Medications and Food Interfering with the Bioavailability of Levothyroxine: A Systematic Review

Proton-pump inhibitors, such as omeprazole17 and lansoprazole,18 have also been shown to influence the absorption of levothyroxine, as assessed by TSH levels in patients, since normal gastric acid secretion plays a major role in the absorption of thyroxine. Of the participating volunteers who started the study, 78 completed the two treatment periods, registering one withdrawal for personal reasons and an exclusion due to a positive dose of drugs of abuse for a subject before admission to the second period of hospitalization. The median age and BMI of the volunteers participating in the bioequivalence study were 25.7years and 24.7, respectively. There were no serious adverse events or voluntary withdrawals due to side effects during the study, and both formulations were well tolerated (Fig. 2).

A retrospective study on congenital hypothyroidism raised concerns about the bioequivalence of 2 liquid products (Tirosint and Tifactor) (216). Approximately 10% of patients declared that the solution was distasteful and then returned to the solid LT4 formulation (212). Normally, liquid solution (predosed ampoule and oral drop) should be poured into a glass of water and swallowed. Some patients may simply squeeze the liquid LT4 ampoule directly into their mouth for convenience, which may cause buccal absorption and poor efficacy (217). A figure depicting the correct dosing method should be added to the package leaflet to provide patients with dosing information. Due to presumed better efficacy, liquid LT4 should be avoided or adjusted with carefulness in elderly and central hypothyroid patients, who are more prone to excessive LT4 treatments (218).

• For most narrow therapeutic index drugs, including LT4, current specifications now require that the 90% CI for the geometric mean ratio of the AUC and Cmax values must lie between 90% and 111%, for the products to be considered to be bioequivalent 51, 52.
• The eluates were subsequently evaporated under an N2 current at 60°C and reconstituted with 150 μL of water/methanol (36/64) and ammonium hydroxide 0.04%.
• 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).

Table 3.

Genetic mutations of thyroid-specific proteins also play a role in the development of fetal goiters (249–251). The conditions are usually detected by ultrasound examinations or amniocentesis in the second or third trimesters (252). Addressing maternal diseases and LT4 replacement is necessary for preventing potential fetal tracheal compression or other developmental malformations (253). A 10 to 150 µg/kg/day dose via IA injection at an interval of 1 to 4 weeks is recommended, depending on the goiter sizes and fetal serum TH levels (250, 254, 255).

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• In this analysis, the sample size was considerably reduced (containing only 21% of the base case cohort), which may contribute to statistical uncertainty.
• After propensity score matching, the Synthroid and GL cohorts each contained 18,382 patients.
• 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.
• When comparing the solution with the capsule (both products administered with water), the 90% confidence intervals for the ratio of log‐transformed values of AUC0‐48 and Cmax were within 90.00% and 111.11%, respectively, for baseline‐corrected levothyroxine.
• Patients with low income may not be able to afford the monthly cost of $150 to $240 (although the actual situations are complex and patients may save money through various methods).
• Nanomaterials in the levothyroxine field are then discussed and compared based on their load and release profile.

Approximately eighty-percent of circulating T3 is derived from peripheral T4 by monodeiodination. 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. A sensitive and specific validated high-performance liquid chromatographic with tandem mass spectrometry (HPLC–MS/MS) method for quantitation of levothyroxine in human serum was developed using an internal isotopically labeled standard.

Label: SYNTHROID- levothyroxine sodium tablet

Liquid solutions and soft-gel capsules could eliminate the malabsorption due to chelation and alkalization. Absorption of orally administered T4 from the gastrointestinal (GI) tract ranges from 40% to 80%. The majority of the levothyroxine 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 soybean infant formula. In addition, many drugs and foods affect T4 absorption (see PRECAUTIONS – Drug Interactions and Drug-Food Interactions ).

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. 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), andClinical Pharmacology (12.3). Administer SYNTHROID at least 4 hours before or after drugs known to interfere with SYNTHROID absorption see Drug Interactions (7.1). At baseline, hospitalizations and ED visits were rare (6–8% all-cause), while most patients in both cohorts had outpatient visits and pharmacy fills (94–99% all-cause), with mean number of all-cause pharmacy fills per patient of 9.2–9.3.

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. The effect of consistent treatment on HCRU and costs was further demonstrated in our comparison of patients who achieved TSH goals versus those who did not. Patients who achieved TSH goals were significantly less likely to have all-cause or hypothyroidism-related inpatient hospitalizations as well as hypothyroidism-related outpatient services than patients who did not achieve TSH goals. Additionally, TSH goal achievers incurred significantly lower average medical and total all-cause and hypothyroidism-related costs than non-achievers. To our knowledge, this is the first real-world study looking into outcomes for goal achievers vs. non-achievers.

This chapter summarises the administration, absorption, distribution, metabolism, and elimination of LT4. In addition, it addresses the therapeutic significance of pharmacologic and other factors that can alter exposure to LT4, synthroid ovulation and of changing regulatory requirements concerning the manufacture of LT4 tablets. Although levothyroxine has long been a mainstay in the treatment of hypothyroidism, its optimal use often remains elusive.

ECG performed 48 hours postdose of period 3 could have been used as the ECG required at study exit. Measurement of vital signs (blood pressure, heart rate, respiratory rate, and oral temperature) were performed at the time of screening and for study exit procedures. In addition, seated blood pressure and heart rate measurements were performed before dosing and approximately 2, 4, 8, 12, and 24 hours postdose in each period. If this condition is treated, a lower levothyroxine sodium dose (e.g., 1 mcg/kg/day) than that used for full replacement may be adequate to normalize the serum TSH level. Patients who are not treated should be monitored yearly for changes in clinical status and thyroid laboratory parameters. Since some more severely affected children may become clinically hypothyroid when treatment is discontinued for 30 days, an alternate approach is to reduce the replacement dose of levothyroxine by half during the 30-day trial period.

Table 1: Summary of Levothyroxine PK.

If, after 30 days, the serum TSH is elevated above 20 mU/L, the diagnosis of permanent hypothyroidism is confirmed, and full replacement therapy should be resumed. However, if the serum TSH has not risen to greater than 20 mU/L, levothyroxine treatment should be discontinued for another 30-day trial period followed by repeat serum T4 and TSH testing. Animal studies have not been performed to evaluate the carcinogenic potential, mutagenic potential or effects on fertility of levothyroxine. The synthetic T4 in SYNTHROID is identical to that produced naturally by the human thyroid gland.