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