Table 2 Details of number of dogs, 95 % CI affected cases, AED doses and serum levels, treatment period and adverse effects
Studies | AED | No of dogs treated | 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 |
|---|---|---|---|---|---|---|---|---|---|---|
Rundfeldt et sl. 2015 | Imepitoin | 127 Imepitoin high dose group: 66 Imepitoin low dose group: 61 | Imepitoin high dose group: 86 % Imepitoin low dose group: 82 % | Imepitoin high dose group: 77.6 %–94.3 % Imepitoin low dose group: 72.3 %–91.6 % | Imepitoin high dose group: 30 mg/kg PO BID Imepitoin low dose group: 1 mg/kg PO BID | NA | 1st phase: 3 m 2nd phase: 3 m | Neurological (hyperactivity, disorientation), musculoskeletal (unspecified), gastro-intestinal (unspecified), respiratory (unspecified), urogenital (unspecified), other systems (unspecified), general (unspecified) | Disorientation, hyperactivity | I |
Tipold et al. 2014 | Imepitoin | 116 | 46.6 % | 37.5 %–55.7 % | 10–30 mg/kg PO BID | NA | 5 m | Neurological (sedation, hyperactivity), GI (PP, diarrhoea), PU, PD, Renal/Urinary disorders, ClinPath (increased creatinine) | PP, PD, PU, sedation, hyperactivity | I |
Tipold et al. 2014 (ELAS) | Imepitoin | 32 | NA | NA | 30, 90 or 150 mg/kg PO BID (adverse effects occurred mainly in the higest doses, i.e. 3X and 5X the recommended dose) | NA | 6 m | Neurological (loss of righting reflex, ataxia, intermittent tremors, decreased activity, nystagmus), GI (vomiting, hypersalivation, white material in the faeces), ClinPath (increased creatinine), Ophtalmological (lacrimation, eye dryness, eye discharges, relaxed nictitating membranes, eyelid closure) | NA (infrequent adverse effects) | I |
Loscher et al. 2004, Rieck et al. 2006 | Imepitoin as monotherapy (12 dogs) and imepitoin as an adjunct to PHB or Primidone (17 dogs) | 29 | 58.6 % | 40.7 %–76.5 % | Imepitoin: Initially 5 mg/kg PO BID for 1 week, then 10–30 mg/kg PO BID. PHB: 6–23 mg/kg PO SID. Primidone: 25–53 mg/kg PO SID | Imepitoin: mean, 4,000; range, 3400–7300 ng/ml (2 h after dosing) and mean, 650 ng/ml (12 h after dosing). PHB: range, 15–45 μg/ml (2 dogs with adverse effects had 56.6–58.9 lg/mL). Prim: NA | mean, 7.7 ± 0.7 m | Neurological (ataxia, sedation), GI (PP), ClinPath (increased ALT, ALP, GLDH) | PP | I |
Löscher et al. 2004 (ELAS) | Imepitoin | 1st experiment: 6 2nd experiment: 6 | 0 % | 0 % | 1st experiment: 5 mg/kg PO BID 2nd experiment: 40 mg/kg PO BID | 1st experiment: range, 20–120 ng/ml 2nd experiment: range, 4800–7400 ng/ml | 1st experiment: 1.2 m 2nd experiment: 1.2 m | 1st experiment: none 2nd experiment: none but increase in body weight | NA | I |
EMA report 2012 (US field trial) | Imepitoin | 110 | NA | NA | range, 10–30 mg/kg PO BID | NA | NA | Neurological (ataxia, hyperactivity, anxiety, disorientation), ClinPath (increased enzymes-unclear which) tachypnoea, PD | ataxia, hyperactivity, anxiety, PD, increased liver enzymes | I |
EMA report 2012 (unpublished clinical trials: Tipold 2006; Heit 2011; de Vries 2011) | Imepitoin | NA | NA | NA | 30 mg/kg PO BID (Unclear if other doses were also used) | NA | NA | Neurological (ataxia, decreased motor activity, disorientation, hyperactivity, decreased sight, increased sensitivity to sound), GI (vomiting, diarrhoea, polyphagia), Renal (increase creatinine) | ataxia, decreased motor activity, disorientation, hyperactivity, decreased sight, increased sensitivity to sound, vomiting, diarrhoea | I |
EMA report (GLP toxicity study 1) | Imepitoin | 32 | 0 % | Doses of 0, 31.6 mg/kg: 0 % Other doses: NA | Doses of 0, 31.6, 100 and 316 mg/kg/day PO | NA | 1 m | Neurological (decreased motor activity), GI (hypersalivation, vomiting), ECG modifications No adverse effects in the recommended doses; adverse effects occurred only in the highest doses | NA | I |
EMA report (GLP toxicity study 2) | Imepitoin | NA | NA | NA | Doses of 0, 31.6, 82.5 and 215 mg/kg/day PO | NA | 3.2 m (followed by a 1.2 m recovery period) | Only vomiting occurred in the 0 and 31.6 mg/kg/day doses; adverse effects occurred only in the highest doses | NA | I |