Clorazepate
Clorazepate (Tranxene) has been used in dogs both as an adjunctive anticonvulsant (usually in conjunction with Phenobarbital) and in the treatment of behavior disorders, primarily those that are anxiety or phobia-related.
Clorazepate is a benzodiazepine derivative similar to diazepam (valium). Benzodiazepines are powerful anti-seizure drugs but unfortunately, their use is limited because they have a short duration of action and they can cause tolerance to their anti-seizure benefits. In dogs, Clorazepate has been reported to be less prone to developing tolerance to it's anticonvulsant effects than other benzodiazepines.
Clorazepate Facts:
Mean Elimination Half-Life: 4 - 6 hours
Time to Reach Steady State Concentrations: less than 24 hours and peak serum levels generally occur within 1 to 2 hours which makes Clorazepate an effective medication to use to offset seizures when a dog has cluster seizures.
Target Serum Concentration: The therapeutic range has not been well established.
Adverse Effects: There is very limited information on the adverse effect profile of Clorazepate. The most common side effects seen in clinical practice are sedation (or less common excitement), ataxia and increased appetite.
In humans side effects such as increased salivation, vomiting, diarrhea, constipation, and anemia have been reported.
Monitoring: There are many monitoring protocols but in general, Clorazepate peak and trough levels should be taken at two weeks, at four weeks and then monthly for the first 3 months of therapy. In addition, if your dog is taking Phenobarbital in addition to Clorazepate, Phenobarbital levels should be monitored at the same time. Clorazepate may cause Phenobarbital concentrations to dramatically increase. After the first three months Clorazepate and Phenobarbital concentrations should be monitored at least every 6 months.
Cautions and Warnings: Clorazepate should not be used in patients who are hypersensitive to it or other benzodiazepines, have significant liver dysfunction or have acute narrow angle glaucoma. Benzodiazepines have been reported to exacerbate myasthenia gravis.
It is very important that you do not miss a dose of Clorazepate as seizures may occur. Be sure to ask your vet what to do if a dose is missed.
Discontinuing Therapy: Patients discontinuing Clorazepate, particularly those who have been on the drug chronically at high dosages, should be tapered off or status epilepticus may occur.
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
