1. Maintenance Anticonvulsants
Megan Stout Steele, DVM, DACVIM-N
VCA NWVS

2. Main 4 Potassium Bromide (KBr) Phenobarbital Zonisamide (Zonegran)
Levetiracetam (Keppra)

3. Overview Mechanism of Action (MOA) Half-life & Steady state Metabolism
Side Effects
Drug Interactions
Dosing & Monitoring

4. Potassium Bromide MOA: suspect cellular hyper-polarization
Half-life ~3 weeks, SS ~ 3-4 months
Excreted unchanged in the urine

5. KBr Cont’d Side Effects Sedation PU/PD/PP PL ataxia, weakness
Cutaneous drug reaction
GI Upset
Pancreatitis
Behavior changes
Pneumonitis, Coughing

6. KBr Cont’d Drug Interactions: diuretics, diet Dosing (DOGS ONLY)
Maintenance: 30mg/kg q24 hours
Loading: 100mg/kg q24 x 5 days
100mg/kg q6 hr for 4 doses
Monitoring
Chem (Cl- falsely elevated), UA, Bromide levels, after dosing change, annually

7. Phenobarbital MOA: GABAA agonist Half-life & Steady state:
40-90 hours, d
Metabolism: primarily by the liver, potent inducer of cytochrome P450

8. Phenobarbital Cont’d Side Effects Sedation, Ataxia, PU/PD/PP, CDR
Myelosuppression, Necrolytic Dermatitis
Dose-dependent hepatotoxicity
Cats
facial pruritus, generalized pruritus, distal limb edema
Elevated ALP, Low T4

9. Phenobarbital Cont’d Drug Interactions Glucocorticoids Mitotane
Ketoconazole
Clompiramine
Chloramphenicol
Lidocaine
Theophylline
Digoxin
Zonisamide
Propranolol.....

10. Phenobarbital Cont’d Dosing
Dogs: 2.2-3mg/kg q12h (loading 4-5mg/kg q6h x 4d)
Cats:2mg/kg q12h (loading 3mg/kg q6h x 4d)
Monitoring
CBC/Chem, phenobarbital drug level 2 weeks, then q6months minimally, after any dosage change

11. Zonisamide MOA: T-type Ca++ channel blocker, Half-life & Steady state:
Dogs:15 h, 3 d
Cats: ~ 30 h, 6-7d
Metabolism: primarily hepatic microsomal enzymes, mild urinary excretion

12. Zonisamide Cont’d Side Effects Sedation, GI upset, Ataxia
Hepatic necrosis, Myelosuppresion, Dry eye
Drug interactions
None, if on phenobarbital, dose should be increased

13. Zonisamide Cont’d Dosing :
Dog: 8-10mg/kg q12h (10-12mg/kg q12h if on Pheno)
Cats: 10mg/kg/day q12 or q24
Monitoring: CBC/Chem/UA 2 weeks after starting therapy, every 6-12 months, after any dosing change, drug levels as needed, not routine

14. Levetiracetam MOA: Synaptic vesicle 2A inhibitor
Half-life: 3-4 hrs, Steady state: < 1d
Metabolism: primarily excreted in the urine, some hydrolyzed in serum

15. Levetiracetam Cont’d Side Effects: typically none sedation ataxia
at exceedingly high doses (400mg/kg/d) salivation, restlessness, GI signs, ataxia
Drug Interactions
None reported

16. Levetiracetam Cont’d Dosing Regular strength: 20mg/kg q8hr
Extended release: 30mg/kg q12hr
Monitoring
2 weeks, CBC/Chem/UA, then q6-12 months or after any dosage adjustment, drug levels not routinely done

17. Drug SS Admin SE Cost KBr Urine 3-4 MONTHS q24h Many $ Pheno Liver
Metabolism SS
Admin SE
Cost
KBr
Urine
3-4 MONTHS
q24h
Many $
Pheno
Liver
2 weeks
q12h $$
Zonisamide
3 days
Few
Keppra
1 day
q8h
Minimal

18. Imepitoin Future use in the US?
MOA : imidazolinone derivative with partial GABAA agonism
Comparable to phenobarbital efficacy with fewer side effects, currently commonly in use in the UK.
BID dosing

19. Questions

20. Thanks