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Anticonvulsants or Antiepileptic Drugs

By Linda Shell, DVM, DACVIM-Neurology, Ross University School of Veterinary Medicine

Anticonvulsants or antiepileptic drugs (AEDs) are used to stop an ongoing seizure or to decrease the frequency or severity of anticipated future seizures. During a seizure episode or status epilepticus, the route of administration for AEDs is IV (see Table: Drugs Used for Treatment of Status Epilepticus). For longterm maintenance, the oral route is preferred, although absorption may be limited or variable depending on the drug used (see Table: Antiepileptic Drugs). SC or IM injections are seldom used because of the variability in drug absorption.

Drugs Used for Treatment of Status Epilepticus

Drug

Species and Dosage

Diazepam

Dogs, cats: 0.5–2 mg/kg, IV bolus; can be repeated 2–3 times at intervals of 5–10 min; CRIa 0.5–2 mg/kg/hr

Foals: 0.05–0.4 mg/kg, IV slowly

Adult horses: 25–50 mg/horse, IV

Ruminants: 0.5–1.5 mg/kg, IV or IM

Midazolam

Dogs, cats: 0.2 mg/kg, IV bolus; can be repeated 2–3 times at intervals of 5–10 min; CRI 0.05-0.5 mg/kg/hr

Phenobarbital

Dogs, cats: For those not already on maintenance phenobarbital, loading dose of 15 mg/kg, slowly IV. Alternatively, 3–6 mg/kg, IV or IM, every 15–30 min until a total dosage of 20 mg/kg is reached. In an animal already receiving maintenance phenobarbital, a single 3 mg/kg bolus, IV or IM, CRI 3–10 mg/hr to effect.

Foals, adult horses: loading dose of 12–20 mg/kg, IV over 20 min, then 6.65–9 mg/kg, IV over 20 min every 8–12 hr

Sodium pentobarbital

Dogs, cats: 2–15 mg/kg, IV, to effect to stop motor activity

Foals, adult horses: 2–4 mg/kg, IV to effect

Levetiracetam

Dogs: 20–60 mg/kg, IV; can be repeated at 8-hr intervals

Propofol

Dogs, cats: 2.5–4 mg/kg, IV, to effect to stop motor activity; CRI 0.1–0.3 mg/kg/min to effect

Phenytoin

Dogs: 2–5 mg/kg as slow IV infusion

Foals, adult horses: 5–10 mg/kg, IV followed by 1–5 mg/kg, IV, IM, or PO, every 2–4 hr until seizures stop and maintenance dose started

a CRI = constant-rate infusion

Antiepileptic Drugs

Drug

Dosage and Frequency

Half-life

Time to Steady State

Therapeutic Level

Adverse Effects/Comments

First-Line Maintenance Antiepileptic Drugs

Phenobarbital

Adjust dosage in all species by monitoring serum levels and seizure diary.

Dogs: 2–4 mg/kg, PO, bid (starting dose); up to 10 mg/kg, bid

40–90 hr (Beagles 25–38 hr)

10–24 days

15–45 mcg/mL (66–200 μmol/L), preferably keep values within 20–35 mcg/mL (85–150 μmol/L)

Sedation, polydipsia, induces P450 system, increase in alkaline phosphatase common; liver failure is possible but uncommon.

Cats: 2–4 mg/kg, PO, bid (starting dose)

34–43 hr

10–30 mcg/mL

Liver enzymes do not typically increase in cats.

Horses: 3–5 mg/kg/day, PO, as a starting dose; up to 11 mg/kg/day, PO

18 hr

10–40 mcg/mL (43–175 μmol/L)

Foals: as above

13 hr

Ruminants: 11 mg/kg/day, PO

Bromide (potassium salt)

Dogs, cats: 20–40 mg/kg, PO, once daily or divided bid if GI upset. Caution using bromide in cats (see comments).

Dogs: loading dose 400–600 mg/kg, PO divided into 4 doses, given over 1–4 days

Horses: 90 mg/kg/day, PO

Dogs: 20–46 days

Cats: 10 days

Horses: 5 days

Dogs: 100–200 days

Cats: 6 wk

Bromide alone: 1–3 mg/mL (15–20 μmol/L)

Bromide/phenobarbital combined: 1–2 mg/mL

Sedation, weakness, polydipsia, vomiting, polyphagia, skin rash. Reduce dose with renal insufficiency. High chloride intake increases bromide elimination. Chloride content of diet should be stable. Use with extreme caution in cats and monitor with thoracic radiographs because bronchial/asthmatic signs may be fatal in cats.

Bromide (sodium salt)

17–30 mg/kg, PO, once daily or divided bid if GI upset. The dose of sodium bromide is less than that of potassium bromide to account for the higher bromide content.

See potassium bromide comments.

Diazepam

Cats: 0.25–0.5 mg/kg, PO, bid-tid

Cats:15–20 hr

While oral diazepam is not effective as maintenance AED in dogs, it can be used in cats as a maintenance AED. Sedation and liver failure are potential problems in cats.

Second-Line (Add-on) Antiepileptic Drugs for Dogs

Clonazepam

Dogs: 0.1–0.5 mg/kg, PO, bid-tid

1.5–3 hr

22–77 ng/mL

Extremely potent benzodiazepine; sedation; withdrawal signs if drug stopped abruptly.

Clorazepate

Dogs: 0.5–1 mg/kg, PO, tid

5–6 hr

1–2 days

20–75 mcg/L

15 times less potent than clonazepam; sedation; withdrawal seizures. Can increase phenobarbital concentration.

Felbamate

Dogs: 15 mg/kg, PO, tid; increase by 15 mg/kg biweekly until seizures controlled; maximal (toxic) dosage 300 mg/kg

5–6 hr

1 day

125–250 μmol/La

Nervousness, keratoconjunctivitis sicca, mild thrombocytopenia, leukopenia; induces P450 system; liver disease. Use with care with other potentially hepatotoxic drugs.

Gabapentin

Dogs: 10 mg/kg, PO, tid; up to 30–60 mg/kg, tid

3–4 hr

<24 hr

4–16 mg/La (70–120 μmol/L)

Sedation, dizziness, ataxia, fatigue, diarrhea; reduce dose with renal dysfunction.

Levetiracetam

Dogs: 20 mg/kg, PO, tid

4–10 hr

2–3 days

35–120 μmol/La

Restlessness, vomiting, ataxia at dosages >400 mg/kg/day

Topiramate

Dogs: 5–10 mg/kg/day, PO, bid

2–4 hr

3–5 days

2–25 mg/L (15–60 μmol/L)a

GI upset, irritability

Valproic acid

Dogs: 10–60 mg/kg, PO, tid

90–120 min

<24 hr

Probably ineffective due to very short half-life; liver, alopecia, and pancreatitis; vomiting usually avoided by giving drug with food.

Zonisamide

Dogs: 5 mg/kg/day, PO, bid, if phenobarbital is not concurrently given; 10 mg/kg, PO, bid if phenobarbital is concurrently administered.

15–20 hr

3–4 days

10–40 mg/L (45–180 μmol/L)

Sedation, ataxia, loss of appetite. Potential adverse effects (eg, keratoconjunctivitis sicca, bone marrow dyscrasia, hepatopathy, vasculitis, and metabolic acidosis) could occur because of sulfonamide base.

a Therapeutic range established for people

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