Osteoarthritis is the most common cause of chronic pain in dogs. Pain management must be the foundation for treating OA and preserving the quality of life. The phrase “quality of life” is most often used when discussing end-of-life decision making and determining if a patient’s pain can sufficiently be managed to maintain comfort.
Why do we wait until the end of life to talk about quality? Shouldn’t this be the first thing we discuss when we diagnose developmental orthopedic disease and OA. Shouldn’t the basis of treatment be about how we are going to provide high quality for the life of this patient? As such, pain management must be part of the OA discussion at the time of diagnosis.
As veterinarians, we understand that OA leads to pain, but our challenge typically lies in educating our clients on what pain looks like, and that medication is indicated to improve the comfort and quality of life of their pet. Have you ever had a client say “my dog isn’t using his leg, but I don’t think he is in pain?” You can use this tool (Pain Quiz Handout) to help clients understand what pain is, what OA pain looks like in dogs and the importance of pain management. Then, it is time to make recommendations for treating pain.
NSAIDs
Which NSAID is the most effective? Safest?
Non-steroidal anti-inflammatory drugs (NSAIDs) (including COX-inhibiting and piprant classes) currently remain the first line in pain management based on the high level of evidence for their efficacy in treating osteoarthritis (OA). No single product of NSAID has demonstrated superior efficacy or safety in dogs. It has been shown that dogs, like humans, respond differently to different NSAIDs, meaning that one particular product may be more effective than another in an individual dog.
How quickly should I see a response to starting an NSAID?
A response to the drug should be seen within 2 weeks of starting therapy (though often some relief if seen after a single dose). Studies have shown that continued improvement should be expected week after week for at least the first 4 weeks of daily treatment, and some dogs show continued improvement for up to a year after starting an NSAID (Autefage A, Vet Rec 2011).
If no improvement is seen after 2 weeks, it may be worth trying an alternative NSAID prior to adding a second pharmacological agent.
Do I need a washout period when switching NSAIDs?
When changing between 2 NSAIDs, a washout period is typically recommended. There are no published studies that give evidence-based support to washout guidelines, and wash out periods have not been established by manufacturers of veterinary NSAIDs.
Some pharmacologists recommend waiting at least 5-10 half-lives (T1/2) of the initial NSAID. The reason for switching NSAIDs may also influence the duration of wash out. If changing due to lack of efficacy, a shorter washout period may be sufficient, whereas changing due to an adverse response to one NSAID should warrant a longer washout period (until the symptoms have fully resolved).
The below chart is a general guideline for the washout period between NSAIDs that is based on NO research. Following these guidelines does not guarantee avoiding adverse effects and the individual veterinarian making washout recommendations is solely responsible for the outcome of their patient. This is meant to be a starting point for your recommendation; clinical experience and personal comfort level with each NSAID should help guide your personal recommendation.
Washout period when switching NSAIDs
This is meant to be a starting point for your recommendation; clinical experience and personal comfort level with each NSAID should help guide your personal recommendation.*Based on the different mechanism of action for Galliprant vs. the other COX-inhibiting NSIADs, a shorter washout period may be considered; however, concurrent use of Galliprant with other NSAIDs is not advised.
| NSAID | Estimated serum half-life (hours): T1/2 | 5 x T1/2 (days) | 10 x T1/2 (days) |
|---|---|---|---|
| Aspirin | 7.5–12 | 10–14 recommended | 10–14 recommended |
| Deracoxib | 3 | 1 | 2 |
| Firocoxib | 7.5 | 2 | 4 |
| Carprofen Oral | 8 | 2 | 4 |
| Carprofen Injectable | 24 | 5 | 10 |
| Meloxicam | 24 | 7 | 14 |
| Grapiprant | 5 | 1 | 3* |
Should I recommend daily use or PRN?
When starting an OA treatment plan, daily administration of an NSAID is recommended. Studies have found that a cumulative effect in efficacy is seen with daily dosing up to 1 year. Mansa, et al (Vet Record 2007) followed 750 dogs with OA receiving daily carprofen for 84 days and found that there was a significant improvement in lameness and other signs of pain between Day 14 and Day 84 of the study.
Autebrage followed 39 dogs with OA receiving daily firocoxib for 52 weeks. Assessment of pain, lameness, range of motion, and functional activities at home improved at each time point tested (Days 15, 90, 180, 270, 360). In other words, the dogs in both of these studies kept getting better and better and better without a plateau effect seen!
There were a few dogs in each study that were removed due to side effects, but the longer the dog was on the medication was not correlated with an increased risk of side effects. Side effects most often occur within the first month but can occur at any time.
So, there is a strong argument for the daily dosing of NSAIDs. However, these studies were observing the effects of NSAIDs alone, not in combination with a multi-modal approach. It is currently unknown whether similar results can be seen with PRN dosing along with a comprehensive plan.
Our current recommendation is to prescribe at least a 3-month course of NSAIDs (choose your favorite NSAID; monitor closely for side effects and discontinue/ change NSAID if indicated). After 3 months, assuming that the patient has improved and other management strategies have been incorporated, reduction to PRN use can be attempted in some cases.
A CSOM should be performed at this time, then repeated 4 weeks later to see if regression in symptoms has occurred. If the dog has relapsed, they would likely benefit from daily dosing. If a setback in symptoms is not seen with PRN dosing, NSAIDs should be given pre-emptively if the dog will be engaging in activity that is expected to increase lameness, then continued as needed to address any increased lameness or pain.
If I under-dose, is the NSAID still effective?
Efficacy studies of all NSAIDs were done with the labeled dose. There is limited evidence that Metacam can be dose-titrated with up to 50% reduction from the label dose, though larger studies are indicated to confirm this finding. At this time, there is no definitive evidence to suggest that under-dosing will be effective. However, when provided a dose range, the lowest effective dose should be given.
Do NSAIDs need to be given with food?
COX-inhibiting NSAIDs should be given with food, and the bioavailability of Rimadyl, Metacam, Previcox and Deramaxx is over 90% when given with a meal.
The bioavailability of Galliprant is much lower when given with food (33% with food, 89% without food), though it has shown efficacy in clinical trials when given with a meal. The FDA approved label for Galliprant does not specify whether Galliprant needs to be given with or without food; the European label does specify giving on an empty stomach.
If a dog is at the high end of the dose range and you would like to effectively give a lower dose, the dose can be given with a meal. On the other hand, if efficacy is not seen and the dose had previously been given with a meal, the dose should be given on an empty stomach to increase bioavailability.
NSAIDs scare me. Can you talk me off the ledge?
In general, the benefits of NSAIDs outweigh the risks. We do not know the true incidence or prevalence of adverse events with NSAID use in dogs, but it is very low compared to the number of doses administered.
Nonetheless, having a healthy respect for the potential side effects associated with NSAIDs is a good thing, because the most common reasons for adverse events are overdosing, concurrent use of multiple NSAIDs or NSAIDs and steroids, and continued administration despite GI symptoms such as anorexia or vomiting.
COX-inhibiting NSAIDs, as a class, carries the potential for adverse effects including gastrointestinal ulceration and nephrotoxicity. These adverse events are typically dose-dependent or related to an underlying, pre-disposing circumstance. For example, stress-induced gastric irritation can be perpetuated by COX-inhibiting NSAIDs, leading to more significant gastric erosion, ulceration or perforation. Administration of an NSAID in the face of hypotension may risk acute renal injury.
Hepatocellular necrosis has also been described and is considered to be an idiosyncratic reaction to the individual drug molecule rather than a dose-dependent adverse effect as seen in the stomach and kidney. This is typically seen within 2-4 weeks after starting the NSAID.
Side effects reported with Galliprant include vomiting, diarrhea, decreased appetite, and lethargy. Gastric ulceration/perforation, nephrotoxicity, and hepatocellular necrosis have not been reported due to Galliprant.
Can I decrease the risk of side effects with NSAID use?
Unless contraindicated, NSAIDs (COX-inhibiting or piprant class) should be used as a part of the Comprehensive Care Plan for canine OA.
By following the precautions below (adapted from the 2015 AAHA Pain Guidelines), the chances of adverse effects can be minimized:
- Avoid use in patients with:
- renal, hepatic or cardiac dysfunction, dehydration, hypovolemia, hypotension
- DO NOT use NSAIDs concurrent with aspirin or corticosteroids.
- Check the label of nutritional supplements—they may contain aspirin or other “natural” anti-inflammatories such as willow bark or meadowsweet (natural forms of aspirin).
- Use caution when starting an NSAID after recent use of steroids or a different NSAID
- Provide CLEAR CLIENT INSTRUCTIONS:
- Verbal and written
- Ensure that the client understands the dose (once or twice a day? ½ or full tablet?)
- Clearly label the dispensing bottle.
- Ensure the client understands the earliest signs of adverse events and what to do.
- Anorexia is the earliest sign of gastric ulceration in dogs taking COX-inhibiting NSAIDs.
- With COX-inhibiting NSAIDs, STOP and CALL if anorexia, vomiting, diarrhea
- Galliprant: vomiting, diarrhea and anorexia may occur; however, the product label does not require stopping the medication. Clients should be advised to call to discuss whether discontinuing is advised.
- Studies with Galliprant reported sporadic vomiting or diarrhea that was not associated with gastric ulceration and the dogs did not seem “sick.” If this is the case, continuing the medication may be OK. This should be the discretion of the attending veterinarian.
- Any adverse event should be reported to the individual drug manufacture’s pharmacovigilance team.
- NSAIDs are highly protein bound.
- Use caution or decrease dose when administering to dogs with decreased protein or those receiving other highly protein-bound medications such as phenobarbital, digoxin, cyclosporine, cefovecin, and chemotherapy agents.
- Avoid use with furosemide, nephrotoxic drugs and use caution with ACE inhibitors
- Blood work monitoring for COX-inhibiting NSAIDs; while not required on the label for Galliprant, monitoring blood work may be considered best practice
- Ideally, check blood work prior to starting and within 1 month after initiating therapy
- For low-risk patients, repeat blood work q 6 months
- For high-risk patients, repeat blood work q 2-4 months
- When treating gastritis associated with COX-inhibiting NSAIDs, use proton pump inhibitors (omeprazole, BID dosing), sucralfate and misoprostol. These should also be considered during washout or in periods of stress.
- Acid reducers are not expected to reduce vomiting/ diarrhea associated with Galliprant.
- Dose based on lean body weight
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