This Scottish NHS document clearly states that narrow therapeutic range medicines should be prescribed by brand name:
Which medicines should be considered for brand-name prescribing in primary care?
Medicines should be prescribed by brand name in the following situations:
1. Where there is a difference in bioavailability between brands of the same medicine, particularly if the medicine has a narrow therapeutic index.
sps.nhs.uk/wp-content/uploa...
The internationally respected Drug Bank website is quite clear they consider levothyroxine a narrow therapeutic range medicine.
Name
Narrow Therapeutic Index Drugs
Accession Number
DBCAT003972
Description
Narrow therapeutic index (NTI) drugs are defined as those drugs where small differences in dose or blood concentration may lead to dose and blood concentration dependent, serious therapeutic failures or adverse drug reactions. Serious events are those which are persistent, irreversible, slowly reversible, or life-threatening, possibly resulting in hospitalization, disability, or even death.
Drugs
Drug
Levothyroxine
Drug Description
A synthetic T4 hormone used to treat hypothyroidism that can be used along with surgery and radioiodine therapy to manage thyrotropin-dependent well-differentiated thyroid cancer.
go.drugbank.com/categories/...
The 2013 MHRA report Levothyroxine Drug Products: A Review of Clinical & Quality Considerations is rather less certain. However, as I read it, that is for the technicality that a 2-fold difference in dose is tolerable.
But the argument they put up is based on a single dose. In healthy volunteers. NOT patients who are ill taking a double every day. This seems a naïve and rather pedantic argument. I suggest it is an argument for reviewing the definition of medicines of narrow therapeutic range. It does not demonstrate that levothyroxine is not such a medicine.
3.3Is levothyroxine a Narrow Therapeutic Index drug?
Levothyroxine has been referred to as a drug with a narrow therapeutic index (NTI) in several published articles although this is debatable.
The therapeutic index (also known as therapeutic ratio), is a comparison of the amount of a therapeutic agent that causes the therapeutic effect with the amount that causes adverse reactions. Drugs with narrow therapeutic index are drugs with small differences between therapeutic and toxic doses. There is no agreed European definition but the U.S. Food and Drug Administration (FDA) provides the following definition for a NTI drug:
a. There is less than a 2-fold difference between the minimum toxic and minimum effective concentrations in the blood,
and
b. Safe and effective use of the drug products requires careful titration and patient monitoring.
Acute toxicity and a possible need for therapeutic dose monitoring are usually key characteristics of NTI drugs in practice. However a weekly dose of thyroxine (usually a multiple of the patient’s daily dose) has been administered in clinical practice under direct observation, when there are concerns over possible compliance issues; this dosage regimen appears to be well tolerated.6
The FDA guidance on bioequivalence studies in levothyroxine advises that a single dose of 600 mcg is administered to healthy volunteers and this dose also appears to be generally well tolerated.
Therefore, acute toxicity with well over double the daily requirement of levothyroxine does not seem to pose safety risks, at least over the short term. In this sense, levothyroxine does not fall into the NTI category.
It has been shown that small changes in serum levothyroxine and liothyronine concentrations, within the normal range, alter serum TSH, indicating a sensitive negative feedback relationship between serum free levothyroxine and TSH.7 It is possible that in some patients once the optimal dose of levothyroxine has been achieved, they could suffer loss of control of their thyroid disease as a result of any subsequent variability in the amount of levothyroxine administered.
Therefore although levothyroxine does not meet the criteria for being a narrow therapeutic index drug, there are strong indications that small changes in the delivered dose of levothyroxine, should they persist over long term treatment, could have significant clinical consequences.
gov.uk/government/publicati...
Above I have argued that levothyroxine is a medicine of narrow therapeutic index. How much more does this argument apply to liothyronine?
The USA's FDA published this paper in 2014 assessing levothyroxine as a medicine of narrow therapeutic index:
accessdata.fda.gov/drugsatf...
The European Medicines Agency classifies levothyroxine as a critical dose drug:
Brand for levothyroxine
Switching back to Levothyroxine/Liothyronine from NP Thyroid - is it okay? (I miss my old self)
Liothyronine Prescribing Survey
