Table 1 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 |
|---|---|---|---|---|---|---|---|---|---|---|
Boothe et al. 2012 | PHB | 20 | 78.5 % | 60.5 %–96.5 % | mean, 4.11+/−1.1; range, 3.9–4.9 mg/kg PO BID | mean, 27+/−6; range, 12.4–36 μg/mL | 6 m | Neurological (ataxia, hyperactivity, sedation), GI (vomiting, diarrhea, PP), PU, PD, ClinPath (increased ALP, decreased albumin) | ataxia, sedation, increased serum ALP, decreased albumin | I |
Heynold et al. 1997 | PHB | 37 | 35 % | 19.6 %–50.4 % | mean, 2.5 mg/kg PO BID | range, 15–40 μg/ml | mean, 50; range, 8–108 m | Neurological (ataxia, sedation, aggression), GI (PP), Dermatological (itching) | sedation | I |
Löscher et al. 2013 | PHB | 8 | NA | NA | range, 10–40 mg/kg PO SID | 14.7 μg/ml | 2.5 m | Neurological (sedation, ataxia), PU, PD | sedation, ataxia, PU, PD | I |
Gaskill et al. 2000 | PHB | 22 | 32 % | 12.5 %–51.5 % | At 3 w: mean, 3.6+/−1.3; range, 1.3–6.0 mg/kg At 6 m: mean, 3.7+/−1.4; range, 1.3–8.3 mg/kg At 12 m: mean, 3.7+/−1.6; range, 1.3–8.3 mg/kg PO SID | At 3 w: mean, 58.6+/−15.0; range, 33–85 mmol/L At 6 m: 62.5+/−25.7; range, 8–120 mmol/L. At 12 m: mean, 62.2+/−23.51; range, 11–116 mmol/L | 12 m | Endocrine (decreased total T4 levels, increased TSH levels, normal TSH stimulation test) | euthyroid sick syndrome | I |
Steinberg 2004 | PHB (monotherapy prior to the addition of other AEDs) | 14 | 26.6 % | 4.8 %–52.1 % | NA | PHB: mean, 32.1+/−14.4 μg/ml. | median, 17; range, 3.3–58.5 m | GI (chronic hepatotoxicity) | chronic hepatotoxicity | I |
von Klopmann et al. 2006 | PHB | 34 | 68 % | 52.3 %–83.7 % | NA | NA | NA | Endocrine (decreased total T4 levels, normal TSH levels, normal TSH stimulation test) | euthyroid sick syndrome | I |
Chang et al. 2006 | PHB | 11 | 92.5 % | 76.9 %–108.1 % | NA | NA | median, 18; range, 3–72 m | Neurological (ataxia, hyperactivity, sedation), GI (vomiting, diarrhea, PP), Dermatological (itching), PU, PD | PD, PU, PP, sedation, hyperactivity | I |
Tipold et al. 2014 | PHB | 110 | 57.3 % | 48.1 %–66.5 % | range, 2–6 mg/kg PO BID | <45 μg/mL | 5 m | Neurological (sedation), GI (PP, diarrhea), PU, PD, ClinPath (increased ALP, γ-GT, ALT and GLDH) | sedation, PP, PU, PD | I |
Fredso et al. 2015 | PHB | 6 | 93 % | 70 %–114 % | median, 2.7; mean, 3; range 2.2–3 mg/kg PO BID | median, 77; mean, 77.3; range 55–111 μmol/L | 2–12 m | Neurological (sedation, ataxia, hyperactivity, disobedience), GI (PP), PU, PD | PD, PP | I |
Schwartz-Porsche et al. 1985 | PHB | 15 | 93 % | 80.1 %–105.9 % | range, 5–17 mg/kg PO SID | range, 19–57 μg/ml | mean, 15; range, 7.3–32 m | Neurological (sedation, ataxia), GI (PP), PD, ClinPath (ALT, ALP, GLDH) | ataxia, sedation, PP, PD | I |
Gaskill et al. 2005 | PHB | 12 | NA | NA | median, 5; range, 2.1–12.9 mg/kg PO SID | mean, 22.8; range, 9.7–44.2 μg/ml | median, 20.4; range, 4–78 m | ClinPath (increased ALT, ALP) | increased ALT, ALP | I |
Farnbach et al. 1984 | PHB | 42 | 2.4 % | −2.2 %−7.2 % | range, 0.3–19.9 mg/kg PO SID | mean, 24.3; range, 6.5–81.3 μg/ml | NA | Neurological (hyperactivity) | hyperactivity | I |
Gaskill and Kimber 2010 | PHB | 30 | 80 % | 65.7 %–94.3 % | NA | NA | 12 m | Neurological (ataxia, sedation, hyperactivity, aggression), GI (PP, anorexia, vomiting, diarrhoea), Dermatological (skin problems), ClinPath (increased ALP, ALT, lipase), PU, PD | PP, PU, PD, vomiting, skin problems, hyperactivity | I |
Aitken et al. 2003 | PHB | 95 | 40 % | 30.1 %–49.8 % | <2–> 10 mg/kg PO SID | <65–> 120 μmol/l | <3–> 12 m | ClinPath (increased ALT, ALP, γ-GT, GLDH, cholesterol, bile acids) | increased ALP, ALT, GLDH | I |
Dayrell-Hart et al. 1991 | PHB | 18 | NA | NA | median, 10.4; range, 3.1–27 mg/kg PO SID | mean, 49.7; range, 16–60 μg/ml (12 dogs had >40) | median, 39; range, 5–82 m | GI (hepatotoxicity) (also all dogs were ataxic and sedated) | NA | I |
Andrik et al. 2010 | PHB | 30 (15 epileptic and 15 non-epileptic) | NA | NA | Epileptic dogs: 2 mg/kg PO BID (increased if necessary) Non-epileptic dogs: Initially at 2 mg/kg PO SID, then increased at 8 mg/kg PO SID | NA | Epileptic dogs: range, 12–60 m Non-epileptic dogs: 5 m | GI (chronic hepatotoxicity), ClinPath (increased ALP, ALT, AST, total bilirubin, decreased albumin and total protein) | increased ALT, ALP | I |
Litchfield et al. 1972 | PHB | 4 | NA | NA | range, 5–40 mg/kg IV SID | NA | 0.5 m | ClinPath (increased ALP) | NA | I |
Foster et al. 2000 | PHB | Experimental dogs: 6 Epileptic dogs: 10 | 70 % | Experimental dogs: 0 % Epileptic dogs: 41.6 %–98.4 % | Experimental dogs: mean, 6 mg/kg; range, 5.9–6.4 mg/kg PO SID Epileptic dogs: range, 3.9–14.4 mg/kg PO SID | Experimental dogs: mean, 63+/−15, range, <65–194 μmol/L Epileptic dogs: mean, 110; range, 72–171 μmol/L | Experimental dogs: 3 m Epileptic dogs: range, 14–92 m | ClinPath (increased ALP, ALT, cholesterol) | increased ALP | I |
Gaskil et al. 1999 | PHB | 78 | 40 % | 28.8 %–50.6 % | median 4; range, 1–16.4 mg/kg PO SID | median, 17.6; range, 4–70 μg/ml | median, 12.5; range, 0.3–96 | Endocrine (decreased total T4, free T4, increased TSH) Also, ClinPath abnormalities were reported, i.e. increased ALT, ALP, AST, γ-GT, fasting bile acids and cholesterol, but no further details are provided. | eythyroid sick syndrome | I |
Muller et al. 2000 | PHB | 12 | 91.6 % | 100 % or 50.5 %–99.5 % | mean, 5; range, 4.8–6.6 mg/kg PO BID | range, 20–40 μg/mL | 7.1 m | Endocrine (decreased total T4, free T4, increased TSH, cholesterol and total T3), Neurological (sedation for the first 3 days) No significant PHB’s effect on either of the adrenal function tests | euthyroid sick syndrome | I |
Muller et al. 2000 | PHB | 12 | 87.5 % | 75.9 %–107.3 % | mean, 5; range, 4.8–6.6 mg/kg PO BID | range, 20–40 μg/ml | 7.1 m | ClinPath (increased ALP, ALT, γ-GT, decreased albumin), Neurological (sedation for the first 3 days) | increased ALP, ALT, γ-GT | I |
Kantrowitz et al. 1999 | PHB | 55 | NA | NA | NA | median, 25.3; range, 8.0–74.3 μg/ml | median, 7 m; range, 1–120 m | Endocrine (decreased T4, increased TSH) | eythyroid sick syndrome | I |
Chauvet et al. 1995 | PHB | 5 | 100 % | 100 % | NA | range, 20–47 μg/ml | 13 m | Endocrine (increased ACTH, altered ACTH stimulation and dexamethasone supression test), ClinPath (increased ALT, ALP, decreased albumin, cholesterol), PU, PD | increased ACTH, altered ACTH stimulation and dexamethasone supression test, increased ALT, ALP, decreased albumin, cholesterol | I |
Balazs et al. 1978 | PHB | 4 | 100 % | 100 % | 40 mg/kg PO SID | NA | 1.8 m | ClinPath (increased ALP) | increased ALP | I |
Conning and Litchfield 1971 | PHB | NA | NA | NA | NA | NA | NA | ClinPath (increased ALP) | increased ALP | I |
Sturtevant et al. 1977 | PHB | 2 | 100 % | 100 % | 4.4 mg/kg PO TID | NA | 1 m | ClinPath (Increased ALT, ALP) | increased ALT and ALP | I |
Thrift et al. 2010 | PHB | 1 | NA | NA | 6.4 mg/kg PO BID | NA | 2 m | ClinPath (anemia, increased ALT, ALP, AST) | idiosyncrasic anemia | I & II |
Kube et al. 2006 | PHB | 1 | NA | NA | Initially 5 mg/kg PO BID for 4 days, then 3 mg/kg PO BID | NA | 2 m | Dyskinesia (twitching episodes) | NA | II |
Steiner et al. 2008 | PHB | 118 | 14.4 % | 8.1 %–20.7 % | NA | Unclear | NA | ClinPath (Increased cPLI) | NA | II |
Gaskill et al. 2000 | PHB | 88 | 9 % | 3.0 %–15.0 % | NA | range, 39–130 mol/L | 16 m | GI (pancreatitis, increased amylase and/or lipase activities) | increased amylase and/or lipase activities | II |
March et al. 2004 | PHB | 11 | NA | NA | mean, 12.4+/−5.7; range, 3.8–19.8 mg/kg PO SID | mean, 43.5+/−15.1; range, 22.8–66 μg/ml | median, 6; range, 20.4–132 m | Dermatological (superficial necrolytic dermatitis) | NA | II |
Weiss 2005 | PHB | 3 | NA | NA | NA | NA | NA | Blood dyscrasias (bone marrow necrosis-myelofibrosis) | NA | II |
Jacobs et al. 1998 | PHB | 2 | NA | NA | Case 1: 2.2 mg/kg PO BID; Case 2: 4.4 mg/kg PO BID | NA | Case 1: 5 m; Case 2: 3 m | Blood dyscrasias (neutropenia, thrombocytopenia), ClinPath (increase ALP) | NA | II |
Weiss et al. 2002 | PHB | 1 | NA | NA | NA | NA | NA | Blood dyscrasias (myelofibrosis) | NA | II |
Bevier et al. 2010 | PHB | 1 | NA | NA | NA | NA | NA | Dermatological (superficial necrolytic dermatitis) | NA | II |
Bersan et al. 2014 | PHB | 16 | NA | NA | median, 3; mean, 2.75+/−0.43; range, 1.60–7.25 mg/kg PO BID | median, 19; mean, 22.4+/−5.5; range, 13.2–30.5 μg/ml | median, 69.5; mean, 72.1+/−sd 45.8; range, 14–157 m | Blood dyscrasias (anemia and/or thrombocytopenia and/or neutropenia and/or pancytopenia) | anemia, pancytopenia | II |
Volk et al. 2008 (case series) | PHB (monotherapy prior to the addition of other AEDs) | 8 | NA | NA | NA but was within normal reference values | NA | Approximately 2–3 m | Blood dyscrasias (bone marrow suppression) | NA | II |
Habock and Pakozdy 2012 | PHB | 37 | 22 % | 16.8 %–57.2 % | NA | NA | >1 m | Blood dyscrasias (anemia and/or thrombocytopenia and/or neutropenia and/or pancytopenia) | NA | II |
Von Klopmann et al. 2006 | PHB | 1 | NA | NA | 2 mg/kg PO BID | NA | Blood dyscrasias (pancytopenia) | NA | II | |
Bizzeti et al. 2006 | PHB | 7 | 14.4 % | −11.6 %−40.2 % | NA | NA | NA | Pancreatitis, ClinPath (Increased amylase, lipase, cPLI) | NA | II |
Mathis et al. 2014 | PHB | 1 | NA | NA | 2.1 mg/kg PO BID | 27.5 μg/dL | 6 m | Blood dyscrasias (bone marrow supression) | NA | II |
Daminet et al. 1999 | PHB | 9 | 0 % | 0 % | Initially 1.8–3 for one week, then 2.7–4.5 mg/kg PO BID | range, 65–150 pmol/L | 0.8 m | No adverse effects | NA | NA |
Dyer et al. 1994 | PHB | 6 | 0 % | 0 % | 5 mg/kg PO BID | range, 18–37 μg/ml | 2 m | No PHB’s effect on endogenous ACTH and ACTH stimulation test | NA | NA |