Optimizing Pain Control A Critical Understanding of NSAIDs James S. Gaynor, DVM, MS, DACVA, DAAPM Colorado Springs, CO USA 719-266-6400 800-791-2578 www.peakvets.com Principles of Acute & Chronic Pain Management Pain control is good medicine Continuous analgesia Multimodal approach brain Wind Up brain NMDA receptormediated innocuous stimuli spinal cord innocuous stimuli Allodynia noxious stimuli noxious stimuli spinal cord periphery periphery PPVG 2013 PPVG 2013 Surgical Patient Delayed Healing Stress Response General Catabolism Lipolysis Common Scenario Wind-up : OsteoArthrtitis NSAID for months -> years successful Now efficacy has diminished Switch? OA Patient Accelerated Muscle Atrophy Greater Dysfunction PPVG 2013 1
Amantidine NMDA antagonist 3-5 mg/kg PO QD x 21 days Continue NSAID Side effects High anxiety Too high of a dose Dry mouth Slow liver metabolism Uncommon Gabapentin is not a substitute! Alleviation of Pain Associated With OA Adjuncts - amantidine Weight loss Controlled exercise & physical rehabilitation Pain relievers Structure modifiers: Cosequin Multi-modal approach Other Webinars Available A Logical Approach to Chronic Pain Therapy What to Use When You Can t Use NSAIDs Out of the Box Approaches to Chronic Pain Cutting Edge Approaches to Chronic Pain Weight Loss and Hip Arthritis J. Am. Vet. Med. Assoc. 2002, 220, 1315 1320 Weight Loss Definitely decreases pain in humans More effective in knee than hip It does matter in dogs! Integral part of any therapy Diet dog food - variable success 5% Slentrol - absolute component of pain control Easy Approach to Weight Reduction Calorie restriction Feed 25% less Goal- 3% weight loss in 30 days Follow up every month Prep owner for Slentrol if they are unsuccessful PPVG 2013 2
Controlled Exercise Build up muscle to support the joints Regular short exercise Rest if painful Some dogs NEED to exercise regularly NSAIDs Carprofen - Rimadyl Meloxicam Metacam OroCAM Deracoxib - Deramaxx Firocoxib - Previcox Robenacoxib Onsior Aspirin Phenylbutazone Flunixin Ketoprofen Piroxicam COX-3! LOX Leukotrienes Inflammation GI Ulceration Important Pathways Non Cox / Non Lox 100% GI Hemorrhage Within 2 doses Aspirin Carprofen (Rimadyl ) Non Cox / Non Lox (NFKB) PPVG 2013 3
Deracoxib (Deramaxx ) Meloxicam Meloxicam (Metacam ) Meloxicam (OroCAM ) Metacam vs OroCAM Metacam Honey flavored vehicle 20% vomiting as placebo Oral OroCAM Oral transmucosal 6% vomiting with placebo OroCAM (meloxicam) is bioequivalent to meloxicam oral suspension PPVG 2013 4
*Approved by FDA ** Up to a maximu DC Academy of Veterinary Medicine October 9, 2013 Firocoxib (Previcox ) Robenacoxib (Onsior ) ONSIOR (robenacoxib)... On Pe Ro m Th ho Robenacoxib Onsior 1 st approved daily NSAID for cats Perioperative use only Concentrates in areas of inflammation Limited indications Cats > 5.5 lbs (2.5 kg) > 6 months of age maximum of 3 days Acetaminophen NONsteroidal Analgesic not an NSAID COX-3! For ACUTE exacerbations of CHRONIC pain Recommend the correct formulation -Infant -Childrens -Regular strength -Extra strength -Arthritis Strength 10-15 mg/kg PO BID Max 5 days Concurrent with NSAID PPVG 2013 5
NSAID Adverse Effects(Compiled from FDA Website) Carprofen Deracoxib Meloxicam (oral) Firocoxib Vomiting Vomiting Vomiting Vomiting Anorexia Anorexia Anorexia Anorexia Inc ALT Inc ALT Lethargy Inc BUN Inc ALP Inc BUN DIarrhea Depression Lethargy Inc Creat Inc BUN Inc ALP Inc T. Bili Diarrhea Inc ALP Inc ALT Diarrhea Inc ALT Inc Creat Inc Creat Death Death Death Diarrhea Inc BUN Euth Bld diarrh Death Inc Creat Anemia Convusions Anemia Euth Inc WBC Anemia Drug Inter Anemia Drug Inter Ataxia Euth http://www.fda.gov/downloads/animalveterinary/safetyhealth/productsafetyinformation (12/31//12) NSAID Adverse Effects Drug / # Cases Rank of GI Perforation Deracoxib / 314 #21 Firocoxib #33 Meloxicam #36 Carprofen #134 NSAID Adverse Effects Drug / Cases Rank of GI Perforation Deracoxib / 276 #21 Firocoxib / 128 #21 Meloxicam #36 Carprofen #134 (Compiled from FDA Website 12/31/12) (Compiled from FDA Website 12/31/12) NSAID Adverse Effects Drug / Cases Rank of GI Perforation Deracoxib / 314 #21 Firocoxib / 124 #21 Meloxicam / 40 #45 Carprofen #134 (Compiled from FDA Website 12/31/12) NSAID Adverse Effects Drug / Cases Rank of GI Perforation Deracoxib / 276 #21 Firocoxib / 124 #21 Meloxicam / 40 #45 Carprofen / 87 #154 Metacam Package Insert: there is some evidence of enhanced drug accumulation and terminal elimination halflife prolongation when dogs are dosed for 45 days or longer. (Compiled from FDA Website 12/31/12) PPVG 2013 6
Canine Human Other Etodolac + - N + - N Carprofen +* N N + Deracoxib D D D** Meloxicam N + N + N Tepoxalin + D N Firocoxib D D D + Positive effect on cartilage - Negative effect on cartilage N No effect on cartilage D No published data * Live dog data ** Positive effect for rofecoxib in a rodent model Carprofen and Cosequin DS Carprofen increases biosynthetic activity of cartilage by 15% Carprofen + Cosequin DS -> 30% = Cosequin DS = Glucosamine, low molecular weight chondroiting + manganese.different than Dasuquin Lippiello L, et al Veterinary Therapeutics 2002; 2(3):128-135. Glucosamine LMW Chondroitin Manganese Cartilage protection Glucosamine LMW Chondroitin (less) ASU Anti-inflammatory PPVG 2013 7
Perioperative NSAIDs Preoperative NSAID Considerations IV fluids Blood pressure measurement Treatment of low blood pressure Low likelihood for bleeding Relatively routine procedure Preoperative Gas Sparing Effect Injectable but NOT oral Allows less gas anesthestic therefore less adverse effects! Injectable Metacam also but NOT approved Yamashita K, et al J Vet Med Sci. 2008 Jan;70(1):29-35. Medicolegal aspects for vets! PPVG 2013 8
NSAIDs in Comparison More efficacious than placebo A few comparisons Little difference in pain relief in the big picture NSAIDs in Comparison Individuals will respond better to one NSAID than another Pain relief Adverse responses Need 2,3,4 NSAIDs on your shelf What About Blood Testing Pre-chronic administration 14-21 days after starting most common timing for adverse effects with NSAIDs Every 6-12 months for dogs What about Tramadol/ Gabapentin? OA is an inflammatory disease Tramadol and gabapentin have ZERO anti inflammatory properties NOT as good as primary pain relievers Good adjuncts with NSAIDs Conclusions Osteoarthritis is complicated Be flexible with the treatment options Try until there is nothing else Get help before committing to euthanasia PPVG 2013 9
For Consultation 719-266-6400 800-791-2578 www.peakvets.com Further Information Other Webinars Available A Logical Approach to Chronic Pain Therapy What to Use When You Can t Use NSAIDs Out of the Box Approaches to Chronic Pain Cutting Edge Approaches to Chronic Pain Contact us at PeakVets.com Injectable Carprofen and Cats 1 mg/kg SQ Last 24-72 hrs Dose and effect well documented Do not follow with any other NSAID administration How to Request an Anesthesia or Pain Management Consultation Lascelles. J Small Anim Pract. 1995 Dec;36(12):535-41 PeakVets.com select Consultation select Consultation Form PPVG 2013 10
Fill out form completely NOTICE The use of this powerpoint presentation is authorized only during an oral presentation by Dr. James Gaynor. It is NOT to be used at any other time. It is NOT to be recorded, printed or emailed for distribution. Use of this powerpoint during an authorized presentation implies acceptance of these terms by the user US Indications: ONSIOR (robenacoxib) tablets are indicated for the control of postoperative pain and inflammation associated with orthopedic surgery, ovariohysterectomy and castration, in cats > 5.5 lbs (2.5 kg) and > 6 months of age; for up to a maximum of 3 days. ONSIOR tablets should not be used in cats that have a hypersensitivity to robenacoxib or known intolerance to NSAIDs. US Dosing The dose of ONSIOR (robenacoxib) tablets is 1mg/kg orally once daily, for a maximum of 3 days. The first dose should be administered approximately 30 minutes prior to surgery, at the same time as the preanesthetic agents are given. ONSIOR tablets may be given with or without food. PPVG 2013 11
Dosing Chart Body weight 6mg ONSIOR (robenacoxib) Tablets Formulation 6 mg flavored non-scored tablets that should not be broken 5.5 13.2 lbs (2.5-6kg) 1 whole tablet once daily 13.3-26.4 lbs (6.1-12kg) 2 whole tablets once daily With its yeast flavoring, Onsior tablets are specifically designed for cats. In Europe, Onsior tablets for cats recently won the 2010 Feline Advisory Bureau Easy to Give award. Packaging Tablets are in blisters, each individual blister card contains 3 tablets, ten cards to a carton Each blister card should be dispensed in an ONSIOR (robenacoxib) dispensing envelope containing the product insert/information for owner sheet. Clinical Pharmacology* Blood T max 0.5 hours Blood T 1/2 life of 1.7 hours Robenacoxib persists longer in the inflammatory exudate of a tissue cage model than in blood. The median robenacoxib elimination half-life in exudate was about 27 hours versus 2.5 hours for blood. *ONSIOR product insert Safety Studies * Laboratory Safety studies 21 day study up to 10X maximum dose 42 day study up to 8X maximum dose 6 month study up to 5X maximum dose PPVG 2013 12