Inconsistent excipient listings in DailyMed: implications for drug safety

[helvella]

DailyMed is the primary source of medicine documentation for patients and doctors in the USA. It contains documents more or less equivalent to UK Summary of Product Characteristics (SPC or SmPC) and Patient Information Leaflets (PIL).

DailyMed

dailymed.nlm.nih.gov/dailymed/

The USA has also relatively recently launched the Inactive Ingredients Database (IID) and assigned UNII (Unique Ingredient Identifier) codes to a large number of excipients.

IID Search

accessdata.fda.gov/scripts/...

This puts their public information way ahead of what is available in the UK.

Yet this paper reports "internal inconsistencies of excipients in 39% of the formulations examined". Despite these strides forward.

And the MHRA doesn't even seem to care whether manufacturers include E-number codes against excipients to which E-numbers have been assigned. Despite doing so being of potential help to patients, in particular, who might already know they must avoid certain E-numbers in their diets but have to go round the houses to check whether the names in PILs are the same substances.

Patients simply do not have the required information and tools. But, in general, doctors do not have the understanding, information, tools, or time, to handle these issues. Nor do pharmacists. If the information isn't available in some form of database, no-one can reasonably be expected to find it. Even when there is a decent supply of inclination.

Inconsistent excipient listings in DailyMed: implications for drug safety.

Kinsella L 1 , Brook J 2 , Briest M 3 , Brook MJ 4

Naunyn-schmiedeberg's Archives of Pharmacology, 02 Apr 2024, 397(9):6851-6854

doi.org/10.1007/s00210-024-... PMID: 38563879

Abstract

Excipients, or inactive ingredients, are a frequent cause of medication intolerance and allergy. Patients and clinicians concerned about medication allergies and sensitivities rely on the U.S. National Library of Medicine's DailyMed for accurate lists of excipients. Based on our anecdotal discovery of several examples of excipient omissions, we wished to examine the accuracy of DailyMed's listings more systematically in a sample of commonly prescribed medications. The objective of the study is to identify the frequency of inconsistency of excipient reporting within the DailyMed website. We performed a database audit of the Structured Product Labeling XML file provided by the drug manufacturer to the Food and Drug Administration and DailyMed for two randomly selected formulations of each of 50 commonly prescribed medications. For each of the 100 formulations, we compared the excipients listed in the "Description" to those in the "Ingredients and Appearance" sections in DailyMed. The Structured Product Labeling data file provided by the drug manufacturer contained internal inconsistencies of excipients in 39% of the formulations examined. Despite the use of Structured Product Labeling, the drug manufacturer's medication labels provided to the FDA and reported by DailyMed often contain conflicting information about inactive ingredients. Patients with allergies and excipient sensitivity should be aware of these discrepancies and consult multiple sections of the label to identify potential allergy-inducing inactive ingredients.

As so often, the full paper is behind a paywall.

europepmc.org/article/MED/3...

[Bertwills]

I recently reacted very badly to Morningside Metformin which the pharmacist replaced my previously acceptable Meijumet. I got a new paper prescription & tried to find some Meijumet but there appears to be none in the country now.

With the knowledge about excipients gained here I tried to search for an acceptable alternative. I found it impossible. I could find some listings which included excipients but some were for medics only. The number of excipients varied hugely from 5 to 15 & included some frightening ones. I wouldn’t want to swallow talc 4 times a day.

It doesn’t seem to be taken seriously in the Uk. The pharmacy couldn’t or wouldn’t help.

Apparently the NHS is no longer paying the full price for drugs that the pharmacies are buying. NHS managers set a price which doesn’t vary with market forces. Pharmacies are having to cover any gap in pricing themselves. No wonder they’re closing down. It’s a reason why patients are given different brands, pharmacies shopping around for the cheapest version & no thought given to the poor patient’s sensitivities. I feel like giving up. I have to try a completely new drug now, maybe it’ll be ok 🤞

[helvella Administrator in reply to Bertwills]

All approved products are on the MHRA database.

This search is for metformin.

products.mhra.gov.uk/search...

You can tick the box to get only Patient Information Leaflets (PILs) or Summary of Product Characteristics (SPC) documents. Or both!

Both documents contain full lists of excipients (section 6.1 in each document).

The search is poor and while the search results start with products containing metformin, it goes on to all documents that contain the word "metformin".

This link finds all current metformin products and - if you follow through the links, finds the NHS prices for each one.

dmd-browser.nhsbsa.nhs.uk/s...

It can take quite some time to work through!

Meijumet 750, for one example, is here, with a price of £3.20 for 28:

dmd-browser.nhsbsa.nhs.uk/a...

[Bertwills in reply to helvella]

Thank you. I’ll play around with those websites & educate myself

[helvella Administrator in reply to Bertwills]

It would be great if the two databases linked to each other!

[Bertwills in reply to helvella]

Products.mhra.gov allows me access to the PIL which lists excipients. Is there a less cumbersome way of accessing the excipients? Examples of the differences between brands in following photos showing the problem of different levels of possible active ingredients

Metformin with many excipients

[helvella Administrator in reply to Bertwills]

Yes and no.

You could go to eMC - but not all products are listed on the eMC. (Even specialist pharmacists do not realise this. But, for example, Accord and Teva levothyroxine are not on eMC. And that means I do not trust eMC to have everything.)

NHS England's Specialist Pharmacy Service has a page explaining how to identify products that contain a specific excipient. But it fails because it doesn't find Teva levothyroxine (not on eMC) and doesn't find Aristo Vencamil (because search is for products *called* levothyroxine and Vencamil is called, well, Vencamil). That is, both available lactose-free levothyroxine tablets are not found!

However, in case it can help you in your search, here's a link:

sps.nhs.uk/articles/prescri...

[Bertwills in reply to helvella]

I’ve mastered it now. It’s a shame it’s so time consuming but better than nothing. Thank you.

[Bertwills]

Here’s an example I might have tolerated better

Metformin with few excipients

[helvella Administrator in reply to Bertwills]

PS You might see that in my UK Thyroid medicines document, I have lifted the text directly from the PIL or SPC without any editing. That is so I cannot make any errors in typing. And it also explains why the layouts vary as different companies prepare them to different standards. So I know exactly how much work it is!

[Bertwills]

Very helpful, thank you. It’s a bit of a nightmare really!