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Table 7 Details of number of dogs, 95 % CI affected cases, AED doses and serum levels, treatment period and adverse effects

From: Antiepileptic drugs’ tolerability and safety – a systematic review and meta-analysis of adverse effects in dogs

Studies AED No of dogs Prevalence 95 % CI affected cases Doses of AEDs Serum levels of AEDs Treatment period Body system affected and adverse effects Most common adverse effects Adverse effect type
Govendir et al. 2005 Gaba as an adjunct to PHB and/or PBr 17 76.5 % 56.3 %–96.6 % Gaba: median, 35; range, 32–40 mg/kg PO SID.
PHB: median, 8; range, 6–26 mg/kg PO SID.
PBr: median, 24; range, 14–56 mg/kg PO SID.
Gabapentin: NA
PHB and PBr: within normal reference values
4 m Neurological (sedation, ataxia), GI (PP, pancreatitis, chronic hepatoxicity), ClinPath (increased ALP, triglycerides), PU, PD ataxia, sedation I
Platt et al. 2006 Gaba as an adjunct to PHB and PBr 11 54.5 % 25.1 %–83.9 % mean, 10.9; range, 9.3–13.6 mg/kg PO TID median, 6.8; mean, 8.4; range, 2.2–20.7 mg/l 3 m Neurological (ataxia, sedation) ataxia, sedation I
Dewey et al. 2009 Pregabalin as an adjunct to PHB and PBr 11 91 % 74.1 %–107.9 % Pregabalin: 2 mg/kg PO TID. The dose was increased by 1 mg/kg PO TID each w until 3 or 4 mg/kg PO TID.
PHB and PBr: NA but were within normal reference values
Pregabalin: median, 7.3; mean, 6.4; range 2–11 μg/ml
PHB: median, 27.1; mean, 27.7; range 19.8–40 μg/ml
PBr: median, 1,6; mean, 1.9; range, 0.2–2.81 mg/ml
3 m Neurological (ataxia, sedation), ClinPath (increased ALP, ALT)
PU, PD, PP were also recorded but were associated to the combination therapy with PHB and PBr
ataxia, sedation I
Ruehlmann et al. 2001 Felbamate as an adjunct to PHB 6 33.3 % −4.4 %–71.0 % Felbamate: median, 63 (initial dose) and 77 (final dose); range, 62–220 mg/kg PO SID.
PHB: 3.75 mg/kg PO BID (discontinued 2 m after felbamate initiation)
median, 35; mean, 13–55 mg/l median, 9 m Haematological (leucopenia, lymphopenia, thrombocytopenia), keratoconjunctivitis sicca leucopenia, lymphopenia, thrombocytopenia I
McGee et al. 1998 Felbamate NA NA NA Sub-chronic group: 250, 500, and 1000 mg/kg PO SID
Chronic group: 100 and 300 mg/kg PO SID
range, 16.5–79 μg/ml Sub-chronic group: 3 m
chronic group: 12 m
Sub-chronic group: Neurological (ataxia, sedation, tremors), GI (vomiting, salivation), ClinPath (increased ALT)
Chronic group: Neurological (ataxia, limb rigidity, tremors), GI (vomiting, salivation), ClinPath (increased ALT, ALP)
Sub-chronic group: ataxia, sedation, tremors, vomiting, salivation, increased ALT.
Chronic group: ataxia, limb rigidity, convulsions, vomiting, salivation, increased ALT, ALP.
I
Dayrell-Hart et al. 1996 Felbamate as an adjunct to PHB and PBr 16 25 % 3.8 %–46.2 % NA NA NA GI (chronic hepatotoxicity) chronic hepatotoxicity I
Bunch et al. 1985 Phenytoin (monotherapy or as an adjunct to Prim) Monotherapy: 8
Adjunctive therapy: 8
Monotherapy: 0 %
Adjunctive therapy: 37 %
Monotherapy: 0 %
Adjunct therapy:−1 %–16.7 %
NA NA NA Monotherapy: None
Adjunctive therapy: GI (anorexia, emaciation), ClinPath (increased ALP, ALT, bilirubin, bile acids, γ-GT, decreased albumin)
These dogs were eventually euthanised.
Monotherapy: NA
Adjunctive therapy: anorexia, increased ALP, ALT, bilirubin, bile acids, γ-GT, decreased albumin
I
Bunch et al. 1984 Phenytoin (monotherapy or as an adjunct to other AED(s)) Monotherapy: 7
Adjunctive therapy: 19
NA ΝΑ Phenytoin: mean, 21+/− 11 mg/kg PO SID
Prim: mean, 33+/−19 mg/kg PO SID.
Other AEDs: NA
NA range, 6–120 m GI (chronic hepatoxicity), ClinPath (increased ALP, ALT, AST, bile acids) Chronic hepatoxicity, increased ALP, ALT, AST, bile acids I
Meyer and Noonan 1981 Phenytoin 6 100 % 100 % 13–19 mg/kg PO TID NA 3 m ClinPath (increased ALP, ALT) increased ALP and ALT I
Sturtevant et al. 1977 Phenytoin 2 100 % 100 % 22 mg/kg PO TID NA 1 m ClinPath (increased ALP, ALT) increased ALP and ALT I
Bunch et al. 1982 Phenytoin as an adjunct to Prim 3 NA NA Case 1: Prim: 250 mg PO BID; Phenytoin: NA.
Case 2: Prim: 750 mg PO BID Phenytoin: 100–233 mg PO TID
Case 3: Prim: NA PHB: 150 mg PO SID Phenytoin: 750 mg PO SID 1000 mg PO SID
NA Case 1: 48 m.
Case 2: 30 m
Case 3: 36 m
GI (chronic hepatoxicity) chronic hepatoxicity I
Weiss et al. 2002 Phenytoin 1 NA NA NA NA NA Blood dyscrasias (myelofibrosis) NA II
Bunch et al. 1987 Phenytoin as an adjunct to PHB and/or Prim 3 NA NA Case 1: Phenytoin: 5 mg/kg PO BID, then increased up to 15 mg/kg PO TID. PHB: 0.8 mg/kg PO BID, then increased up to 13 mg/kg PO BID
Case 2: Phenytoin: 7.5 mg/kg PO BID, then increased up to 15 mg/kg PO TID. PHB: 1.1 mg/kg PO BID, then increased up to 4.5 mg/kg PO TID. Prim: 18.5 mg/kg PO TID
Case 3: Phenytoin: 5 mg/kg PO SID, then increased up to 21 mg/kg PO BID. PHB: 3 mg/kg PO BID.
Prim: 13 mg/kg PO SID, then increased up to 26 mg/kg PO BID
Case 1: NA
Case 2: NA
Case 3: NA
Case 1: 27 months
Case 2: 15 months
Case 3: 8 months
GI (hepatotoxicity) NA II
Nash et al. 1977 Phenytoin 1 NA NA 100 mg in total NA 1 d Idiosyncrasic hepatitis NA II
Bunch et al. 1990 Phenytoin 8 0 % 0 % 40 mg/kg PO TID NA 13.5 m No adverse effects NA NA
Nafe 1981 Valproate (monotherapy or as an adjunct to PHB and/or Prim and/or phenytoin) Monotherapy: NA
Adjunctive therapy: 57
Monotherapy: NA
Adjunctive therapy: 2 %
Monotherapy: NA
Adjunctive therapy:−1.7 %–5.1 %
Sodium Valproate: Monotherapy: 200 mg/kg. Adjunctive therapy: range, 25–40 mg/kg PO SID.
PHB, Prim and Phenytoin: NA.
NA mean, 4.9; range, 1–8 m Neurological (ataxia, sedation), dermatological (alopecia), GI (vomiting) Sedation, alopecia I
Kiviranta et al. 2013 TPM 10 NA NA TPM: Initially 2 mg/kg PO BID for 0.5 m, then 5 mg/kg PO BID for 2 m, and then 10 mg/kg PO BID for 2 m and then 10 PO TID for 2 m.
PHB, PBr and LEV: NA but were within normal reference values
NA 2–6 m Neurological (sedation, ataxia), ClinPath (increased ALP, ALT), weight lose sedation, ataxia, increased ALP, ALT I
  1. Abbreviations: AED(s) anti-epileptic drug(s), BID bis in die (twice daily), Chloraz Chlorazepate, CSF cerebrospinal fluid, CL confidence level, Gaba Gabapentin, IE idiopathic epilepsy, LEV Levetiracetam, m month(s), NA Not Available, PHB phenobarbital, PD polydipsia, PU polyuria, PP polyphagia, PBr potassium bromide, Prim primidone, PO per os, SID semel in die (once daily), TID ter in die (three times daily), TPM Topiramate, w week(s), y year(s)