Table 2.

Twelve non-serious hepatobiliary ADR case reports recorded during clinical trials with 397 patients on Petadolex^®. Information on 12 hepatobiliary events recorded during clinical studies and suspected to be related to exposure with Petasites hybridus extracts.

Case No.	Gender (Age)	Time to Onset of ADRs (days)	Duration of Drug Intake (Days)	Daily Dose (mg)	ALT (Max) [×ULN *]	AST (Max) [×ULN *]	Co-Medications	Notes	WHO/UMC Score	Year of Report
1	Female	3 months	3 months	100	0.80	1.17	Acute migraine medication possible, other unknown	Clinical study [3] Minimal transaminase changes	No clinical relevance	1993
2	Female	3 months	3 months	100	0.69	1.11	Acute migraine medication possible, other unknown	Clinical study [3] Minimal transaminase changes	No clinical relevance	1993
3	Female	3 months	3 months	100	0.63	1.00	Acute migraine medication possible, other unknown	Clinical study [3] Minimal transaminase changes	No clinical relevance	1993
4	Female	4 months	4 months	50	0.66	0.80	L-Thyroxine, Rizatriptan, Cyclandelat, Acetylsalicylic acid + Paracetamol, Sumatriptan	Clinical study [5] Minimal transaminase changes	No clinical relevance	1999
5	Female	4 months	4 months	50	0.59	0.60	L-Thyroxine, Estradiol, Enalapril + Hydrochlorothiazid, Paracetamol, Meatmizol, Ibuprofen, Acetylsalicylic acid, Acetylsalicylic acid + Paracetamol	Clinical study [5] Minimal transaminase changes	No clinical relevance	1999
6	Female	4 months	4 months	50	0.77	0.87	Acetylsalicylic acid, Phenazone/caffeine, Paracetamol, dihydroergotamin, DL-Lysinmono(acetylsalicylat) (Aspisol), Metamizole, Acetylsalicylic acid + Paracetamol	Clinical study [5], Cardiac insufficiency since 1993, Hypertension since 1997, Hypercholesterinaemia, Hyperthyroidism since 1992; GGT approximate 1.3 ×ULN Cardiac arrhythmia since 1998, Bilirubin increased approximately 1.35 ×ULN and recovered in the follow up period	No clinical relevance	1999
7	Male	4 months	4 months	50	0.93	1.26	Albuterol, Salmeterol, Rizatriptan, Lisinopril + Hydrocholorothiazide, Rizatriptan, Acetaminophen	Clinical study [5], chronic obstructive pulmonary disease; Minimal transaminase changes	No clinical relevance	1999
8	Female	4 months	4 months	50	0.63	0.57	Naratriptan, Butabital + Acetaminophen + caffeine	Clinical study [5], GGT (1.52 ×ULN)	Possible	1999
9	Male	4 months	4 months	75	1.09	0.83	Naratriptan, Acetylsalicylic acid, Metoclopramide	Clinical study [5] Minimal transaminase changes	No clinical relevance	1999
10	Male	4 months	4 months	75	1.23	0.95	Sumatriptan, Rizatriptan	Clinical study [5], GGT at screening: 5 ×ULN; final visit 5.24 ×ULN)	Unlikely	1999
11	Female	4 months	4 months	75	0.48	0.26	Nabumetone, Loratidine, Albuterol, Acetaminophen, Acetaminophen + Acetylsalicylic acid + caffeine	Clinical study [5] Minimal transaminase changes	No clinical relevance	1999
12	Female	4 months	4 months	75	1.05	0.71	Norethindrone, Ethinyl Estradiol, Celecoxib, Acetaminophen + Acetylsalicylic acid + caffeine, Ibuprofen	Clinical study [5] Minimal transaminase changes	No clinical relevance	1999

* Reference values of the clinical study centres: Diener et al. [3] and Grossmann et al. [4]: AST ≤ 18 U/L, ALT ≤ 17 U/L; Lipton et al. [5]: AST ≤ 42 U/L, ALT ≤ 40 U/L.