Levothyroxine and potential risk of fractures

An increase in the risk of fractures associated with the use of levothyroxine has been observed in a recent study.

Levothyroxine (Euthyrox®, Merck Pte Ltd) has been licensed locally since May 1998 for the treatment of benign euthyroid goitre and the prophylaxis of relapse after surgery for euthyroid goitre. It is also indicated as a substitution therapy in hypothyroidism, a concomitant therapy during anti-thyroid medicinal treatment of hyperthyroidism and a suppression therapy in thyroid cancer. Other brands of levothyroxine include Eltroxin® (A. Menarini Singapore Pte Ltd), Thyrosit® (Joyson Pte Ltd) and Levothyroxine sodium for injection 500mcg/vial (United Italian Trading Corporation (Pte) Ltd).

Potential risk of fractures

In a recent large study examining the risk of fractures in patients on levothyroxine, a strong dose-response relation between levothyroxine treatment and increased risk of fracture was observed.¹ This was a nested case-control study involving 213,511 adult levothyroxine users, with a mean age of 82 years, who were followed up for a mean duration of 3.8 years. Of these users, 22,236 (10%) experienced at least one fracture during follow-up.

Outcomes of the study found that current and recent pastⁱ levothyroxine use were associated with a significantly increased risk of any fractures when compared to remote levothyroxine useⁱⁱ. Their respective adjusted odds ratio (AOR) were 1.88 (95% CI=1.71,2.05) and 1.33 (95% CI=1.19, 1.48). Among current levothyroxine users, a higher risk of any fractures was observed for high (>0.093mg/day) and medium (0.044 to 0.093mg/day) cumulative doses of levothyroxine when compared to low (<0.044mg/day) cumulative doses. Their respective AOR were 3.45 (95% CI=3.27, 3.65) and 2.62 (95% CI=2.50, 2.76).

_{ⁱRecent past treatment is defined as discontinuation of levothyroxine within 15 to 180 days of index date}

_{ⁱⁱRemote treatment is defined as discontinuation of levothyroxine more than 180 days before index date}

Local situation and HSA's advisory

HSA has not received any local reports of fractures associated with the use of levothyroxine and is currently monitoring this safety signal.

Healthcare professionals should be aware that long-term suppressive doses of levothyroxine therapy has been associated with increased bone resorption and reduced bone mineral density, especially in post-menopausal women.^2,3 Currently, there is limited information on the effect of levothyroxine on bone mineral density in the local package inserts (PIs) of levothyroxine . The PIs for all levothyroxine products will be further strengthened with this safety information.

Healthcare professionals are also advised to take into consideration the above safety information when prescribing levothyroxine to their patients and to prescribe the minimum dose necessary to achieve the desired clinical and biochemical response. Additionally, they are encouraged to report any adverse reactions or fractures associated with the use of levothyroxine to the Vigilance Branch of HSA.

References

1. BMJ 2011; 342: d2238
2. J Clin Endocrinol Metab 1991; 72: 1184-8
3. J Med Assoc Thai 1996; 79: 563-7

Published: 29 Apr 2013

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