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Drugs Affecting Levothyroxine

 

Drugs that interact with levothyroxine: an observational study from the Thyroid Epidemiology, Audit and Research Study (TEARS)

Clinical Endocrinology Volume 82, Issue 1, pages 136–141, January 2015
Savannah A. Irving, Thenmalar Vadiveloo and Graham P. Leese

Abstract
Objective

The aim of this study was to determine the extent of drug interactions affecting levothyroxine, using study drugs often co-administered to patients on long-term levothyroxine therapy.

Design
A retrospective population analysis linking biochemistry and prescription data between 1 January 1993 and 31 December 2012 was used.
Patients
The study population was Tayside residents prescribed levothyroxine on at least three occasions, within a six-month period, prior to the start of a study drug. Individuals acted as their own controls pre- and postinitiation of study drug. Overall, 10 999 patients (mean age 58 years, 82% female) being treated with thyroxine were included in the study.
Measurements
Changes in TSH following initiation of study drug.
Results
Iron, calcium, proton pump inhibitors and oestrogen all increased serum TSH concentration: an increase of 0·22 mU/l (P < 0.001), 0·27 mU/l (P < 0·001), 0·12 mU/l (P < 0·01), and 0·08 mU/l (P < 0·007), respectively. For these four study drugs, there was a clinically significant increase of over 5 mU/l in serum TSH, in 7·5%, 4·4%, 5·6% and 4·3% patients, respectively. There was a decrease of 0·17 mU/l (P-value 0.01) in the TSH concentration for those patients on statins. The TSH decreased by 5 mU/l in 3·7% of patients. There was no effect with H2 receptor antagonists or glucocorticoids.

Conclusion

This large population-based study demonstrates significant interaction between levothyroxine and iron, calcium, proton pump inhibitors, statins and oestrogens. These drugs may reduce the effectiveness of levothyroxine, and patients' TSH concentrations should be carefully monitored.

Link to abstract in PubMed https://www.ncbi.nlm.nih.gov/pubmed/25040647

The full article is available here http://onlinelibrary.wiley.com/doi/10.1111/cen.12559/full

 


 

Ciprofloxacin interacts with thyroid replacement therapy

John G Cooper endocrinologist, Knut Harboe, senior house officer, Sofia K Frost, pharmacist, Oyvind Skadberg, consultant physician BMJ 2005;330:1002 (30 April).

Ciprofloxacin is an antibacterial and antibiotic that is often used for patients who are allergic to penicillin or who have a resistance to antibiotics.

This paper reports two case studies where the patient’s thyroid levels dropped dramatically whilst on this drug, a possible reason being lack of absorption of thyroxine.

This is yet another drug that interacts with thyroxine.  Maybe it’s time the medical profession started to realise that many other drugs may interact too.  I wonder if the same thing would happen if using a natural thyroid hormone?  Something to think about.

The full article is available here:
http://www.bmj.com/content/330/7498/1002.1



Variable Effects of Nonsteroidal Anti-inflammatory Agents on Thyroid Test Results

M. H. Samuels, K. Pillote, D. Asher and J. C. Nelson
The Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 12 5710-5716

(2003)

M H Samuels, et.al looked at the effects of a single dose study and/or a one week study on 25 healthy subjects.  They tested total and free thyroid hormones along with TSH over an eight hour period after a single dose and daily in the one week study. 

The researchers found that ibuprofen, naproxen or indomethacin did not change the levels of any of the hormones measured.  However, various total and free thyroid hormone measurements were decreased by single doses of aspirin and salsalate and increased by meclofenamate.  Treatment for one week with aspirin or salsalate decreased total T4, free T4 (salsalate only), total T3, free T3 and TSH.

They concluded that, “These data confirm that aspirin, salsalate, and meclofenamate affect total and free thyroid hormone measurements and identify three NSAIDs that did not change thyroid tests. TSH remained within the normal range during acute or 1-wk administration of all of the NSAIDs.

The full article is available here:
http://press.endocrine.org/doi/full/10.1210/jc.2002-021869



Altered intestinal absorption of L-thyroxine caused by coffee.

Abstract taken from:
Thyroid. 2008 Mar;18(3):293-301.
Benvenga S, Bartolone L, Pappalardo MA, Russo A, Lapa D, Giorgianni G, Saraceno G, Trimarchi F.

Objective:  To report eight case histories, and in vivo and in vitro studies showing coffee's potential to impair thyroxine (T4) intestinal absorption.
Design: Of eight women with inappropriately high or nonsuppressed thyroid-stimulating hormone (TSH) when T4 was swallowed with coffee/espresso, six consented to the evaluation of their T4 intestinal absorption. This in vivo test was also administered to nine volunteers. In three separate tests, two 100 mcg T4 tablets were swallowed with coffee, water, or water followed, 60 minutes later, by coffee. Serum T4 was assayed over the 4-hour period of the test. Two patients and two volunteers also agreed on having tested the intestinal absorption of T4 swallowed with solubilized dietary fibers. In the in vitro studies, classical recovery tests on known concentrations of T4 were performed in the presence of saline, coffee, or known T4 sequestrants (dietary fibers, aluminium hydroxide, and sucralfate).

Main Outcome
: For the in vivo test, average and peak incremental rise of serum T4 (AIRST4 and PIRST4), time of maximal incremental rise of serum T4 (TMIRST4), and area under the curve (AUC) were determined. In patients and volunteers, the four outcome measures were similar in the water and water + coffee tests. In patients and volunteers, compared to water, coffee lowered AIRST4 (by 36% and 29%), PIRST4 (by 30% and 19%), and AUC (by 36% and 27%) and delayed TMIRST4 (by 38 and 43 minutes); bran was a superior interferer. In the in vitro studies, coffee was weaker than known T4 sequestrants.

Conclusion
: Coffee should be added to the list of interferers of T4 intestinal absorption, and T4 to the list of compounds whose absorption is affected by coffee.

http://www.ncbi.nlm.nih.gov/pubmed/18341376