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Question Posted December 21, 2004
Amantadine has been mentioned on several occasions on our list serve. I am not familiar using this agent in SA practice. Can anyone take the time and educate me on how they are using it in practice (inc. dosage, duration of action, potency, interaction with other chronic pain meds, etc)
I will greatly appreciate the education.
Carolina Nyarady
Response 1
Very briefly, amantadine is an antiviral drug which has been used in managing Parkinson's Disease in humans. In addition, it has been shown to have pretty good NMDA receptor blocking activity, which is why we are using it.
It is used in conjunction with your primary analgesic to prevent dorsal horn windup. It has no significant analgesic effects of its own, so must be considered a supplement for those animals that opoids and/or NSAIDs are not quite doing the job. The dose most use is 3mg/kg once daily. It is available in 100mg tablets or a syrup.
R. L. Headley
Response 2
Will block the NMDA receptors used 3mg/kg sid for chronic windup pain.
Amantadine-- as an oral NMDA receptor antagonist, it not only reduces central sensitization (always helpful in chronic pain), but also seems to enhance opioid receptor sensitivity and help abolish opioid tolerance. I use it in 7-10 days increments when opioid effectiveness seems to be waning, and subjectively feel it helps quite a bit (I realize this is anecdotal; Duncan Lascelles is the main advocate of this use, and until he publishes something anecdotal is all we have). Dosage is 3 mg/kg SID (it's available as a 10 mg/ml generic liquid as well as 100 mg tablets); excretion is principally renal (dose reductions may be necessary in severe renal failure) and side effects are minimal (occasional agitation or diarrhea).
Gary T Old
Response 3
Anyone tried this in rabbits? Other rodents or livestock?
Many thanks,
Sara
Response 4
Some references regarding amantadine for those interested.
Analgesia: Now and When
International Veterinary Emergency and Critical Care Symposium 2003
Karol Mathews, DVM, DVSc, DACVECC; Bernie Hansen, DVM, MS
"N-methyl D-aspartate (NMDA) receptors appear to be pivotal in the induction and maintenance of some chronic and pathological pain states, in part due to sensitization of sensory neurons in the dorsal horn of the spine. In these conditions, sustained afferent input increases results in sustained release of glutamate, a ligand for this receptor. Prolonged NMDA receptor activation has been implicated in the phenomenon of spinal cord 'wind-up' and hyperexcitability, both of which enhance the intensity, anatomical distribution, and duration of pain following injury. Administration of antagonists for this receptor within weeks of neuronal injury inhibits nociceptive responses, and these agents have been used to treat various pathological pain states in humans. However, because of the wide distribution and multitude of functions of this receptor, most agents currently under investigation produce a variety of side effects that limits their usefulness for treating chronic pain. Ketamine is a commercially available NMDA receptor antagonist that has demonstrated analgesic efficacy. Currently its best use appears to be as an adjunct analgesic in the immediate perioperative period. Amantadine (SymmetrelTM, Endo Labs), another NMDA antagonist, appears less useful for acute pain in humans but because it has a less severe spectrum of side effects at clinically relevant dosages it is more useful as an adjunct for chronic pain. It has been used as an adjunct to NSAIAs to treat pain due to osteoarthritis dogs weighing 25-40 kg at a dosage of a single 100 mg capsule daily."
Case Examples in the Management of Cancer Pain in Dogs and Cats, and the Future of Cancer Pain Alleviation
ACVIM 2003
B Duncan X Lascelles, BSc, BVSc, PhD, MRCVS, CertVA DSAS(ST), DECVS Raleigh, NC
" Table of ORAL drug doses
The following table outlines the doses for some of the oral drugs used by the author in the alleviation of chronic cancer pain in dogs and cats. Although all the drugs are available in the United States , not all are approved for use in dogs and cats. Many of the drugs have not had comprehensive efficacy, kinetic or toxicity studies carried out in the cat or dog, and are being used empirically based on extrapolation from human medicine and the author's and colleagues clinical experience. Evaluation of these drugs is being undertaken by a number of investigators and new information may result in changes in the recommended doses.
DrugDose for DogsDose for Cats(mg/kg)
Acetaminophen10-15mg/kg of the acetaminophen PO q 12 hrs TOXIC
Acetaminophen + Codeine 10-15mg/kg of the acetaminophen PO q 12 hrs TOXIC
Amantadine1.0-4.0 mg/kg PO SID 1.0-4.0 mg/kg PO SID"
Managing Chronic Pain in Dogs: The Next Level
Pfizer Managing Pain Symposium 2003
Elizabeth M. Hardie, DVM, PhD, Diplomate, ACVA; B. Duncan X Lascelles, BSc, BVSc PhD, MRCVS, CertVA, DSAS(ST), Diplomate, ECVS, Diplomate, ADVS; James S. Gaynor, DVM, MS. Diplomate, ACDVA, CVA (IVAS)
Extensive references to amantadine
Can Chronic Pain in Cats Be Managed? YES!
Pfizer Managing Pain Symposium 2003
B. Duncan X. Lascelles, BSc, BVSc, PhD, MRCVS, CertVA, DSAS(ST), Diplomate ECVS, Diplomate ACVS; Sheilah A. Robertson, BVMS (Hons), PhD, MRCVS, CertVA, Diplomate, ADVA, Diplomate, ECVA; James S. Gaynor, DVM, MS, Diplomate, ADVA, CVA (IVAS)
Extensive references to amantadine
Chronic Pain
Western Veterinary Conference 2002
Peter W. Hellyer, DVM, MS, DACVA College of Veterinary Medicine and Biomedical Sciences, Colorado State University Fort Collins, Colorado, USA
"Several dogs at the CSU Veterinary Teaching Hospital have been successfully treated with infusions of ketamine and fentanyl to break the chronic pain cycle. The use of ketamine is restricted to continuous IV or SQ infusions; however, other oral NMDA receptor antagonists are available, such as amantadine. Ketamine infusions are also used intraoperatively at CSU to improve recovery and prevent the development of chronic pain states in animals undergoing painful procedures such as amputations."
VIN anesthesia/analgesia boards have been discussing its use since early 2002 without any negative consequences that I can find.
Bob Stein
Response 5
I agree with everything which has been mentioned for amantidine. Based on my experience of relapsing back into wind-up in some of my patients, I prescribe a 21 day course of amantidine along with the primary analgesic. Someone mentioned the formulation coming as a tablet. I have only found it to come as a capsule and a liquid.
Duncan Lascelles and I are conducting a well-designed multi-center clinical trial to determine if we have all been lucky or there is some efficacy in dogs. We should have results sometime in 2005.
In response to Dr. Pascoe's comment of pooling information, I would like to see the IVAPM develop a central database of outcome information similar to what the AAPM has. It would take some work to standardize, but I think it would be vitally important.
James S. Gaynor