Abstract
This Hospital Pharmacy feature is extracted from Off-Label Drug Facts, a quarterly publication available from Wolters Kluwer Health. Off-Label Drug Facts is a practitioner-oriented resource for information about specific drug uses that are unapproved by the US Food and Drug Administration. This new guide to the literature enables the health care professional or clinician to quickly identify published studies on off-label uses and determine if a specific use is rational in a patient care scenario. A summary of the most relevant data is provided, including background, study design, patient population, dosage information, therapy duration, results, safety, and therapeutic considerations. References direct the reader to the full literature for more comprehensive information before patient care decisions are made. Direct questions or comments regarding Off-Label Drug Uses to hospital
Background
The routine management of hypothyroidism is based on replacement of thyroid hormone to restore euthyroidism, which typically requires lifetime daily administration of thyroid supplementation and raises issues of potential noncompliance. Levothyroxine (T4), the treatment of choice for the management of hypothyroidism, is manufactured in various dosages to allow for titration of individual doses. 1 Although T4 has an elimination half-life of 7 days, its biological life may be longer. The active hormone triiodothyronine (T3) is formed from T4 in the peripheral tissues, and it has been suggested that the conversion rate of T4 to T3 is decreased when the serum T4 level is high. Thus, higher doses of thyroxine at weekly intervals may provide effects similar to those of daily dosing and decrease the risk of noncompliance.
Patientc Population
Adults with hypothyroidism from various causes.
Dosage and Duration
Weekly administration of 7 times the daily dose of thyroxine. 2 In case reports approximately 2 to 4 times the daily dose was given once weekly. 3
Results
Guidelines from the American Thyroid Association and the American Association of Clinical Endocrinologists for the management of hypothyroidism do not include weekly administration of thyroxine.1,4,5 The weekly administration of thyroxine for patients with hypothyroidism has been studied in fewer than 50 patients in controlled and noncontrolled settings.
Guidelines
Guidelines from the American Thyroid Association and the American Association of Clinical Endocrinologists for the management of hypothyroidism do not include weekly administration of thyroxine.1,4,5 The mean replacement dosage for T4 is 1.6 mcg/kg daily, although the dosage may vary among patients.
Controlled Trial
In a double-blind crossover trial, 12 patients with hypothyroidism from various causes were randomly assigned for continuation of their usual daily maintenance dose of thyroxine or for receipt of 7 times the usual daily dose once weekly. The first treatment phase lasted 6 weeks, and it was followed by 1 week of testing and another 5-week treatment phase. Thyroid function tests were assessed at baseline, at the end of the first phase of treatment (6 weeks), and at the end of the second phase of treatment (12 weeks). The mean peak free thyroxine 4 (FT4) concentrations were significantly higher in the weekly administration group compared with daily dosing (2.71 vs 1.59 ng/dL; P < 0.0001). In addition, the mean peak free thyroxine 3 (FT3) levels were also significantly higher in the weekly group (285 vs 246 pg/dL; P < 0.01). However, there were no significant differences between the daily and weekly groups for markers of tissue effects, including serum sex hormone–binding globulin, gammaglutamyltransferase, aspartate aminotransferase, alanine aminotransferase, osteocalcin, alkaline phosphatase, and low-density lipoprotein. The authors concluded that weekly administration of 7 times the daily dose maintained near euthyroidism and that for complete biochemical euthyroidism, a dose slightly larger than 7 times the normal daily dose might be required. 2
Case Reports
In 2 patients (47 and 48 years of age) with primary hypothyroidism, daily thyroxine therapy (375 and 200 mcg daily) did not restore biochemical euthyroidism, but weekly thyroxine therapy (750 mcg weekly in both patients), which was approximately 2 to 4 times the daily dose, was successful. In both cases noncompliance with the daily regimen was suspected as a contributing factor to poor control of disease. 3
Safety
This is a limited safety profile. Refer to package labeling for complete prescribing information (eg, warnings/precautions, adverse reactions, drug interactions).
Thyroid products have a black box warning that cautions against the use of these products for the treatment of obesity or for promoting weight loss.
In reviewed publications all patients tolerated thyroxine treatment without adverse events, including cardiovascular changes in one study that evaluated echocardiograms.2,3
Therapy Considerations
It appears that initial data regarding the use of a single weekly dose of thyroxine show that this regimen is as effective as daily dosing in maintaining biochemical euthyroidism and may be useful in combating noncompliance with a daily regimen. However, the exact dose has not been clearly established, with one small study suggesting that a dose slightly larger than 7 times the normal daily dose may be needed. Larger, controlled trials are needed to confirm these results.