Synthroid (Page 5 of 8)

11 DESCRIPTION

SYNTHROID (levothyroxine sodium tablets, USP) is L-thyroxine (T4) and contains synthetic crystalline L-3,3′,5,5′-tetraiodothyronine sodium salt. Synthetic T4 is chemically identical to that produced in the human thyroid gland. Levothyroxine (T4) sodium has an empirical formula of C15 H10 I4 N NaO4 • H2 O, molecular weight of 798.86 (anhydrous), and structural formula as shown:

SYNTHROID (levothyroxine sodium tablets, USP) contain synthetic crystalline L-3,3',5,5'-tetraiodothyronine sodium salt [levothyroxine (T4) sodium]. Synthetic T4 is chemically identical to that produced in the human thyroid gland. Levothyroxine (T4) sodium has an empirical formula of C15H10I4N NaO4• H2O, molecular weight of 798.86 (anhydrous), and structural formula as shown:
(click image for full-size original)

SYNTHROID tablets for oral administration are supplied in the following strengths: 25 mcg, 50 mcg, 75 mcg, 88 mcg, 100 mcg, 112 mcg, 125 mcg, 137 mcg, 150 mcg, 175 mcg, 200 mcg, and 300 mcg. Each SYNTHROID tablet contains the inactive ingredients acacia, confectioner’s sugar (contains corn starch), lactose monohydrate, magnesium stearate, povidone, and talc. SYNTHROID tablets contain no ingredients made from a gluten-containing grain (wheat, barley, or rye). Each tablet strength meets USP Dissolution Test 3. Table 9 provides a listing of the color additives by tablet strength:

Table 9: SYNTHROID Tablet Color Additives
Strength (mcg) Color additive(s)
25FD&C Yellow No. 6 Aluminum Lake*
50None
75FD&C Red No. 40 Aluminum Lake, FD&C Blue No. 2 Aluminum Lake
88FD&C Blue No. 1 Aluminum Lake, FD&C Yellow No. 6 Aluminum Lake*, D&C Yellow No. 10 Aluminum Lake
100D&C Yellow No. 10 Aluminum Lake, FD&C Yellow No. 6 Aluminum Lake*
112D&C Red No. 27 & 30 Aluminum Lake
125FD&C Yellow No. 6 Aluminum Lake*, FD&C Red No. 40 Aluminum Lake, FD&C Blue No. 1 Aluminum Lake
137FD&C Blue No. 1 Aluminum Lake
150FD&C Blue No. 2 Aluminum Lake
175FD&C Blue No. 1 Aluminum Lake, D&C Red No. 27 & 30 Aluminum Lake
200FD&C Red No. 40 Aluminum Lake
300D&C Yellow No. 10 Aluminum Lake, FD&C Yellow No. 6 Aluminum Lake*, FD&C Blue No. 1 Aluminum Lake
* Note – FD&C Yellow No. 6 is orange in color.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Thyroid hormones exert their physiologic actions through control of DNA transcription and protein synthesis. Triiodothyronine (T3) and L-thyroxine (T4) diffuse into the cell nucleus and bind to thyroid receptor proteins attached to DNA. This hormone nuclear receptor complex activates gene transcription and synthesis of messenger RNA and cytoplasmic proteins.

The physiological actions of thyroid hormones are produced predominantly by T3, the majority of which (approximately 80%) is derived from T4 by deiodination in peripheral tissues.

12.2 Pharmacodynamics

Oral levothyroxine sodium is a synthetic T4 hormone that exerts the same physiologic effect as endogenous T4, thereby maintaining normal T4 levels when a deficiency is present.

12.3 Pharmacokinetics

Absorption

Absorption of orally administered T4 from the gastrointestinal tract ranges from 40% to 80%. The majority of the SYNTHROID dose is absorbed from the jejunum and upper ileum. The relative bioavailability of SYNTHROID 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 t 1/2 (days) Protein Binding (%)*
Levothyroxine (T4) 10 — 20 1 6-7** 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

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2024. All Rights Reserved.