Eldad Kisch, MD; Hermil S. Segall, MD
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.
Kisch E., Segall H.; Interaction between Simvastatin and l-Thyroxine. Ann Intern Med. 2005;143:547. doi: 10.7326/0003-4819-143-7-200510040-00025
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Published: Ann Intern Med. 2005;143(7):547.
TO THE EDITOR:
Background: Simvastatin and l-thyroxine are often prescribed together in clinical practice, and interaction between them has rarely been reported.
Objective: To describe 2 cases of interaction between simvastatin and l-thyroxine.
Case Report: Patient 1 is a 75-year-old woman who had had hypothyroidism for many years and whose condition was well-controlled with l-thyroxine, 800 µg/wk (thyroid-stimulating hormone [TSH] level, 2.26 µIU/L). She was taking alendronate, 10 mg/d, with calcium supplementation. On 19 December 2003, the patient began taking simvastatin, 10 mg/d, for high levels of low-density lipoprotein cholesterol. Gradually, she felt tired and had abdominal pain (due to sluggish gastric emptying). Because the patient's TSH values were increasing (47.83 µIU/L on 20 April 2004 with free thyroxine [T4] level at the lower limit of normal), the weekly l-thyroxine dose was increased to 900 µg. However, the patient's symptoms did not improve (TSH level, 28.63 µIU/L on 6 May 2004). The patient stopped taking simvastatin, and her symptoms slowly resolved. The dose of l-thyroxine was reduced to the previous level. In June, the patient's TSH level had reverted to and remains at normal limits; the patient feels well. Bezafibrate treatment was started without ill effects. Results of liver function tests increased to slightly above normal during this period of hypothyroidism.
David N. Juurlink
University of Toronto
October 6, 2005
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 email@example.com
Steven L. Shumak, MD
Division of General Internal Medicine, Sunnybrook and Women's College Health Sciences Centre, Toronto, Canada M4N 3M5
(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.
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