Yet one distributor — Penn Veterinary Supply Inc.
— says it has plenty of small-animal strength atropine in stock. When asked what manufacturer makes the drug, a company representative dodged the question, replying, "We get it from various sources."
The shortage, whether perceived or reality, began last year, when IVX Animal Health, formerly Phoenix Pharmaceuticals, shut down atropine production to bring its facilities into compliance with new, more stringent Food and Drug Administration regulations. The move, while voluntary, created a shortfall of atropine because, at the time, IVX supplied 99 percent of the veterinary marketplace.
That's according to John Nicholson, director of private labels with distributor Butler Animal Health. While IVX did not return interview requests by press time, Nicholson says Butler can't get the product, at least in a consistency formulated for small animals. Med-Pharmex Inc., of California, supposedly is picking up the production slack, but Nicholson says he hasn't received anything from the manufacturer. Med-Pharmex Inc. did not return phone calls seeking comment.
In the meantime, Butler is considering selling human atropine off-label to DVMs. The problem: The concentration is different and, for humans, the drug only is used in an emergency setting. Additionally, it is formulated for single-use injections, rather than as a multi-injection formulation. Nicholson expresses concerns that it could be used improperly in veterinary medicine.
There are three main uses for atropine in veterinary medicine: pre-anesthetic and anesthetic maintenance of an appropriate heart rate, performing an atropine response test and treatment of organophosphate (OP) toxicity. Doses for these uses vary substantially, experts say.
According to VIN consultant and cardiologist Dr. Mark Rishniw, glycopyrrolate can be substituted without problem for pre-anesthetic and anesthetic applications. Standard doses for this application can be found in Plumb's Drug Formulary.
Glycopyrrolate has not been critically evaluated in performing a heart-rate response test, commonly known as the atropine response test, Rishniw adds. However, similar doses to those used pre-anesthetically have been recommended previously.
OP poisoning can be incompletely addressed by glycopyrrolate because it fails to cross the blood brain barrier, and evidence in humans suggests that at least some of the toxicity is centrally mediated, Rishniw says. Studies in humans with severe OP toxicity suggest that glycopyrrolate might not prevent mortality as well as atropine. Additionally, the dose of glycopyrrolate required to treat OP toxicity may be higher than that used for arrhythmia control. According to 2002 recommendations published in the Israel Medical Association Journal, in human intoxications, the alternate therapy to atropine involves glycopyrrolate intravenously at 0.01mg/kg every 15 minutes to 20 minutes until signs subside, coupled with diazepam and scopolamine (both of which have central nervous system effects that complement the peripheral muscarinic blockade caused by glycopyrrolate). Whether similar doses and drug combinations would be effective in small animal OP toxicity is speculative, Rishniw adds.
VIN consultant and toxicologist Dr. Mark Grossman says that "since it takes 10 times the preanesthetic dose of atropine for OP toxicosis, speculation suggests that 10 times the preanesthetic dose of glycopyrrolate, or 0.1 - 0.2 mg/kg, will do the same."