From: A systematic review of agomelatine-induced liver injury
Study [reference number] | No. Patients enrolled | Duration (weeks) | Indication | Liver enzymes >3X ULN | Serious hepatic reactions (i.e., hepatitis, liver enzymes >10X ULN and hepatic failure) and deaths due to hepatic reaction |
---|---|---|---|---|---|
European clinical trials (2008) [8] | 40681 | up to 52 weeks | All indications (Overall safety set) | Ago25: 1.04%2 Ago50: 1.39%2 Pbo: 0.72% | • >10X ULN: 1:1000-10 0003 1 case hepatitis4 |
511 | 8 | MDD | Ago25: 0% Ago50: 4.5% Pbo: 0% | 0% | |
503 | 8 | MDD | Ago25: 0.6% Ago50: 3.0% Pbo: 0.6% | 0% | |
CAGO178A2303 [26] | 503 | 8 | MDD | Ago25: 1.3% Ago50: 0.6% Par20: 0.6% Pbo: 0% | 0% |
Hale et al. (2010) [27] | 515 | 8 | MDD | Ago25/50: 1.6%5 Flx20/40: 0.4% | 0% |
Kasper et al. (2010) [28] | 313 | 6 | sleep in MDD | Ago25/50: 0.7%5 Ser50/100: 0% | 0% |
CAGO178A2301E1 (2009) [29] | 329 | 52 | MDD | Ago25/50: 2.0% | 0% |
CAGO178A2302E1 (2009) [30] | 358 | 52 | MDD | Ago25/50: 2.0% | 0% |
CAGO178A2303E1 (2010) [31] | 334 | 52 | MDD | Ago25: 1.2%6 Ago50: 2.0%6 | 0% |
CAGO178A2304 [32] | 633 | 52 | MDD | Ago25/50: 4.6% (open-label phase) Pbo: 2.1% (double-blind continuation phase)7 | 0% |
Calabrese et al. (2007) [33] | 21 | 6, plus optional 46 (total 52) | bipolar I disorder | Ago25: N/A | 0% |
Olié & Kasper (2007) [34] | 238 | 6 | MDD | Ago25/50 and Pbo: N/A | 0% |
Goodwin et al. (2009) [35] | 339 | 34 | MDD | Ago25/50 and Pbo: N/A | 0% |
Demyttenaere et al. (2013) [36] | 8628 | up to 24 | MDD | Ago25: 1.79% Ago50: 2.61% SSRIs: 0.34% | 0% |
Bruno et al. (2013) [37] | 15 | 12 | Fibromyalgia | Ago25: 0% | 0% |
Martinotti et al. (2012) [38] | 60 | 8 | MDD | Ago25/50 and Vlx75/150: N/A | 0% |
Stein et al. (2012) [39] | 477 | 43 | GAD | N/A | 0% |
Stein et al. (2014) [40] | 412 | 12 | GAD | N/A | 0% |
Heun et al. (2013) [41] | 222 | 8 | MDD | Ago25/50: 1.3%5 Pbo: 0% | 0% |
Laux and the VIVALDI Study Group (2012) [42] | 3356 | 12 | MDD | Ago25/50: 0.2%8 | 0% |
Sparshatt et al. (2013) [43] | 110 | 12 | MDD | Ago25/50: -Baseline: 0.9%9 -Week 8: 0% | 0% |
Karaistos et al. (2013) [44] | 40 | 16 | Depression in type II diabetes | Ago25/50 and Ser50/100: N/A | 0% |
Quera-Slava et al. (2011) [45] | 138 | 24 | MDD | Ago25/50 and Esci10/20: N/A | 0% |
Montejo et al. (2010) [46] | 92 | 8 | healthy volunteers | Ago25/50, Par20, and Pbo: N/A | 0% |