Canada currently lists 1748 actual drug shortages at its database right now, some of which it has labelled as Tier 3 — meaning they have a great impact on health care. Among those are five actual shortages of nitroglycerin sublingual medication–5 out of the total of 6 such products currently marketed in Canada.
The earliest of the current nitro shortages was announced in January 2023 by Mylan — and the cause was identified as “quality issues,” although media reports suggest that difficulty accessing the raw materials may be the real cause. By March and continuing into May, shortages were reported for other nitro products, and they were attributed to “increased demand.” This is scarcely surprising: if the most important product vanishes, supply of alternate sources will be stressed. Health Canada sent alerts ( (here).
Canada initially saw an increase in companies making nitroglycerin products, especially in the 1990s — and then from about the year 2000, it has seen a steady decrease in the number of products and the number of companies engaged in its production (source).
The graph below shows the timeline of nitro product launches and declines in Canada. The asterisk shows which products are still marketed. It also shows in blue the 43 reported shortages, documented from 2014, all of which have resolved except the most recent cluster since January 2023. Six of these shortages ended in the completed discontinuation of the product. (My source on the shortages is https://www.drugshortagescanada.ca and information gathered from its predecessor for our 2018 report.)
Since 1962, Canada has had a total of 38 nitro products made by 15 companies over the years. It now has only 19 products still on the market made by 8 companies (actually only 7 companies because BGP was bought by Mylan in 2015; Mylan itself is now part of the new Viatris formed from a merger with Pfizer’s Upjohn in 2020).
The pattern is similar to Tamoxifen and kids Tylenol (which I blogged about here and here) and to beta blockers (which I wrote about here), and it probably applies to many generic drugs in the Canadian pharmacopeia.
When suppliers pull out of a market, any drug will be more vulnerable to shortages because margins in the system have decreased — or vanished. That certainly is one reason for the current shortage of nitro.
But there may be other reasons. Of the 19 nitro products still on the market, 5 are sublingual spray or tablet; 11 are patches; and 3 are for IV use (usually in emergency rooms). Only the sublingual products are currently in short supply, although there have been a few shortages of patches and IV products in the past.
I have several questions about this current shortage
- Why is it mostly in Canada and not elsewhere (yet)? Is it because our market is small and scant resources are directed to countries with a larger client base? American reports in late March of a shortage of the IV format appeared with little follow up.
- What were the “quality issues” named in Mylan’s shortage report of January 2023?
- Why is it only the sublingual products (spray or tablets) that are reported in short supply and not also the IV nitro products or the patches? A shortage of raw materials –especially the API (active pharmaceutical ingredient) –should result in shortages of all the formats. It should also affect other countries.
- Given, #3, is it possible that the shortage has more to do with the shortage of the pump spray device, similar to what was seen during the Epipen shortage in the summer of 2019? I once suggested that those injectors be recycled. Indeed, Mylan once had a problem with its pump spray device that led to a recall back in 2014. The US FDA list of device shortages has no indication that nitro spray pumps are in short supply — but unfortunately, Canada has no such list.
- Did changing practice guidelines for the management of angina chest pain play a role in the decline of nitro products as they did for beta blockers? Nitro used to be the mainstay of managing chest pain — but now a combination with ASA, or ASA alone is preferred. Decreasing numbers of prescriptions would translate into decreased demand and the incentive for manufacturing is less. It may have contributed to the loss of companies making nitro products.
As always — we need more transparency about the supply chains. We need Canada to measure the shortages year by year to understand the gravity of the problem and measure the impact of policies implemented to deal with them. We need Canada to lead an international discussion about the causes of drug shortages everywhere. This shortage — and all the others–did not originate in Canada; it cannot be solved by Canada alone.