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 |
---|---|---|---|---|---|---|---|---|---|---|
Boothe et al. 2012 | PBr | 23 | 78.5 % | 61.7 %–95.3 % | mean, 30.6; range, 26–35 mg/kg PO BID | mean, 1.9 +/− 0.6; range, 0.9–3.3 mg/ml | approximately 6 m | Neurological (ataxia, hyperactivity, sedation), GI (vomiting, diarrhoea, PP), PU, PD | sedation, hyperactivity, ataxia, PD, PU | I |
Pearce 1990 | PBr as an adjunct to PHB | 10 | 40 % | 9.6 %–70.4 % | PBr: 22 mg/kg PO SID (dose increases occurred) PHB: median, 3.3; mean, 3.8 mg/kg PO BID (dose was reduced by a mean of 50 % in 7/10 dogs during the PBr treatment) | PBr: mean, 810; range, 500–1625 mg/l PHB: mean, 29.7; range, 17–45 ug/ml | median, 7; mean, 7.8 m | Neurological (ataxia, sedation, hyperactivity), PU, PD | ataxia, letargy, PU, PD | I |
March et al. 2002 | PBr | 6 | 20 % | −12.0 %−52.0 % | 30 mg⁄kg PO BID | median, 245; range, 178–269 mg/dL | 3.9 m (adverse effects occurred after this period when dose adjustments occurred (NA)) | Neurological (ataxia, paraparesis, hyperactivity) | ataxia, paraparesis | I |
Rossmeisl et al. 2009 | PBr as an adjunct to PHB and/or other AEDs | 1298 | 2 % | 1.2 %–2.8 % | PBr: 44.9+/−1.7 mg/kg PO SID PHB: 6.3+/−0.4 mg/kg PO SID | PBr: 3.7+/−0.3 mg/ml PHB: 31.4+/−1.2 μg/dl | NA | Neurological (sedation, ataxia, paraparesis, tetraparesis) | sedation, ataxia, paraparesis, tetraparesis | I |
Dayrell-Hart B et al. 1996 | PBr | 238 | 10.9 % | 6.9 %–14.9 % | NA | 21 affected dogs had >2.3 mg/ml and 5 affected dogs had <0.5 mg/ml | NA | Neurological (ataxia, sedation) | ataxia, sedation | I |
Podell and Fenner 1993 | PBr as an adjunct to PHB and/or other AEDs | 23 | 78 % | 61.1 %–94.9 % | PBr: mean, 20.75; range, 13–40 PO BID PHB: NA | PBr: 161 mg/dl PHB: 37.8 mcg/ml | mean, 15; range, 4–33 m | Neurological (ataxia, sedation), GI (PP), ClinPath (increased serum chloride), PU, PD | PU, PD, PP, sedation | I |
Chang et al. 2006 | PBr (monotherapy or as an adjunct to PHB) | Monotherapry: 4 Adjunctive Therapy: 10 | Monotherapry: 62.5 % Adjunctive Therapy: 95 % | Monotherapy: 15.0–110.0 % Adjunctive therapy: 81 %–109 % | NA | NA | median, 18; range, 3–72 m | Neurological (ataxia, hyperactivity), Dermatological (pruritus), GI (PP), The adjunctive therapy group had also PU, PD and vomiting/diarhoea | Ataxia, hyperactivity, pruritus, PP | I |
Yohn et al. 1992 | PBr as an adjunct to PHB | 1 | NA | NA | NA | 2.7 mg/ml | 1 m | Neurological (sedation, ataxia, paraparesis, anisocoria) | NA | I |
Kantowitz et al. 1999 | PBr (monotherapy or as an adjunct to PHB) | Monotherapry: 15 Adjunctive therapy: 8 | NA | NA | NA | Monotherapy: median, 1985; range, 500–3419 mg/dL Adjunctive therapy: PBr: median, 1399; range, 584–2438 mg/dL. PHB: median, 22.4; range, 10.9–40 μg/ml | Monotherapy: median, 14.5; range, 3–37 m Adjunctive therapy: PBr: median, 5; range, 3–72 m. PHB: median, 22; range, 3–96 m | Monotherapy: Normal Adjunctive therapy: Endocrine (decreased total T4, free T4) | NA | I |
Srivastava et al. 2013 | PBr as an adjunct to PHB | 6 | 100 % | 100 % | PBr: 30 mg/kg PO SID PHB: Initially 2.5 mg/kg, then 5 mg/kg PO SID. | NA | mean, 11.50+/− 1.23; range, 8–15 m (on PHB). Then, PBr started and 3 m later a reduction of 50 % in the dose of PHB was performed. After 6 m, PHB was completely withdrawn. | Neurological (ataxia), GI (hepatoxicity, anorexia, PP), ClinPath (increased ALT, ALP, AST, bile acids), PU, PD (polyphagia, PU, PD appeared after 1–1.5 years of PBr therapy) | PU, PD, PP | I |
Shaw et al. 1996 | PBr as an adjunct to PHB | 1 | NA | NA | PBr: 20 mg/kg PO SID PHB: 3.75 mg/kg PO BID | PBr: 1100 mg/l. PHB: 20.4 μg/ml | Approximately 21 m | After PBr initiation: Neurological (sedation, ataxia) | NA | I |
Paull et al. 2003 | PBr | 5 | 60 % | 17.1 %–102.9 % | Initially 100 mg/kg PO BID for 2 days. Then, 30 mg/kg PO SID for 180 days. | range, 88–300 mg/dL (only one dog was >300 mg/dl) | 6 m | Endocrine (Euthyroid sick syndrome with decreased TT4 and normal TSH) Placebo group had the same results | NA | I |
Stabile et al. 2014 | PBr as an adjunct to PHB | 1 | NA | NA | PBr: Initially, 400 mg/kg divided in six daily doses for four days. Then, 14 mg/kg PO BID PHB: Initially, 2.7 mg/kg, then 5 mg/kg and finally 6.4 mg/kg PO BID. | PBr: 15.9 mg/ml; PHB: 23.7 μg/ml | ≥26 m | Neurological (sedation, ataxia, generalised appendicular repetitive myoclonus), ClinPath (pseudohyperchlormia, increased ALP) | NA | I & II |
Gaskill and Kimber 2010 | PBr | 32 | 85.9 % | 73.8 %–98.0 % | NA | NA | 12 m | Neurological (ataxia, sedation, hyperactivity, aggression), GI (PP, anorexia, vomiting, diarrhoea, pancreatitis), Dermatological (skin problems), ClinPath (increased ALP, ALT, amylase, lipase), PU, PD | vomiting, sedation, PP, PU, PD | I & II |
Volk et al. 2008 | PBr as an adjunct to PHB (prior to addition of other AEDs) | 14 | 100 % | 100 % | PBr and PHB: NA but were within normal reference values | PBr: 1.7+/−0.4 mg/ml PHB: 35.5+/−6.3 μg/ml | ≥2–6 m | Neurological (ataxia, aggression), GI (PP, vomiting, pancreatitis), ClinPath (increased ALT, ALP) PU, PD | increased ALT, ALP, ataxia, aggression | I & II |
Gaskill et al. 2000 | PBr as an adjunct to PHB | Clinical trial: 6 Case series: 19 | Clinical trial: 50 % Case series: 37 % | Clinical trial: 10.0 %–90.0 % Case series: 15.3 %–58.7 % (pancreatitis); 47.5 %–89.3 % (increased enzymes only) | Clinical trial: NA Case series: NA | Clinical trial: NA Case series: PBr: range, 12.5-37.5 mmol/L; PHB: range, 54–190 imol/L | Clinical trial: approximately 1 year Case series: NA | GI (pancreatitis, increased amylase and/or lipase activities) | pancreatitis, increased amylase and/or lipase activities | II |
Steinmetz et al. 2012 | PBr as an adjunct to PHB | 1 | NA | NA | 101.19 mg/kg SID PO (added at the beginning of the 4th year) PHB: 4.9 mg/kg BID PO | PBr: 45 mmol/l PHB: 168.52 μmol/l | 48 m (adverse effect occurred after the 48 m) | Neurological (neuromyopathy with generalised low motor signs) | NA | II |
Mackay and Mitchell 1998 | PBr as an adjunct to PHB | 1 | NA | NA | PBr: Initially 200 mg/kg PO BID for 3 days, then 30 mg/kg PO SID PHB: 5 mg/kg PO BID. | PBr: NA. PHB: 126 umol/L | 3 d (signs started 3 d after the loading dose of PBr was initiated) | ClinPath (artifactual hyperchloraemia and negative anion gap), Neurological (pacing, disorientation), GI (vomiting) The Neurological and GI signs were attributed to hypercloraemia | NA | II |
Boynosky and Stokking 2014 | PBr as an adjunct to PHB | 2 | NA | NA | Initially 40 mg/kg PO SID, then 60 mg/kg PO SID (case 1) or 86 mg/kg PO SID (case 2) | Case 1: 2.9 mg/mL; Case 2: initially 0.8, then 3 mg/ml (after 7.5 months of treatment) | 12 m [adverse effects occured 3 (case 1) and 8 (case 2) m after the dose increase] | Dermatological (panicculitis) accompanied by sedation and anorexia | NA | II |
Steiner et al. 2008 | PBr (monotherapy or as an adjunct to PHB) | Monotherapy: 98 Adjunctive therapy: 121 | 14 % | Monotherapy: 8.2 %–22.4 % Adjunctive: 5.9 %–17.3 % | NA | range, 0.5–4.2 mg/ml (majority of dogs; range, 1–2 mg/ml) | NA | ClinPath (increased cPLI) | NA | II |
Bizzeti et al. 2006 | PBr as an adjunct to PHB | 7 | 43 % | 6.1 %–79.4 % | NA | NA | NA | Pancreatitis, ClinPath (increased amylase, lipase,cPLI) | NA | II |