Prescription Drug Information: Levothyroxine Sodium (Page 5 of 6)

12.3 Pharmacokinetics

Absorption

Absorption of orally administered T4 from the gastrointestinal tract ranges from 40% to 80%. The majority of the levothyroxine sodium dose is absorbed from the jejunum and upper ileum. The relative bioavailability of levothyroxine sodium tablets, compared to an equal nominal dose of oral levothyroxine sodium solution, is approximately 93%. T4 absorption is increased by fasting, and decreased in malabsorption syndromes and by certain foods such as soybeans. Dietary fiber decreases bioavailability of T4. Absorption may also decrease with age. In addition, many drugs and foods affect T4 absorption [see Drug Interactions (7)].

Distribution

Circulating thyroid hormones are greater than 99% bound to plasma proteins, including thyroxine-binding globulin (TBG), thyroxine-binding prealbumin (TBPA), and albumin (TBA), whose capacities and affinities vary for each hormone. The higher affinity of both TBG and TBPA for T4 partially explains the higher serum levels, slower metabolic clearance, and longer half-life of T4 compared to T3. Protein-bound thyroid hormones exist in reverse equilibrium with small amounts of free hormone. Only unbound hormone is metabolically active. Many drugs and physiologic conditions affect the binding of thyroid hormones to serum proteins [see Drug Interactions (7)]. Thyroid hormones do not readily cross the placental barrier [see Use in Specific Populations (8.1)].

Elimination

Metabolism

T4 is slowly eliminated (see Table 10). The major pathway of thyroid hormone metabolism is through sequential deiodination. Approximately 80% of circulating T3 is derived from peripheral T4 by monodeiodination. The liver is the major site of degradation for both T4 and T3, with T4 deiodination also occurring at a number of additional sites, including the kidney and other tissues. Approximately 80% of the daily dose of T4 is deiodinated to yield equal amounts of T3 and reverse T3 (rT3). T3 and rT3 are further deiodinated to diiodothyronine. Thyroid hormones are also metabolized via conjugation with glucuronides and sulfates and excreted directly into the bile and gut where they undergo enterohepatic recirculation.

Excretion

Thyroid hormones are primarily eliminated by the kidneys. A portion of the conjugated hormone reaches the colon unchanged and is eliminated in the feces. Approximately 20% of T4 is eliminated in the stool. Urinary excretion of T4 decreases with age.

Table 10. Pharmacokinetic Parameters of Thyroid Hormones in Euthyroid Patients

Hormone

Ratio in Thyroglobulin

Biologic Potency

t1/2 (days)

Protein Binding (%)*

Levothyroxine (T4)

10 to 20

1

6 to 7**

99.96

Liothyronine (T3)

1

4

≤ 2

99.5

* Includes TBG, TBPA, and TBA

** 3 to 4 days in hyperthyroidism, 9 to 10 days in hypothyroidism

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term carcinogenicity studies in animals to evaluate the carcinogenic potential of levothyroxine have not been performed. Studies to evaluate mutagenic potential and animal fertility have not been performed.

16 HOW SUPPLIED/STORAGE AND HANDLING

How Supplied

Levothyroxine sodium tablets, USP are flat, beveled edge capsule shaped scored tablets and are supplied as follows (Table 11):

Table 11: Levothyroxine Sodium Tablets, USP Presentations

Strength

Color/Shape

Debossed Tablet Markings

NDC # for bottles of 90

NDC # for bottles of 100

NDC # for bottles of 1000

25 mcg

Orange/ Capsule Shaped

25 on the unscored side and T bisect V on the scored side, with side scores

0480-8682-98

0480-8682-01

0480-8682-10

50 mcg

White/ Capsule Shaped

50 on the unscored side and T bisect V on the scored side, with side scores

0480-8687-98

0480-8687-01

0480-8687-10

75 mcg

Violet/ Capsule Shaped

75 on the unscored side and T bisect V on the scored side, with side scores

0480-8690-98

0480-8690-01

0480-8690-10

88 mcg

Olive/ Capsule Shaped

88 on the unscored side and T bisect V on the scored side, with side scores

0480-8693-98

0480-8693-01

0480-8693-10

100 mcg

Yellow/ Capsule Shaped

100 on the unscored side and T bisect V on the scored side, with side scores

0480-8701-98

0480-8701-01

0480-8701-10

112 mcg

Rose/ Capsule Shaped

112 on the unscored side and T bisect V on the scored side, with side scores

0480-8704-98

0480-8704-01

0480-8704-10

125 mcg

Brown/ Capsule Shaped

125 on the unscored side and T bisect V on the scored side, with side scores

0480-8707-98

0480-8707-01

0480-8707-10

137 mcg

Turquoise/ Capsule Shaped

137 on the unscored side and T bisect V on the scored side, with side scores

0480-8710-98

0480-8710-01

0480-8710-10

150 mcg

Blue/ Capsule Shaped

150 on the unscored side and T bisect V on the scored side, with side scores

0480-8715-98

0480-8715-01

0480-8715-10

175 mcg

Lilac/ Capsule Shaped

175 on the unscored side and T bisect V on the scored side, with side scores

0480-8718-98

0480-8718-01

0480-8718-10

200 mcg

Pink/ Capsule Shaped

200 on the unscored side and T bisect V on the scored side, with side scores

0480-8722-98

0480-8722-01

0480-8722-10

300 mcg

Green/ Capsule Shaped

300 on the unscored side and T bisect V on the scored side, with side scores

0480-8725-98

0480-8725-01

0480-8725-10

Storage and Handling

Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from light and moisture.

Dispense in a tight, light-resistant container as defined in the USP.

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