482 Canine Sports Medicine and Rehabilitation
client education. Seventy five percent of indi-
viduals reporting adverse NSAID events to the
US Food and Drug Administration (FDA) hot-
line feel that their veterinarian did not inform
them adequately of possible side effects, and/
or failed to give the client the drug information
sheets (Hampshire et al., 2004).
Tips for use
In the transoperative setting, an edge in efficacy
in both human and canine studies goes to pre-
surgical over postsurgical use (Lascelles et al.,
1998). Systematic reviews in humans suggest the
safety of preoperative NSAID use (Lee et al.,
2007), as do studies in healthy dogs, even with
moderate intraoperative hypotension (Bostrom
et al., 2002). It is axiomatic in veterinary medicine
today that patients undergoing general anesthe-
sia should have the benefit of intravenous fluid
support and blood pressure monitoring.
New drugs in class
● Grapiprant (Galliprant®) is the first in a
new “priprant” class of “non‐COX‐inhibit-
ing non‐steroidal anti‐inflammatory”
drugs, approved in the United States in
2016 and launched in 2017. Instead of inhib-
iting COX2, it targets downstream to block
the EP4 receptor, one of four “EP” receptors
on cell membranes to which PGE2 binds.
EP1, EP2, and EP3 are largely (but not exclu-
sively) responsible for GI homeostasis and
motility, while EP4 is largely (but not exclu-
sively) responsible for pain and inflamma-
tion of osteoarthritis (OA) (Konya et al.,
2013). Thus grapiprant is most accurately
described as a non‐COX‐inhibiting, targeted
“EP4 receptor antagonist.” Its pharmacol-
ogy suggests anti‐inflammatory, analgesic
activity in OA while improving upon the
adverse event (especially GI) profile so well
described with traditional COX‐inhibiting
NSAIDs. Indeed, it has demonstrated excel-
lent safety in young dogs even at >15× the
labeled dose administered daily for 9
months (no GI erosions, ulcers, perfora-
tions, or nephrotoxicity observed; Rausch‐
Derra et al., 2015), and in successful clinical
studies of older dogs with OA (Rausch‐
Derra et al., 2016).
● Robenacoxib (Onsior®) is a unique (coxib
class) COX2 selective NSAID now approved
for canine and feline perioperative use in
the United States for postsurgical pain
(Sackett et al., 1996; King et al., 2010). It has
an unusually short plasma half‐life in both
species (<1.7 hours) yet accumulates in
inflammatory exudates for over 24 hours
(Silber et al., 2010). Safety and toxicity data
for this molecule are among the most
impressive of the traditional COX2‐inhibit-
ing veterinary NSAIDs, being well tolerated
in young dogs even at a dose of 20–40× the
labeled dose administered daily for 1 month
and 5–10× daily for 6 months. In the
European Union, canine Onsior® carries a
label for OA rather than postsurgical pain.
● Mavacoxib (Trocoxcil®, Europe only) is a
sustained‐release NSAID approved for
chronic pain in dogs. Its pharmacokinetics
are established in dogs with OA (Cox et al.,
2010) and suggest once‐monthly adminis-
tration. Efficacy and safety appear similar to
the daily administration of other veterinary
NSAIDs (Walton et al., 2014; Payne‐Johnson
et al., 2015). However, if an adverse event
were to occur, treatment is complicated by
the fact that the drug’s effects cannot be rap-
idly withdrawn.
● Nitronaproxen (Naproxcinod®, Europe
only for humans) is a cyclooxygenase‐inhib-
iting nitric oxide‐donating drug (CINOD)
that appears to have the analgesic efficacy
of the parent NSAID (Geusens, 2009) but
with a greatly reduced incidence of gastrop-
athy (Fritsch et al., 2010).Acetaminophen
Acetaminophen may elicit some of its antipy-
retic and analgesic properties by inhibiting one
or more centrally acting COX variants (Kuo,
2006), and also appears to have central cannabi-
noidergic pain‐modifying effects (Ghanem et
al., 2016). Studies suggest that peripherally it
may inhibit COX2‐mediated production of
PGE2 in cases of mild, but not severe, inflam-
mation (Graham et al., 2013). Its postoperative
pain‐modifying (and possible anti‐inflamma-
tory) effects have been demonstrated clinically
in dogs (Mburu et al., 1988), although these