Table 1.
Clinically significant interactions—pharmacokinetics
| Natural product (dosage) | Anti-cancer agent (dose) | Proposed mechanism of interaction | Study population | Outcome | Reference |
|---|---|---|---|---|---|
| St John’s wort (Hypercium perforatum) (300 mg three times daily) | Irinotecan (350 mg/m2) | Induction of CYP3A4 | Colorectal cancer (n = 2) | Reduced formation of the active compound SN-38 | Mathijssen et al. 2002 [38] |
| lung cancer (n = 2) | |||||
| sarcoma (n = 1) | |||||
| Imatinib (400 mg) | Induction of CYP3A4 and P-glycoprotein | Healthy individuals (n = 10) | Reduced absorption and increased elimination of imatinib, increased serum imatinib metabolite N-desmethyl-imatinib | Smith et al. 2004 [41] | |
| Docetaxel (135 mg intravenously) | Induction of CYP3A4 | Bladder cancer (n = 6) | Reduced docetaxel plasma level and increased clearance | Goey et al. 2014 [45] | |
| Lung cancer (n = 3) | |||||
| Ovarian cancer (n = 1) | |||||
| Ureteral cancer (n = 1) | |||||
| Grapefruit juice (100–600 mL daily)^ | Nilotinib (400 mg daily) | Inhibition of hepatic CYP3A4 | Healthy individuals (n = 21) | Increased serum nilotinib level | Yin et al. 2010 [48] |
| Sirolimus (dose escalation manner to achieve sirolimus AUC of 3810 ng h/mL) | Inhibition of hepatic CYP3A4 | Cancer patients* (n = 41) | Significantly increased whole blood concentrations of sirolimus | Cohen et al. 2012 [49] | |
| Etoposide (50 mg orally) | Unclear mechanism, but possibly inhibition of intestinal OATP2B1 | Small cell lung cancer (n = 6) | Decreased bioavailability of etoposide | Reif et al. 2002 [50] | |
| Schisandra sphenanthera (three capsules of Schisandra sphenanthera extract containing 11.25 mg deoxyschizandrin twice daily for 13 days) | Sirolimus (2 mg single dose) | CYP3A4 inhibition | Healthy individuals (n = 18) | Enhanced bioavailability and reduced elimination | Li et al. 2012 [58] |
| Curcumin in combination with piperine (curcumin 1200 mg three times daily, piperine 10 mg three times daily) | Tamoxifen (20–30 mg daily) | Unknown | Breast (n = 16) | Decreased tamoxifen and endoxifen AUC0–24 h and Ctrough | Hussaarts et al. 2019 [67] |
*Colorectal sarcoma, pancreas, ovarian, head and neck, lung, thyroid, prostate and oesophagus cancer
^240 mL double-strength grapefruit juice once daily