1. Table e-1 Geometric Mean Ratio 90% Confidence Limit of AUC(0-t)
Carbamazepine
5 formulations
14 studies
Divalproex
7 formulations
Lamotrigine
17 studies
Levetiracetam
15 formulations
41 studies
Phenytoin
8 formulations
11 studies
Total
42 formulations
97 studies
0%-5%
1 (7.14%)
2 (14.29%)
1 (5.88%)
23 (56.10%)
2 (18.18%)
29 (29.00%)
5%-10%
3 (21.43%)
8 (47.06%)
16 (39.02%)
5 (45.45%)
34 (35.05%)
10%-15%
8 (57.14%)
7(50.00%)
5 (29.41%)
1 (2.44%)
23 (23.71%)
15%-25%
3 (17.65%)
11 (11.34%)
14 (100.00%)
17 (100.00%)
41 (100.00%)
11(100.00%)
97 (100.00%)
90% CI includes 1
5 (35.71%)
13 (92.86%)
15 (88.23%)
36 (87.80%)
6 (54.54%)
75 (77.32%)
Geometric Mean Ratio 90% Confidence Limit of Cmax
Carbamazepine
Divalproex
Lamotrigine
Levetiracetam
Phenytoin
Total
0%-5%
0 (0.00%)
1 (5.88%)
5 (12.20%)
6 (6.19%)
5%-10%
1 (7.14%)
4 (28.57%)
5 (29.41%)
19 (46.34%)
2 (18.18%)
31 (31.96%)
10%-15%
5 (37.71%)
5 (35.71%)
8 (47.06%)
12 (29.27%)
5 (45.45%)
35 (36.08%)
15%-25%
8 (57.14%)
3 (17.65%)
4 (36.36%)
25 (25.77%)
14 (100.00%)
17 (100.00%)
41 (100.00%)
11(100.00%)
97 (100.00%)
90% CI includes 1
3 (21.43%)
13 (76.47%)
18 (43.90%)
7 (63.63%)
49 (50.52%)

2. Figure e-1: Comparison of standard deviations of total drug exposure (AUC, figure 1A), and peak concentrations (Cmax, figure 1B) for generic and reference antiepilepsy drug formulations in bioequivalence studies. Standard deviations are presented in log scales. Abbreviations: PHT = phenytoin; CBZ = carbamazepine; DVP = divalproex; LEV = levetiracetam; LTG = lamotrigine.
Cmax A
AUC B

3. Figure e-2. Differences in fed and fasting bioequivalence (BE) studies.
Tmax A
AUC B
Cmax C
2A: Fed and fasting studies of total drug exposure (AUC). 2B: Fed and fasting studies of maximum concentration (Cmax). 2C: Fed and fasting studies of time to maximum concentration (Tmax). Tmax had the largest food effects, with 60% of studies showing a >20% difference in Tmax between fed and fasting states.