levothyroxine

Levothyroxine is a synthetic form of thyroid hormone produced by the human thyroid gland, a butterfly-shaped organ located at the base of the neck. The thyroid gland produces thyroid hormones using iodine absorbed from dietary intake. Levothyroxine is prescribed to treat hypothyroidism, a condition in which the thyroid gland produces insufficient thyroid hormones. Levothyroxine medication replaces or supplements deficiency in natural thyroxine.

Thyroid hormones have many important functions in maintaining mental and physical health in adults, and normal physical growth and mental development in children. Hypothyroidism leads to several metabolic disorders, weight gain, infertility, bone disorders, and heart problems. Hypothyroidism may be caused by thyroid disorders, due to radiation for neck and head cancers, certain medications or thyroid surgery/removal.

Thyroid hormone secretion is regulated by the hypothalamus-pituitary-thyroid axis. Based on feedback from blood levels of thyroid hormones, the hypothalamus region in the brain secretes thyrotropin-releasing hormone (TRH). TRH stimulates the pituitary gland to secrete thyrotropin-stimulating hormone (TSH), which in turn stimulates the thyroid gland to produce thyroid hormones T3 and T4. Impairment in the normal functioning of any part of this axis can cause hypothyroidism.

Levothyroxine is used in the following conditions:

• Hypothyroidism, acquired or congenital, from any cause including:
  • Primary hypothyroidism (thyroid disorder)
  • Secondary hypothyroidism (pituitary disorder)
  • Tertiary hypothyroidism (hypothalamus disorder)
  • Subclinical hypothyroidism (normal thyroid hormone levels, but mildly elevated TSH)
• Myxedema coma, a rare medical emergency with loss of brain function due to severe long-standing hypothyroidism
• Pituitary TSH suppression:
  • To prevent and treat thyroid enlargement (goiter), nodules and inflammation in patients with normal thyroid function (euthyroid)
  • As an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer
• Organ preservation in brain-dead organ donors (Orphan designation)

• Do not use levothyroxine for weight loss, either alone or with other therapeutic agents. In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction; larger doses may produce serious or even life-threatening signs of toxicity, especially when used with drugs that cause loss of appetite (anorexia)
• Do not use in patients with an acute heart attack (myocardial infarction)
• Do not use in patients with hypersensitivity to levothyroxine or any of its ingredients
• Do not use in patients with suppressed TSH and elevated thyroid hormone levels in the blood (thyrotoxicosis)
• Do not use oral levothyroxine to treat myxedema coma, use intravenous formulations
• Avoid use in patients with goiter or thyroid nodules with low TSH levels
• Use with caution in the treatment of goiter or nodules in patients with normal thyroid function
• Do not use in patients with uncorrected adrenal insufficiency; thyroid hormones may precipitate an acute adrenal crisis
• Do not use levothyroxine to treat male or female infertility, unless it is associated with hypothyroidism
• Avoid undertreatment or overtreatment; may cause several adverse effects. Dosage must be carefully titrated to maintain optimal levels to treat hypothyroidism and prevent hyperthyroidism
• Use with caution in patients with cardiovascular disease, hypertension, endocrine disorders, osteoporosis and myxedema
• Long-term levothyroxine therapy reduces bone mineral density; use minimal doses in postmenopausal women
• Avoid use in postmenopausal women with osteoporosis, cardiovascular disease or systemic illness
• Levothyroxine can worsen glycemic control in diabetes mellitus patients; monitor glycemic control
• Monitor for presence of drug or food interactions when using levothyroxine and adjust dose as necessary

Side effects associated with levothyroxine are primarily from hyperthyroidism due to therapeutic overdosage. Common side effects of levothyroxine may include:

• Fatigue
• Increased appetite
• Weight loss
• Heat intolerance
• Fever
• Excessive sweating
• Increase in pulse rate
• Increase in blood pressure
• Irregular heart rhythm (arrhythmia)
• Palpitations
• Rapid heartbeat (tachycardia)
• Chest pain (angina pectoris)
• Congestive heart failure
• Heart attack (myocardial infarction)
• Cardiac arrest
• Shortness of breath (dyspnea)
• Abdominal cramps
• Diarrhea
• Vomiting
• Elevated liver function tests
• Headache
• Nervousness
• Anxiety
• Choking sensation
• Hyperactivity
• Irritability 
• Mood swings (emotional lability)
• Insomnia
• Tremors
• Muscle weakness (myasthenia)
• Decrease in bone mineral density
• Hair loss (alopecia)
• Flushing
• Menstrual irregularities
• Impairment of fertility
• Less common side effects include:
• Increase in intracranial pressure (pseudotumor cerebri)
• Hip joint disorder in children that causes shifting of the top portion of the thighbone (slipped capital femoral epiphysis)
• Premature skull bone fusing (craniosynostosis) in infants
• Premature closure of the ends of long bone (epiphyses) which can compromise height in adulthood
• Seizures (rare)

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Tablet (Levo-T, Levoxyl, Unithroid, generic)

• 25mcg, 50mcg, 75mcg, 88mcg, 100mcg, 112mcg
• 125mcg, 137mcg, 150mcg, 175mcg, 200mcg, 300mcg

Capsule (Tirosint, generic)

• 13mcg, 25mcg, 50mcg, 75mcg, 88mcg
• 100mcg, 112 mcg, 125mcg, 137 mcg, 150mcg

Oral Solution

Tirosint-SOL

• 13mcg/mL, 25mcg/mL, 37.5mcg/mL, 44mcg/mL, 50mcg/mL, 62.5mcg/mL
• 75mcg/mL, 88mcg/mL, 100mcg/mL, 112mcg/mL, 125mcg/mL, 137mcg/mL
• 150mcg/mL, 175mcg/mL, 200mcg/mL

Thyquidity

• 20mcg/mL

Injection

• 100mcg/vial
• 200mcg/vial
• 500mcg/vial

Adult

Mild Hypothyroidism

• 1.7 mcg/kg or 100-125 mcg oral every day; not to exceed 300 mcg/day

Above 50 years (or below 50 years with cardiovascular disease)

• Usual initial dose: 25-50 mcg/day
• May adjust dose by 12.5-25 mcg every 6-8 weeks

Above 50 years with cardiovascular disease

• Usual initial dose: 12.5-25 mcg oral every day
• May adjust dose by 12.5-25 mcg every 4-6 weeks until patient becomes euthyroid and serum TSH concentration normalized; adjustments every 6-8 weeks also used
• Dose range: 100-125 mcg oral every day

Severe Hypothyroidism

• Initial: 12.5-25 mcg oral every day
• Adjust dose by 25 mcg/day every 2-4 week as needed

Subclinical Hypothyroidism

• Initial: 1 mcg/kg oral every day may be adequate, OR  
• If replacement therapy not initiated, monitor patient annually for clinical status

Myxedema Coma

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

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 every 6-8 week
• Once normalization of thyroid function and serum TSH concentration is achieved, evaluate every 6-12 months

Geriatric

• 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

Pediatric

Hypothyroidism

Age 1-3 months

• 10-15 mcg/kg/day oral  
• 5-7.5 mcg/kg/day intravenous/intramuscular (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 oral, OR  
• 25-50 mcg/day oral
• 4-7.5 mcg/kg/day IV/IM

Age 6-12 months

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

Age 1-5 years

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

Age 6-12 years

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

Above 12 years

• 2-3 mcg/kg/day oral, OR  
• 150 mcg/day oral
• 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 every week

• In case of overdosage, levothyroxine dosage should be reduced or temporarily discontinued, and symptomatic and supportive therapy should be initiated based on the patient’s condition.
• For current information on overdose or poisoning, contact the National Poison Control Center.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Severe interactions of levothyroxine include:
  • sodium iodide I-131
  • sucroferric oxyhydroxide
• Serious interaction of levothyroxine include:
  • antithrombin alfa
  • antithrombin III
  • argatroban
  • bemiparin
  • bivalirudin
  • bremelanotide
  • fondaparinux
  • heparin
  • phenindione
  • protamine
• Levothyroxine has moderate interactions with at least 45 different drugs.
• Levothyroxine has mild interactions with at least 31 different drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• Use of levothyroxine is safe in pregnancy, studies show no fetal risk.
• Pre-existing hypothyroidism and new-onset hypothyroidism must be treated during pregnancy; untreated maternal hypothyroidism carries risk to the mother and the fetus.
• Untreated maternal hypothyroidism has higher rate of complications, including spontaneous abortions, gestational hypertension, preeclampsia, stillbirth and premature delivery.
• Levothyroxine is excreted in breast milk, but there is insufficient information on its effects on breastfed infant or milk production. Adequate levothyroxine treatment may induce normal milk production in nursing mothers.

• Do not use levothyroxine sodium formulations interchangeably
• Check for bioequivalence if changing generics/brands
• Synthroid and Unithroid tablets contain lactose
• Levoxyl tabs swell in the mouth; take with a full glass of water to avoid choking