Four drugs listed as products with the greatest risk of supply disruption and vulnerability after a U.S. drugmaker closed in February are on back order. The U.S. now has no supply of four others.
The backordered drugs are tropicamide 1% ophthalmic solution, orphenadrine citrate injection, sufentanil, and fluorescein sodium injection solutions. These shortages are partly because Akorn Operating Co., a Gurnee, Ill.-based drugmaker, shut down all operations, according to the American Society of Health-System Pharmacists.
Akorn made 100 percent of the nation’s supply of calcitriol injection, alfentanil injection, dimercaprol injection and physostigmine salicylate injection solutions. All four are discontinued.
A few weeks after Akorn shuttered all production, the End Drug Shortages Alliance compiled a report of 16 drugs most vulnerable to supply disruptions based on the drug company’s market share and the likelihood of whether a product will be in shortage by March 2024.
Three of the discontinued drugs are an essential medication, according to Vizient.
For backordered products, here are the shortage details and mitigation strategies:
1. Tropicamide 1% ophthalmic solution: Akorn’s solution is unavailable and two drugmakers, Bausch Health and Sandoz, have their solutions on back order. Bausch Health told ASHP it cannot estimate a release date for its 2 milliliter bottles, and Sandoz said it estimates a resupply date of its 15 milliliter bottles in April.
Alcon has Mydriacyl and Somerset has tropicamide 1% ophthalmic drops available, according to ASHP.
The anticholinergic agent is used to produce mydriasis and cycloplegia in diagnostic procedures, according to the report. Other suppliers may have the product, and “for healthy eye penalization, nonpharmacological options may be considered,” the End Drug Shortages Alliance wrote.
Akorn accounted for 33 percent of the drug’s market share, and its vulnerability score is 89.9 percent.
2. Orphenadrine citrate injection: There are no presentations available, and Hikma Pharmaceuticals has its 30 milligram/mL, 2 milliliter solutions on back order with a release date of mid-April. Hikma did not provide a reason for the back order, according to ASHP.
The report said there are no mitigation strategies for the muscle relaxer used to treat muscle spasms and pain. Akorn made 75 percent of the market share, and the drug has a 57.1 percent vulnerability score.
3. Sufentanil injection: Three of Akorn’s solutions — 1 milliliter, 2 milliliter and 5 milliliter ampoules — are not available, and the ASHP did not list any available products. Pfizer has its 1 milliliter vial on back order and estimates a release date in April.
The report said healthcare workers should “evaluate use of other opioids in this class as an alternative,” such as fentanyl and remifentanil. Sufentanil is used to relieve pain during and after procedures such as childbirth, according to the Mayo Clinic.
Akorn was responsible for 79 percent of the market share, and the drug has a 81.8 percent vulnerability score.
4. Fluorescein sodium injection: Increased demand pushed Alcon Labs’ 10 percent, 5 milliliter vial of Fluorescite (fluorescein sodium injection) into a shortage, the drugmaker told ASHP. Whether the solution is on back order or on allocation, or when its shortage will end, was not stated.
The drug “is considered the gold standard for diagnostic use in evaluating certain disorders, such as retinal vasculitis,” the report said. For clinical uses, the End Drug Shortages Alliance recommended reserving supply for “essential” diagnostic purposes, using indocyanine green if appropriate, and consulting with ophthalmology specialists.
Akorn made 82 percent of the market share, and the supply chain vulnerability score was not reported.
For discontinued drugs, here are the details and mitigation strategies:
1. Calcitriol injection, an essential drug, is a vitamin D drug used for managing hypocalcemia in patients undergoing chronic renal dialysis, according to the report. “It significantly reduces elevated parathyroid hormone levels which has been shown to result in an improvement in renal osteodystrophy,” the alliance said.
Akorn’s 1 microgram/milliliter, 1 mL ampoule is discontinued, according to ASHP.
“Calcimimetics, calcitriol, or vitamin D analogs, or a combination may be utilized” in some patients, the report said, adding that some conversion ratios have been studied. Another mitigation strategy is using oral calcitriol formulations.
Its vulnerability score is 82.4 percent.
2. Alfentanil injection: There are no more 2 milliliter or 5 milliliter solutions, according to ASHP. A vulnerability score was not reported, and the recommended mitigation strategy is to consider use of other opioids in this class as an alternative, including fentanyl and remifentanil.
3. Dimercaprol injection is an essential medication with a 28.6 percent vulnerability score. It’s an antidote intended to treat heavy metal poisoning, including arsenic, gold, lead and mercury, the report said.
“Akorn [was] the sole manufacturer of dimercaprol and there are no other intramuscular chelating agents for heavy metal poisoning on the market,” the report said. For clinical uses, recommended strategies include considering the use of oral succimer when appropriate and consulting with the “regional poison control center or institutional toxicologists to ensure administration is necessary on a case-by-case basis.”
4. Physostigmine salicylate injection is an essential medication with an 88.4 percent vulnerability score.
It is a “reversible carbamate anticholinesterase inhibitor indicated to reverse the effect on the central nervous system caused by clinical or toxic dosages of drugs capable of producing anticholinergic syndrome,” the report said. “In past shortages of physostigmine, oral rivastigmine — a tertiary amine — has been used as a treatment alternative for patients with anticholinergic delirium; however, limited evidence does not allow for recommending this product for routine use for this indication.”
The End Drug Shortages Alliance recommends that, in clinical uses, workers save remaining supply for patients when pure anticholinergic poisoning is suspected and for those who need the “reversal of significant toxic anticholinergic effects on the central nervous system,” including instances of moderate to severe agitation or delirium. The report also recommends consulting with toxicologists and poison control centers.