Levothyroxine Sodium: Package Insert and Label Information

LEVOTHYROXINE SODIUM- levothyroxine sodium tablet
Alvogen, Inc.

levothyroxine-structure25mcg-label50mcg-label75mcg-label88mcg-label100mcg-label112mcg-label125mcg-label137mcg-label150mcg-label175mcg-label200mcg-label300mcg-label

1 INDICATIONS AND USAGE

Hypothyroidism

Levothyroxine Sodium Tablets are indicated as a replacement therapy in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism.

Pituitary Thyrotropin (Thyroid-Stimulating Hormone, TSH) Suppression

Levothyroxine Sodium Tablets are indicated as an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer.

Limitations of Use:

• Levothyroxine Sodium Tablets are 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 Sodium Tablets may induce hyperthyroidism [see Warnings and Precautions (5.4)].
• Levothyroxine Sodium Tablets are not indicated for treatment of hypothyroidism during the recovery phase of subacute thyroiditis.

2 DOSAGE AND ADMINISTRATION

2.1 General Administration Information

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

Administer Levothyroxine Sodium Tablets at least 4 hours before or after drugs known to interfere with Levothyroxine Sodium Tablets absorption [see Drug Interactions (7.1)].

Evaluate the need for dose adjustments when regularly administering within one hour of certain foods that may affect Levothyroxine Sodium Tablets absorption [see Drug Interactions (7.9) and Clinical Pharmacology (12.3)].

Administer Levothyroxine Sodium Tablets to infants and children who cannot swallow intact tablets by crushing the tablet, suspending the freshly crushed tablet in a small amount (5 mL to 10 mL or 1 teaspoon to 2 teaspoons) of water and immediately administering the suspension by spoon or dropper. Do not store the suspension. Do not administer in foods that decrease absorption of Levothyroxine Sodium Tablets, such as soybean-based infant formula [see Drug Interactions (7.9)].

2.2 General Principles of Dosing

The dose of Levothyroxine Sodium Tablets 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 dose adjustments made based on periodic assessment of the patient’s clinical response and laboratory parameters [see Dosage and Administration (2.4)].

The peak therapeutic effect of a given dose of Levothyroxine Sodium Tablets may not be attained for 4 to 6 weeks.

2.3 Dosing in Specific Patient Populations

Primary Hypothyroidism in Adults and in Adolescents in Whom Growth and Puberty are Complete

Start Levothyroxine Sodium Tablets at the full replacement dose in otherwise healthy, non-elderly individuals who have been hypothyroid for only a short time (such as a few months). The average full replacement dose of Levothyroxine Sodium Tablets is approximately 1.6 mcg per kg per day (for example: 100 mcg per day to 125 mcg per day for a 70 kg adult).

Adjust the dose by 12.5 mcg to 25 mcg increments every 4 to 6 weeks until the patient is clinically euthyroid and the serum TSH returns to normal. Doses greater than 200 mcg per day are seldom required. An inadequate response to daily doses of greater than 300 mcg per day is rare and may indicate poor compliance, malabsorption, drug interactions, or a combination of these factors.

For elderly patients or patients with underlying cardiac disease, start with a dose of 12.5 mcg per day to 25 mcg per day. Increase the dose every 6 to 8 weeks, as needed until the patient is clinically euthyroid and the serum TSH returns to normal. The full replacement dose of Levothyroxine Sodium Tablets may be less than 1 mcg per kg per day in elderly patients.

In patients with severe longstanding hypothyroidism, start with a dose of 12.5 mcg per day to 25 mcg per day. Adjust the dose in 12.5 mcg to 25 mcg increments every 2 to 4 weeks until the patient is clinically euthyroid and the serum TSH level is normalized.

Secondary or Tertiary Hypothyroidism

Start Levothyroxine Sodium Tablets at the full replacement dose in otherwise healthy, non-elderly individuals. Start with a lower dose in elderly patients, patients with underlying cardiovascular disease or patients with severe longstanding hypothyroidism as described above. Serum TSH is not a reliable measure of Levothyroxine Sodium Tablets dose adequacy in patients with secondary or tertiary hypothyroidism and should not be used to monitor therapy. Use the serum free-T4 (L-thyroxine) level to monitor adequacy of therapy in this patient population. Titrate Levothyroxine Sodium Tablets dosing per above instructions until the patient is clinically euthyroid and the serum free-T4 level is restored to the upper half of the normal range.

Pediatric Dosage — Congenital or Acquired Hypothyroidism

The recommended daily dose of Levothyroxine Sodium Tablets in pediatric patients with hypothyroidism is based on body weight and changes with age as described in Table 1. Start Levothyroxine Sodium Tablets at the full daily dose in most pediatric patients. Start at a lower starting dose in newborns (0-3 months) at risk for cardiac failure and in children at risk for hyperactivity (see below). Monitor for clinical and laboratory response [see Dosage and Administration (2.4)].

Table 1. Levothyroxine Sodium Tablets Dosing Guidelines for Pediatric Hypothyroidism

AGE	Daily Dose Per Kg Body Weight *
* The dose should be adjusted based on clinical response and laboratory parameters [see Dosage and Administration (2.4) and Use in Specific Populations (8.4)].
0-3 months	10 mcg/kg/day to 15 mcg/kg/day
3-6 months	8 mcg/kg/day to 10 mcg/kg/day
6-12 months	6 mcg/kg/day to 8 mcg/kg/day
1-5 years	5 mcg/kg/day to 6 mcg/kg/day
6-12 years	4 mcg/kg/day to 5 mcg/kg/day
Greater than 12 years but growth and puberty incomplete	2 mcg/kg/day to 3 mcg/kg/day
Growth and puberty complete	1.6 mcg/kg/day

Newborns (0-3 months) at risk for cardiac failure: Consider a lower starting dose in newborns at risk for cardiac failure. Increase the dose every 4 to 6 weeks as needed based on clinical and laboratory response.

Children at risk for hyperactivity: To minimize the risk of hyperactivity in children, start at one-fourth the recommended full replacement dose, and increase on a weekly basis by one-fourth the full recommended replacement dose until the full recommended replacement dose is reached.

Pregnancy

Pre-existing Hypothyroidism: Levothyroxine Sodium Tablets dose requirements may increase during pregnancy. Measure serum TSH and free-T4 as soon as pregnancy is confirmed and, at minimum, during each trimester of pregnancy. In patients with primary hypothyroidism, maintain serum TSH in the trimester-specific reference range. For patients with serum TSH above the normal trimester-specific range, increase the dose of Levothyroxine Sodium Tablets by 12.5 mcg/day to 25 mcg/day and measure TSH every 4 weeks until a stable Levothyroxine Sodium Tablets dose is reached and serum TSH is within the normal trimester-specific range. Reduce Levothyroxine Sodium Tablets dosage to pre-pregnancy levels immediately after delivery and measure serum TSH levels 4 to 8 weeks postpartum to ensure Levothyroxine Sodium Tablets dose is appropriate.

New Onset Hypothyroidism: Normalize thyroid function as rapidly as possible. In patients with moderate to severe signs and symptoms of hypothyroidism, start Levothyroxine Sodium Tablets at the full replacement dose (1.6 mcg per kg body weight per day). In patients with mild hypothyroidism (TSH less than 10 units per liter) start Levothyroxine Sodium Tablets at 1 mcg per kg body weight per day. Evaluate serum TSH every 4 weeks and adjust Levothyroxine Sodium Tablets dosage until a serum TSH is within the normal trimester specific range [see Use in Specific Populations (8.1)].

TSH Suppression in Well-differentiated Thyroid Cancer

Generally, TSH is suppressed to below 0.1 units per liter, and this usually requires a Levothyroxine Sodium Tablets dose of greater than 2 mcg per kg per day. However, in patients with high-risk tumors, the target level for TSH suppression may be lower.

2.4 Monitoring TSH and/or Thyroxine (T4) Levels

Assess the adequacy of therapy by periodic assessment of laboratory tests and clinical evaluation. Persistent clinical and laboratory evidence of hypothyroidism despite an apparent adequate replacement dose of Levothyroxine Sodium Tablets 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 dose. In patients on a stable and appropriate replacement dose, evaluate clinical and biochemical response every 6 to 12 months and whenever there is a change in the patient’s clinical status.

Pediatrics

In patients with congenital 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 children 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 dose 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.

While 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 Levothyroxine Sodium Tablets therapy and/or of the serum TSH to decrease below 20 units per liter within 4 weeks may indicate the child is not receiving adequate therapy. Assess compliance, dose of medication administered, and method of administration prior to increasing the dose of Levothyroxine Sodium Tablets [see Warnings and Precautions (5.4) 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.

3 DOSAGE FORMS AND STRENGTHS

Levothyroxine Sodium Tablets, in the shape of caplet are available as follows:

Tablet Strength	Tablet Color	Tablet Markings
25 mcg	Orange	“T|4” and “25”
50 mcg	White	“T|4” and “50”
75 mcg	Violet	“T|4” and “75”
88 mcg	Mint Green	“T|4” and “88”
100 mcg	Yellow	“T|4” and “100”
112 mcg	Rose	“T|4” and “112”
125 mcg	Brown	“T|4” and “125”
137 mcg	Deep Blue	“T|4” and “137”
150 mcg	Light Blue	“T|4” and “150”
175 mcg	Lilac	“T|4” and “175”
200 mcg	Pink	“T|4” and “200”
300 mcg	Green	“T|4” and “300”

4 CONTRAINDICATIONS

Levothyroxine Sodium Tablets are contraindicated in patients with uncorrected adrenal insufficiency [see Warnings and Precautions (5.3)].

5 WARNINGS AND PRECAUTIONS

5.1 Cardiac Adverse Reactions in the Elderly and in Patients with Underlying Cardiovascular Disease

Over-treatment with levothyroxine may cause an increase in heart rate, cardiac wall thickness, and cardiac contractility and may precipitate angina or arrhythmias, particularly in patients with cardiovascular disease and in elderly patients. Initiate Levothyroxine Sodium Tablets therapy in this population at lower doses than those recommended in younger individuals or in patients without cardiac disease [see Dosage and Administration (2.3) , Use in Specific Populations (8.5)].

Monitor for cardiac arrhythmias during surgical procedures in patients with coronary artery disease receiving suppressive Levothyroxine Sodium Tablets therapy. Monitor patients receiving concomitant Levothyroxine Sodium Tablets and sympathomimetic agents for signs and symptoms of coronary insufficiency.

If cardiac symptoms develop or worsen, reduce the Levothyroxine Sodium Tablets dose or withhold for one week and restart at a lower dose.