magnesium supplement

  magnesium supplement will decrease the level or effect of levothyroxine by Other (see comment). Modify Therapy/Monitor Closely. Drug may adsorb to magnesium; may decrease absorption by the intestinal tract; applies to oral forms; may separate administration of drugs by 4 hr

• metformin

  levothyroxine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• nateglinide

  levothyroxine decreases effects of nateglinide by pharmacodynamic antagonism. Use Caution/Monitor. Coadministration may reduce nateglinide's hypoglycemic action.

• nortriptyline

  levothyroxine increases effects of nortriptyline by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• orlistat

  orlistat decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Risk of hypothyroidism. Separate by 4 hours.

• patiromer

  patiromer will decrease the level or effect of levothyroxine by drug binding in GI tract. Use Caution/Monitor. May administer 3 hours apart

• polysaccharide iron

  polysaccharide iron decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• protriptyline

  levothyroxine increases effects of protriptyline by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• raloxifene

  raloxifene decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• ropeginterferon alfa 2b

  ropeginterferon alfa 2b will increase the level or effect of levothyroxine by Other (see comment). Use Caution/Monitor. Certain proinflammatory cytokines, including interferons, can suppress CYP450 enzymes resulting in increased exposures of some CYP substrates. Therefore, monitor patients who are receiving concomitant drugs that are CYP450 substrates with a narrow therapeutic index from toxicities to such drugs.

• rose hips

  rose hips decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• sodium sulfate/?magnesium sulfate/potassium chloride

  sodium sulfate/?magnesium sulfate/potassium chloride decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Administer levothyroxine at least 4 hr after each dose to avoid chelation with magnesium. .

• sodium sulfate/potassium sulfate/magnesium sulfate

  sodium sulfate/potassium sulfate/magnesium sulfate decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Administer levothyroxine at least 4 hr after each dose to avoid chelation with magnesium. .

• teduglutide

  teduglutide increases levels of levothyroxine by Other (see comment). Use Caution/Monitor. Comment: Teduglutide may increase absorption of concomitant PO medications; caution with with drugs requiring titration or those with a narrow therapeutic index; dose adjustment may be necessary.

• trimagnesium citrate anhydrous

  trimagnesium citrate anhydrous decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• trimipramine

  levothyroxine increases effects of trimipramine by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• ustekinumab

  ustekinumab, levothyroxine. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of ustekinumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• warfarin

  levothyroxine increases effects of warfarin by unspecified interaction mechanism. Use Caution/Monitor.

Minor (31)

• alendronate

  levothyroxine decreases levels of alendronate by unspecified interaction mechanism. Minor/Significance Unknown. Bioavailability of alendronate decreases slightly.

• amobarbital

  amobarbital decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.

• butabarbital

  butabarbital decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.

• butalbital

  butalbital decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.

• carbamazepine

  carbamazepine decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.

• colestipol

  colestipol decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• dexlansoprazole

  dexlansoprazole decreases levels of levothyroxine by increasing gastric pH. Applies only to oral form of both agents. Minor/Significance Unknown. Conflicting evidence regarding this interaction exists.

• eptifibatide

  levothyroxine decreases levels of eptifibatide by increasing renal clearance. Minor/Significance Unknown.

• eslicarbazepine acetate

  eslicarbazepine acetate decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.

• esomeprazole

  esomeprazole decreases levels of levothyroxine by increasing gastric pH. Applies only to oral form of both agents. Minor/Significance Unknown. Conflicting evidence regarding this interaction exists.

• ethotoin

  ethotoin decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.
  
  ethotoin decreases levels of levothyroxine by plasma protein binding competition. Minor/Significance Unknown.

• fosphenytoin

  fosphenytoin decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.
  
  fosphenytoin decreases levels of levothyroxine by plasma protein binding competition. Minor/Significance Unknown.

• furosemide

  furosemide increases toxicity of levothyroxine by Other (see comment). Minor/Significance Unknown. Comment: High doses (greater than 80 mg) of furosemide may inhibit binding of thyroid hormones to carrier proteins and result in transient increase in free thyroid hormones, followed by overall decrease in total thyroid hormone levels.

• glandular products

  glandular products increases effects of levothyroxine by pharmacodynamic synergism. Minor/Significance Unknown. Additive effects with thyroid glandular extract.

• guggul

  guggul decreases effects of levothyroxine by pharmacodynamic antagonism. Minor/Significance Unknown.

• lansoprazole

  lansoprazole decreases levels of levothyroxine by increasing gastric pH. Applies only to oral form of both agents. Minor/Significance Unknown. Conflicting evidence regarding this interaction exists.

• omeprazole

  omeprazole decreases levels of levothyroxine by increasing gastric pH. Applies only to oral form of both agents. Minor/Significance Unknown. Conflicting evidence regarding this interaction exists.

• oxcarbazepine

  oxcarbazepine decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.

• pantoprazole

  pantoprazole decreases levels of levothyroxine by increasing gastric pH. Applies only to oral form of both agents. Minor/Significance Unknown. Conflicting evidence regarding this interaction exists.

• pentobarbital

  pentobarbital decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.

• phenobarbital

  phenobarbital decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.

• phenytoin

  phenytoin decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.
  
  phenytoin decreases levels of levothyroxine by plasma protein binding competition. Minor/Significance Unknown.

• piracetam

  piracetam, levothyroxine. Mechanism: unknown. Minor/Significance Unknown. Combination of piracetam and T3+T4 produced confusion, sleep disorder in single case.

• primidone

  primidone decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.

• rabeprazole

  rabeprazole decreases levels of levothyroxine by increasing gastric pH. Applies only to oral form of both agents. Minor/Significance Unknown. Conflicting evidence regarding this interaction exists.

• rifampin

  rifampin decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.

• secobarbital

  secobarbital decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.

• shepherd's purse

  shepherd's purse decreases effects of levothyroxine by unspecified interaction mechanism. Minor/Significance Unknown. Theoretical interaction.

• sodium polystyrene sulfonate

  sodium polystyrene sulfonate decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• theophylline

  levothyroxine decreases levels of theophylline by increasing elimination. Minor/Significance Unknown.

• tirofiban

  levothyroxine decreases levels of tirofiban by increasing renal clearance. Minor/Significance Unknown.

• alendronate

  Minor (1)levothyroxine decreases levels of alendronate by unspecified interaction mechanism. Minor/Significance Unknown. Bioavailability of alendronate decreases slightly.

• amitriptyline

  Monitor Closely (1)levothyroxine increases effects of amitriptyline by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• amobarbital

  Minor (1)amobarbital decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.

• amoxapine

  Monitor Closely (1)levothyroxine increases effects of amoxapine by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• antithrombin alfa

  Serious - Use Alternative (1)levothyroxine increases effects of antithrombin alfa by pharmacodynamic synergism. Avoid or Use Alternate Drug.

• antithrombin III

  Serious - Use Alternative (1)levothyroxine increases effects of antithrombin III by pharmacodynamic synergism. Avoid or Use Alternate Drug.

• apalutamide

  Monitor Closely (1)apalutamide will decrease the level or effect of levothyroxine by increasing elimination. Use Caution/Monitor. Apalutamide induces UGT and may decrease systemic exposure of drugs that are UGT substrates.

• argatroban

  Serious - Use Alternative (1)levothyroxine increases effects of argatroban by pharmacodynamic synergism. Avoid or Use Alternate Drug.

• bemiparin

  Serious - Use Alternative (1)levothyroxine increases effects of bemiparin by pharmacodynamic synergism. Avoid or Use Alternate Drug.

• bivalirudin

  Serious - Use Alternative (1)levothyroxine increases effects of bivalirudin by pharmacodynamic synergism. Avoid or Use Alternate Drug.

• bremelanotide

  Serious - Use Alternative (1)bremelanotide will decrease the level or effect of levothyroxine by Other (see comment). Avoid or Use Alternate Drug. Bremelanotide may slow gastric emptying and potentially reduces the rate and extent of absorption of concomitantly administered oral medications. Avoid use when taking any oral drug that is dependent on threshold concentrations for efficacy. Interactions listed are representative examples and do not include all possible clinical examples.

• butabarbital

  Minor (1)butabarbital decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.

• butalbital

  Minor (1)butalbital decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.

• caffeine

  Monitor Closely (1)caffeine decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. COFFEE binds levothyroxine in the GI tract. Separate by 2 hours.

• calcium acetate

  Monitor Closely (1)calcium acetate decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate administration by 4 hours.

• calcium carbonate

  Monitor Closely (1)calcium carbonate decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

• calcium chloride

  Monitor Closely (1)calcium chloride decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

• calcium citrate

  Monitor Closely (1)calcium citrate decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

• calcium gluconate

  Monitor Closely (1)calcium gluconate decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

• carbamazepine

  Minor (1)carbamazepine decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.

• carbonyl iron

  Monitor Closely (1)carbonyl iron decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• cholestyramine

  Monitor Closely (1)cholestyramine decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• clomipramine

  Monitor Closely (1)levothyroxine increases effects of clomipramine by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• colesevelam

  Monitor Closely (1)colesevelam decreases levels of levothyroxine by drug binding in GI tract. Use Caution/Monitor. Concomitant administration decreases levothyroxine absorption; however, absorption is not reduced when levothyroxine is administered 4 hr before colesevelam.

• colestipol

  Minor (1)colestipol decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• crofelemer

  Monitor Closely (1)crofelemer increases levels of levothyroxine by Other (see comment). Use Caution/Monitor. Comment: Crofelemer has the potential to inhibit transporters MRP2 and OATP1A2 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

• desipramine

  Monitor Closely (1)levothyroxine increases effects of desipramine by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• dexlansoprazole

  Minor (1)dexlansoprazole decreases levels of levothyroxine by increasing gastric pH. Applies only to oral form of both agents. Minor/Significance Unknown. Conflicting evidence regarding this interaction exists.

• didanosine

  Monitor Closely (1)didanosine will decrease the level or effect of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Applies to didanosine chewable tablets and powder for oral solution; administer 2 hr before or several hours after didanosine oral solution or chewable tablet administration

• digoxin

  Monitor Closely (1)levothyroxine decreases effects of digoxin by unknown mechanism. Use Caution/Monitor.

• doxepin

  Monitor Closely (1)levothyroxine increases effects of doxepin by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• doxepin cream

  Monitor Closely (1)levothyroxine increases effects of doxepin cream by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• dulaglutide

  Monitor Closely (1)dulaglutide, levothyroxine. Other (see comment). Use Caution/Monitor. Comment: Dulaglutide slows gastric emptying and may impact absorption of concomitantly administered oral medications; be particularly cautious when coadministered with drugs that have a narrow therapeutic index.

• eluxadoline

  Monitor Closely (1)eluxadoline increases levels of levothyroxine by decreasing metabolism. Use Caution/Monitor. Eluxadoline may increase the systemic exposure of coadministered OATP1B1 substrates.

• epinephrine

  Monitor Closely (1)levothyroxine will increase the level or effect of epinephrine by unspecified interaction mechanism. Use Caution/Monitor.

• eptifibatide

  Minor (1)levothyroxine decreases levels of eptifibatide by increasing renal clearance. Minor/Significance Unknown.

• eslicarbazepine acetate

  Minor (1)eslicarbazepine acetate decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.

• esomeprazole

  Minor (1)esomeprazole decreases levels of levothyroxine by increasing gastric pH. Applies only to oral form of both agents. Minor/Significance Unknown. Conflicting evidence regarding this interaction exists.

• ethotoin

  Minor (2)ethotoin decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.
  
  ethotoin decreases levels of levothyroxine by plasma protein binding competition. Minor/Significance Unknown.

• ferric maltol

  Monitor Closely (2)ferric maltol decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  ferric maltol, levothyroxine. Either increases effects of the other by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Coadministration of ferric maltol with certain oral medications may decrease the bioavailability of either ferric maltol and some oral drugs. For oral drugs where reductions in bioavailability may cause clinically significant effects on its safety or efficacy, separate administration of ferric maltol from these drugs. Duration of separation may depend on the absorption of the medication concomitantly administered (eg, time to peak concentration, whether the drug is an immediate or extended release product).

• ferrous fumarate

  Monitor Closely (1)ferrous fumarate decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• ferrous gluconate

  Monitor Closely (1)ferrous gluconate decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• ferrous sulfate

  Monitor Closely (1)ferrous sulfate decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• fondaparinux

  Serious - Use Alternative (1)levothyroxine increases effects of fondaparinux by pharmacodynamic synergism. Avoid or Use Alternate Drug.

• food

  Monitor Closely (1)food decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. COFFEE binds levothyroxine in the GI tract. Separate by 2 hours.

• fosphenytoin

  Minor (2)fosphenytoin decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.
  
  fosphenytoin decreases levels of levothyroxine by plasma protein binding competition. Minor/Significance Unknown.

• furosemide

  Minor (1)furosemide increases toxicity of levothyroxine by Other (see comment). Minor/Significance Unknown. Comment: High doses (greater than 80 mg) of furosemide may inhibit binding of thyroid hormones to carrier proteins and result in transient increase in free thyroid hormones, followed by overall decrease in total thyroid hormone levels.

• glandular products

  Minor (1)glandular products increases effects of levothyroxine by pharmacodynamic synergism. Minor/Significance Unknown. Additive effects with thyroid glandular extract.

• guggul

  Minor (1)guggul decreases effects of levothyroxine by pharmacodynamic antagonism. Minor/Significance Unknown.

• heparin

  Serious - Use Alternative (1)levothyroxine increases effects of heparin by pharmacodynamic synergism. Avoid or Use Alternate Drug.

• imipramine

  Monitor Closely (1)levothyroxine increases effects of imipramine by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• insulin degludec

  Monitor Closely (1)levothyroxine decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Thyroid hormones regulate carbohydrate metabolism, gluconeogenesis, and glycogen stores mobilization; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

• insulin degludec/insulin aspart

  Monitor Closely (1)levothyroxine decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Thyroid hormones regulate carbohydrate metabolism, gluconeogenesis, and glycogen stores mobilization; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

• insulin inhaled

  Monitor Closely (1)levothyroxine decreases effects of insulin inhaled by pharmacodynamic antagonism. Use Caution/Monitor. Thyroid hormones regulate carbohydrate metabolism, gluconeogenesis, and glycogen stores mobilization; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

• iron dextran complex

  Monitor Closely (1)iron dextran complex decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• iron sucrose

  Monitor Closely (1)iron sucrose decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• ketamine

  Monitor Closely (1)levothyroxine increases toxicity of ketamine by unspecified interaction mechanism. Use Caution/Monitor. Coadministration may cause marked hypertension and tachycardia.

• lansoprazole

  Minor (1)lansoprazole decreases levels of levothyroxine by increasing gastric pH. Applies only to oral form of both agents. Minor/Significance Unknown. Conflicting evidence regarding this interaction exists.

• lanthanum carbonate

  Monitor Closely (1)lanthanum carbonate decreases levels of levothyroxine by cation binding in GI tract. Use Caution/Monitor. Administer oral thyroid products at least 2 hr before or after lanthanum. Interaction applies only to oral thyroid products only. .

• letermovir

  Monitor Closely (1)letermovir increases levels of levothyroxine by Other (see comment). Use Caution/Monitor. Comment: Letermovir, an OATP1B1/3 inhibitor may increase plasma concentrations of coadministered OATP1B1/3 substrates.

• levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

  Monitor Closely (1)levonorgestrel oral/ethinylestradiol/ferrous bisglycinate will decrease the level or effect of levothyroxine by unknown mechanism. Modify Therapy/Monitor Closely. The estrogen component of combined hormonal contraceptives (CHCs) may raise the serum concentrations of thyroxine-binding globulin. Women on thyroid hormone replacement therapy may need increased doses of thyroid hormone with use of CHCs.

• lycopus

  Serious - Use Alternative (1)lycopus decreases effects of levothyroxine by pharmacodynamic antagonism. Contraindicated. Lycopus blocks peripheral conversion of T4 to T3.

• magnesium supplement

  Monitor Closely (1)magnesium supplement will decrease the level or effect of levothyroxine by Other (see comment). Modify Therapy/Monitor Closely. Drug may adsorb to magnesium; may decrease absorption by the intestinal tract; applies to oral forms; may separate administration of drugs by 4 hr

• metformin

  Monitor Closely (1)levothyroxine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• nateglinide

  Monitor Closely (1)levothyroxine decreases effects of nateglinide by pharmacodynamic antagonism. Use Caution/Monitor. Coadministration may reduce nateglinide's hypoglycemic action.

• nortriptyline

  Monitor Closely (1)levothyroxine increases effects of nortriptyline by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• omeprazole

  Minor (1)omeprazole decreases levels of levothyroxine by increasing gastric pH. Applies only to oral form of both agents. Minor/Significance Unknown. Conflicting evidence regarding this interaction exists.

• orlistat

  Monitor Closely (1)orlistat decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Risk of hypothyroidism. Separate by 4 hours.

• oxcarbazepine

  Minor (1)oxcarbazepine decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.

• pantoprazole

  Minor (1)pantoprazole decreases levels of levothyroxine by increasing gastric pH. Applies only to oral form of both agents. Minor/Significance Unknown. Conflicting evidence regarding this interaction exists.

• patiromer

  Monitor Closely (1)patiromer will decrease the level or effect of levothyroxine by drug binding in GI tract. Use Caution/Monitor. May administer 3 hours apart

• pentobarbital

  Minor (1)pentobarbital decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.

• phenindione

  Serious - Use Alternative (1)levothyroxine increases effects of phenindione by pharmacodynamic synergism. Avoid or Use Alternate Drug.

• phenobarbital

  Minor (1)phenobarbital decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.

• phenytoin

  Minor (2)phenytoin decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.
  
  phenytoin decreases levels of levothyroxine by plasma protein binding competition. Minor/Significance Unknown.

• piracetam

  Minor (1)piracetam, levothyroxine. Mechanism: unknown. Minor/Significance Unknown. Combination of piracetam and T3+T4 produced confusion, sleep disorder in single case.

• polysaccharide iron

  Monitor Closely (1)polysaccharide iron decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• primidone

  Minor (1)primidone decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.

• protamine

  Serious - Use Alternative (1)levothyroxine increases effects of protamine by pharmacodynamic synergism. Avoid or Use Alternate Drug.

• protriptyline

  Monitor Closely (1)levothyroxine increases effects of protriptyline by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• rabeprazole

  Minor (1)rabeprazole decreases levels of levothyroxine by increasing gastric pH. Applies only to oral form of both agents. Minor/Significance Unknown. Conflicting evidence regarding this interaction exists.

• raloxifene

  Monitor Closely (1)raloxifene decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• rifampin

  Minor (1)rifampin decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.

• ropeginterferon alfa 2b

  Monitor Closely (1)ropeginterferon alfa 2b will increase the level or effect of levothyroxine by Other (see comment). Use Caution/Monitor. Certain proinflammatory cytokines, including interferons, can suppress CYP450 enzymes resulting in increased exposures of some CYP substrates. Therefore, monitor patients who are receiving concomitant drugs that are CYP450 substrates with a narrow therapeutic index from toxicities to such drugs.

• rose hips

  Monitor Closely (1)rose hips decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• secobarbital

  Minor (1)secobarbital decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.

• shepherd's purse

  Minor (1)shepherd's purse decreases effects of levothyroxine by unspecified interaction mechanism. Minor/Significance Unknown. Theoretical interaction.

• sodium iodide I-131

  Contraindicated (1)levothyroxine will decrease the level or effect of sodium iodide I-131 by Other (see comment). Contraindicated. Use of thyroid products or iodine before and during treatment with sodium iodide I-131 decreases uptake of sodium iodide I-131 by the thyroid gland

• sodium polystyrene sulfonate

  Minor (1)sodium polystyrene sulfonate decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• sodium sulfate/?magnesium sulfate/potassium chloride

  Monitor Closely (1)sodium sulfate/?magnesium sulfate/potassium chloride decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Administer levothyroxine at least 4 hr after each dose to avoid chelation with magnesium. .

• sodium sulfate/potassium sulfate/magnesium sulfate

  Monitor Closely (1)sodium sulfate/potassium sulfate/magnesium sulfate decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Administer levothyroxine at least 4 hr after each dose to avoid chelation with magnesium. .

• sucroferric oxyhydroxide

  Contraindicated (1)sucroferric oxyhydroxide decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Contraindicated. No interaction anticipated with parenteral levothyroxine.

• teduglutide

  Monitor Closely (1)teduglutide increases levels of levothyroxine by Other (see comment). Use Caution/Monitor. Comment: Teduglutide may increase absorption of concomitant PO medications; caution with with drugs requiring titration or those with a narrow therapeutic index; dose adjustment may be necessary.

• theophylline

  Minor (1)levothyroxine decreases levels of theophylline by increasing elimination. Minor/Significance Unknown.

• tirofiban

  Minor (1)levothyroxine decreases levels of tirofiban by increasing renal clearance. Minor/Significance Unknown.

• trimagnesium citrate anhydrous

  Monitor Closely (1)trimagnesium citrate anhydrous decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• trimipramine

  Monitor Closely (1)levothyroxine increases effects of trimipramine by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• ustekinumab

  Monitor Closely (1)ustekinumab, levothyroxine. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of ustekinumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• warfarin

  Monitor Closely (1)levothyroxine increases effects of warfarin by unspecified interaction mechanism. Use Caution/Monitor.