Synthroid

SYNTHROID is indicated in adult and pediatric patients, including neonates, as a replacement therapy in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism.

SYNTHROID is indicated in adult and pediatric patients, including neonates, as an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer.

• SYNTHROID is 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 SYNTHROID may induce hyperthyroidism
  [see Warnings and Precautions (
  5.1 Serious Risks Related to Overtreatment or Undertreatment with SYNTHROID

  SYNTHROID has a narrow therapeutic index. Overtreatment or undertreatment with SYNTHROID may have negative effects on growth and development, cardiovascular function, bone metabolism, reproductive function, cognitive function, gastrointestinal function, and glucose and lipid metabolism in adult or pediatric patients.

  In pediatric patients with congenital and acquired hypothyroidism, undertreatment may adversely affect cognitive development and linear growth, and overtreatment is associated with craniosynostosis and acceleration of bone age

  [see Use in Specific Populations (

  8.4

  )]

  .

  Titrate the dose of SYNTHROID carefully and monitor response to titration to avoid these effects

  [see Dosage and Administration

  (2.4)

  ]

  . Consider the potential for food or drug interactions and adjust the administration or dosage of SYNTHROID as needed

  [see

  Dosage and Administration (

  2.1

  ),

  Drug Interactions

  (7.1)

  ,

  and Clinical Pharmacology

  (12.3)

  ]

  .
  )].
   
  
  
• SYNTHROID is not indicated for treatment of hypothyroidism during the recovery phase of subacute thyroiditis.

• Administer once daily, preferably on an empty stomach, one-half to one hour before breakfast. (
  2.1

  Important

  Administration

  Instructions

  Administer SYNTHROID as a single daily dose, on an empty stomach, one-half to one hour before breakfast.

  Administer SYNTHROID at least 4 hours before or after drugs known to interfere with SYNTHROID absorption

  [see Drug Interactions

  (

  7.1

  )

  ]

  .

  Evaluate the need for dosage adjustments when regularly administering within one hour of certain foods that may affect SYNTHROID absorption

  [see

  Dosage and Administration (

  2.2

  and

  2.3

  ),

  Drug Interactions

  (

  7.9

  )

  ,

  and

  Clinical Pharmacology

  (

  12.3

  )

  ]

  .

  Administer SYNTHROID to pediatric patients who cannot swallow intact tablets by crushing the tablet, suspending the freshly crushed tablet in a small amount (5 to 10 mL) of water and immediately administering the suspension by spoon or dropper. Ensure the patient ingests the full amount of the suspension. Do not store the suspension. Do not administer in foods that decrease absorption of SYNTHROID, such as soybean-based infant formula

  [see Drug Interactions

  (

  7.9

  )

  ]

  .
  )
  
  
• Administer at least 4 hours before or after drugs that are known to interfere with absorption. (
  2.1

  Important

  Administration

  Instructions

  Administer SYNTHROID as a single daily dose, on an empty stomach, one-half to one hour before breakfast.

  Administer SYNTHROID at least 4 hours before or after drugs known to interfere with SYNTHROID absorption

  [see Drug Interactions

  (

  7.1

  )

  ]

  .

  Evaluate the need for dosage adjustments when regularly administering within one hour of certain foods that may affect SYNTHROID absorption

  [see

  Dosage and Administration (

  2.2

  and

  2.3

  ),

  Drug Interactions

  (

  7.9

  )

  ,

  and

  Clinical Pharmacology

  (

  12.3

  )

  ]

  .

  Administer SYNTHROID to pediatric patients who cannot swallow intact tablets by crushing the tablet, suspending the freshly crushed tablet in a small amount (5 to 10 mL) of water and immediately administering the suspension by spoon or dropper. Ensure the patient ingests the full amount of the suspension. Do not store the suspension. Do not administer in foods that decrease absorption of SYNTHROID, such as soybean-based infant formula

  [see Drug Interactions

  (

  7.9

  )

  ]

  .
  )
  
  
• Evaluate the need for dose adjustments when regularly administering within one hour of certain foods that may affect absorption. (
  2.1

  Important

  Administration

  Instructions

  Administer SYNTHROID as a single daily dose, on an empty stomach, one-half to one hour before breakfast.

  Administer SYNTHROID at least 4 hours before or after drugs known to interfere with SYNTHROID absorption

  [see Drug Interactions

  (

  7.1

  )

  ]

  .

  Evaluate the need for dosage adjustments when regularly administering within one hour of certain foods that may affect SYNTHROID absorption

  [see

  Dosage and Administration (

  2.2

  and

  2.3

  ),

  Drug Interactions

  (

  7.9

  )

  ,

  and

  Clinical Pharmacology

  (

  12.3

  )

  ]

  .

  Administer SYNTHROID to pediatric patients who cannot swallow intact tablets by crushing the tablet, suspending the freshly crushed tablet in a small amount (5 to 10 mL) of water and immediately administering the suspension by spoon or dropper. Ensure the patient ingests the full amount of the suspension. Do not store the suspension. Do not administer in foods that decrease absorption of SYNTHROID, such as soybean-based infant formula

  [see Drug Interactions

  (

  7.9

  )

  ]

  .
  )
  
  
• Advise patients to stop biotin and biotin-containing supplements at least 2 days before assessing TSH and/or T4 levels. (
  2.2

  Important Considerations for

  Dosing

  The dosage of SYNTHROID for hypothyroidism or pituitary TSH suppression depends on a variety of factors including: the patient's age, body weight, cardiovascular status, concomitant medical conditions (including pregnancy), concomitant medications, co-administered food and the specific nature of the condition being treated

  [see Dosage and Administration (

  2.3

  ), Warnings and Precautions (

  5

  ),

  and

  Drug Interactions (

  7

  )]

  . Dosing must be individualized to account for these factors and dosage adjustments made based on periodic assessment of the patient's clinical response and laboratory parameters

  [see Dosage and Administration (

  2.4

  )]

  .

  For adult patients with primary hypothyroidism, titrate until the patient is clinically euthyroid and the serum TSH returns to normal

  [see Dosage and Administration (

  2.3

  )]

  .

  For secondary or tertiary hypothyroidism, serum TSH is not a reliable measure of SYNTHROID dosage adequacy and should not be used to monitor therapy. Use the serum free-T4 level to titrate SYNTHROID dosing until the patient is clinically euthyroid and the serum free-T4 level is restored to the upper half of the normal range

  [see Dosage and Administration (

  2.3

  )]

  .

  Inquire whether patients are taking biotin or biotin-containing supplements. If so, advise them to stop biotin supplementation at least 2 days before assessing TSH and/or T4 levels

  [see Dosage and Administration (

  2.4

  ) and

  Drug Interactions (

  7.10

  )].

  The peak therapeutic effect of a given dose of SYNTHROID may not be attained for 4 to 6 weeks.
  )
  
  
• Starting dose depends on a variety of factors, including age, body weight, cardiovascular status, and concomitant medications. Peak therapeutic effect may not be attained for 4-6 weeks. (
  2.2

  Important Considerations for

  Dosing

  The dosage of SYNTHROID for hypothyroidism or pituitary TSH suppression depends on a variety of factors including: the patient's age, body weight, cardiovascular status, concomitant medical conditions (including pregnancy), concomitant medications, co-administered food and the specific nature of the condition being treated

  [see Dosage and Administration (

  2.3

  ), Warnings and Precautions (

  5

  ),

  and

  Drug Interactions (

  7

  )]

  . Dosing must be individualized to account for these factors and dosage adjustments made based on periodic assessment of the patient's clinical response and laboratory parameters

  [see Dosage and Administration (

  2.4

  )]

  .

  For adult patients with primary hypothyroidism, titrate until the patient is clinically euthyroid and the serum TSH returns to normal

  [see Dosage and Administration (

  2.3

  )]

  .

  For secondary or tertiary hypothyroidism, serum TSH is not a reliable measure of SYNTHROID dosage adequacy and should not be used to monitor therapy. Use the serum free-T4 level to titrate SYNTHROID dosing until the patient is clinically euthyroid and the serum free-T4 level is restored to the upper half of the normal range

  [see Dosage and Administration (

  2.3

  )]

  .

  Inquire whether patients are taking biotin or biotin-containing supplements. If so, advise them to stop biotin supplementation at least 2 days before assessing TSH and/or T4 levels

  [see Dosage and Administration (

  2.4

  ) and

  Drug Interactions (

  7.10

  )].

  The peak therapeutic effect of a given dose of SYNTHROID may not be attained for 4 to 6 weeks.
  )
  
  
• See full prescribing information for dosing in specific patient populations. (
  2.3

  Recommended Dosage and Titration

  Primary, Secondary, and Tertiary Hypothyroidism in Adults

  The recommended starting daily dosage of SYNTHROID in adults with primary, secondary, or tertiary hypothyroidism is based on age and comorbid cardiac conditions, as described in Table 1. For patients at risk of atrial fibrillation or patients with underlying cardiac disease, start with a lower dosage and titrate the dosage more slowly to avoid exacerbation of cardiac symptoms. Dosage titration is based on serum TSH or free-T4

  [see Dosage and Administration (

  2.2

  )]

  .

  Table 1. SYNTHROID Dosing Guidelines for Hypothyroidism in Adults*

  Patient Population	Starting Dosage	Dosage Titration Based on Serum TSH or Free-T4
  Adults diagnosed with hypothyroidism	Full replacement dose is 1.6 mcg/kg/day. Some patients require a lower starting dose.	Titrate dosage by 12.5 to 25 mcg increments every 4 to 6 weeks, as needed until the patient is euthyroid.
  Adults at risk for atrial fibrillation or with underlying cardiac disease	Lower starting dose (less than 1.6 mcg/kg/day)	Titrate dosage every 6 to 8 weeks, as needed until the patient is euthyroid.
  Geriatric patients	Lower starting dose (less than 1.6 mcg/kg/day)

  * Dosages greater than 200 mcg/day are seldom required. An inadequate response to daily dosages greater than 300 mcg/day is rare and may indicate poor compliance, malabsorption, drug interactions, or a combination of these factors

  [see Dosage and Administration (

  2.1

  ) and Drug Interactions

  (7)

  ]

  .

  Primary, Secondary, and Tertiary Hypothyroidism in Pediatric Patients

  The recommended starting daily dosage of SYNTHROID in pediatric patients with primary, secondary, or tertiary hypothyroidism is based on body weight and changes with age as described in Table 2. Titrate the dosage (every 2 weeks) as needed based on serum TSH or free-T4 until the patient is euthyroid

  [see Dosage and Administration (

  2.2

  )]

  .

  Table 2. SYNTHROID Dosing Guidelines for Hypothyroidism in Pediatric Patients

  Ag e	Starting Daily Dos ag e Per Kg Body Weight *
  0-3 months	10-15 mcg/kg/day
  3-6 months	8-10 mcg/kg/day
  6-12 months	6-8 mcg/kg/day
  1-5 years	5-6 mcg/kg/day
  6-12 years	4-5 mcg/kg/day
  Greater than 12 years but growth and puberty incomplete	2-3 mcg/kg/day
  Growth and puberty complete	1.6 mcg/kg/day
  * Adjust dosage based on clinical response and laboratory parameters [see Dosage and Administration ( 2.4 ) and Use in Specific Populations ( 8.4 ) ] .

  Pediatric Patients from Birth to 3 Months of Age at Risk for Cardiac Failure

  Start at a lower starting dosage and increase the dosage every 4 to 6 weeks as needed based on clinical and laboratory response.

  Pediatric Patients at Risk for Hyperactivity

  To minimize the risk of hyperactivity, start at one-fourth the recommended full replacement dosage, and increase on a weekly basis by one-fourth the full recommended replacement dosage until the full recommended replacement dosage is reached.

  Hypothyroidism in Pregnant Patients

  For pregnant patients with pre-existing hypothyroidism, measure serum TSH and free-T4 as soon as pregnancy is confirmed and, at minimum, during each trimester of pregnancy. In pregnant patients with primary hypothyroidism, maintain serum TSH in the trimester-specific reference range.

  The recommended daily dosage of SYNTHROID in pregnant patients is described in Table 3.

  Table 3. SYNTHROID Dosing Guidelines for Hypothyroidism in Pregnant Patients

  Patient Population	Starting Dosage	Dose Adjustment and Titration
  Pre-existing primary hypothyroidism with serum TSH above normal trimester-specific range	Pre-pregnancy dosage may increase during pregnancy	Increase SYNTHROID dosage by 12.5 to 25 mcg per day. Monitor TSH every 4 weeks until a stable dose is reached and serum TSH is within normal trimester-specific range. Reduce SYNTHROID dosage to pre-pregnancy levels immediately after delivery. Monitor serum TSH 4 to 8 weeks postpartum.
  New onset hypothyroidism (TSH ≥ 10 mIU per liter)	1.6 mcg/kg/day	Monitor serum TSH every 4 weeks and adjust SYNTHROID dosage until serum TSH is within normal trimester-specific range.
  New onset hypothyroidism (TSH < 10 mIU per liter)	1.0 mcg/kg/day

  TSH Suppression in Well-differentiated Thyroid Cancer

  in Adult and Pediatric Patients

  The SYNTHROID dosage is based on the target level of TSH suppression for the stage and clinical status of thyroid cancer.
  ) 
  
  
• Adequacy of therapy determined with periodic monitoring of TSH and/or T4 as well as clinical status. (
  2.4 Monitoring TSH and/or Thyroxine (T4) Levels

  Assess the adequacy of therapy by periodic assessment of laboratory tests and clinical evaluation.

  Biotin supplementation may interfere with immunoassays for TSH, T4, and T3, resulting in erroneous thyroid hormone test results. Stop biotin and biotin-containing supplements for at least 2 days before assessing TSH and/or T4 levels

  [see Drug Interactions (

  7.10

  )].

  Persistent clinical and laboratory evidence of hypothyroidism despite an apparent adequate replacement dose of SYNTHROID may be evidence of inadequate absorption, poor compliance, drug interactions, or a combination of these factors.

  Adults

  In adult patients with primary hypothyroidism, monitor serum TSH levels after an interval of 6 to 8 weeks after any change in dosage. In patients on a stable and appropriate replacement dosage, evaluate clinical and biochemical response every 6 to 12 months and whenever there is a change in the patient’s clinical status.

  Pediatric

  Patients

  In patients with hypothyroidism, assess the adequacy of replacement therapy by measuring both serum TSH and total or free-T4. Monitor TSH and total or free-T4 in pediatric patients as follows: 2 and 4 weeks after the initiation of treatment, 2 weeks after any change in dosage, and then every 3 to 12 months thereafter following dosage stabilization until growth is completed. Poor compliance or abnormal values may necessitate more frequent monitoring. Perform routine clinical examination, including assessment of development, mental and physical growth, and bone maturation, at regular intervals.

  The general aim of therapy is to normalize the serum TSH level. TSH may not normalize in some patients due to in utero hypothyroidism causing a resetting of pituitary-thyroid feedback. Failure of the serum T4 to increase into the upper half of the normal range within 2 weeks of initiation of SYNTHROID therapy and/or of the serum TSH to decrease below 20 mIU per liter within 4 weeks may indicate the patient is not receiving adequate therapy. Assess compliance, dose of medication administered, and method of administration prior to increasing the dose of SYNTHROID

  [see Warnings and Precautions (

  5.1

  )

  and

  Use in Specific Populations (

  8.4

  )]

  .

  Secondary and Tertiary Hypothyroidism

  Monitor serum free-T4 levels and maintain in the upper half of the normal range in these patients.
  )

SYNTHROID tablets are available as follows (

Pregnancy may require the use of higher doses of SYNTHROID. (