Drug shortages, recalls, and discontinuations of medications are occuring with greater frequency within the United States and this can adversely affect veterinary patients. Just this past July, Altaire Pharmaceuticals (headquartered in Aquebogue on Long Island) issued a voluntary recall of 99 different prescribed products including ophthalmic ointments of neomycin, polymyxin B and dexamethasone; neomycin, polymyxin B and bacitracin zinc with hydrocortisone; and neomycin, polymyxin B and bacitracin zinc. Subsequent high demand for an alternative suspension of neomycin, polymyxin B and dexamethasone (Figure 1) quickly depleted its supply. Altaire also recalled 16 over-the-counter products including OCuSoft (hypochlorous acid 2%) and Puralube (petrolatum) that were routinely stocked at CVS, Walmart, and Walgreens. One of Altaire’s manufacturing plants could not ensure the sterility of its output. However, there have been no reports of the recalled products adversely affecting human or veterinary patients.
The Food and Drug Adminstration (FDA) typically regulates drug manufacturing to make up for the scarcity of any “medically necessary” product. A drug is considered by the FDA to be “medically necessary” only if it is used to treat a serious human ailment and if there are inadequate alternatives as determined by the general medical community. The FDA does not regulate temporary or self-limiting drug shortages, or those involving a specific strength or package size of a drug. For example, the FDA probably determined that neomycin, polymyxin B and dexamethasone ointment prescribed for uveitis could be substituted by prednisolone acetate 1%, or difluprednate 0.05%. The FDA did not consider the vast cost increases associated with these alternatives, but rather that neomycin, polymyxin B and dexamethasone ointment was not “medically necessary” by definition.
The primary causes for drug shortages are manufacturing issues, and typically affect only one specific type of a drug at any time. However, sudden recalls may not give other manufacturers enough time to make up for deficiencies. Other delays can involve the complexity of the manufacturing process itself (e.g. antibiotics or vaccines). The FDA also approves a specific fabrication line to produce a specific drug at a specific facility. Therefore, manufacturing cannot just be quickly set up elsewhere even within a specific company. Manufacturing equipment is often used to make several different products on a line, so increasing production of one drug may cause the delay or shortage of another. Alternatively, setting up new dedicated equipment, or contracting a new company to produce a drug, can further increase delays. Drug manufacturers are also increasingly dependent on raw materials from other countries making them reliant on a global supply chain. It is estimated that 80% of the raw materials that are used in pharmaceuticals sold from the United States are imported from abroad (e.g. Europe, India, or China). These supplies can be affected by armed conflicts, political upheavals, trade disputes, transportation degradation or contamination, and environmental conditions. The packaging of a successfully produced drug also relies on yet another set of manufacturers.
In the United States the scarcity of a generic medication can be particularly adverse for veterinary clients who usually lack pet insurance and must pay out-of-pocket for medications. Companies that produce generic drugs have little financial incentive to produce an off-patient product. Consequently, there are very few manufacturers of a particular generic drug and shortages are therefore inevitable. Shortages of generic drugs in the United States have tripled since 2006.
In the veterinary office the first sign of a possible drug shortage are back-orders. Suppliers should be able to explain why a drug is back-ordered and how long the shortage is expected to last. Problems involving raw materials will affect most manufacturers of a given drug, but problems at a single manufacturing line typically do not. Ideally, prescribers should be notified of a medication’s limited supply prior to their depletion.
Attempts to stockpile medications are limited as distributors usually allocate products based on prior history. However, it can be useful to assess how much of a drug is on hand, and at what rate it is lost from inventory. A veterinary practice can also preserve its inventory by using external pharmacies. Large commercial companies (e.g. Walmart, Target, Walgreens, Sam’s Club, and CVS) usually maintain extremely large inventories and can survive drug shortages by shifting their stocks between stores. These suppliers can help offset the depletion of a drug from a practice’s inventory.
During a drug shortage, alternative drugs or therapeutic equivalents should be identified. For example, neomycin, polymyxin B and dexamethasone ointment are often prescribed to treat uveitis, but prednisolone acetate 1% is a viable, but expensive, alternative. Similarly, prednisolone acetate 1% can be used to reduce ocular surface inflammation (e.g. chronic superficial keratitis) when dexamethasone sodium phosphate is not available. Topical cyclosporine can also be used to supplement a reduction in the amount of dexamethasone applied to a patient.
During drug shortages, veterinary practices should dispense drugs prudently to their patients. The needs of clients also need to be considered. For example, clients with transportation issues (e.g. blind, elderly, or disabled) may struggle to reach an external pharmacy.
If you have further questions concerning alternatives to diminishing supplies of ophthalmics, please feel free to contact a veterinary ophthalmologist.
Noelle La Croix, DVM, DACVO
The Veterinary Medical Center of Long Island
75 Sunrise Highway
West Islip, N.Y. 11795
(631) 587-2006 (fax)
Figure 1. Part of the limited stock of neomycin, polymyxin B, and dexamethasone.