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Table 2 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 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
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
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
  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)