Levothyroxine: Conventional and Novel Drug Delivery Formulations

The researchers suggested the elevated costs in the GL group may be attributed to complications resulting from inadequate treatment or to the need for increased monitoring 18. At follow-up, TSH goal-achievers had significantly lower all-cause medical costs than those who did not reach TSH goals (adjusted mean $7324 vs. $7822, respectively, p ≤ 0.001; Fig.4; for unadjusted results, see Supplemental Material Table 5). The same pattern was also observed for total costs (adjusted mean $10,438 TSH achievers vs. $10,904 TSH non-achievers, p ≤ 0.001). All-cause pharmacy costs, however, were significantly higher for TSH achievers than for non-achievers (adjusted mean $2601 vs. $2529, p ≤ 0.001). Hypothyroidism-related pharmacy costs were also lower for TSH achievers than for non-achievers (adjusted mean $156 vs. $163, p ≤ 0.001).

Table 1: Summary of Levothyroxine PK.

A portion of the conjugated hormone reaches the colon unchanged and synthroid insurance is eliminated in the feces. 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. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

Study Population

The underlying mechanisms of impaired efficacy due to these diseases or medical conditions vary. Pylori infection and autoimmune gastritis, reduce drug efficacy via hypochlorhydria. Gastroparesis may delay stomach emptying and enable residual food to adsorb more oral LT4 (48). Similarly, gastric sleeve surgery and other bariatric surgery can cause malabsorption in some LT4-treated patients (49).

• Closely monitor coagulation tests to permit appropriate and timely dosage adjustments.
• Ultimately, the patch consisted of 10 × 10 microneedles on a 0.64 cm2 area (Fig. 7F).
• Reduce the SYNTHROID dosage or discontinue temporarily if signs or symptoms of overdosage occur.
• Therefore, measurements of only T4 may be insufficient to explain changes in elderly patients’ thyroid function.

Patient Characteristics

If the free T4 comes back elevated, the clinician should decrease the dose of levothyroxine to prevent cardiac complications and other symptoms of hyperthyroidism. Finally, clinicians should refer the patient to an endocrinologist if hypothyroidism is due to central causes. In all the scenarios mentioned above, pharmacists should ensure proper dosing and report to the clinician if there is any potential drug-drug interaction or if supplies may dictate a change to a different formulation. The clinical impact of severe cirrhosis on thyroid hormone levels is also influenced by other factors, such as lower levels of thyroxine binding proteins such as albumin. Overall, this possibly leads to an increase in free T4 concentrations or the ratio of free T3 to bound T3, meaning that despite overall lower levels of T3, more free T4 and T3 is available.

• Exposure to direct sunlight for 80 minutes results in more than 60% decomposition (121).
• Topf et al successfully restored the TH levels of a female patient treated with SC LT4 injections.
• The serum was then separated by centrifugation (approximately 1240g × 10 minutes at room temperature) and harvested within 148 minutes of collection.
• A randomised clinical trial compared the clinical pharmacokinetics of a new formulation of LT4 that meets these updated, narrowed requirements for bioequivalence with the previous formulation, in 216 healthy subjects 11, 56.
• The induction of cytochrome P450 enzyme activity in the liver by statins or protease inhibitors can accelerate the catabolism of LT4, and hence decrease serum T4 levels (84, 85).
• For Cmax, the test/reference ratio was 96.2% with CI90% of 91.6–100.9%, and for AUC0−t the test/reference ratio was 99.9 with CI90% of 93.3–107.0%.

Some medications are revealed or supposed to interfere with the absorption of LT4. Certain ingredients or excipients in interfering medications could bind to the LT4 molecules and inhibit their transmembrane transport. Examples include calcium and iron supplements, basic antacids, bile acid sequestrants, etc. The treatments for malabsorption induced by chelation are similar in many ways.

Although there has been a reported association between prolonged thyroid hormone therapy and breast cancer, this has not been confirmed. Patients receiving SYNTHROID for appropriate clinical indications should be titrated to the lowest effective replacement dose. Thyroid hormone synthesis and secretion is regulated by the hypothalamic-pituitary-thyroid axis.

Serum digitalis glycoside levels may decrease when a hypothyroid patient becomes euthyroid, necessitating an increase in the dose of digitalis glycosides. Many drugs can exert effects on thyroid hormone pharmacokinetics and metabolism (e.g., absorption, synthesis, secretion, catabolism, protein binding, and target tissue response) and may alter the therapeutic response to SYNTHROID (Tables 5 to 8). Pseudotumor cerebri and slipped capital femoral epiphysis have been reported in pediatric patients receiving levothyroxine therapy.

An elevation in TBG reduces the free T3 and free T4 and leads to hypothyroxinemia. Ratios and 90% geometric confidence intervals for AUC0‐48 and Cmax for baseline‐corrected serum levothyroxine. Levothyroxine is an endogenous compound and therefore was analyzed both with and without baseline correction. For each subject and treatment period, the baseline levothyroxine value was defined as the mean of the ‐0.5‐, ‐0.25‐, and 0‐hour sample concentrations, and this value was attributed to the predose sample concentration. For baseline correction, the baseline value (mean of the 3 predose samples) was subtracted from each measured concentration, including the predose concentration, meaning that the predose concentration was equal to zero.

The bioavailability of LT4 is about 70% following an oral dose, with absorption occurring mainly in the ileum and jejunum. Maximum plasma concentrations of LT4 are achieved about 3 h after an oral dose in patients with hypothyroidism. The long terminal half-life of orally administered LT4, about 7.5 days, is consistent with once-daily dosing. The introduction of novel formulations of LT4, with more precise delivery of the active ingredient and higher levels of bioequivalence with existing products will facilitate accurate titration of LT4 for patients with hypothyroidism.

In the initial stage of overdose (6 to 12 hours post-ingestion), the common signs of toxicity would be tremulousness, tachycardia, hypertension, anxiety, and diarrhea. Rarely convulsions, thyroid storms, acute psychosis, arrhythmias, and acute myocardial infarction may occur. Laboratory workup usually reveals elevated serum total T4 and T3, suppressed serum TSH, and elevated Free T4 and Free T3.