Maintenance Anticonvulsants Megan Stout Steele, DVM, DACVIM-N VCA NWVS 1-28-18

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

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

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

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

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

Phenobarbital MOA: GABAA agonist Half-life & Steady state: 40-90 hours, 10-15 d Metabolism: primarily by the liver, potent inducer of cytochrome P450

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

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

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

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

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

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

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

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

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

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

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

Questions

Thanks