Sunday, March 23, 2014

What "Does Lowest Effective Dose" Mean?

Sam, cruciate ligament rupture repair
There are a few key terms that veterinarians use daily that we mistakenly presume our clients are comfortable with and understand. One term that I use daily is "lowest effective dose" or LED. I thought it would be helpful if I explained what this term means, and why we use it. I use it most commonly when I am talking about NSAID's, or non-steroidal anti-inflammatory drugs. All licensed NSAID's have a label statement on LED, and label mandate is for LED.

We use this term when we are trying to customize a drug dose for a specific patient. I use it when I am treating a pet with a drug that has either a narrow therapeutic index, and/or for a condition that either will likely need long term management, and/or a condition that I expect to change with time and therapy.

Another cruciate ligament rupture repair.
I rely heavily on NSAID's with orthopedic surgeries.
NSAID's are useful for a whole host of diseases and ailments, but because they are so tightly protein bound they have a narrow therapeutic index. This narrow therapeutic index means that your pet needs to be given the exact amount prescribed, or less. Over dosing, even by a little bit, by giving a higher dose of the medication, or by giving it more frequently than listed on the prescription can be detrimental to your pet. NSAID's as a family are the most widely reported drug to the FDA by about a 1:5-10 ratio because of their common and sometimes very serious adverse side effects.

Daisy Mae

And her broken femur

The most common side effects I see in practice are vomiting and diarrhea, but I have also seen perforated gastric ulcers that caused severe illness and required emergency surgery. I have unfortunately also seen a dog die because the owner kept giving the drug days after their dog stopped eating and began acting ill. For these drugs I have a lengthy conversation about possible side effects, things I want the owner to monitor and be aware of, and I always repeat two things;

Post-op re-check

1. Only give the NSAID if your pet is eating and drinking normally.

2. If you ever have any hint of a concern that there is a problem DO NOT GIVE THIS DRUG!

Before I prescribe a NSAID I give the pet a thorough examination, take a detailed history understanding what the client is seeing, what they are concerned about, and how the pets condition might improve with use of an NSAID. I usually always perform a baseline blood and urinalysis. If there is a problem with the pet I want to know what their kidney, liver, urine, and red and white blood cell counts are before starting the drug.

Examples of NSAID's used in veterinary medicine include; Rimadyl (generic name carprofen), Metacam (meloxicam), Deramaxx (deracoxib), Previcox (Firocoxib), Onsior (Robenacoxib). 

Because NSAID's are heavily protein bound they need to be dosed based on lean body weight, (not actually body weight). Therefore use the exact dose (your vet will tell you what your pet’s optimal body weight is. (Hint, this is the number on the scale you and your pet should be working towards). That milligram size is the maximum amount of the NSAID that you can give in the prescribed time frame.

Post-op she barely toe touches with that leg.

The key to finding LED is understanding when the drug is working and then attempting to customize to the lowest effective dose your pet needs to maintain resolution of the clinical signs that your vet prescribed the NSAID for. So for instance, if your vet prescribes an NSAID because your dog is limping in the morning due to osteoarthritis or joint pain, we would like to get the inflammation to dissipate by using a week or two of the NSAID. You should see an improvement in the form of ease of rising, ease of moving the joint, and an overall improvement in activity level and comfort. It is very important for you, as the parent, to understand and appreciate the changes that the medication makes in your pet. Without appreciating these changes it is difficult to understand how to identify their lowest effective dose. For some of my clients I ask them to keep a daily journal that describes how their pet is doing each day. The daily journal entries should also include how much of the drug was administered.

One month later she is using the leg very well.

The game plan for LED is to administer the labeled dose and represents the maximum amount that can be safely given. I always ask for a re-check phone call, or update from my clients within the first week of using the NSAID. I also place them on our call back list so that we make sure that we are touching base with them at this critical time period. Most adverse reactions to NSAID’s seem to occur within the first week. This is done to assess efficacy, ensure there are no adverse effects, and to boost compliance. Once efficacy is confirmed go over a titration plan with the owner. The key is to decreasing an NSAID is to do it very slowly. Statistically about 5-10% of all patients need to stay on labeled dose, but most can go to about 25% below label dose. This saves the client money and protects our patients from the possible side effects. I remind owners to begin to look for recurrence of the clinical signs that brought the pet in the door in the beginning. How well are they still moving? Are they reluctant to use stairs? Or climb onto the couch? Or get up for all of the things that they used to  want to be a part of, for instance, when the door bell rings, when a loud car drives by, when the neighbors visit, etc. It is also important to mention that your pet will give you some indication of pain/comfort by their facial expressions and body language movements. For pets on tablets I recommend trying half the original dose on the same frequency. For dogs on liquid NSAID's decrease by 5 pound dose per week if over 20 pounds, or decrease by 1 pound per week if less than 20 pounds. When the clinical signs begin to recur it is time to increase the dose of the NSAID, this means go back to the last dose that controlled the clinical signs. This is your maintenance dose. If the dog at some point in the future has a return of clinical signs go back to the original prescribed dose for 2-3 days.

For the pet's who I do not think need the NSAID long term, like my cruciate repair surgeries, spays, neuters, and minor wound repairs or surgeries I advise my clients to use the NSAID for a short post-operative period of time (usually 2 days for a neuter, 4 for a spay, and 7 for an orthopedic surgery), and after this period I want them to try to skip a dose, or use half of the intended dose to see how their pet does. Over those next few days I want the pet to be asking for the NSAID instead of the client just assuming they need it and giving it. In my experience outside of the prescribed times listed above most pets do not need any further NSAID therapy. 

Getting better.

Our biggest concern is that a dog being titrated will exhibit clinical signs that the owner doesn't recognize and we have a painful dog. The journal is a helpful visual cue to help understand if we are using an effective dose and an effective drug. Pets should be monitored weekly until the maintenance dose is realized. After they should be monitored monthly. While your pet is on an NSAID routine examinations and blood works should be monitored. NSAID practice tips: Give NSAIDs only if eating and drinking. This means that the NSAID should only be given if the pet is feeling well. I want your pet to be pain free, but I also want your pet to be safe. The safest way to give an NSAID, a long term is to find LED and understand that your pet’s disease, ability to tolerate medication, and the treatment options will all change with time. 

The best advice; keep an open dialogue with your vet and never hesitate to ask for help in navigating the ever changing current and direction of the waters your are traveling with your pet.

I think that I am as happy as Daisy Mae is that her leg healed so well.
Daisy Mae had a serious fracture to her leg.
She required NSAID's for many weeks.
If you have any questions about NSAID's, or any other pet related question, you can find me and a whole bunch of other pet loving people at Please check us out and join our community. We are all about helping people take care of their pets, and we are free to use!

Or you can find me at the clinic, Jarrettsville Vet, or on Twitter @FreePetAdvice.

And as always, please be kind.

Many Thanks to Danny Joffe, DVM Dip ABVP who gave a talk on Metacam that was incredibly insightful and the backbone for this discussion.

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