Vet webinar- Feline handout


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Vet webinar- Feline handout

  1. 1. Compounding for FelinesVeterinary Medicine Webinar A.J. Day, PharmD, RPh Manager of Pharmacy Consulting Chris Simmons, RPh VP Creative Development
  2. 2. Disclosure AJ Day, PharmD and Chris Simmons, RPh are employed by and have a financial interest with PCCA. Goals & Objectives• Explain basic terminology for the anatomy of felines.• Discuss common problems affecting felines including hypertension, nutrition, thyroid disease, pain management, appetite and gastrointestinal issues and more.• Evaluate feline case studies requiring pharmaceutical compounding.• Describe unique compounding solutions for feline patients, including dosage forms, flavors, potential toxicities, salt forms of drugs, and QC/QA.• Describe effective ways to market a compounding pharmacy practice to a veterinarian.
  3. 3. Basic A & P• Cats are – Carnivorous • Don’t grind food – think of texture of solid dosage forms • Keen sense for rotting meat/nitrogens; will avoid – Nocturnal • Administration time of meds, esp hormones? – Nose-breathers • If panting at rest, they need to see a vet immediately • Think of particle size when compounding nebulized medicines Basic A & P• Cats have – Acidic urine (pH 5 – 7) – Acidic GI tract (pH 1 – 2) • Makes sense for digesting meats – Alkaline salivary pH (8 – 9) – A very rough tongue surface – Fast GI Transit Time (GITT) – relative to humans Unique Dosage Forms• Transdermal• Oral Treat• Oral solution/Suspension – Anhydrous (oil) – Aqueous• Powder packets• Poloxamer Gel – make from scratch, do NOT use pre-made gel• Paw Paste
  4. 4. Potential ToxicitiesBenzoates (most common = metronidazole benzoate)
  5. 5. Potential Toxicities• Metronidazole USP vs Metronidazole Benzoate BP• Benzoate form tastes better• BUT…cats cannot metabolize this salt – This becomes an issue with chronic administration accumulation• Metronidazole Benzoate is generally OK to use in cats, provided they – Are not hepatically compromised – Do not have other organ failure (particularly kidneys)• Discontinue use immediately if the cat shows signs/symptoms of CNS disturbances or marked behavioral changes Potential Toxicities• Acetaminophen• Ethylene Glycol• Pyrethrins (dog products contain 40-60% permethrin vs. cat products which contain 0.5% permethrin)• Doxycycline – Solid dosage forms (which would include powders) may cause severe, life-threatening esophageal erosions & strictures – Use Fixed Oil Base for stability – Flush (have cat swallow) with at least 6 ml of non- irritating liquid following Doxycycline administration
  6. 6. Potential Toxicities• Enrofloxacin – Fluoroquinolones as a class, potentially? – Blindness
  7. 7. Flavoring for Animals• Ask the owner – The owner has a better idea of what the animal likes/dislikes.• Give a taste test – Let the animal decide if the flavor works Flavoring for Animals Liquids Oil Soluble/Miscible Water Soluble/Miscible Grape – NEW Apple-ade Cherry - NEW Beef Beef Liver Bacon Licorice Caviar Fish Maple Ham Chicken grilled Liver Shrimp Pizza 1
  8. 8. Flavoring for Animals• Powder FlavorsApplePassion fruit AlfalfaMango BeefTangerine Chicken broth spraySweetened Flavor Powder dried MangoSweetened Flavor Powder Liver powder Passion Fruit Molasses-adeSweetened Flavor Powder Tangerine What Is the Ideal Flavor for Each Animal?• Feline: Cats usually • Flavor: Fish, liver, don’t like too much tuna, cod liver oil, sweetness and hate sardine, beef, bitter taste; animal chicken, cheese, treat; flavored paste bacon, molasses, to the paw as a peanut butter, shrimp, alternative. caviar, butter, marshmallow, etc 2
  9. 9. FlavoringFlavoring
  10. 10. FlavoringFlavoring
  11. 11. Salt Conversions• Chloramphenicol Palmitate USP vs. Chloramphenicol USP – Palmitate form tastes much better – 1.738 mg of the palmitate salt will give you 1 mg of base chloramphenicol – Both powders cost the same Salt Conversions• Metronidazole benzoate is virtually tasteless compared to metronidazole base.• Doses listed in literature are for metronidazole base.• No veterinary approved products• Metronidazole 1 milligram is equivalent to Metronidazole benzoate 1.6 milligrams. Commonly Requested Feline Compounds• Enalapril – Indicated for hypertension – Pro-drug but still works as transdermal• Cyclosporin – Indicated for immune-modulated conditions • Typically for immunosuppressive, feline asthma, inflammatory bowel disease, keratoconjunctivitis sicca• Itraconazole – Antifungal• Interferon alpha – Stimulate immune system – Antiviral indicated for treatment of FIV – Roferon-A®, Intron-A®• Ketorolac – NSAID 1
  12. 12. Mirtazapine (Remeron®)• Mirtazapine (Remeron®) – Developed for human use as an antidepressant for moderate to severe depression – Off label treatment for use in dogs and cats as an appetite stimulant and to treat nausea.• Doses – Dogs: 2.75mg/10lb orally once a day – Cats: 3.75mg orally every 48-72 hours – In the event of liver disease or kidney disease, the clearance of this drug from the body is reduced by approximately 30% so ideally the dose should be reduced. Calcitriol (1,25-Dihydroxyvitamin D3)• 60,000 ng/60ml in Almond Oil• Human Dialysis Patients• Feline dosing – To suppress secondary Hyperparathyroidism in CRF: 1.65 – 3.63 ng/kg PO qd – Less than 0.3 cents per nanogram – Less than 6 cents for average dose of 20 ng 2
  13. 13. SAMe• Trade name - Denosyl® – S-adenosylmethionine (SAMe) – Nutritional agent, Supports liver function (hepatic glutathione)• Very unstable around air and moisture• Use Fixed Oil Base Tramadol• Analgesic, post-op especially common• Tastes horrible• Transdermal is a great, proven option! – F 9764, Tramadol HCl 10 mg/0.12 mgL Topical Lipoderm [R] (AccuPen [TM]-15) – Document 98036, 98037 = study in feline ear tissue that shows absorption 3
  14. 14. Diltiazem• Indicated for hypertension and myocardial ischemia• Due to unique nature of feline GI tract, each product exhibits a unique pharmacokinetic profile – Particularly with extended release • Cardizem CD® can have once daily dosing • Dilacor-XR® requires twice daily dosing
  15. 15. Cisapride• Gastrointestinal prokinetic agent• Indicated for GI stasis• Do NOT use in human population (FDA negative list) – Potential for serious cardiac events
  16. 16. Buprenorphine - Transmucosal Absorption• From April 2010 PCCA Apothagram• Basic chemistry can heal your patients!• Speakers William Howard, DVM, and Gigi Davidson, BSPh, DICVP, discussed many important details for compounded drug delivery. One of the basic points to keep in mind is the relationship between pH of body fluids and pKa of the drug you need to deliver.• For example, feline salivary pH is quite alkaline (pH 8-9) and the pKa of buprenorphine is around 8.3, which means that the cat’s saliva will not ionize the drug.• This will increase lipophilicity, which translates to better transmucosal absorption. That is why buprenorphine is a great candidate for feline transmucosal administration, whereas other species (with less alkaline salivary pH) do not get the same benefits
  17. 17. Methimazole• Used to treat hyperthyroidism• Preferred > propylthiouracil due to side effect profile Methimazole
  18. 18. MethimazoleMethimazole
  19. 19. Start with a Plan
  20. 20. Suggeted References • Plumb’s • The Feline Patient The Answer: The Result:Debbie just stopped by yesterday and showed me the AccuPen. I cannot wait to get itin and use it for my patients. I am especially looking forward to using for my felinepatients and hospice. Its great that the caregiver doesnt have to come in contact withthe medicine!!
  21. 21. Firstline: Behaviors suggestive of postoperative pain in cats Page 1 of 3November 1, 2009Behaviors suggestive of postoperative pain in catsBy Sheilah A. Robertson, BVMS (Hons), PhD, DACVA, DECVAA, CVA, MRCVSIn people, pain is what the patient says it is. But in animals, its what we say it is. To betterrecognize acute pain in cats, observe patients for the behavioral changes described here.In the United States, pet cats outnumber pet dogs, yet our understanding and treatment of pain in cats haslagged behind that in dogs. Veterinarians consider surgical procedures in dogs and cats to be equally painfulbut treat cats perioperatively for pain less often than dogs.1 This undertreatment of pain results, in part, fromthe difficulty in recognizing and assessing pain in cats.Various pain-scoring systems have been used to assess postoperative pain. These systems measurephysiologic data (objective) or evaluate behavior (subjective) or do both. Algometers and pressure platformgait analysis are objective pain measuring tools, whereas the visual analog scale (VAS) is an example of awidely used subjective scoring system. The basic VAS used for assessing pain consists of a continuous lineanchored at either end with a description of the scales limits. For example, "no pain" would be at one end ofthe scale and "severe pain" would be at the other. The observer places a mark on the line that he or shethinks correlates to the animals degree of pain. This mark is later converted to a number by measuring thedistance of the mark from zero.Each practice should choose or design a scoring system that meets its own specific needs; finding thissystem may require some trial and error. The system chosen should be user-friendly for veterinarians andteam members. It should also be an integral part of an animals postoperative evaluation. That is, afterchecking temperature, pulse, and respiration, you should assess the patient for pain—the fourth vital sign.The scale choosen should include both noninteractive and interactive components and should rely heavilyon changes in behavior. For example, with the dynamic and interactive visual analog scale (DIVAS)—anextension of the VAS—animals are first observed undisturbed from a distance and are then approached,handled, and encouraged to walk or move around. Finally, the surgical incision and surrounding area arepalpated, and an overall assessment of pain is made.BEHAVIORS CORRELATED WITH PAINTo assess postoperative pain, evaluate a cats posture and orientation and position in the cage, facialexpression, loss of normal behaviors, and response to palpation.Posture 10/5/2010
  22. 22. Firstline: Behaviors suggestive of postoperative pain in cats Page 2 of 3 A cat that adopts a hunched posture with its head hung low, sits quietly and seeks no attention, or resents being handled is likely experiencing pain (Figure 1). In one of the few studies in which detailed behavioral ethograms (quantitative descriptions of animal behavior) have been constructed, a hunched or tucked up posture appears to be correlated with acute pain in cats after abdominal surgery.2 This observation has been corroborated by preliminary work at the University of Glasgow (Robertson SA, College of Veterinary Medicine, University of Florida. Unpublished data, 2007). Orientation in cage1. After surgery, this cats posture—hunchedwith a lowered head—indicates pain. A cat experiencing postoperative pain will often sit in the back of its cage.This subtle sign of pain will remain unrecognized if the caregiver expects to see more active signs of pain,such as pacing, agitation, or vocalizing.Facial expressionA head-down posture, with eyelids half-closed and eyes held in a slantedposition may correlate with pain (Figure 2).Loss of normal behaviors The absence of normal behaviors in a specific patient (e.g. grooming or playing with string) should prompt you to assess that patient for pain. Many cats that are fearful or stressed will stay at the back of their cages and hunch themselves up, but 2. This cats posture and facial expression are consistent with abdominal pain. if you observe these cats before and after surgery, you can detect subtle changes. For example, if pain relief is inadequate, a cat may be even more hunched than before. And instead of just being at the back of the cage, it may actively try to hide under things3. A friendly cat that played at the front of itscage before surgery hides afterward. (Figure 3), and its facial expression will be different from that before surgery.It is important to assess patients before and after surgery. Each cat is unique, and some will have alteredbehavior due to stress. The trick is to pick up small changes for that specific cat that can be attributed topain. However, stress and fear are aversive emotions that can worsen pain, so they should not bedismissed. Instead, give some thought as to how to also relieve stress and fear, such as by providing a cat-only area, boxes for cats to hide in, and favorite toys and blankets from home or by using a synthetic felinepheromone (Feliway—Ceva Santé Animale).Response to palpationWound palpation is an important component of pain assessment; youshould be able to apply gentle pressure to a surgical wound without a catsflinching or turning to bite (Figure 4). One of the many commonly reportedproblems after onychectomy is excessive licking and chewing of the feet.3Cats will often shake their paws and try to bite at their feet if bandages areplaced on onychectomy wounds. These behaviors could indicatepostoperative pain, pain from an incorrectly placed bandage, or a dislike ofthe bandage, so it is important to differentiate among these.HOW OFTEN SHOULD PAIN BE ASSESSED? 4. Palpating a bone graft site to assess for pain.The patients health status, the extent of the surgery or injuries, and theanticipated duration of effect of the analgesic drugs administered determine the frequency and interval ofevaluations. If a cat, for example, is resting comfortably (normal posture and facial expression) afterpostoperative buprenorphine administration, it may not need to be reevaluated for two to four hours. Allow 10/5/2010
  23. 23. Firstline: Behaviors suggestive of postoperative pain in cats Page 3 of 3animals to sleep after analgesic therapy. Vital signs can often be checked without unduly disturbing asleeping animal. In general, do not wake an animal to check its pain status; however, the patient should stillreceive scheduled analgesics.Continuous, undisturbed observations coupled with periodic interactive observations (e.g. palpating thewound) are likely to provide more information than occasionally observing the animal through the cage door.Unfortunately, continuous observations are not practical for most clinical situations. But the more frequentthe observations, the more likely that subtle signs of pain will be detected.Sheilah A. Robertson, BVMS (Hons), PhD, DACVA, DECVA, CVA, MRCVSSection of Anesthesia and Pain ManagementDepartment of Large Animal Clinical SciencesCollege of Veterinary MedicineUniversity of FloridaGainesville, FL 32610REFERENCES1. Lascelles B, Capner C, Waterman-Pearson AE. A survey of current British veterinary attitudes to peri-operative analgesia for cats and small mammals. Vet Rec 1999;145:601-604.2. Waran N, Best L, Williams V, et al. A preliminary study of behaviour-based indicators of pain in cats. AnimWelfare 2007; 16(S):105-108.3. Patronek GJ, Assessment of claims of short- and long-term complications associated with onychectomy incats. J Am Vet Med Assoc 2001;219(7):932-937.1. After surgery, this cats posture—hunched with a lowered head—indicates pain.2. This cats posture and facial expression are consistent with abdominal pain.3. A friendly cat that played at the front of its cage before surgery hides afterward.4. Palpating a bone graft site to assess for pain. 2009 Advanstar Communications Inc.. Permission granted for up to 5 copies. All rights reserved. You may forward this article or get additional permissions by typing into any web browser. Advanstar Communications Inc. and Firstline logos are registered trademarks of Advanstar Communications Inc.The iCopyright logo is a registered trademark of iCopyright, Inc. 10/5/2010
  24. 24. PetMD Newsletter Page 1 of 4A. J. DayFrom: Fully Vetted []Sent: Tuesday, October 05, 2010 12:17 AMTo: A. J. DaySubject: Yeowch! Hissss! On the Hows, Whys and Stresses of Modern Feline Pain ControlAre you having trouble viewing this e-mail? View it online: Click here | Unsubscribe Yeowch! Hissss! On the Hows, Whys and Stresses of Modern Feline Pain Control OCTOBER 05 Analgesia, we call it. It’s the absence of pain. The holy grail for so many conditions. But it’s not enough not to feel pain. It’s got to be safe, comfortable, appropriate, reliable and effective. A tall order, especially for cats. Why so? As far as drugs are concerned, cats have historically been treated like small dogs. And dogs, in turn, as small humans. Is it any wonder we’ve got so few drugs that really work well for our feline companions? Pain relief, in particular, is a surprisingly frustrating issue in feline medicine for a couple of reasons: 1. Pain in cats is a tough thing to assess. Their silent stoicism, while admirable, doesn’t exactly lend itself well to ready interpretation in the event of pain. Even severe pain often goes undiagnosed in cats. How do we know? Good question. Here’s an article that addresses the behavioral characteristics we’ve now come to associate with post-operative pain in felids. We’re getting smarter on this issue. 2. The presence of few reasonable alternatives to long term pain control in cats typically means NO long term pain control in cats. So while severe acute or post-op pain can be managed with heavy duty narcotics (think, strong opiates like hydromorphone), there’s little available to treat long term illnesses10/5/2010
  25. 25. PetMD Newsletter Page 2 of 4 (think, osteoarthritis, a very common condition in cats). Still, I’m proud to report that pain relief in cats has come a long way over the last couple of decades. Here’s an excerpt from a 2003 World Small Animal Veterinary Association meeting lecture on the subject to illustrate the [newly enlightened] motivation for feline analgesia: Pain interferes with healing and can, in fact, make the disease process more harmful. Hypotension, gastrointestinal injury, hypothermia and immunosuppression may all occur as negative physiologic results of pain. The body, in response to the trauma, releases all sorts of leukotrienes: some of these are helpful, but many aggravate the problem. As a result, if a patient has, or is going to have tissue trauma, analgesic therapy is required. Makes lots of sense, right? It’s more than just the humane approach, it also happens to be the more effective approach when it comes to healing. Above all do no harm? It’s now clear that to deny a patient a pain control drug on the basis of "safety" may not make so much sense if the patient’s pain score is significant. The impact on the patient’s long term well being is now considered in a more "holistic" manner. And that’s undoubtedly a good thing. But the sad truth remains that few drugs are available for certain kinds of pain. While opiates (morphine-like drugs) are eminently useful, they’re only helpful for relatively short term pain control or hospice care. With some exceptions, cats are just too whacked out by these meds to live normal lives. As I said, there are some exceptions. Transdermal fentanyl patches, tramadol and, butorphanol are all opiates that are used for acute and sub-acute pain control. (The difference? Acute: think, post-op or trauma. Sub-acute: think, a flare-up of arthritis.) For chronic pain control, these drugs are typically considered just too drowse-inducing. But not for all. Sometimes it’s worth a try. For dogs we’ve got lots of pain meds for long term pain. Osteoarthritic dogs are living longer than ever before, now that they’ve got great drugs to control their chronic discomfort. NSAIDs (non-steroidal anti-inflammatory drugs) are our go-to meds for this purpose. And while they’ve got plenty of side-effects, the vast majority of dogs will safely enjoy their benefits for years without them. No drowsiness. No vomiting or diarrhea. No liver or kidney disease. Not so with felines. Gastrointestinal and renal side effects (think, kidney failure) are much more common with NSAIDs when used in cats. Though we will tap these meds for their anti-inflammatory effects, we tend to do so only in well hydrated cats whose renal status is demonstrably normal ... and only for one dose. Metacam (meloxicam) is one such drug whose one-dose injectable formulation that is approved by the FDA for use in cats. It’s great for spays and neuters and other procedures we undertake in young, healthy cats …10/5/2010
  26. 26. PetMD Newsletter Page 3 of 4 … not so much for those who suffer chronic pain, as in the case of arthritis, or slow- moving cancers that require some anti-inflammatory palliation. In fact, a recent FDA labeling advisory cautioned us strongly against the use of oral Metacam for long-term care. It’s just too toxic to the kidneys. Here are other NSAIDs that are sometimes used instead: Aspirin Ketoprofen Ketorolac tromethamine Carprofen (Rimadyl) But I approach these with caution, and I suggest you do the same. Nonetheless, I’ve used them all to great effect in cats. After all, there is no "one size fits all" in medicine. Even less so when it comes to controlling pain, and nowhere is this more true than when trying hard to control pain in cats. In the absence of approved drugs, sometimes cautious creativity is the only key. Dr. Patty Khuly Pic of the day: "Cat on the water" by me and my CatPaint app10/5/2010
  27. 27. PetMD Newsletter Page 4 of 4 All opinions are welcome on FullyVetted. So bark away... I dont bite. ©1999-2010 PetMD Ventures, Ltd. All Rights Reserved | Unsubscribe | www.petmd.com10/5/2010
  28. 28. Drug shortages and recalls –– How they may be compromisingyour pets’ careNOV 03, 2010I have four words for you: frustrating, confusing, scary,and stressful. Thats what happens when the drugs youneed aren’t available for your patients. And it’s been abig problem for the past few months as physicians andveterinarians struggle to make do without the crucialdrugs that are used for anesthesia, seizure control, andpain management.According to The Wall Street Journal, the trouble poses more than a merechallenge for the clinicians involved. According to a recent study, patient safety isclearly being compromised: Pharmacists and other health-care practitioners say ongoing drug shortages are accompanied by difficulties including a lack of available information, trouble finding alternative medications, and deadly errors, according to a survey conducted by the nonprofit Institute for Safe Medication Practices.And here are some of their findings:  A variety of difficulties associated with drug shortages, including a lack of information about a shortage’s duration (85% of respondents said this was frequently or always a problem during the past year), a lack of advanced warning from manufacturers or the FDA (84%), difficulty finding a good alternative (80%), internal hoarding (58%), and physician anger towards pharmacists, nurses or hospital in response to a shortage (55%).  Some 64% of respondents reported there was a risk of adverse patient outcomes associated with a drug shortage, and one in three said their facility had a shortage-related "near miss." One in four reported errors, and one in five reported adverse patient outcomes.  Most of the drugs involved in the shortages are so-called "high alert medications," which have the highest risk of injury if misused. Those 11-03-2010 Page 1 of 3
  29. 29. include the blood thinner heparin, chemotherapy drugs, morphine, epinephrine and the neuromuscular blocking agents used in surgery.Troublesome, right? To say the least.How scary is this? This scary: I believe it contributed to the death of one of mypatients last week. Here’s the story …Floreana, Flor, is a toad huntress. I’ve told her stories here many times before.That’s partly because she has been our worst serial offender (you know, somedogs will learn to stay away from the creatures that do them wrong, while others— typically terriers — will keep going back for more), but it’s also because shewas my parents’ dog.Last Thursday I received a call: Flor got another toad and this time it was verybad. The housekeeper had no car (my parents were out of the country), so Idropped everything and picked her up. She was seizuring on my lap as we droveto my place of work.At this point it was already on my mind: We have no propofol! And the last timeshe received such a big dose of toad toxin (secreted onto the skin), the onlymedication that had any ability to quiet her seizure activity was propofol (yes, thesame drug that killed Michael Jackson).So when it became clear that the third dose of Valium and the second dose ofphenobarbital were achieving a less-than-desired effect, I decided to wrap her upand take her to the specialty hospital for better drugs than I had on hand. By thenit was too late. She vomited and subsequently suffered a respiratory arrest andprofound bradycardia (very slow heart rate).CPR. Drugs. Oxygen. Recovery. And then a mad dash to the specialty hospitalensued … only to discover that they also didnt have propofol on hand.She continued to seizure through the night, developing aspiration pneumonia(after all that vomiting I knew it was coming) and severe arrhythmias (toad toxinis a powerful cardiotoxin, too), so that shed have to spend the night in an oxygencage with a continuous EKG and constant attention.Honestly, I considered euthanizing her at this point. My parents wouldn’t haveblamed me, but the boyfriend urged me to give her a chance. And by the nextmorning she did look better. She even sat up when I tried to leave. But she wasstill horribly groggy from all the drugs.So it was that I took her home that following night, wobbly and urpy as she was.Thinking she was out of the woods and would be more comfy with me, I set her 11-03-2010 Page 2 of 3
  30. 30. to sleep in a crate next to Slumdog — only a few short inches from my bed.At 3 a.m., Slumdog awoke me with his piteous whining. Flor’s breathing hadbecome dangerously shallow. Though still curled into a comfy little ball, herpulses were imperceptible, her heart rate slow as a horse’s. She was dying.Right there and then I told her she would be OK, and that she was loved. Andshe went.Sure, the lack of propofol, which had helped her so quickly in the past, may nothave had anything to do with it. Yet the fact that neither hospital had the drugavailable may well have been the deciding factor. In light of her previoussuccessful recovery with the drug, can you blame me for wondering?Then there’s this less obvious, less personal issue to consider: Does the fact thatphysicians and veterinarians have to change their anesthetic and pain controlprotocols so suddenly factor into medical errors? Of course it does!Imagine your place of work suddenly altering its basic practices from one week tothe next. Wouldnt some errors be expected? It’s no different in medicine, onlythe stakes are changed.Yet here’s the thing: Word of this problem has only recently started trickling downto patients and pet owners. Though it’s been frustrating for me, I haven’t thoughtabout it in terms of my patients’ care until this episode.But as with so many profoundly important issues, sometimes things have to hityou broadside — and hard — before they make their true impact known.Dr. Patty Khuly 11-03-2010 Page 3 of 3
  31. 31. Finding the cure for drug delivery ills in veterinary medicineNOV 12, 2010Getting pets to pop their pills is a huge issue. So huge, in fact, that a drugs delivery method ofteninforms veterinary decision making, sometimes more than the drug’s other properties. Sideeffects, for example, matter far less when the alternative is no treatment at all. The "drug delivery" issue is getting more play recently, what with the growing list of drugs werenow prescribing for our patients. This, coupled with issues of accessibility, availability and pricefuels a sizable niche industry created specifically to meet the needs of pets who won’t — or can’t —tolerate drugs and supplements designed to treat and/or prevent their ills. After all, pets can bepicky about what we put in their mouths or mix into their meals. And you would be too if youdidn’t understand why you needed to take that multivitamin, glucosamine, or fatty acid gelcap ona daily basis.This is why compounding pharmacies exist. For the modern veterinarian, being able to access ourfavorite compounding pharmacy’s expertise in the formulation of new versions of the same-olddrugs that line our shelves is a boon to our profession. But few veterinary clients fully understandwhat it is our compounding pharmacies do for us. To help unmuddy the waters, heres a brief listof how these places help us bring better care to our patients:1. Delivery, delivery, deliveryAs for the real estate and location truism, so too does the veterinary drug industry rely on the "D"word.As a pet owner, you know how it is. We try everything to get meds into our pets. Some of us hideour pets’ pills in foodstuffs or treats: cream cheese, peanut butter (chunky works best, IMO), ham,chicken breast, pill pockets, filet mignon …As veterinarians, we also do whatever it takes to get the meds into our patients. And, yes,sometimes it takes a lot of trial and error.More than anything else, what we all want is a cure that requires no daily discomfort, wriggling,stressing, in-the-towel-burrito-ing or the potential for biting, scratching or generalized inter-species strife. This is where the compounding pharmacy comes in with their ability to turn...a. chalky to chewyb. bitter to tastyc. oral to topicalYes, topical. So it is that sometimes compounding pharmacies can manage the seeminglyimpossible.
  32. 32. 2. AvailabilityIs your drug on back-order? Discontinued? Supply chain hassles? Never fear. You dont have tocompromise your pets care if you can find a compounding pharmacy willing to make it for you.That’s what lots of veterinarians are doing now with drugs like ophthalmic cyclosporine. Whenthe supply goes dry, compounding pharmacies production ramps up.3. SafetyIm not big on doing chemotherapy in-house. Id always rather send my patients to the specialistswhere the required drugs are more safely housed. Yet I have plenty of clients who prefer that Iadminister these drugs personally, citing their pets greater comfort in a place they already knowwell.This is where compounding pharmacies come in. Theyll ship pre-measured doses to me, alreadyin their syringes and ready to inject. Safer for me, my staff, and my patients.4. ConvenienceWant your meds shipped directly to you? Your vet can arrange for that. Pharmacies will shipmonthly, on cue, if thats what you need.It’s hard to quantify, but we suspect that non-compliance resulting from an inability to administermeds is among the biggest drivers of poor clinical outcomes in veterinary medicine (if not thebiggest). Then there’s the issue of antibiotic resistance to deal with when antibiotics are started.The pill is found under the sofa … started again … spit out again … repeat …Given this setup, is it any wonder that compounding pharmacies are finding veterinary medicinea lucrative place to invest their time and money?But the take-home message here is not about building new businesses with our pet-dedicateddollars; it’s more about the willingness to meet our pets’ needs by making medications workthrough any means necessary.Trouble is, clients don’t always inform us when the meds aren’t going down the gullet. Not everypet owner is educated enough about drug choices to know they can ask us for alternatives. And,truth be told, we don’t always pointedly ask whether an unhappy outcome might be the result ofpoor drug compliance. (It just seems kind of rude to ask, you know?)However, now that you’ve read this, you know what you need to do. When you come across a tidystack of tablets your dog has hidden under the bed, or your cat drools for hours after taking herpill, consider asking for another method. No one needs to suffer when so many other options areavailable.Dr. Patty Khuly
  33. 33. 2008 ACVSc College Science Week HOW COMPOUNDING PHARMACISTS CAN MAKE OUR JOB EASIER, IMPROVE CLIENT PERCEPTIONS AND THEREBY HELP OUR PATIENTS Professor Richard Malik DVSc DipVetAn MVetClinStud PhD FACVSc FASM Post Graduate Foundation of Veterinary Science and Faculty of Veterinary Science, Building B22, The University of Sydney, NSW 2006 Many years ago, I thought I had little need for compounding pharmacists. I had learned or learnt over the years how to cuttablets into portions (with scalpel blades and pill cutters), use pill crushers, open capsules, reformulate them into size 00gelatin capsules (often containing more than 1 drug) and present them for administration to my patients. I had the time, and I also had the luxury of working in a Veterinary Teaching Hospital where (somewhat) willing helpers(students, nurses and even the odd resident) would help with this task. I was firmly of the view that nearly all owners couldbe taught how to successfully give capsules or tablets to their cat, without resorting to flavoured vehicles, while transdermalformulations held no great attraction for me, especially in relation to the management of hyperthyroidism (where I firmlybelieve radio-iodine is the way to go). Over the last half dozen years, however, I have come to work more and more closely with compounding pharmacists, andthe more I work with them, the more ways I can see that they greatly contribute to positive patient outcomes by improvingthe quality of veterinary care. Many of the points I will make below will be compelling to the majority of readers. Some may take exception to the oddpoint, depending on their perspective, and experiences. Regulatory authorities may not be happy with all the suggestions I amabout to make, but I am not afraid of providing a dissenting view. My brief is simple – I am an advocate for the client andtheir patients. The points I will make, lend themselves to presentation as bullet points, using pertinent examples, to illustrate situationswhere compounders have something special to offer. In closing this introduction, I want to emphasise the value ofdeveloping a special relationship with one or two compounding pharmacists. They might be geographically convenient,or the least expensive, or appear to have the greatest interest in helping veterinary patients. But for whatever reason, if youforge a relationship with one or two pharmacies, you are likely to receive reliable, prompt, courteous and individual service,which will bode well for you and your clients.1. Reformulating drugs (typically human drugs) into doses appropriate to smaller patients. A common and important example is in relation to management of cats with hypertension with the human drugamlodipine, whose dose is typically somewhere between 1/8 to ¼ of a 2 mg tablet of Norvas® once or twice daily – this ishard to achieve (without losing quite a deal of an expensive drug), so getting the material in the correct dose into gelatincapsules is very helpful when treating renal hypertension in elderly cats. The gelatin capsule is helpful in itself, as the drug isbitter. As an aside, a small amount of butter or margarine helps gelatin capsules go down the throat of cats, and rub a bit onthe end of their nose to make sure they keep swallowing. In exotics practice (ferrets, birds and the like) – the reformulation of drugs is even more compelling, especially if they canbe suspended in a tasty vehicles to improve compliance. For birds and ferrets, there are too many examples to list. Gels andsuspensions both have their place. In small animal oncology, there is a problem reformulating cytotoxic drugs in the practice because of O.H.S. issues, andalso because these drugs are not evenly dispersed within coated tablets. Again, compounding pharmacists can come to therescue, e.g. getting correct doses (typically 25-30 mg) of cyclophosphamide for treating small/thin cats with lymphoma (a 50mg enteric coated tablet is generally suitable for cats weighing between 4 and 6 kg, as the dose is generally 10 mg/kg). There is a long list of drugs that we routinely reformulate for feline practice including the anti-infectives moxifloxacin,clarithromycin, flucytosine, clofazimine and fluconazole. As well as likely improving compliance, without doubt there isan increase in the precision of dosing. The cost of having this done for a lengthy course of therapy is trivial. Importantly, by providing a compounding pharmacist with a prescription for the drug and how it should be reformulated,the owner often gets the benefit of the cheaper wholesale rate available to pharmacists, and critically as most compounderswork on MUCH SMALLER MARGINS than the average veterinary practice, the owner ends up paying far less. This mightbe perceived to be bad from your boss’s perspective, but it’s very good for the client, who can then pay for your expertise andnot for maintaining your practice pharmacy with esoteric drugs with a finite limited shelf-life. And if your boss is smart,he/she will come around! Finally, compounders are usually fast and efficient. If you e-mail or FAX them a prescription, thedrug is generally in the post on the way to the client within 24-48 hours. That’s good service! 2. Creating completely novel formulations for special purposes. For example, treating mycotic keratitis in horses can be problematic as the organisms involved may be resistant to manyavailable formulations, while certain human drugs e.g. natamycin ophthalmic suspension may be difficult to obtain because Small Animal Medicine Chapter 36
  34. 34. 2008 ACVSc College Science Weekof regulatory authorities. Compounding pharmacists can extemporaneously make up ophthalmic formulation of drugs such asitraconazole, posaconazole, voriconazole and amphotericin B. That gives us quite a range of agents capable of being used ineither ophthalmic drops or ointments. Dr Andrew Turner (and others) have used such formulations with great success intreating even advanced fungal infections of the equine cornea. Some years ago I had a topical ointment made up consisting of petroleum jelly containing rifampicin and clofazimine fortreating canine leproid granuloma lesions topically, without resorting to systemic therapy. It seemed to help in severalrefractory cases, although it was a messy formulation which stained the skin of both the patient and the client (who weretherefore advised to wear gloves). The emerging infectious disease feline trichomoniasis is best treated using a drug called ronidazole. Colleagues at NorthCarolina Sate University have suggested that the best way for this to be given, so as to minimise the possibility ofneurotoxicity, is by purchasing analytically pure drug and formulating a specific colon-targeted delivery using a guar gumformulation. This can be arranged by diligent compounders. No doubt you can think of a number of special situations where you would have liked to have a suitable formulationavailable, e.g. treating some nasty resistant ear infection in atopic dogs. 3. Getting drugs that are of proven benefit for treating companion animal diseases that have not yet become, orwill likely never become, commercially available in Australia. By far the best example of this scenario is the drug trilostane, which has a number of advantages over mitotane fortreating pituitary dependent hyperadrenocorticism. Compounding pharmacists are generally expert is locating RELIABLEmanufactures of drugs like this, generally from China or India, from internationally accredited human laboratories. They aremuch better at filling in the appropriate paper work (import permits and the like), and further can EXACTLY tailor the doseof the agent for an individual patient. Ironically, this has meant that trilostane for veterinary use in Australia is less expensive than in countries where itis commercially available. Certainly it has opened up this treatment option for a whole range of general veterinarypractitioners and their clients that might not otherwise be able to afford treatment provided by a specialist referral centre. Andafter all, Cushing’s disease is as common as dirt, so it’s nice for us to all be able to effectively manage these cases. Although there may be concerns about the quality and purity of drugs sourced in this manner, my experiences have beenuniformly favourable, and in the case of trilostane, the effect of the drug is always TITRATRED for the individual patientusing sequential Synactin response testing. If bioavailability is a bit different from the original manufacturer, it usually willjust mean you will use a consistently different dose, with which you will rapidly become familiar as you treat more and morecases. Another pertinent example is the oral hyperglycaemic drug diazoxide, which is of great benefit in the long term palliationof dogs and ferrets with metastatic insulinoma. This drug is very difficult to obtain (and very expensive) in its originalformulation from its manufacturer, as it is not licensed for this indication in Australia. Compounders can generally obtain it,although there is often a wide variation in price according to where they source it from, how much they buy (much cheaper ifthey buy in large aliquots), and what their margin and handling costs are. A further example is cisapride – a prokinetic agent thought to be useful in managing early cases of megacolon in cats andpost-operative ileus in horses. It was taken off the human market as the result of a rare cardiac phenomenon, which has beenencountered in veterinary patients. This drug is available and generally inexpensive from many compounders. Unfortunatelyit has not proven to be very helpful for most megacolon cats in my hands. Others may have different experiences. A somewhat different situation is applicable to the drug phenytoin. The commercial formulation (Dilantin®) was shownmany years ago to be ineffective for managing canine seizure disorders because of rapid metabolism through hepaticbiotransformation. However, veterinarians in the Netherlands have developed sustained-release formulation of phenytoin thathas shown to be of substantial efficacy in managing many types of canine seizure disorders. This type of formulation can bemade up by switched on compounders in Australia like Bova Pharmacy1. Occasionally, medications of proven benefit become temporarily unavailable in Australia due to changes in policy ofnational and multinational drug manufacturers. For example, the sedative/hypnotic/anaesthetic oxybarbituratepentobarbitone, which had been available for many years as a solution in propylene glycol (Nembutal®), was discontinuedby Abbotts who had originally manufactured the agent. Until a local manufacturer took up commercial production ofpentobarbitone, it could be obtained by a single compounder (Stenlake Compounding) who had gone to some considerabletrouble to ensure safe production of a sterile formulation for veterinary use (thereby circumventing the practice of diluting“euthanasia solution” to administer the agent for certain indications, e.g. treatment of 1080 poisoning in working dogs in thecountry).1 BOVA CHEMIST, Shop 1 304-318 The Kingsway CARINGBAH NSW 2229 Ph: 02 9525 3044 Small Animal Medicine Chapter 37
  35. 35. 2008 ACVSc College Science Week 4. Obtaining generic drugs not currently available in Australia, except in their original (expensive) humanformulations. For example, in most situations the triazole drug fluconazole is the drug of choice for treating feline cryptococcosis,being better tolerated than itraconazole (no hepatotoxicity) and somewhat more effective, based on the recent paper byCarolyn O’Brien et al in the Australian Veterinary Journal. However, the cost of treating an average cat with Diflucan®, theoriginal formulation from Pfizer, is in excess of $120 per week wholesale (to the client without mark up).This is clearlybeyond the reach of most clients, and accordingly for many years we advocated itraconazole as the drug-of-first-choice,largely on the basis of cost. It is now possible to get fluconazole manufactured in India (where it is used extensively in humanpatients) that permits cost effective treatment of virtually all cats with sinonasal cryptococcosis using fluconazole. We havemeasured blood concentrations in cats and dogs during treatment using the high performance liquid chromatographyavailable at St Vincent’s hospital, and in all cases effective blood concentrations s were obtained using fluconazole sourcedfrom reputable manufacturers in India. This is good news for cats and dogs with cryptococcosis! Indeed, it is likely that evenif a veterinary manufacturer would take on licensing and marketing of this drug, it would not be available at the sameexcellent price as it is through reputable compounders. Another pertinent example is ondansetron. This is one of a new highly effective class of centrally acting anti-emeticdrugs, the central 5HT-3 (serotonin) receptor antagonists. The cost of this drug as sold by its original manufacturer is soexpensive that its use is virtually precluded in small animal practice. The availability of compounded ondansetron capsules ata substantially reduced cost makes their routine use affordable in a variety of clinical situations – including pancreatitis cases(after the first day or so, when injectable Anzemet® is still a better option), Parvo virus enteritis, to prevent motion sicknesswhen travelling and to prevent nausea, anorexia and vomiting associated with cytotoxic drugs such as carboplatinum anddoxorubicin. Indeed, ondansetron is now so inexpensive that I believe it should be used routinely in all cats and dogsreceiving chemotherapy for cancer, and you could make a case for its routine use in elective surgery cases to prevent nauseaand vomiting in the post-operative period. A further example is the immunomodulator cyclosporine. Although this is available as a veterinary formulation(Atopica®), the cost of this formulation is prohibitive for many owners. Utilisation of extemporaneously formulationsindividually made up for a given patient can provide a cost effective solution in many instances. Using this approach, it isprudent to use therapeutic monitoring of cyclosporine blood levels, to ensure bioavailability in individual patients is similarto the original formulation.5. Obtaining drugs that are very difficult to obtain through regular channels. The drug clofazimine, for instance, is very difficult to get because the World Health Organisation. has attempted tolargely restrict its use to treatment of leprosy in developing nations. This makes it very difficult to obtain, which isunfortunate if you are trying to treat unusual mycobacterial infections in cats (mainly feline leprosy syndromes and theoccasional refractory rapidly growing mycobacterium) where this drug is of proven efficacy and inexpensive. Again,compounders can really make a big difference here, although probably it is in everybody’s interest if one compoundersupplies the drug, so they can buy it in large and therefore cost effective quantities, thereby maintaining low cost to allclients. This also circumvents the need for the veterinarian to prepare special submissions to the AVPMA, and alliedadministrative costs. Similar considerations apply to the drug 5-flucytosine, a potent antifungal agent that is especially effective in themanagement of cryptococcosis in cats (and to a lesser extent dogs – due to a predictable drug eruption which limits its use inthis species); this agent can be extremely difficult to obtain through regular channels, but at least one compoundingpharmacist (Bova) has a reliable stockpile. Another example is the drug thalidomide. This drug – which is both a potent tumour necrosis factor-alpha inhibitor andan inhibitor of angiogenesis, has an evidence-based role in the management of some inflammatory diseases of cats(lymphocytic plasmacytic gingivostomatitis and FIP) and the treatment of certain tumours. A further example is the anti-viral agent trifluorothymidine. This agent is said my many veterinary authorities to be themost potent drug available for treatment of Herpes virus keratitis in cats, but is not commercially available and is made upcontemporaneously by human eye hospitals on a need-by-need basis. The availability of sterile appropriately stabilisedsolutions of this agent are of great benefit in the timely management of rapidly- developing dendritic corneal ulcers in the cat. 6. Use of “polypills” i.e. fixed dose combinations of drugs used to treat a single disease condition. There are a number of situations in which optimal therapy for our patients involves the simultaneous administration ofseveral drugs concurrently. One example may be treatment of Helicobacter-related gastritis, when it is desirable to use acombination such as amoxicillin/metronidazole/bismuth or clarithrlomycin/omeprazole for several weeks to clear the Small Animal Medicine Chapter 38
  36. 36. 2008 ACVSc College Science Weekinfection. Another may be the treatment of certain refractory mycobacterial infections (M avium, M genavense, M ulcerans,feline leprosy syndromes) where two or three drug combinations e.g. rifampicin/clarithromycin/ moxifloxacin may berequired for the initial period of therapy. In these instances, ESPECIALLY for feline patients, having all the medications in asingle gelatin capsule is of GREAT BENEFIT! A case in point which I am currently working on related to management of congestive heart failure due to mitralinsufficiency. In my view, there is currently sufficient evidence that most dogs will benefit from the simultaneousadministration of three or four drugs – the inodilator pimobendan, a long acting ACE inhibitor (e.g. enalopril), furosemideand spironolactone. Currently many clients are “forced” to choose between furosemide/pimobendan andfurosemide/veterinary ACE inhibitor (typically Fortekor®) based on the high cost of drugs. However, as all the “best” drugs(except pimobendan) are out of patent, it is easy to come up with a fixed dose combination of FOUR drugs that can be giventwice daily (on am empty stomach) to perhaps 70% of dogs with symptomatic mitral regurgitation. This should improveefficacy, compliance and reduce cost for many owners. Stated another way, the great majority of dogs may benefit from fixeddose combination marginally more expensive than pimobendan monotherapy and easy to give twice daily. This article is really a work in progress. I am sure many readers will have different pertinent examples of howCompounding Pharmacists can help them do a better job. I encourage them to SHARE THESE EXPERIENCES withme and your colleagues through forums such as the Control & Therapy Series of the Post Graduate Foundation, or bywriting letters to the editor of The Veterinarian or Australian Veterinary Journal. Small Animal Medicine Chapter 39
  37. 37. Vets view: Pet medications dont have tobe a bitter pill ■ VIEWS FROM A VETAugust 5, 2010By Patty Khuly, Special for USA TODAYNever underestimate the gag reflex of a cat or the ability ofa fleshy-faced dog to hide a pill deep within the cavernousfolds of his oral cavity before spitting it out a few minutesafter hes out of your sight. Pets are amazing that way —amazingly frustrating, that is.Delivering drugs to pets is a huge issue in veterinarymedicine. So big that it fuels a sizable niche industrycreated specifically to meet the needs of pets who cant orwont tolerate drugs and supplements designed to treatand/or prevent their ills. Which is why its nearly every daywe veterinarians access our favorite compoundingpharmacys expertise in the formulation of new versions ofthe same old drugs that line our shelves.Yes, just like us (our kids, especially), pets can be picky Patty Khuly, a small-animal veterinarian inabout what we put in their mouths or mix into their meals. Miami, is author of FullyVetted, a blog on petYou would be, too, if you didnt understand why you needed health at She also writes weekly forto take that niacin, glucosamine or Centrum Silver on a the Miami Herald and monthly for Veterinarydaily basis. Practice News. Her USA TODAY guest column appears each Friday.I hate taking pills, too. The physical act of downing the trio Khuly lives in South Miami with her son, Max,of tablets I take every day is an uncomfortable, abhorrent dogs Vincent and Slumdog, goats Poppy andone for reasons I cant even explain. I just dont enjoy Tulip, and a backyard flock of chickens.downing a glug of chalky solids. So why would our pets?Some of us hide our pets pills in food or treats: cream cheese, peanut butter (chunky worksbest, IMO), ham, chicken breast, pill pockets, filet mignon. In vet school, I even spent timedevising a protocol for getting fish to take an antibiotic called enrofloxacin (I soaked brineshrimp in 100mg/ml solution for three to five minutes before feeding them). As veterinarians,we do whatever it takes to get the meds into our patients. And, yes, sometimes it takes a lotof trial and error. 08-05-10Page 1 of 2
  38. 38. Others switch to liquid meds (readily available through compounding pharmacies) hopingthese will make all the difference. And sometimes they do. But more than anything else, whatwe all want is a cure that requires no daily discomfort, wriggling, stressing, in-the-towel-burrito-ing or the potential for biting, scratching or generalized inter-species strife.Its for this reason we seek drug delivery methods that require once-daily dosing instead oftwo to three doses per day. Its also why Pfizers new injectable antibiotic, Convenia, makesus jump for joy (one painless subcutaneous shot equals two weeks of antibiotic coverage).Its another reason we believe certain surgical or even radioactive treatments may best alifetime of pills —— expensive and aggressive though we know them to be. Its why topicalmedications are so revered when theyre found to work as effectively as the oral or injectableversions.And its what keeps compounding pharmacies in business. In case youve never heard ofthese places, these are pharmacies that serve the veterinary profession primarily by grantinghard-to-administer drugs greater approachability. Yes, its a niche industry. But its one that(despite all the hand-wringing that goes on in the pharmacy industry) is highly profitable …and growing.Why such a big deal?Its hard to quantify, but we suspect that drug non-compliance as a result of an inability toadminister meds is among the biggest drivers of poor clinical outcomes in veterinarymedicine (if not the biggest). Then theres the issue of antibiotic resistance to deal with whenantibiotics are started, found under the sofa, started again, spit out, repeat.Given this setup, is it any wonder compounding pharmacies are finding veterinary medicine alucrative place to invest their time and money?But the take-home message here is not about building new businesses with our pet-dedicated dollars. Its more about meeting the needs of our pets with the willingness to makemedications work through any means necessary.Trouble is, clients dont always inform us when the meds arent going down the gullet. Notevery pet owner is educated enough about drug choices to know they can ask us foralternatives. And, truth be told, we dont always pointedly ask whether an unhappy outcomemight be the result of poor drug compliance. (It just seems kind of rude to ask, you know?)Now that youve read this, however, you know what you need to do. When your dog hides atidy stack of tablets under the bed and your cat drools for hours after her pill, consider askingfor another method. No one need suffer when so many other options are available. 08-05-10Page 2 of 2