Hidden Dangers of Concurrent Use of Herbal Products and Oncology Drugs
- contact pharmaca
- Sep 6
- 6 min read
Complementary and alternative medicine refers to the use of products and practices that are not part of standard medical care. These therapies include a wide range of herbal and nutritional products, and studies show that up to 90% of cancer patients use them during at least part of their oncological treatment. However, only 25% of patients report this to their physician. Despite limited data on the safety and efficacy of herbal products, the use of herbal remedies and complementary medicine is increasing worldwide. This phenomenon is attributed to patients’ desire for holistic treatment, personal control over therapeutic choices, and, understandably, the hope of a cure.
However, these products, like synthetic and natural medicines, can alter physiological processes and cause toxicity. They are insufficiently regulated by law, easily available (especially via the internet), and their active ingredient content and impurity levels may vary. One of the main under-researched risks is their concurrent use with oncology drugs and the potential for interactions. The most common mechanism of interactions is pharmacokinetic—inhibition or induction of metabolic enzymes or transport proteins—which leads to altered plasma concentrations of the drug. Interactions are particularly risky with drugs that have a narrow therapeutic window, such as chemotherapeutics used in oncology. One study found that 78% of patients receiving chemotherapy used herbal and complementary preparations, and 27% of patients were at risk of clinically significant interactions.
Oncology drugs are associated with a range of acute and chronic toxicities, and the risk may increase with concurrent use of drugs that affect their metabolism. Therefore, it is important to know (and specifically ask) which medications and other preparations patients are taking.
Potential for Interactions
Most research has focused on laboratory studies, which do not necessarily reflect the clinical significance of interactions. However, for certain interactions between herbal preparations and chemotherapeutics, case reports and clinical studies exist that have confirmed the possibility of clinically observable interactions of many herbal products with oncology drugs. A study investigating reported cases of interactions between oncology drugs and 10 selected herbal products in the World Health Organization’s VigiBase database identified 1,057 individual adverse event reports as possible consequences of such interactions. The most commonly reported were hepatotoxicity, hematological toxicity, and nausea.
Some of the pharmacokinetic interactions between oncology drugs and herbal products documented in the literature are shown in Table 1.
Table 1. PK interactions between oncology drugs and herbal products.
Herbal product (Latin name) | Oncology drug | Study type | Result |
Echinacea (Echinacea purpurea) | Etoposide | Case report | Significant reduction in platelet count |
Echinacea (Echinacea purpurea) | Docetaxel | Prospective study in 10 patients | No significant effect on docetaxel PK |
Garlic (Allium sativum) | Docetaxel | Prospective, controlled study | Decreased clearance of docetaxel |
Ginseng (Panax ginseng) | Imatinib | Case report | Hepatotoxicity; recovery after discontinuation of ginseng |
Grapefruit (Citrus paradisi) | Docetaxel | Case report | Increased concentration and prolonged t½ of docetaxel |
Grapefruit (Citrus paradisi) | Nilotinib | Open-label, randomized study | Increased concentration of nilotinib |
Milk thistle (Silybum marianum) | Irinotecan | PK study | Decreased clearance of irinotecan (not statistically significant) |
Milk thistle (Silybum marianum) | Gefitinib | Multiple adverse event reports (VigiBase) | PK: ↑ toxicity (pruritus, dry mouth, somnolence, etc.) |
Milk thistle (Silybum marianum) | Sorafenib | Multiple adverse event reports (VigiBase) | PK: ↑ toxicity (alopecia, nail discoloration) |
Milk thistle (Silybum marianum) | Imatinib | Adverse event report (VigiBase) | PK: ↑ toxicity (anemia, pyrexia) |
Milk thistle (Silybum marianum) | Capecitabine | Multiple adverse event reports (VigiBase) | PK: ↑ toxicity (pruritus, nausea) |
Milk thistle (Silybum marianum) | Doxorubicin | Adverse event report (VigiBase) | PK: ↑ toxicity (arrhythmia) |
Ginger (Zingiber officinale) | Imatinib | Adverse event report (VigiBase) | PK: ↑ hepatotoxicity |
Ginger (Zingiber officinale) | Dabrafenib/Trametinib | Adverse event report (VigiBase) | PK: ↑ thrombocytopenia, rectal bleeding |
Ginger (Zingiber officinale) | Crizotinib | Adverse event report (VigiBase) | PK: ↑ hepatotoxicity |
Green tea (Camellia sinensis) | Erlotinib | Adverse event report (VigiBase) | PK: ↑ hemoptysis, rash |
Cannabis (Cannabis sativa) | Everolimus | Adverse event report (VigiBase) | PK: ↑ nausea |
Cannabis (Cannabis sativa) | Nintedanib | Adverse event report (VigiBase) | PK: ↑ elevated transaminases |
Cannabis (Cannabis sativa) | Palbociclib | Adverse event report (VigiBase) | PK: ↑ tumor markers, discomfort |
Turmeric (Curcuma longa) | Everolimus + Palbociclib | Adverse event report (VigiBase) | PK: ↑ triglycerides, dry skin |
Turmeric (Curcuma longa) | Ibrutinib | Multiple adverse event reports (VigiBase) | PK: ↑ toxicity (thrombocytopenia, bleeding, hypertension, etc.) |
Turmeric (Curcuma longa) | Palbociclib | Adverse event report (VigiBase) | PK: ↑ hematologic toxicity |
Turmeric (Curcuma longa) | Bortezomib | Multiple adverse event reports (VigiBase) | PK: ↑ toxicity (constipation, leukopenia, sweating) |
St. John’s wort (Hypericum perforatum) | Docetaxel | PK study | Significant decrease in docetaxel concentration |
St. John’s wort (Hypericum perforatum) | Imatinib | Two open-label studies | Decrease in imatinib concentration by 32% and 30% |
Most oncology drugs are substrates of CYP enzymes and transport proteins, and many herbal products act as their inducers or inhibitors. The most common clinically significant interactions involve the cytochrome P450 (CYP) enzyme CYP3A4, but CYP2D6, CYP1A2, CYP2C9, and CYP2C19 are also important.
Pharmacokinetic interactions at the level of CYP enzymes occur through inhibition or induction of the enzyme, resulting in either an increase (with an inhibitor) or a decrease (with an inducer) of the concentration of the substrate drug. An increase in drug concentration above therapeutic levels raises the risk of toxicity, while a decrease reduces treatment efficacy.
Table 2 presents selected CYP enzymes, their substrates, and herbal products that may induce or inhibit their metabolic activity.
Metabolic enzyme | CYP enzyme inducer | CYP enzyme inhibitor | Substrate(s) |
CYP1A1/1A2 | Cannabis (THC – tetrahydrocannabinol) | St. John’s wort (extract: biapigenin) | axitinib, bendamustine, bortezomib, dacarbazine, etoposide, exemestane, flutamide, pazopanib, pomalidomide, tegafur |
CYP2A6 | — | — | cyclophosphamide, ifosfamide, letrozole, tegafur |
CYP2B6 | St. John’s wort | — | busulfan, cyclophosphamide, docetaxel, doxorubicin, ifosfamide, procarbazine, thiotepa |
CYP2C8 | — | — | anastrozole, dabrafenib, cyclophosphamide, enzalutamide, ifosfamide, imatinib, lapatinib, nilotinib, paclitaxel, pazopanib, tegafur |
CYP2C9 | — | Milk thistle; St. John’s wort (extracts: biapigenin, hyperforin, hypericin) | busulfan, ifosfamide, idarubicin, ruxolitinib, tamoxifen |
CYP2C19 | St. John’s wort | Ginkgo | axitinib, bortezomib, cyclophosphamide, ifosfamide, lapatinib, pomalidomide, tamoxifen, thalidomide |
CYP2D6 | — | St. John’s wort (extracts: hyperforin, hypericin); Cannabis (cannabidiol) | brentuximab, doxorubicin, gefitinib, idarubicin, pomalidomide, tamoxifen, vinblastine, vinorelbine |
CYP2E1 | St. John’s wort | — | dacarbazine, etoposide, cisplatin, vinorelbine |
CYP3A4/3A5 | Echinacea, kava-kava, St. John’s wort, garlic, ginseng | Echinacea, ginkgo, grapefruit, milk thistle, St. John’s wort (extract: biapigenin, hypericin), turmeric, ginger | anastrozole, axitinib, bortezomib, bosutinib (orig. “bositinib”), brentuximab, cabazitaxel, cisplatin, crizotinib, cyclophosphamide, dabrafenib, dasatinib, docetaxel, doxorubicin, enzalutamide, etoposide, exemestane, gefitinib, imatinib, fulvestrant, ifosfamide, irinotecan, lapatinib, letrozole, mitoxantrone, nilotinib, olaparib, paclitaxel, pazopanib, pomalidomide, ponatinib, procarbazine, regorafenib, ruxolitinib, sorafenib, sunitinib, temsirolimus, teniposide, thiotepa, topotecan, trabectedin, vandetanib, vemurafenib, vinblastine, vincristine, vinorelbine |
P-glycoprotein (ABCB-1, MDR-1) | Echinacea, St. John’s wort | Green tea, cannabis, turmeric, ginger | axitinib, bicalutamide, bosutinib, cytarabine, dactinomycin, dasatinib, daunorubicin, docetaxel, doxorubicin, epirubicin, etoposide, gefitinib, idarubicin, imatinib, irinotecan, methotrexate, mitoxantrone, paclitaxel, sunitinib, vincristine |
The most frequently recorded interactions occur at the level of CYP3A4, since most oncology drugs, as well as drugs in general, are metabolized by this enzyme. Oncology drugs metabolized by CYP3A4 include tyrosine kinase inhibitors, MEK and BRAF inhibitors, CDK4/6 inhibitors, taxanes, cyclophosphamide, and many others. In addition to those listed, other herbal products also have the potential to interact with oncology drugs. For many herbal products, especially combined formulations, the risk cannot be assessed due to lack of data.
Phytovigilance
The importance of pharmacovigilance is well recognized for understanding the benefits and risks of various drugs in real-world conditions outside controlled clinical trials. In recent years, there has been increasing recognition of the need for phytovigilance, which refers to the systematic monitoring of adverse effects and interactions of herbal products. Phytovigilance is supported by the European Medicines Agency and the European Food Safety Authority, and it is particularly important for ensuring the safe use of oncology drugs.
Conclusion
Knowledge of the potential impact of herbal preparations on medications is important for both physicians and patients. Physicians should ask patients about their use of herbal products and discuss possible risks and benefits. Since patients often do not disclose their use of complementary and alternative products, it is important to approach them with understanding and without judgment.
Studies show that patients are willing to discontinue herbal product use if they know these may negatively affect cancer treatment. This highlights the importance of open communication with patients and active listening. Such an approach helps build trust and encourages better patient adherence to treatment.
References:
1. McCune JS, Hatfield AJ, Blackburn AA, i sur. Potential of chemotherapy-herb interactions in adult cancer patients. Support Care Cancer. 2004;12(6):454-62. doi: 10.1007/s00520-004-0598-1.
2. Fasinu PS, Rapp GK. Herbal Interaction With Chemotherapeutic Drugs-A Focus on Clinically Significant Findings. Front Oncol. 2019 3;9:1356. doi: 10.3389/fonc.2019.01356.
3. NaturalMedicines. https://naturalmedicines.therapeuticresearch.com/
4. Pochet S, Lechon AS, Lescrainier C, i sur. Herb-anticancer drug interactions in real life based on VigiBase, the WHO global database. Sci Rep 2022;12,:14178. https://doi.org/10.1038/s41598-022-17704-z
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