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Interaction between levothyroxine and calcium carbonate

Correspondence to: Dr Elias Mazokopakis, Iroon Polytechniu 38A, Chania 73 132, Crete, Greece; telephone 30 282 1082754; fax 30 282 1089307; e-mail emazokopakis{at}yahoo.gr

Levothyroxine (L-T₄) is one of the most commonly prescribed medications. It is given as either physiologic replacement therapy in patients with hypothyroidism or as interventional therapy to suppress thyroid-stimulating hormone (TSH) secretion in patients with nodular thyroid disease or thyroid cancer.

Patients treated with L-T₄ suppressive therapy (a state known as exogenous subclinical hyperthyroidism) might be at increased risk for osteoporosis. Because of this, patients are encouraged to take a calcium supplement, such as calcium carbonate.¹ Calcium supplementation is especially important for preventing or treating osteoporosis in post-menopausal women. However, several conditions or drugs might alter L-T₄ requirements for both replacement and interventional therapy.² We report a case of clinically significant interaction between L-T₄and calcium carbonate.

Case description

A 64-year-old woman with hypothyroidism visited our hospital because of clinically significant changes shown in results of thyroid function tests. For many years her hypothyroidism was well controlled with 88 µg/d of (TSH 2 mIU/L; normal range 0.3 to 4 L-T₄ mIU/L). She had been diagnosed with osteopenia 1 year earlier and was treated with oral calcium carbonate (2500 mg/d = 1 g elemental calcium/d). Three months after the patient started taking calcium carbonate, a clinical examination and results of laboratory tests revealed hypothyroidism; thyroid function test results showed an increase in TSH serum level (9.8 mIU/L) and a decrease in serum free thyroxine (FT₄) level (0.2 ng/dL; normal range 0.8 to 2 ng/dL). The L-T₄ dose was increased to 112 µg/d, which improved the patient’s symptoms during the following months (TSH level 6.4 mIU/L).

Because the hypothyroidism persisted, the L-T₄ dose was increased to 125 µg/d, and her symptoms slowly resolved (TSH level 2.7 mIU/L). The patient stopped taking calcium carbonate during the following months, without medical advice, and her TSH level decreased to 0.1 mIU/L (exogenous subclinical hyperthyroidism). Because of the obvious interaction between L-T₄ and calcium carbonate in our patient, we decreased the dose of L-T₄ to 88 µg/d. A more detailed history revealed that our patient was taking the calcium carbonate at the same time as L-T₄. After more than a year following the patient’s initial presentation, her TSH level reverted to and remained at normal limits. The patient refused to take calcium carbonate again despite our recommendation.

Discussion

This case report confirms the importance of timing for patients taking calcium carbonate and L-T₄ Recent studies^3–5 have shown that taking calcium carbonate within 4 hours of L-T₄ might decrease absorption of L-T₄ by nearly a third. Also, patients knowing about this interaction seems to be insufficient.⁶ Patients who have taken L-T₄ with calcium carbonate consistently for years might have had their doses adjusted so they remained at therapeutic levels. However, patients who receive calcium carbonate sporadically or inconsistently might unknowingly change the absorption of L-T₄, causing variations in their medication levels.

Conclusion

It is important for patients and health care providers to know that calcium carbonate can interact with L-T₄ and affect its absorption. Education and warning labels on bottles of L-T₄ might help to decrease the risk of this clinically significant interaction.

Footnotes

Competing interests

None declared

References

1. Mazokopakis EE, Starakis IK, Papadomanolaki MG, Batistakis AG, Papadakis JA. Changes of bone mineral density in pre-menopausal women with differentiated thyroid cancer receiving L-thyroxine suppressive therapy. Curr Med Res Opin 2006;22:1369-73.[Medline]
2. Mandel SJ, Brent GA, Larsen PR. Levothyroxine therapy in patients with thyroid disease. Ann Intern Med 1993;119:492-502.[Abstract/Free Full Text]
3. Singh N, Singh PN, Hershman JM. Effect of calcium carbonate on the absorption of levothyroxine. JAMA 2000;283:2822-5.[Abstract/Free Full Text]
4. Singh N, Weisler SL, Hershman JM. The acute effect of calcium carbonate on the intestinal absorption of levothyroxine. Thyroid 2001;11:967-71.[Medline]
5. Neafsey PJ. Levothyroxine and calcium interaction: timing is everything. Home Healthc Nurse 2004;22:338-9.[Medline]
6. Mazokopakis EE. Counseling patients receiving levothyroxine (L-T₄) and calcium carbonate. Mil Med 2006;171:vii, 1094.[Medline]

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