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The Other AEDs

by Maureen Setter & Sandie Snider

 

 

Primidone : (Mylepsin and Mysoline).

Primidone (PR) is the only antiepileptic drug (AED) that is specifically approved for dogs in the United States. Phenobarbital and other AEDs are approved in some other countries. It is not a controlled substance, but still needs a prescription. As with most AEDs, Phenobarbital (PB) is first prescribed. At one time, if the seizures were not controlled by PB, then Primidone might have been prescribed. However there are newer AEDs, like Potassium Bromide (KBr) that might be more effective.

How does Primidone work?
Primidone is converted to phenobarbital, PEMA & primidone. All three have antiseizure properties, it is believed that almost all the antiseizure activity of Primidone is due to Phenobarbital. In fact,
when monitoring Primidone therapy, it is blood Phenobarbital that is usually measured. The mean half-life of Primidone is 10 hours and that of PEMA 14 hours. It is estimated that 80-85% of the antiseizure effects of Primidone is due to the Phenobarbital.

What are the side effects of Primidone?
In dogs, the side effects of Primidone and Phenobarbital are essentially the same. These are sedation, ataxia (loss of coordination), and the 3 P's: polydipsia (excessive thirst), polyuria (excessive urination) and polyphagia (excessive eating). It is also suggested that there are some behavioral side-effects. However, the risk of liver disease with Primidone is probably greater than with Phenobarbital.

How effective is Primidone?
What slight advantage there might be to using primidone is outweighed by the potential for liver damage.

How is the intitial doseage determined?
It is recommended that you start with 14.3mg/kg every 12 hours. Then increase dosage as needed to control the seizures.

What are the effective blood serum levels?

Since Primidone is broken down to PB, Primidone and PEMA, the PB level range is 15-40 ug/ml while the Primidone range is 5-15 ug/ml.

How is Primidone available?
Primidone is available in tablet form or as a solution. Dosage is usually every 12 hours. Primidone levels are tested the same as for PB.

In summary....
A few dogs might be helped by the use of Primidone, but this is offset by the potential for liver damage. One vet calls primidone "Primidon't".

References:

Schwartz-Porsche D, et al. Therapeutic efficacy of Phenobarbital and Primidone in canine epilepsy: a comparison. Jour.Vet.Pharmacol.Therap. 8:113-119,1985.

Farnbach GC. Efficacy of Primidone in dogs with seizures unresponsive to Phenobarbital. J.Am.Vet.Med.Assoc. 185:867-868,1984.

Chrisman, CL. Problems in Small Animal Neurology, 2nd ed (textbook), Chpt. 8.

Roby K/Southam L., The Pill Book Guide to Medication For Your Dog and Cat. Bantam Books

********************
The above information is NOT intended to replace that provided by your
veterinarian. Always discuss any changes regarding your dog's health
or medication with your veterinarian.

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Phenytoin:(Dilantin)

Phenytoin (PT) is relative of Phenobarbital. Although it is not in the same class (barbiturate) as phenobarbital It was the first non-sedating drug effective for epilepsy in people and for that reason may be the antiepileptic drug (AED) of choice in working or show dogs. It is the drug of choice for certain types of seizures in people.

How efffective is Phenytoin?
Dogs metabolize Phenytoin much faster than people. In fact its half-life is just 3-7 hours (7-42 hours in humans; 24-108 hours in cats). It is very difficult to maintain adequate blood levels of this drug in dogs, making it very ineffective for treatment of canine epilepsy. In one clinical study, only 1 of 77 epileptic dogs could be controlled with this drug. Because it is rapidly metabolized and after just a week of usage, the half-life is reduced by as much as 66%. PT requires very high doses even to attain minimal blood levels and doesn't reach adequate therapeutic blood levels. It use to be used in combination with phenobarbital and was thought to be effective. All the anecdotal stories of its success were made before blood serum level monitoring became practical, once it was (practical that is) it was soon realized that the beneficial effects were actually coming from the Phenobarbital.

What are the side -effects of Phenytoin?
There are few side-effects. However there have been some reports of loss of appetite, vomiting, ataxia and liver problems. Some say that the potential for liver damage is greater if used concomitantly (together) with primidone or phenobarbital.

How is the intitial dose determined?
It is recommended that you start with 20-35 mg/kg every 6 to 8 hours.

What are the effective blood serum levels
Effective levels are in the range of 10-20 ug/ml.

How is Phenytoin available?
Phenytoin in tablet, capsule or as a solution. If using a solution, it must be mixed well before each use.

In summary...
Many vets would NOT consider adding or switching to phenytoin.

References:

Farnbach GC. Serum concentrations and efficacy of Phenytoin, Phenobarbital, and primidone in canine epilepsy. Jour Am Vet Med Assoc
184:1117-1120,1984,

Chrisman, CL. Problems in Small Animal Neurology, 2nd ed (textbook), Chpt. 8.

Roby K/Southam L., The Pill Book Guide to Medication For Your Dog and Cat. Bantam Books

 

*******************
The above information is NOT intended to replace that provided by your
veterinarian. Always discuss any changes regarding your dog's health
or medication with your veterinarian.

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Valproic Acid (Valproate, Depekene)

Valproic Acid (VPA) is chemically unrelated to the other AEDs. Its purpose is to increase GABA and improve its levels in the brain.

VPA may be most useful for generalized seizures when combined with PB.

How effective is Valproic Acid?
VPA in dogs is eliminated (half-life 1.2-3.7 hours) more quickly than in people, which makes it more difficult to maintain adequate blood levels. Because of this, it is usually used as add-on therapy in dogs that are not controlled with first-line drugs.

In one study of dogs with idiopathic epilepsy poorly controlled by other medications, the addition of Valproate (a trade name for Valproic acid) improved seizure control in 29 dogs (51%). In some of these, the other drug(s) were stopped and the dogs were successfully maintained on Valproate alone. In 9 dogs the seizures became worse. Two dogs had side effects attributed to the Valproate (vomiting in one dog and hair loss in one dog). One limitation of this study was the fairly short period of evolution, less than one year.

What are the side effects of Valproic Acid?
Side-effects are the usual sedation and potential liver problems.

How is the intitial doseage determined?
It is recommended that you start with 15-200 mg/kg/day divided and given every 6 to 8 hours.

What are the effective blood serum levels?
Effective levels (in humans) is in the range of 500-1000 ug/ml.

In summary...
VPA may be most useful for generalized seizures when combined with PB.

References:
Nafe LA, et al. Sodium valproate: a preliminary clinical trial in
epileptic dogs. Jour Am Anim Hosp Assoc 17:131-133,1981.

Chrisman, CL. Problems in Small Animal Neurology, 2nd ed (textbook),
Chpt. 8.

Silverman, HM. The Pill Book, 7th ed. Bantam Books

 

********************
The above information is NOT intended to replace that provided by your
veterinarian. Always discuss any changes regarding your dog's health
or medication with your veterinarian.

back to the top

 

 


 

 

Tegretol (Carbamazepine )

Carbamazepine (CBZ) was first approved for the relief of the severe pain of trigeminal neuralgia. Over the years, though, it has gained much greater acceptance for seizure control, especially for people whose seizures are not controlled by Phenytoin, Phenobarbital or Primidone or who have suffered severe side effects from these medicines.

How effective is Carbamazepine?
CBZ has a relatively short half-life of 1.5 hours and after 8 days of continued use, the half-life drops to .6 hours.

What are the side-effects of Carbamazine?
Side-effects are the usual sedation, potential liver problems, vomiting and nystagmus (spontaneous jerking of the eyeballs).

How is the initial doseage determined?
It is recommended that you start with 2-6 mg/kg/day divided and given every 8 to 12 hours.

What are the effective blood serum levels?
Effective levels are unknown

In summary......
CBZ's short half-life would be a challenge to maintain adequate serum levels and depending on the cost, could also be expensive because of possible frequent dosing. Also, the clinical efficacy of CBZ has not been done in animals. Long term effects are unknown.

References:
Lane/Bunch."Medical Management of Recurrent Seizures in Dogs and cats", Journal of Veterinary Medicine 1990; 4:26-29

Chrisman, CL. Problems in Small Animal Neurology, 2nd ed (textbook). Chpt. 8.

Silverman, HM. The Pill Book, 7th ed. Bantam Books

 

********************
The above information is NOT intended to replace that provided by your
veterinarian. Always discuss any changes regarding your dog's health
or medication with your veterinarian.

 

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Felbamate: (Felbatol)

Felbamate is one of the newer AEDs that has become available for humans within the last few years after some 15 years of research. However it does offer some exciting potential for use in dogs.

What are the side efffects of Felbamate?
Recently, a higher incidence of aplastic anemia and liver toxicity was found in people treated with Felbamate than in the general population. In humans, Felbamate may increase sensitivity to the sun.

How effective is Felbabmate?
Several dogs with complex partial and generalized seizures have been successfully managed with Felbamate.

How is the initial dose of Flebamate determined?
The recommended dosage in human adults is to start at 1200 mg/day and gradually increasing the dosage upwards to 3600 mg/day divided and given every 8 hours.

What are the effective blood serum levels?
Effective levels are unknown.

Are there drawbacks to using Felbamate?
Yes. Felbamate is rather expensive - somewhere in the vicinity of $100 a month ($1 a pill, 3 pills a day). There is no generic available since the patent has not expired.

In summary.....
Felbamate may prove to be a beneficial AED in dogs. Stay tuned.

References:
Podell, M. "Seizures in Dogs", Veterinary Clinics of North America: Small Animal Practice, Vol 26, Number 4 (pages 779-809). July 1996

Podell, M. "Neurology", Seminar: Cleveland Academy of Veterinary Medicine, March 19, 1997

Silverman, HM. The Pill Book, 7th ed. Bantam Books

 

********************
The above information is NOT intended to replace that provided by your
veterinarian. Always discuss any changes regarding your dog's health
or medication with your veterinarian.

back to the top

 


 

 

Gabapentin (Neurontin)

Gabapentin is one of the newer AEDs that has become available for humans within the last few years after some 15 years of research. However it does offer some exciting potential for use in dogs. In humans, it is most often used as a secondary (or add-on) drug to help treat refractory seizures. Also, it is suggested that PB and KBr blood serum values be within therapeutic range before starting on Gabapentin therapy.

How does Gabapentin Work?
The researchers do not fully understand how Gabapentin works.Gabapentin/Neurontin is related to gamma amino butyric acid (GABA) which is a natural neuro chemical found in the nervous system.

What are the side effects of Gabapentin?
A major advantage to this drug (in humans) is that is not metabolized by the liver like some of the other AEDs. It also can be used in combination with liver-metabolized anticonvulsants (ie: PB). In dogs, Gabapentin is metabolized partially by the liver and no one is completely sure of the anticonvulsant effects of this metabolite.

How effective is Gabapentin?
No one knows for sure yet. However, according to one vet, he feels that Gabapentin really seems to work. For a couple of dogs that were given Gabapentin, they were not seizure-free, but improved significantly. Gabapentin must also be given at least three times a day to have effective serum drug concentrations.

Are there drawbacks to using Gabapentin?
Yes. Gabapentin is rather expensive. The dosage for gabapentin is 7 to 15mg/kg every 8hrs. It would cost $75 a month for a 60lb dog starting at 7mg/kg. The basis for this cost is 42 cents per 100mg of gabapentin. By comparison, it would cost $87 a month for a 90lb dog starting at 7mg/kg. The basis for this cost is 97 cents per 300mg of gabapentin. Gabapentin comes in 100mg, 300mg & 400mg capsules. A good source to obtain this drug can be found on the Compounding Pharmacy page.

In summary....
Because gabapentin is only partially metabolized by the liver, it looks very promising for our dogs. Hopefully clinical trials will prove this to be true and answer many of the unknown questions. Stay tuned.

References:

Podell, M. "Seizures in Dogs", Veterinary Clinics of North America: Small Animal Practice, Vol 26, Number 4 (pages 779-809). July 1996

Podell, M. "Neurology", Seminar: Cleveland Academy of Veterinary Medicine, March 19, 1997

********************
The above information is NOT intended to replace that provided by your
veterinarian. Always discuss any changes regarding your dog's health
or medication with your veterinarian.

back to the top

 

 

Clorazepate (ClorazeCaps, Cloraze Tabs, Tranxene)


Clorazepate is used to treat cluster seizures as well as an adjunctive daily anticonvulsant (usually in conjunction with Phenobarbital). Clorazepate is part of the benzodiazepine family of drugs along with diazepam, lorazepam, and clonazepam.

How does clorazepate work?
Clorazepate is converted to nordiazepam (also called N-desmethyldiazepam) in the stomach. It’s this metabolite that provides the anti-seizure effect. Various parts of the central nervous system are depressed by benzodiazepines and produce the sedative, skeletal muscle relaxant and anticonvulsant effects seen.


What are the side effects of clorazepate?

The most common side effects seen in clinical practice are sedation (or less common excitement), ataxia and increased hunger. In humans side effects such as increased salivation, vomiting, diarrhea, constipation and anemia have been reported.

How is the initial dose determined?
A dose of 2 mg/kg every 8 to 12 hours has been suggested.

How is clorazepate available?
Clorazepate is available in regular release and sustained release tablets. In dogs, the sustained release tables offer no advantage over regular-release tablets.

How is clorazepate monitored?
When used as a daily medication, levels of nordiazepam should be monitored on a regular basis. Since clorazepate can cause increases in Phenobarbital levels even when there is no change in the dose, Phenobarbital serum levels should also be monitored.

What other information should I know?
Although it is not as common with clorazepate, most benzodiazepines can cause tolerance (reduction in anti-seizure effects with long-term daily use). For this reason clorazepate and other benzodiazepines are usually reserved for the treatment of cluster seizures.

References:
Forrester SD et al, Disposition of clorazepate in dogs after single and multiple-dose oral administration;Amer Jor of Vet Res 51:2001-2005, 1990
Plumb, DC, Veterinary Drug Handbook
Sherkl R et al;Clorazepate in dogs:tolerance to the anticonvulsant effect and signs of physical dependence:Epilepsy Research 3:144-150, 1989
Thomas, WB; Idiopathic Epilepsy in Dogs;Small Anim Prac;Jan 2000 183-206

 

********************
The above information is NOT intended to replace that provided by your
veterinarian. Always discuss any changes regarding your dog's health
or medication with your veterinarian.

 

 

Zonisamide (Zonegram)


Zonisamide is one of the newer anticonvulsants approved in the United States for focal seizures in people, however it appears to be effective for generalized seizures in dogs as well.

How does zonisamide work?
The precise mechanism (s) by which zonisamide exerts it’s antiseizure effect is unknown however it may produce these effects through action at sodium and calcium channels.

What are the side effects of zonisamide?
This drug has not been used extensively in dogs. In limited clinical practice the side effects appear to be rare and mild. The most common side effects appear to be sedation, ataxia and nausea.

How is the initial dose determined?
Zonisamide is usually given at a dose of 10 mg/kg every 12 hours

Have toxicity studies been done on dogs?
Zonisamide is on of the few newer drugs where toxicity studies have been done in dogs. In a study by Parke-Davis dogs tolerated doses as high as 75 mg/kg.How effective is zonisamide?
Curtis Dewey presented an abstract on using zonisamide in dogs at the 2003 ACVIM forum in Charlotte, NC. In 12 dogs with epilepsy refractory to other drugs (mostly phenobarbital and bromide), seven dogs (58%) had a decrease in the number of seizures after starting zonisamide, with a mean decrease in seizures frequency of 81%. In 8 of these dogs it was possible to decrease the dose or withdraw concurrent anti-seizure drugs. Side effects were mild.

References:
Walker RM, DiFonzo CJ, Barsoum NJ, Smith GS, Macallum GE.; Chronic toxicity of the anticonvulsant zonisamide in beagle dogs; Parke-Davis Research Institute, Mississauga, Ontario, Canada.

 

 

Page last update: 12/26/2013

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