II. Indications

III. Preparations

  1. Generic Levothyroxine are of similar quality to brand drugs
    1. However agents from different manufacturers are not bioequivalent
    2. When manufacturer changes, recheck TSH level in 6 weeks after change
  2. See oral and intravenous dosing below

IV. Drug Interactions (Take 4 hours apart)

  1. Grapefruit should be avoided regardless of time taken
  2. Interfere with GI absorption (lower levels)
    1. Cholestyramine
    2. Colestipol
    3. Ferrous Sulfate
    4. Orlistat
    5. Sucralfate
    6. Aluminum hydroxide Antacids
    7. Calcium Supplementation
    8. Soy products
  3. Increase metabolism of Thyroxine (lowers levels)
    1. Phenytoin (Dilantin)
    2. Carbamazepine (Tegretol)
    3. Rifampin
    4. Phenobarbital
    5. Warfarin (Coumadin)
    6. Oral Hypoglycemic agents
    7. Selective Serotonin Reuptake Inhibitors or Tricyclic Antidepressants
      1. Most common with Sertraline (Zoloft)
  4. Medications interfere with T4 production (lower levels)
    1. Lithium
    2. Amiodarone
    3. Medications containing Iodine
  5. Medications increasing protein binding (lowers levels)
    1. Pregnancy (high Estrogenic state)
    2. Oral Contraceptive
    3. Estrogen Replacement
  6. Medications decreasing protein binding (raises levels)
    1. Furosemide (Lasix)
    2. Mefenamic acid (Ponstel)
    3. Salicylates
    4. Androgens
    5. Decreased Serum Proteins with aging
    6. Nephrotic Syndrome
    7. Cirrhosis
    8. Protein-losing Enteropathy

V. Dosing

  1. Use lower dosing in Subclinical Hypothyroidism
    1. See Subclinical Hypothyroidism
  2. Dosing precautions
    1. Take Levothyroxine at a consistent time each day
      1. However, any time of day is just as efficacious as another
    2. Doses should be taken 1 hour before a meal or 4 hours after the last meal (e.g. at bedtime)
      1. Commonly taken before breakfast or at bedtime
    3. Avoid within 4 hours of products that decrease Levothyroxine absorption
      1. See Drug Interactions above
  3. Anticipated total dose (50 to 200 mcg/day)
    1. Children: up to 4 mcg/kg/day (full replacement)
    2. Adults: 1.6 mcg/kg/day
    3. Elderly: 1 mcg/kg/day
  4. Younger persons (no comorbid conditions)
    1. Usual starting dose: 75 to 100 mcg daily
    2. Options for initiating dosing
      1. Option 1
        1. Start at 75 to 100 mcg qd
      2. Option 2
        1. Start at 0.8 mcg/kg/day (50% of anticipated dose)
        2. Increase to 1.6 mcg/kg/day at 2 weeks
  5. Age over 50 years or history of heart disease
    1. Start at 25-50 mcg daily
    2. Increase by 25 mcg increments every 4 weeks until full replacement dose reached
    3. Follow Thyroid Stimulating Hormone (TSH) closely
  6. Pregnancy
    1. See Hypothyroidism in Pregnancy
    2. Maintaining euthyroid state in pregnancy is critical

VI. Management: Intravenous dosing

  1. Indicated if unable to take oral dose for >7 days
  2. Parenteral dose is 70-80% of usual oral dose

VII. Adverse Effects: Excessive Thyroid Replacement

  1. Osteoporosis
  2. Atrial Fibrillation
  3. Cardiac hypertrophy
    1. Increased Intraventricular septum thickness
    2. Increased Left Ventricular posterior wall thickness
    3. Increased End Diastolic Dimension
    4. Increased Left Ventricular Mass Index
  4. Decreased Exercise Tolerance
    1. Decreased VO2 Max
    2. Decreased Anaerobic threshold

VIII. Monitoring

  1. Protocols for monitoring
    1. Monitoring every 6 to 8 weeks
      1. TSH not yet stabilized after initiation
      2. Recent change in Thyroid Replacement dosing
      3. Recent change in manufacturer
    2. Consider monitoring less frequently than annually (usually done annually in this group)
      1. Requires dose stable
      2. Age under 50 years with weight stable
      3. No comorbid condition
      4. Levothyroxine dose 125 mcg or less
      5. Pecina (2014) Am J Med 127(3): 240-5 [PubMed]
    3. Monitoring at least annually (when on stable dose)
      1. Age over 50 years
      2. Weight change
  2. Specific Testing
    1. Thyroid Stimulating Hormone
      1. Lags Levothyroxine dose change by 6 weeks
      2. Target adjusting TSH to the normal mid-range (<3 mg/dl)
    2. Thyroxine (T4)
      1. Lags Levothyroxine dose change by 1-2 weeks

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Cost: Medications

Levothyroxine (on 6/18/2017 at Walmart.com)
Levothyroxine 100mcg #30 tablets for $4.00 $0.13 each
Levothyroxine 100mcg #90 tablets for $10.00 $0.11 each
Levothyroxine 112mcg #30 tablets for $4.00 $0.13 each
Levothyroxine 112mcg #90 tablets for $10.00 $0.11 each
Levothyroxine 125mcg #30 tablets for $4.00 $0.13 each
Levothyroxine 125mcg #90 tablets for $10.00 $0.11 each
Levothyroxine 137mcg #30 tablets for $4.00 $0.13 each
Levothyroxine 137mcg #90 tablets for $10.00 $0.11 each
Levothyroxine 150mcg #30 tablets for $4.00 $0.13 each
Levothyroxine 150mcg #90 tablets for $10.00 $0.11 each
Levothyroxine 175mcg #30 tablets for $4.00 $0.13 each
Levothyroxine 175mcg #90 tablets for $10.00 $0.11 each
Levothyroxine 200mcg #30 tablets for $4.00 $0.13 each
Levothyroxine 200mcg #90 tablets for $10.00 $0.11 each
Levothyroxine 25mcg #30 tablets for $4.00 $0.13 each
Levothyroxine 25mcg #90 tablets for $10.00 $0.11 each
Levothyroxine 50mcg #30 tablets for $4.00 $0.13 each
Levothyroxine 50mcg #90 tablets for $10.00 $0.11 each
Levothyroxine 75mcg #30 tablets for $4.00 $0.13 each
Levothyroxine 75mcg #90 tablets for $10.00 $0.11 each
Levothyroxine 88mcg #30 tablets for $4.00 $0.13 each
Levothyroxine 88mcg #90 tablets for $10.00 $0.11 each
levothyroxine (on 5/17/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
LEVOTHYROXINE 100 MCG TABLET Generic $0.37 each
LEVOTHYROXINE 112 MCG TABLET Generic $0.45 each
LEVOTHYROXINE 125 MCG TABLET Generic $0.46 each
LEVOTHYROXINE 137 MCG TABLET Generic $0.46 each
LEVOTHYROXINE 150 MCG TABLET Generic $0.48 each
LEVOTHYROXINE 175 MCG TABLET Generic $0.58 each
LEVOTHYROXINE 200 MCG TABLET Generic $0.58 each
LEVOTHYROXINE 25 MCG TABLET Generic $0.30 each
LEVOTHYROXINE 300 MCG TABLET Generic $0.72 each
LEVOTHYROXINE 50 MCG TABLET Generic $0.33 each
LEVOTHYROXINE 75 MCG TABLET Generic $0.37 each
LEVOTHYROXINE 88 MCG TABLET Generic $0.38 each
synthroid (on 2/22/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
SYNTHROID 100 MCG TABLET Generic $0.37 each
SYNTHROID 112 MCG TABLET Generic $0.45 each
SYNTHROID 125 MCG TABLET Generic $0.46 each
SYNTHROID 137 MCG TABLET Generic $0.46 each
SYNTHROID 150 MCG TABLET Generic $0.48 each
SYNTHROID 175 MCG TABLET Generic $0.58 each
SYNTHROID 200 MCG TABLET Generic $0.58 each
SYNTHROID 25 MCG TABLET Generic $0.30 each
SYNTHROID 300 MCG TABLET Generic $0.72 each
SYNTHROID 50 MCG TABLET Generic $0.33 each
SYNTHROID 75 MCG TABLET Generic $0.37 each
SYNTHROID 88 MCG TABLET Generic $0.38 each

Ontology: Levothyroxine Sodium (C0079691)

Definition (NCI) The sodium salt of levothyroxine, a synthetic levoisomer of thyroxine (T4) that is similar to the endogenous hormone produced by the thyroid gland. In peripheral tissues, levothyroxine is deiodinated by 5'-deiodinase to form triiodothyronine (T3). T3 enters the cell and binds to nuclear thyroid hormone receptors; the activated hormone-receptor complex in turn triggers gene expression and produces proteins required in the regulation of cellular respiration; thermogenesis; cellular growth and differentiation; and the metabolism of proteins, carbohydrates and lipids. T3 also exhibits cardiostimulatory effects.
Definition (PDQ) The sodium salt form of levothyroxine, a synthetic levoisomer of thyroxine (T4), similar to the endogenous hormone produced by the thyroid gland. Thyroxine is de-iodinated to form triiodothyronine (T3) in the peripheral tissues. T3 enters the cell and binds to nuclear thyroid hormone receptors, and the hormone-receptor complex in turn triggers gene expression and produces proteins required in the regulation of cellular respiration, thermogenesis, cellular growth and differentiation, and metabolism of proteins, carbohydrates and lipids. T4 and T3 also posses cardiac stimulatory effect. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39117&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39117&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C888" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Amino Acid, Peptide, or Protein (T116) , Hormone (T125)
MSH D013974
SnomedCT 26456008, 325317009, 126202002, 38076006
English Sodium Levothyroxine, T4 thyroxine sodium preparation, T<sub>4</sub> thyroxine sodium preparation, levothyroxine sodium, Therapeutic Levothyroxine, LEVOTHYROXINE SODIUM, sodium levothyroxine (medication), thyroid preparations sodium levothyroxine, sodium levothyroxine, thyroid preparations sodium levothyroxine (Synthroid, IV), Levothyroxine Sodium [Chemical/Ingredient], sodium thyroxine, thyroxine sodium, LEVOTHYROXINE sodium, Thyroxine sodium (product), Sodium levothyroxine, Thyroxine sodium, L-thyroxine sodium preparation, Levothyroxine sodium preparation, Sodium thyroxine, Levothyroxine sodium, T>4< thyroxine sodium preparation, Laevothyroxine sodium preparation, Laevothyroxine sodium, Levothyroxine sodium (substance), Levothyroxine sodium preparation (product), Levothyroxine Sodium, Levothyroxine sodium preparation (substance), Thyroxine sodium (substance)
Spanish preparado de T4 tiroxina sódica, preparado de L-tiroxina sódica, preparado con levotiroxina sódica (producto), preparado de T>4< tiroxina sódica, T4 tiroxina sódica, T<sub>4</sub> tiroxina sódica, preparado de T<sub>4</sub> tiroxina sódica, T>4< tiroxina sódica, levotiroxina sódica (producto), preparado con levotiroxina sódica, tiroxina sódica (producto), tiroxina sódica, levotiroxina sódica (sustancia), levotiroxina sódica, preparado de levotiroxina sódica (producto), preparado de levotiroxina sódica (sustancia), preparado de levotiroxina sódica
French Lévothyroxine sodique
Norwegian Levotyroksinnatrium, Natrium-levotyroksin

Ontology: Synthroid (C0728762)

Definition (CHV) thyroid hormone in a drug form
Concepts Pharmacologic Substance (T121) , Amino Acid, Peptide, or Protein (T116)
MSH D013974
French Synthroid
English synthroid, Abbot Brand of Levothyroxine Sodium, Synthroid
Norwegian Synthroid

Ontology: Thyroid hormone replacement therapy (C2242640)

Concepts Therapeutic or Preventive Procedure (T061)
English Thyroid hormone replacement therapy
Spanish Tratamiento de sustitución de hormona tiroidea
Dutch schildklierhormoonvervangingstherapie
German Schilddruesenhormonsubstitutionstherapie
Japanese コウジョウセンホルモンホジュウリョウホウ, 甲状腺ホルモン補充療法
Czech Léčba substituce tyreoidálních hormonů
Portuguese Hormonoterapia de substituição da tiróide
Italian Terapia di sostituzione di ormoni tiroidei
French Hormonothérapie thyroïdienne substitutive
Hungarian Pajzsmirigy hormonhelyettesítő terápia