14 – Small Animal NSAIDs

Question 1

Small animal NSAIDs examples

Answer 1

• Carprofen (dogs)
• Meloxicam (cats+dogs)
• Coxibs

Question 2

Carprofen

Answer 2

• Considered ‘COX2 selective’
• Racemic mixtures (S+R enantiomers)
  o S-enantiomer more potent
• Oral chews and injectable
• *only DOGS

Question 3

Carprofen indications

Answer 3

• Osteoarthritis (chronic)
  o *strong evidence
• Post-op pain

Question 4

Carprofen adverse events

Answer 4

• Low, but variable incidence of vomiting and diarrhea
• Idiosyncratic (NOT dose-dependent) hepatic toxicity in dogs!
  o Very rare (NOT HIGHER in LABS)
  o Within few days/weeks of therapy
  o Pre-treatment blood samples necessary to know (check liver enzymes)

Question 5

Meloxicam

Answer 5

• ‘COX-2 preferential’
• Oral suspension, tablets, infectable
• EBM analysis for arthritis=’high level of comfort’

Question 6

Oral suspension of meloxicam: dog vs. cat doses

Answer 6

• Dogs: 1.5mg/ml
• Cats: 0.5mg/ml
• *useful formulations=can come up with WHATEVER DOSE you want
• **can use the LOWEST EFFECTIVE DOSE and TITRATE your way down

Question 7

Meloxicam indications

Answer 7

• Acute AND CHRONIC musculoskeletal disorders (dogs)
• Acute musculoskeletal disorders (cats)
• Post-op pain (orthopedic, soft tissue surgery)
  o Better than post-op butorphanol

Question 8

Meloxicam adverse events

Answer 8

• Dogs: typical
  o Low incidence of vomiting and diarrhea (similar to carprofen)
• USA: NO musculoskeletal claim in cats (‘black box warning’)

Question 9

Coxibs

Answer 9

• COX-2 selective

Question 10

Coxibs examples

Answer 10

• Deracoxib (tablets, dogs)
• Firocoxib (tablets, EQUINE as well)
• Robenacoxib (oral+injectable, dogs and cats)

Question 11

Coxibs indications

Answer 11

• Chronic osteoarthritis
• Orthopedic post-op pain (dogs)’

Question 12

Coxibs adverse events

Answer 12

• Low incidence of vomiting and diarrhea
• Renal tubular degeneration at high doses
• Cases of GI perforation at high doses

Question 13

Firocoxib dose between dogs and horses

Answer 13

• Dog dose is 50x more (5mg/kg dog vs. 0.1mg/kg horse)
  o Both get a 57mg tablet!

Question 14

Robenacoxib (Onsior tablets) indications for cats

Answer 14

• Relief of ACUTE pain and inflammation with cat bites and scratches
• As an adjunctive medication in control of postoperative pain and inflammation
• *Control of pain and inflammation with CHRONIC MUSCULOSKELETAL disorders (only one that has chronic)
• *highly COX2 selective (maybe not great?)

Question 15

Robenacoxib (Onsior tablets) indications for dogs

Answer 15

• Control of pain and inflammation associated with OSTEOARTHRITIS
• As an adjunctive medication in control of POSTOPERATIVE pain and inflammation with soft tissue surgery

Question 16

‘old’ small animal NSAIDs

Answer 16

• Ketoprofen (only large animal now)
• Tolfenamic acid
• Phenylbutazone
• Dipyrone
• Vedaprofen

Question 17

What about human NAIDS to use in vet med?

Answer 17

• Not approved for vet med
• *toxicity
  o Ibuprofen is a big one! (most cases do survive)
• *’cheap alternative’ (NOT worth the RISK!)

Question 18

Safety and efficacy of human NSAIDs for small animals?

Answer 18

• Not nearly as good as approved vet drugs
• *smaller therapeutic window (increased effective dose and decreased toxic concentration)

Question 19

Small animal ‘not NSAIDs’ for osteoarthritis

Answer 19

• Galliprant (dogs)
• Solensia (cats)
• Liberla (dogs)

Question 20

Galliprant

Answer 20

• Recently approved for use in dogs with arthritis
• Oral tablet
• *PGE2 receptor antagonist (NOT a COX inhibitor)
  o Blocks EP4 receptor

Question 21

Galliprant blocks EP4 receptor

Answer 21

• Involved in mediating pain and PGE2-elicted sensitization of sensory neurons

Question 22

Why use galliprant?

Answer 22

• Theory might be safer than NSAIDs?
  o Since not blocking the production of PG, just the PG receptors
• Data shows efficacy is likely worse!
• Concurrent use with NSAIDs not recommended
  o Adverse events likely to occur
• Ex. animal that already has GI problems or kidney issues

Question 23

Gallipratn adverse reactions

Answer 23

• *relatively low incidence=safer than NSAIDs
• Vomiting
• Diarrhea
• Anorexia
• Lethargy
• Buccal ulcer and IMHA (lower)

Question 24

Galliprant efficacy

Answer 24

• Not fantastic treatment success
• Slight difference between treatment and placebo

Question 25

Solensia

Answer 25

- Recently approved to use in cats with arthritis - *monoclonal Ab specific for FELINE nerve growth factor (NGF) - Not really a drug, technically a ‘biologic’ - Dose: 1-2mL/cat SC, repeated monthly - *doesn’t fix the osteoarthritis

Question 26

Nerve growth factor (NGF)

Answer 26

- Upregulated during chronic inflammatory conditions (Ex. osteoarthritis) - Involved in pain response

Question 27

Solensia pharmacokinetic(PK) highlights

Answer 27

- Long-acting injection o Half-life of 10-12 days o One injection per month o Two injections to reach steady state - **doesn’t get broken down quickly o Proteolysis (inactive peptides)

Question 28

o Proteolysis (inactive peptides) Solensia efficacy and safety

Answer 28

- It works and seems safe - Hard to do the studies in cats - Not necessarily better than NSAIDs

Question 29

Librela (bedinvetmab)

Answer 29

- Approved for dogs with arthritis o Monoclonal antibody specific for canine NERVE GROWTH FACTOR (NGF) - Safe (only 1% do dogs developed anti-drug antibodies

Question 30

Is it good idea to combine NSAIDs with ‘not-NSAIDs’ for multi-modal osteoarthritis analgesia?

Answer 30

- Don’t really know yet - *benefits of multimodal analgesia is well documented - BUT o Efficacy may not be synergistic for theses types o Choric use might be riskier than other analgesic regimes - ADVICE: be cautious, use LOWEST NSAID dose

Question 31

Pharmacovigilance (adverse event reporting): NSAID safety

Answer 31

- Increased reported AE does NOT mean less safe (need a denominator) - Conditions of use vary between NSAIDs (one time vs. life-long) - Voluntary reporting can be skewed - Hard to find accurate data, objective comparisons are difficult

Question 32

Systematic review of NSAID safety in dogs

Answer 32

- High evidence for carprofen, firocoxib and meloxicam - Less evidence for deracoxib, ketoprofen, robenacoxib (not necessarily less safe) - Vomiting and diarrhea most common clinical signs - Hepatic events more likely to be an idiosyncratic hepatoxicity (dose independent) - Kidney and GI can be DOSE-dependent

Question 33

NSAIDs in cats and safety

Answer 33

- Decrease glucuronidation and hepatic clearance of NSAIDs=increase half-life - *approved products: meloxicam and robenacoxib - Firocoxib: minimal safety data - Carprofen: highly variable half-life between cats

Question 34

Meloxicam adverse drug events in cats

Answer 34

- Renal failure caused by hypovolemia? o No change in GFR in euvolemic, healthy cats! o No change in GFR in euvolemic cats with azotemia o *dehydrated cats (and other animals)=more at risk of renal injury - Idiosyncratic or other mechanisms - Did NOT appear to reduce lifespan - Relatively now

Question 35

Is it okay to use Meloxicam in cats with chronic renal failure?

Answer 35

- Make sure HYDRATED - Progression of renal failure is NO worse than a control group - Using a very small dose - Some evidence: may slow down progression of kidney disease?

Question 36

Long term NSAID use in cats summary

Answer 36

- *can be done successfully

Question 37

What have we learned about NSAID use in small animals?

Answer 37

o GI lesions o Other GI signs o Hepatic and renal damage - *no newer NSAIDs are consistently more effective than others - *USE THE LOWEST EFFECTIVE DOSE!