其 他 安 全 警 示
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| The United Kingdom: Levothyroxine: new prescribing advice for patients who experience symptoms on switching between different levothyroxine products (English only) |
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Medicines and Healthcare products Regulatory Agency (MHRA) announces new prescribing advice for patients who experience symptoms on switching between different levothyroxine products.
Levothyroxine is authorised for the control of hypothyroidism. In the United Kingdom, prescribing of levothyroxine is usually generic, with no named product specified on the prescription. Patients may thus be changed between different levothyroxine products according to what is available at their local pharmacies, with the prescriber generally unaware of the specific product that the patient is taking at any particular time. This generic prescribing approach is supported by strict United Kingdom regulatory requirements for licensing to ensure compatibility (bioequivalence) between products. Nevertheless, the MHRA receives reports of patients experiencing adverse events on switching between different levothyroxine products. The MHRA has conducted a review of the available data and sought advice from the Commission on Human Medicines (CHM) as to whether any regulatory action is needed to minimise the risk of adverse events on switching between different levothyroxine products.
For the 5-year period between 1 Jan 2015 and 31 Dece 2019, the MHRA received 335 Yellow Cards reporting one or more of the terms ‘product substitution issue’, ‘condition aggravated’ or ‘drug ineffective’ with levothyroxine. The majority of reports were received from patients rather than healthcare professionals, with 47 of the cases having a healthcare professional reporter. Associated symptoms were mostly consistent with hypothyroidism or hyperthyroidism, and included fatigue, headache, malaise, anxiety, palpitations, pruritus, nausea, myalgia, dizziness, arthralgia, feeling abnormal, alopecia, depression, abnormal weight gain, and insomnia. Of the 335 cases, 12 reported a recurrence of their symptoms after a second trial with the medicine concerned. Only 27 of the 335 cases included reference to thyroid function test results. Of these, 9 suggested a hypothyroid state, with 4 hyperthyroid and 14 euthyroid. In most cases, thyroid function test data from before the product switch were not available to confirm that thyroid function was well controlled before the switch, or to indicate whether a substantial change in parameters within reference range had occurred.
The underlying causes for the symptoms experienced by patients switching between levothyroxine products are generally unclear. Potential causative factors could include:
- gastrointestinal comorbidities potentially affecting levothyroxine absorption
- concomitant use of medication reducing gastric acidity, which can also affect levothyroxine absorption
- very low thyroid reserve
- intolerance or allergy to an excipient in a particular brand
- specific genotypes relating to thyroid hormone synthesis or thyroid receptor function
For the most part, the symptoms experienced on switching levothyroxine tablet formulations could indicate the need for dose adjustment. However, some patients experience symptoms despite thyroid function testing showing them as biochemically euthyroid.
These symptoms experienced by a minority of patients are acknowledged in United Kingdom professional guidelines. These guidelines note that although generic prescribing of levothyroxine is appropriate for the vast majority of patients, in rare cases a patient may require a specific levothyroxine brand to be prescribed. In some patients, better control of thyroid function may be achieved with oral solution forms of levothyroxine than with tablets.
CHM considered the reports in the Unied Kingdom and advised that levothyroxine should continue to be prescribed generically for most patients. If a patient reports symptoms after their brand of levothyroxine is changed, healthcare professionals are advised to consider testing of thyroid function and follow the ‘Advice for healthcare professionals’ section below.
Advice for healthcare professionals:
- generic prescribing of levothyroxine remains appropriate for the majority of patients and the licensing of these generic products is supported by bioequivalence testing
- a small proportion of patients treated with levothyroxine report symptoms, often consistent with thyroid dysfunction, when their levothyroxine tablets are changed to a different product; these cases are noted in United Kingdom professional guidelines
- if a patient reports symptoms after changing their levothyroxine product, consider testing thyroid function
- if a patient is persistently symptomatic after switching levothyroxine products, whether they are biochemically euthyroid or have evidence of abnormal thyroid function, consider consistently prescribing a specific levothyroxine product known to be well tolerated by the patient
- if symptoms or poor control of thyroid function persist despite adhering to a specific product, consider prescribing levothyroxine in an oral solution formulation
The product information for levothyroxine tablets is being updated to include this advice for prescribers.
Please refer to the following website in MHRA for details:
http://www.gov.uk/drug-safety-update/levothyroxine-new-prescribing-advice-for-patients-who-experience-symptoms-on-switching-between-different-levothyroxine-products
In Hong Kong, there are 9 registered pharmaceutical products containing levothyroxine. All products are prescription-only medicines. So far, the Department of Health (DH) has received 3 cases of adverse drug reaction related to levothyroxine, but these cases are not related to product switching. The risk of adverse effects (e.g. manifestations of hypothyroidism or hyperthyroidism) on switching between different levothyroxine products is documented in overseas reputable drug references such as the “Martindale: The Complete Drug Reference” and “AHFS Drug Information”. The DH will remain vigilant on safety update of the drug issued by other overseas drug regulatory authorities.
Ends/Thursday, May 20, 2021
Issued at HKT 18:00
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