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Interaction between Simvastatin and l-Thyroxine

Eldad Kisch, MD; and Hermil S. Segall, MD
[+] Article and Author Information

From Le'umi Sick Fund, Tel Aviv, Israel.


Acknowledgment: The authors thank patient 1 and her treating physician for supplying full medical data. They also thank the staff of the Ichilov Hospital Pharmacy, Tel-Aviv, for conducting a thorough search of the relevant literature on drug interaction.

Potential Financial Conflicts of Interest: None disclosed.


Ann Intern Med. 2005;143(7):547. doi:10.7326/0003-4819-143-7-200510040-00025
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Simvastatin-Levothyroxine Interaction
Posted on October 6, 2005
David N. Juurlink
University of Toronto
Conflict of Interest: None Declared

To the Editor,

Kisch and Segall describe two patients treated with levothryoxine who developed hypothyroidism during simvastatin therapy.(1) Cessation of simvastatin resulted in clinical and biochemical improvement, suggesting a previously unappreciated interaction between simvastatin and levothyroxine. However, the mechanism postulated by the authors to explain the interaction is flawed, because cytochrome P450 isoenzyme 3A4 (CYP 3A4) does not metabolize levothyroxine and is not upregulated by simvastatin.

Calcium can impair levothyroxine absorption.(2) We wonder if, like their first patient, the second (an 81-year old man with chronic renal insufficiency) might also have been taking calcium in addition to vitamin D. If so, this might explain the clinical course of these patients. Otherwise, the actual mechanism of the levothyroxine/simvastatin interaction must remain uncertain for now.

While we agree with Kisch and Segall that clinicians should be aware of this potential drug interaction given how often these two medications are co-prescribed, drug-drug interactions are complex enough without complicating matters further by postulating implausible mechanisms.

David N. Juurlink, MD, PhD

Divisions of General Internal Medicine and Clinical Pharmacology, Sunnybrook and Women's College Health Sciences Centre, Toronto, Canada M4N 3M5 dnj@ices.on.ca

Steven L. Shumak, MD

Division of General Internal Medicine, Sunnybrook and Women's College Health Sciences Centre, Toronto, Canada M4N 3M5

Reference List

(1) Kisch E, Segall HS. Interaction between simvastatin and L- thyroxine. Ann Intern Med. 2005;143:547.

(2) Singh N, Singh PN, Hershman JM. Effect of calcium carbonate on the absorption of levothyroxine. JAMA. 2000;283:2822-25.

Conflict of Interest:

None declared

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