GRAPIPRANT

BRAND NAME: GALLIPRANT

AVAILABLE IN
20 mg, 60 mg, and 100 mg
TABLETS

BACKGROUND

The importance of pain relief cannot be overemphasized. Dogs, especially large breed dogs, commonly suffer from arthritis pain and loss of mobility especially as they age. The issue can become so extreme that life quality is impaired. Human pain relievers abound but because many are toxic or dangerous to dogs, medications made just for dogs have evolved . The development of canine-friendly non-steroidal anti-inflammatory drugs (NSAIDS) created a revolution in pain management for dogs to a point where NSAIDs have become standard components of arthritis pain relief as well as surgery-related analgesia.

One of the limitations of the NSAID group has stemmed from the biochemistry of the prostaglandin suppression which NSAIDs use to relieve pain and inflammation. NSAIDs work by suppressing prostaglandins. The problem is that we do not want to suppress all prostaglandins, just the ones associated with pain and inflammation. As more sophisticated NSAIDs were developed to suppress only certain pathways, we still found that even prostaglandins typically considered "bad" can still have some "good" effects. In other words, even the use of the most innovative NSAIDs has been a double-edged sword in certain situations. We only want to suppress pain and inflammation; we don't want to decrease blood flow to the GI tract or kidneys nor interfere with the ability to clot blood.

Enter the piprant class of anti-flammatory drugs. Grapiprant is the first priprant anti-inflammatory to come market with its release in 2017. Grapiprant does not suppress prostaglandin production; instead, it interferes with a specific prostaglandin receptor called the "EP4" receptor. The EP4 receptor is the receptor is involved in the generation of pain and inflammation. By interfering with only the EP4 receptor, grapiprant suppresses pain with no effect on the kidney, blood clotting mechanisms, or GI tract. In this way, the side effects and drug reactions that have been concern for patients on NSAIDs should not be concerns with grapiprant.

HOW THIS MEDICATION IS USED

Grapiprant is used once a day in the management of pain in dogs. It works best when given on an empty stomach.

Unlike the NSAIDs where pre-screening lab work is important to be sure the patient does not have a kidney or liver condition that could be exacerbated by an NSAID, pre-screening labs are theoretically not necessary with grapiprant. With NSAIDs, periodic monitoring blood tests are recommended to be sure the patient's metabolic situation has not changed and that NSAIDs are still safe. Similar monitoring is still recommended with grapipriant and is prudent in any patient on long term medications.

SIDE EFFECTS

• Intestinal
  Most side effects are GI related: diarrhea, appetite loss, vomiting. It is not uncommon for minor intestinal upset to be seen in patients starting grapiprant but symptoms were mild and transient. Vomiting has been the most common side effect noted with this medication.
  
  
• Albumin Reduction
  Albumin is an important blood protein. It is involved in transporting materials through the body. Albumin levels can be reduced with grapiprant use. This is probably not an important side effect in a normal animal but if a patient already has a disease that lowers blood albumin, it is probably best not to lower albumin further.
  
  
• Heart Disease Patients
  The way grapiprant works is by blocking the EP4 receptor. This prostaglandin receptor is involved in pain and inflammation which is why we want to block it but it is also involved in the heart muscle's response to stress. It is unknown whether grapiprant is a problem for patients with known heart disease but it might be. More study is needed for this issue but it may be prudent to either use a different pain medication or to use extra monitoring and caution with grapiprant use.
  
  
• Sulfa Drug Reactions
  Grapiprant is a sulfa-based medication. Sulfa-based medications of other types have been associated with reduced tear production as well as some immune-mediated conditions. No such conditions were seen in any of the test dogs studied prior to the release of grapiprant but the extent to which sulfa-type side effects are possible is still considered unknown.
  

INTERACTIONS WITH OTHER DRUGS

The use of grapiprant may decrease the effectiveness of angiotensin converting enzyme inhibitors (ACEI's) such as enalapril or benazepril. Grapiprant may also decrease the activity of angiotensin receptor blockers (ARB's) such as telmisartan.

Concurrent use with a bisphosphonate can increase the toxicity of the bisphosphonate. This is particularly of note for dogs treated for osteosarcoma where concurrent use of these medications is likely.

Bleeding risk increases when grapiprant is used along with the anticoagulant clopidogrel.

Intestinal side effects such as vomiting and diarrhea are made worse or more likely with concurrent use with steroids.

Grapiprant should not be used with more traditional NSAIDs and a 1-2 week wash out period between their use is recommended.

The Issue of Protein-binding

Grapiprant is highly protein-bound and this is a potential problem when it is used with other highly protein-bound medications. What this means is that drugs that have a high-protein affinity, will fight with each other to bind with blood proteins. The drug that "loses" must float free in the bloodstream where it is more active in its effects and potentially more likely to show toxicity or side effects. When two protein-bound drugs are used together, one is likely to be a problem in this way and it is not predictable which of the two drugs will be a problem.

CONCERNS AND CAUTIONS

Grapiprant should not be given with food. It will not absorb into the body predictably.

Grapiprant is not approved for dogs under 9 months of age and cannot be accurately dosed in dogs under 8 lbs of body weight.

Grapirant has also not been evaluated in breeding, pregnant, or nursing dogs.

Unlike traditional NSAIDs, grapiprant has no ability to reduce fever.

Grapiprant has only been tested in healthy dogs, though in healthy dogs given 15 times the recommended dose for 9 months no serious consequences resulted. This represents a very broad safety margin.

Dogs with the MDR1 mutation have altered metabolism of this medication and are more prone to intestinal side effects. A dose reduction will be necessary. If you are unfamiliar with the MDR1 mutation (common in collie-related breeds) click here.

Grapirant has not been studied in dogs with heart disease. This is important because there are a lot of EP4 receptors in heart tissue. The consequences of this are unknown.

Monitoring blood tests are recommended when grapirant is used long term.

Grapirant is not approved for cats.

Store at room temperature.

If a dose is missed, do not double up on the next dose; just give as usual. This medication can be given regularly or on an "as needed" basis as long as it is not used more than once daily.

Page posted 3/5/2019