Published: 21 May 2020
Updated:  10 December 2020

Safety Information

Monitoring Communication

Medsafe emphasises that patients should NOT stop using any medicine or medical device subject to a monitoring communication. If you have any concerns with a medicine or medical device you are using, please contact your health professional. A monitoring communication does not mean that the medicine or medical device causes an adverse event.

Potential interaction between fluoxetine and levothyroxine

Update information

10 December 2020

During the monitoring period (21 May 2020 to 30 November 2020), the Centre for Adverse Reactions Monitoring (CARM) did not receive any further reports of a potential interaction between fluoxetine and levothyroxine.

Medsafe will continue to monitor this issue through routine pharmacovigilance. The benefit-risk balance for fluoxetine and levothyroxine remains positive and no further action is required at this time.

Original communication

21 May 2020

Description

Monitoring finishes 30 November 2020

Medsafe is highlighting a potential interaction between fluoxetine and levothyroxine leading to reduced serum levels of levothyroxine and increased thyroid-stimulating hormone (TSH) levels. The aim is to encourage further reports to obtain more information on this potential interaction.

This investigation into a potential interaction between fluoxetine and levothyroxine was triggered by a report received by the Centre for Adverse Reactions Monitoring (CARM). The report (CARM ID 132039) describes a 40-year-old female patient who was already on levothyroxine and was found to have an increased TSH level (reduced thyroid function) about two months after she started taking fluoxetine. Her TSH level decreased to near normal after fluoxetine was stopped.

Products affected
Additional information
Regulator actions
Reporting
References

Products affected

Product name and dose form	Sponsor
Fluoxetine
Arrow - Fluoxetine capsules, dispersible tablets	Teva Pharma (New Zealand) Limited
Fluox capsules, dispersible tablets	Mylan New Zealand Ltd
Fluoxetine - AFT oral solution	AFT Pharmaceuticals Ltd
Prozac capsules	Eli Lilly and Company (NZ) Limited
Levothyroxine
Eltroxin tablets	Pharmacy Retailing (NZ) Ltd
Levothyroxine Mercury Pharma tablets	Boucher & Muir (NZ) Ltd
Synthroid tablets	Mylan New Zealand Ltd

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) indicated for depression, bulimia, obsessive-compulsive disorder (OCD) and premenstrual dysphoric disorder (PMDD).

Levothyroxine is a synthetic form of the natural hormone thyroxine (T4) indicated for the treatment of hypothyroidism.

Additional information

There are some published case reports describing reduced thyroid function during treatment with other SSRIs (escitalopram, paroxetine, sertraline) and/or increased thyroid function after the SSRI is stopped [1-4].

The mechanism for this potential interaction and whether this is a class effect of SSRIs are not clear. However, both fluoxetine and levothyroxine are tightly bound to plasma proteins. The fluoxetine data sheets state coadministration with another medicine tightly bound to protein may cause a shift in plasma concentrations of either medicine. In addition, the levothyroxine data sheets state the concurrent use of sertraline can reduce serum levels of levothyroxine (with concomitant increased TSH levels).

More information, including advice on how to take this medicine and known side effects, can be found in the consumer medicine information (CMI) and data sheet.

Search for consumer medicine information and data sheets

Regulator actions

Medsafe is placing this safety concern on the Medicines Monitoring () scheme to encourage reporting of cases where concomitant use of fluoxetine and levothyroxine leads to decreased serum thyroxine levels and/or increased TSH levels.

Reporting

Consumers and healthcare professionals are encouraged to report suspected adverse reactions to medicines to the Centre for Adverse Reactions Monitoring (CARM).

References

1. Eker SS, Akkaya C, Ersoy C, et al. 2010. Reversible escitalopram-induced hypothyroidism. Gen Hosp Psychiatry 32(5): 559 e5-7. DOI: 10.1016/j.genhosppsych.2010.01.003 (accessed 17 April 2020).
2. Takahashi M, Sawayama E, Sawayama T, et al. 2007. Reversible paroxetine-induced symptomatic hypothyroidism. Pharmacopsychiatry 40(5): 201-2. DOI: 10.1055/s-2007-985884 (accessed 17 April 2020).
3. McCowen KC, Garber JR and Spark R. 1997. Elevated serum thyrotropin in thyroxine-treated patients with hypothyroidism given sertraline. N Engl J Med 337(14): 1010-1. DOI: 10.1056/nejm199710023371415 (accessed 17 April 2020).
4. Harel Z, Biro FM and Tedford WL. 1995. Effects of long term treatment with sertraline (Zoloft) simulating hypothyroidism in an adolescent. J Adolesc Health 16(3): 232-4. DOI: 10.1016/1054-139x(94)00069-q (accessed 17 April 2020).