TABLE 3.
Comparative safety and tolerability evidence of HP versus NSAIDs or conventional therapies.
| Formulation category | HP intervention | Comparator | Study design | Sample size (n) | Main safety findings | Comparative interpretation | References |
|---|---|---|---|---|---|---|---|
| Monotherapy | Harpadol® 2,610 mg/day (harpagoside 57 mg) | Diacerein 100 mg/day | RCT | 122 | Lower overall AE rate and lower incidence of diarrhea observed in the HP group | HP demonstrated generally favorable gastrointestinal tolerability under study conditions | Chantre et al. (2000) |
| Doloteffin® 2,400 mg/day (harpagoside 60 mg) | Rofecoxib 12.5 mg/day | RCT, DB | 88 | Similar overall AE rates reported between groups; fewer discontinuations observed in the HP group | Comparable short-term tolerability was reported; interpretation limited by small sample size | Chrubasik et al. (2003) | |
| HP extract 6,000 mg/day (harpagoside 50 mg) | Placebo | RCT, DB, PC | 109 | Lower total AE events observed in the HP group compared with placebo | Findings suggest acceptable short-term tolerability under study conditions | Chrubasik et al. (1996) | |
| Combination | MA212 (Rosaxan®) containing HP extract 108 mg | Placebo | RCT, DB, PC | 90 | Lower AE incidence and no treatment discontinuation reported in the HP group | Suggests generally favorable tolerability profile | Moré et al. (2017) |
| Artipotect® containing HP extract 150 mg | None | Single-arm, OL | 130 | Low incidence of gastrointestinal adverse events and high medication adherence reported | Long-term tolerability appeared acceptable in this observational study | Puigdellivol et al. (2019) | |
| Tregocel® containing HP extract 1,000 mg | None | Single-arm, OL | 137 | Gastrointestinal and laboratory-related adverse events were reported at relatively low frequency | Observational findings suggest generally acceptable tolerability | Żęgota et al. (2021) | |
| Artipotect Forte® containing HP extract 150 mg | None | Single-arm, OL | 186 | Very low AE incidence and high medication adherence reported | Suggests favorable patient-reported tolerability | Puigdellívol Grifell et al. (2024) |
Abbreviations: VAS = RCT, randomized controlled trial; DB, Double-blind; AC, Active-controlled; PC, Placebo-controlled; AEs, Adverse events; HP, harpagophytum procumbens; OL, Open-label.