Am posting this as major news!
Will most likely come back and add some comments.
As I see it, if the issues described apply, any GP not only can but MUST prescribe by specific product.
Levothyroxine: new prescribing advice for patients who experience symptoms on switching between different levothyroxine products
If a patient reports persistent symptoms when switching between different levothyroxine tablet formulations, consider consistently prescribing a specific 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.
Medicines and Healthcare products Regulatory Agency
19 May 2021
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 UK 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
report suspected adverse reactions to levothyroxine medicines, including symptoms after switching products, to the Yellow Card scheme
Levothyroxine is authorised for the control of hypothyroidism. In the UK, 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 UK 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.
Reports considered by the review
Levothyroxine is one of the most commonly prescribed medicines in the UK. Between 1 January 2016 and 31 December 2020 there were a total of nearly 260 million packs of levothyroxine dispensed against a prescription in UK retail and hospital pharmacies. [footnote 1]
For the 5-year period between 1 January 2015 and 31 December 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 [footnote 2]
concomitant use of medication reducing gastric acidity, which can also affect levothyroxine absorption[footnote 3]
very low thyroid reserve[footnote 4]
intolerance or allergy to an excipient in a particular brand
specific genotypes relating to thyroid hormone synthesis or thyroid receptor function [footnote 5] [footnote 6] [footnote 7]
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 UK 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.[footnote 7] In some patients, better control of thyroid function may be achieved with oral solution forms of levothyroxine than with tablets.[footnote 8] [footnote 9] [footnote 10]
Management of symptoms after product switching
CHM considered the reports in the UK 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 above.
The product information for levothyroxine tablets is being updated to include this advice for prescribers – see example Summary of Product Characteristics and Patient Information Leaflet.
Report on a Yellow Card
Please continue to report suspected adverse drug reactions to the Yellow Card scheme.
Healthcare professionals, patients, and caregivers are asked to submit reports using the Yellow Card scheme electronically using:
the Yellow Card website
the Yellow Card app; download from the Apple App Store or Google Play Store
some clinical IT systems for healthcare professionals (EMIS, SystmOne, Vision, MiDatabank, and Ulysses)
When reporting please provide as much information as possible, including information about batch numbers, medical history, any concomitant medication, onset timing, treatment dates, and product brand name.
Report suspected side effects to medicines, vaccines or medical device and diagnostic adverse incidents used in coronavirus (COVID-19) using the dedicated Coronavirus Yellow Card reporting site or the Yellow Card app. See the MHRA website for the latest information on medicines and vaccines for COVID-19.
Article citation: Drug Safety Update volume 14, issue 10: May 2021: 1.