Skip to main content

The prevalence and predictors of herb-drug interactions among Iranian cancer patients during chemotherapy courses

Abstract

Background

The concurrent usage of herbal medicines with conventional therapies is an important concern in cancer treatment which can lead to unexpected consequences like herb-drug interactions. This study aimed to determine the prevalence of potential herb-drug interactions and to predict factors associated with herb-drug interactions for cancer patients.

Methods

This cross-sectional study was conducted among a convenience sample of 315 cancer patients referring to the oncology clinics of Kerman city in 2018. Data were collected via comprehensive face-to-face interviews and medical chart reviews. A drug interaction checker was used to determine herb-drug interactions. The information of patients was compared based on herb-drug interactions using bivariable logistic regression models, and predictors were determined by the multivariable logistic regression model. All analyses were performed by Stata software version 16.

Results

Of 262 patients (83.2% of the patients) who used herbal medicines, 209 patients [79.8% (95% Confidence Intervals (CI): 75.2 – 85.1)] had potential herb-drug interactions. Chamomile was the most popular herbal medicine (n = 163, 78.0%), and minor and moderate herb-drug interactions were caused by green tea (n = 34, 16.3%) and peppermint (n = 78, 37.5%). The number of chemotherapeutic agents (OR: 1.92, 95% CI: 1.43–2.58; P-value < 0.0001) and the experienced of pain during chemotherapy courses (OR = 2.22, 95%CI:1.00–4.94; P-value = 0.04) were some of the predictors of herb-drug interactions among cancer patients.

Conclusion

Herbal medicine use during chemotherapy was found prevalent among cancer patients; of them, the experience of potential herb-drug interactions was highly frequent. Oncologists and clinical pharmacologists are recommended to take into account challenges associated with herb-drug interactions in their routine practices, particularly during chemotherapy among these patients.

Peer Review reports

Introduction

Cancer is one of the leading causes of death worldwide [1]. World Health Organization (WHO) reports that breast, colorectal, lung, and liver cancers had the highest incidence and mortality rate in the Eastern Mediterranean Region in 2020 [2]. These types of cancers with similar incidence and mortality are also observed in Iran, and there is an increment trend in the incidence and mortality rate for most cancers [3]. Surgery, radiation therapy, and systemic treatment are the main cancer treatment protocols applied separately or in combination for cancer patients [4]. Chemotherapy, as a systemic treatment of cancer, has many side effects, such as nausea and vomiting, diarrhea, mucositis, fatigue, and hair loss [5, 6].

To reduce the short-term and long-lasting side effects of chemotherapy, a great proportion of cancer patients use Complementary and Alternative Medicines (CAM) [7]; this usage is common without consultation provided by physicians and healthcare workers [8]. Among CAM therapies, herbal medicines are more popular among patients. Current reports show a remarkable and variable prevalence of using herbal medicine by cancer patients from 14% to 66.7% [9, 10], especially during conventional treatments or palliative care and chemotherapy (37% -38%) [11, 12]. In fact, concurrently using herbal medicines with conventional therapies is one of the most important concerns in cancer treatment which can lead to unexpected consequences [13].

In the pharmacokinetic interactions, herbal medicines, due to their pharmacokinetic properties, interact with chemical agents and affect the absorption, distribution, metabolism, and excretion of chemotherapeutic agents when orally used. The pharmacodynamics interactions are often lower clinically significant than pharmacokinetic interactions [14]. The herb-drug interactions in cancer patients are more important. However, the prevalence of this event among cancer patients is unknown, and limited studies have reported only a proportion of patients at risk for herb-drug interactions [13, 15]. Along with the unclear prevalence of herb-drug interactions in cancer patients, the epidemiological predictors of it are also unknown. Several studies have only reported the mechanisms of some herb-drug interactions [13, 16]. In this regard, a great proportion of Iranian cancer patients use herbal medicine in combination with a chemotherapeutic agent [17]. According to the lack of updated studies on this issue, this study aimed to determine the prevalence of potential herb-drug interactions among these patients and also identify the epidemiological predicting factors of herb-drug interactions for Iranian cancer patients.

Material and methods

subject and setting

The present cross-sectional study was conducted among 315 cancer patients referred to the oncology clinics of Kerman (one private and two governmental clinics) from February to June 2018. These patients were selected via a convenience sampling method, and sampling was not restricted to sex, cancer site, and clinical stage of cancer. The inclusion criteria were age above 18 years, and receiving at least one chemotherapy course through infusion, injection, or oral route. Patients who had completed the chemotherapy course one month before the survey were also eligible for the study.

Data collection

Data were collected via comprehensive face-to-face interviews and also medical chart reviews. An interview form consisting of three parts was developed to conduct the reviews. In the first part, demographic variables like age, sex, marital status, place of residence, and educational level of patients were collected. The second part included the common name of herbal medicines that patients used in oral route during chemotherapy courses. In the last part of the form, common side effects of chemotherapy, such as constipation and diarrhea, nausea and vomiting, pain, and skin, or oral lesions, were asked. In this part, the status of other comorbidity illnesses was recorded. The first author interviewed all patients in waiting rooms of clinics before the start of the chemotherapy course or after its completion. Additional clinical information was obtained through a medical chart review. The cancer site, clinical stage, metastatic status, and recurrence status were in the clinical information category. To protect patients’ privacy, this part of the data collection was done by the staff of the oncology clinics.

herb-drug interaction assessment

For checking herb-drug interactions, we used a drug interaction checker supported by natural medicine collaboration (URL: https://naturalmedicines.therapeuticresearch.com/). The scientific names of herbal medicines and the generic name of chemotherapeutic agents are checked together as a pair of herb-drug. In this part, two herbalists determined and approved the scientific name of herbal medicines. According to the interaction checker tool's results, which reports published evidence results, interactions were stratified into three levels: minor, moderate, and major based on the evidence (anecdotal evidence, theoretically based on pharmacology, in vitro studies, randomized and non-randomized clinical trials). If the risk of the adverse outcome appeared small, the potential minor drug interactions occurred. Moderate drug interactions may exacerbate the patient's disease and/or a change in the therapy. The severe drug interactions are life-threatening and/or require medical treatment or intervention to minimize or to prevent the severe adverse effects [18].

Data analysis

Data were described using mean ± Standard Deviation (SD), frequency, percentage, and 95% Confidence Intervals (CIs). Demographic and clinical information of patients were compared based on herb-drug interactions by bivariable logistic regression models. Every variable with a P-value < 0.2 in bivariable models was selected and entered into the multivariable logistic regression model. The final model was fitted using backward elimination. In every step of multivariable models, variables with higher P-values were continuously removed from the model set until all remaining variables in the model were significant (P-value < 0.05). All descriptive and analytical analyses were performed by using Stata software version 16.

Results

Demographic and clinical information of cancer patients with herbal medicines

Of 315 cancer patients recruited for the study, 262 patients (83.2%; 95% CI: 78.6, 87.1) used at least one herbal medicine during chemotherapy courses and were included in this analysis. The mean ± SD age of cancer patients who used herbal medicines was 51.1 ± 14.0 years (age range: 18 to 92). More than 70% of the patients were females (n = 188, 71.8%) and urban residents (n = 204, 77.9%). The majority of cancer patients were married (n = 248, 94.7%). More than half of the patients were under diploma (n = 152, 58.0%). The breast was the most prevalent cancer site among patients (n = 98, 37.4%). Almost half of the patients had metastatic cancers (n = 117, 44.7%), but recurrence was not frequent among them (n = 45, 17.2%). More than half of the patients suffered from comorbidities (n = 138, 52.7%). Common complications among patients were nausea and vomiting (n = 186, 71.0%), constipation and diarrhea (n = 169, 64.5%), and pain (n = 160, 61.1%) (Table 1).

Table 1 Prevalence of herb-drug interactions based on demographic and clinical information of cancer patients referred to the outpatient clinics to receive chemotherapy courses (n = 262)

Prevalence of herb-drug interactions

Of 262 patients with herbal medicine, 209 patients [79.8% (95% CI: 75.2–85.1)] had potential herb-drug interaction. The prevalence of herb-drug interactions based on demographic and clinical information is shown in Table 1.

Properties of chemotherapy regimens of cancer patients with interaction

Thirty-three different chemotherapeutic agents were prescribed for cancer patients. The mean ± SD of prescribed medications was 4.0 ± 1.8 per patient (range: 1 to 10). Cyclophosphamide was the most frequent chemotherapeutic agent (n = 105, 50.2%). Arsenic Trioxide, Flutamide, Nivolumab, and Thalidomide (n = 1, 0.48%) were the least prescribed chemotherapeutic agents (Fig. 1).

Fig. 1
figure 1

The common prescribed chemotherapeutic agents and popular herbal medicines among cancer patients with herb-drug interaction in oncology outpatient clinics, Kerman (n = 209) (Right: herbal medicines; Left: chemotherapeutic agents)

Properties of herbal medicines used by cancer patients with potential interaction

Cancer patients with potential herb-drug interaction reported 78 different herbal medicines used during chemotherapy courses. The mean ± SD number of herbal medicines among these patients was 12.6 ± 5.5 per patient (range: 2 to 29). Matricaria chamomilla L. (chamomile) was the most popular herbal medicine among cancer patients (Fig. 1).

Frequency and types of herb-drug interactions

Based on the findings, 128 pairs of herbs and drugs can lead to potential herb-drug interactions. Of them, 19 and 116 pairs of herbs and drugs caused potential minor and moderate herb-drug interactions, respectively. No major herb-drug interaction was found. Potential moderate herb-drug interactions occurred in all patients (n = 209, 100%), while potential minor herb-drug interactions happened in less than a third of the patients (n = 67, 32.1%). The frequent potential minor and moderate herb-drug interactions were caused by Camellia sinensis L. (green tea) (n = 34, 16.3%) and Mentha piperita L. (peppermint) (n = 78, 37.5%), respectively, when used in combination with Cyclophosphamide. Among herbal medicines, Camellia sinensis L. (green tea), Matricaria chamomilla L. (chamomile), Curcuma longa L. (Turmeric), and Silybum marianum L.Gaertn (milk thistle) caused both potential minor and moderate herb-drug interactions. Potential minor and moderate herb-drug interactions are detailed in Additional file 1: Appendix A.

Frequency of confirmed evidence for herb-drug interactions

A considerable number of herb-drug interactions was determined or confirmed by in vitro (66 studies) or clinical studies (46 studies, randomized and non-randomized clinical trials), and only four herb-drug interactions were based on anecdotal evidence (Fig. 2). All herb-drug interactions were confirmed by evidence except nine herb-drug interactions, which were confirmed by more evidence. These pairs were “Cyclophosphamide and Mentha piperita L.” (Vitro and randomized clinical trial), “Cyclophosphamide and Glycyrrhiza glabra L.” (Vitro and randomized clinical trial), “Docetaxel and Glycyrrhiza glabra L.” (Vitro and randomized clinical trial), “Doxorubicin and Valeriana officinalis L.” (Vitro and non-randomized clinical trial), “Paclitaxel and Glycyrrhiza glabra L.” (Vitro and randomized clinical trial), “Tamoxifen and Mentha piperita L.” (Vitro and randomized clinical trial), “Tamoxifen and Foeniculum vulgare Mill” (Vitro and theoretically based on pharmacology), “Tamoxifen and Valeriana officinalis L.” (Vitro and non-randomized clinical trial) and “Tamoxifen and Glycyrrhiza glabra L.” (Vitro and randomized clinical trial). The type of evidence for other herb-drug interactions is presented in Additional file 1: Appendix A.

Fig. 2
figure 2

The frequency of confirmed evidence of herb-drug interactions among cancer patients in the oncology outpatient clinics, Kerman (n = 209)

Mechanisms of actions of herb-drug interactions

Based on the reported evidence, in most drug interactions, induction or inhibition of hepatic and intestinal Cytochrome P450 3A4 (CYP3A4) occurred (139 cases; 69.8%). The first phase of metabolism of chemotherapeutic agents, which mostly depend on CYP3A4, was impaired. Other frequent mechanisms of herb-drug interactions were the dip in GI transit time (11 cases) and the plunge in the hepatotoxicity of chemotherapeutic agents (8 cases) (Table 2).

Table 2 Frequency of action mechanisms of herb-drug interactions among cancer patients referred to outpatient clinics to receive chemotherapy courses (n = 209)

Demographic and clinical correlates of herb-drug interaction among cancer patients

The bivariable logistic regression models showed that herb-drug interactions were related to sex, cancer site, recurrence status, pain experienced as a chemotherapy complication, and the number of chemotherapeutic agents and herbal medicines. Based on the results, females (OR: 2.28, 95% CI: 1.22–4.26; P-value = 0.01) and patients with pain experienced during chemotherapy (OR: 3.16, 95% CI: 1.70–5.87; P-value < 0.0001) had greater odds of herb-drug interactions. By increasing the number of chemotherapeutic agents (OR: 1.75, 95% CI: 1.40–2.19; P-value < 0.0001) and herbal medicines (OR: 1.12, 95% CI: 1.05–1.20, P-value < 0.0001) the odds of herb-drug interactions increased. Patients with gastrointestinal cancers (OR: 0.09, 95% CI: 0.03–0.24, P-value < 0.0001) and other types of cancers (OR: 0.20, 95% CI: 0.04–0.95, P-value = 0.04) versus patients with breast cancer had a lower odd of herb-drug interactions. Also, patients with unclear recurrence status had lower odds of herb-drug interaction compared to patients with negative recurrence status (OR: 0.19, 95% CI: 0.04–0.89, P-value: 0.03) (Table 3).

Table 3 The bivariate logistic regression for comparing demographic and clinical information of cancer patients

Predictors of herb-drug interactions

According to the results of the multivariable logistic regression model, the number of chemotherapeutic agents (OR: 1.92, 95% CI: 1.43–2.58; P-value < 0.0001), number of herbal medicines (OR: 1.15, 95% CI: 1.06–1.24, P-value < 0.0001), gastrointestinal cancers (OR: 0.08, 95% CI: 0.02–0.30, P-value < 0.0001), thorax cancers (OR: 0.10, 95% CI: 0.01–0.61, P-value = 0.01), stage IV cancer (OR: 8.42, 95% CI: 1.10–64.04, P-value = 0.04), unclear recurrence status (OR: 0.06, 95% CI: 0.005–0.67, P-value = 0.02) and the experience of pain during chemotherapy (OR = 2.22, 95%CI:1.00–4.94; P-value = 0.04) were determined as the predictors of herb-drug interactions among cancer patients (Table 4).

Table 4 The predicting factors for potential herb-drug interaction among cancer patients

Discussion

We found that more than eight out of ten cancer patients used herbal medicines during chemotherapy courses, and around eight patients out of ten with a history of herbal medicine consumption had potential herb-drug interactions. Potential moderate herb-drug interactions occurred in all patients, while potential minor herb-drug interactions happened in a third of patients. Chamomile was the most popular herbal medicine, and green tea leads to frequent potential minor and moderate herb-drug interactions. The number of chemotherapeutic agents, the number of herbal medicines, gastrointestinal cancers, thorax cancers, stage IV cancer, unclear recurrence status, and the experience of pain during chemotherapy courses were determined as the predictors of herb-drug interactions among cancer patients.

The high prevalence of using herbal medicines in combination with conventional treatments is an important issue addressed in many studies with different populations [19,20,21,22]. This finding has also been discussed in our study. Most cancer patients used herbal medicines during chemotherapy courses, and according to our previous study, this consumption was also hidden from physicians’ view [17]. Regardless of current treatments, patients use herbal medicines for various reasons. For example, patients believe they can use herbal medicines without trouble because they are natural, effective in treating diseases, reduce cancer symptoms, and have no side effects [23, 24]. These patients have mistaken beliefs about herbal medicines because herbs, when used in combination with drugs, influence the induction and inhibition of metabolic enzymes and, finally, on drug absorption [25]. Herb-drug interaction is the consequence of this combination and may lead to unexpected adverse clinical outcomes such as hepatotoxicity [26]. Studies showed that the prevalence of herb-drug interactions among cancer patients is considerable, and it varies from 2.3% [27] to 46% [28]. The findings of our study showed that more than three-quarters of cancer patients had herb-drug interactions, and this prevalence was higher in comparison to other studies. Some of the reasons for this discrepancy were related to more consumption of herbal medicines by our patients, consumption of herbal medicines which lead to herb-drug interactions such as garlic, green tea [29], and chamomile [30] and identification of new pairs of herb and drugs which result in interactions over time.

The results of our study are consistent with similar related studies [31, 32], indicating that most of the herb-drug interactions are caused by inhibition or induction of the CYP3A4 enzyme. As regards the metabolization of many drugs depending on this enzyme, induction or inhibition of it can lead to unexpected toxicity and under-treatment of cancer. In this regard, physicians and other healthcare workers must pay more attention and better prevent patients from using herbal medicines in combination with other drugs.

We also found that the number of herbal medicines and also chemotherapeutic agents as predictors increased the odds of herb-drug interactions among the patients. This result is in line with the study conducted by Levy et al. (2017) on hospitalized patients [33] and the study by Chi et al. (2020) on community-dwelling older adults [34]. The reason for this event is clear, and by increasing the number of each drug (herbal or chemotherapy), the odds of herb-drug interaction subsequently increased. Another predicting factor was experiencing pain during chemotherapy. A related study shows that a considerable proportion of patients with chronic pain used CAM [35]. Licorice [36], chamomile [37], and peppermint [38] as analgesics are popular herbal medicines and interact with chemotherapeutic agents. As a result, the experience of pain causes the use of herbal medicines, and the herb-drug interaction is the potential outcome of this usage.

Type of cancer and advanced cancer were other predictors of herb-drug interactions. Patients with gastrointestinal and thorax cancer had lower odds of herb-drug interactions versus patients with breast cancer. Two reasons can justify this difference. First, most patients with breast cancer are females, and females are more likely to use herbal medicines in combination with other drugs [39]. The second reason was related to the type of drugs used for patients with breast cancer. Tamoxifen, Letrozole, and Exemestane are common drugs that are usually prescribed for postmenopausal breast cancer patients. These patients used specific herbal medicines to reduce complications of menopause, such as licorice, fennel, and valerian, a supplement with an estrogenic activity that interacts with chemotherapeutic agents [40].

In contrast, patients with advanced cancers had greater odds of herb-drug interaction versus other patients. The results of one study showed that patients with advanced cancer were inclined to use CAM and the prevalence of using herbal medicines among these patients was considerable [41]. There are several reasons for these patients to use herbal medicines. They look for a way to reduce severe cancer symptoms and the side effects of chemotherapy courses. Also, they hope to live longer.

Limitations

This study had four limitations. First, because some of the herbal medicines with one common name have several scientific names, we have restrictions on finding the scientific name of the herbal medicines. For this issue, the herbalists selected the prevalent species of herbal medicines in our country (Iran). Second, some patients may not remember the herbal medicines used due to recall bias. In this regard, we underestimated the prevalence of using herbal medicines in general and in each specific herbal medicine and the potential interactions. Third, we could not determine the exact time for using herbal medicine. So some of the used herbal medicines were not during the chemotherapy time. But based on the experience of cancer therapists in the region, patients prefer to use herbal medicine during chemotherapy to reduce the side effects of medicines. Fourth, as this was a cross-sectional study, we could not confirm the causation of the predictors with the potential herb-drug interaction as the outcome.

Conclusion

Herbal medicine use during chemotherapy was found prevalent among cancer patients (more than eight out of ten patients). Among those with a history of herbal medicine use, the experience of potential herb-drug interactions was highly frequent (around eight out of ten). Some patients were at higher risk of the interaction including, patients with breast cancer, end-stage patients, and those with experienced pain during the treatment course. Oncologists and clinical pharmacologists are recommended to take into account challenges associated with herb-drug interactions in their routine practices, particularly during chemotherapy among these patients. Also, it is necessary to reduce the risk of herb-drug interactions with proper patient education, training their families, and consulting patients to prevent them from self-medication with herbal medicines by involving traditional medicine specialists in the treatment process of cancer patients. Extensive studies are recommended to determine the interactions between herbal medicines and chemotherapeutic agents.

Availability of data and materials

The datasets generated and analyzed during the current study are not publicly available due to confidentiality but are available from the corresponding author at a reasonable request.

References

  1. Watson CJ. The ever-expanding landscape of cancer therapeutic approaches. FEBS J. 288:6082-6086. https://doi.org/10.1111/febs.16228.

  2. WHO cancer regional profile. World Health Organization. 2020. Available from: https://www.who.int/teams/noncommunicable-diseases/surveillance/data/cancer-profiles.

    Google Scholar 

  3. Farhood B, Geraily G, Alizadeh A. Incidence and mortality of various cancers in Iran and compare to other countries: a review article. Iran J Public Health. 2018;47(3):309–16.

    Google Scholar 

  4. Miller KD, Nogueira L, Mariotto AB, Rowland JH, Yabroff KR, Alfano CM, et al. Cancer treatment and survivorship statistics, 2019. CA Cancer J Clin. 2019;69(5):363–85.

    Article  Google Scholar 

  5. Hauner K, Maisch P, Retz M. Side effects of chemotherapy. Der Urologe Ausg A. 2017;56(4):472–9.

    Article  CAS  Google Scholar 

  6. Hsu H, Tsai S, Wu S, Jeang S, Ho M, Liou W, et al. Longitudinal perceptions of the side effects of chemotherapy in patients with gynecological cancer. Support Care Cancer. 2017;25(11):3457–64.

    Article  Google Scholar 

  7. Abdalla MEAH, Ali AM, Loong L. The use of complementary and alternative medicine (CAM) among cancer patients at a tertiary hospital in Malaysia. Complement Ther Med. 2020;50:102343.

    Article  Google Scholar 

  8. Greener M. The hidden problem of herb-drug interactions. Prescriber. 2016;27(9):22–7.

    Article  Google Scholar 

  9. Asiimwe JB, Nagendrappa PB, Atukunda EC, Kamatenesi MM, Nambozi G, Tolo CU, et al. Prevalence of the Use of Herbal Medicines among Patients with Cancer: A Systematic Review and Meta-Analysis. Evid Based Complement Alternat Med. 2021;2021:9963038.

    Article  Google Scholar 

  10. Ong’udi M, Mutai P, Weru I. Study of the use of complementary and alternative medicine by cancer patients at Kenyatta National Hospital, Nairobi Kenya. J Oncol Pharm Pract. 2019;25(4):918–28.

    Article  Google Scholar 

  11. Cheng CW, Fan W, Ko SG, Song L, Bian ZX. Evidence-based management of herb-drug interaction in cancer chemotherapy. Explore. 2010;6(5):324–9.

    Article  Google Scholar 

  12. Engdal S, Steinsbekk A, Klepp O, Nilsen OG. Herbal use among cancer patients during palliative or curative chemotherapy treatment in Norway. Support Care Cancer. 2008;16(7):763–9.

    Article  Google Scholar 

  13. Ramos-Esquivel A, Víquez-Jaikel Á, Fernández C. Potential drug-drug and herb-drug interactions in patients with cancer: a prospective study of medication surveillance. J Oncol Pract. 2017;13(7):e613–22.

    Article  Google Scholar 

  14. Awortwe C, Makiwane M, Reuter H, Muller C, Louw J, Rosenkranz B. Critical evaluation of causality assessment of herb–drug interactions in patients. Br J Clin Pharmacol. 2018;84(4):679–93.

    Article  Google Scholar 

  15. Alsanad SM, Howard RL, Williamson EM. An assessment of the impact of herb-drug combinations used by cancer patients. BMC Complement Altern Med. 2016;16(1):1–9.

    Article  Google Scholar 

  16. Fasinu PS, Rapp GK. Herbal interaction with chemotherapeutic drugs—a focus on clinically significant findings. Front Oncol. 2019;9:1356.

    Article  Google Scholar 

  17. Bazrafshani MS, Khandani BK, Pardakhty A, Tajadini H, Malek Pour Afshar R, Moazed V, et al. The prevalence and predictors of using herbal medicines among Iranian cancer patients. Complement Ther Clin Pract. 2019;35:368–73.

    Article  Google Scholar 

  18. Soherwardi S, Chogtu B, Faizal P. Surveillance of the Potential Drug-Drug Interactions in the Medicine Department of a Tertiary Care Hospital. J Clin Diagn Res. 2012;6(7):1258-61.

  19. Wolf CP, Rachow T, Ernst T, Hochhaus A, Zomorodbakhsch B, Foller S, et al. Complementary and alternative medicine (CAM) supplements in cancer outpatients: analyses of usage and of interaction risks with cancer treatment. J Cancer Res Clin Oncol. 2022;148(5):1123–35.

    Article  Google Scholar 

  20. Azizah N, Halimah E, Puspitasari IM, Hasanah AN. Simultaneous use of herbal medicines and antihypertensive drugs among hypertensive patients in the community: a review. J Multidiscip Healthc. 2021;14:259.

    Article  Google Scholar 

  21. McIntyre E, Saliba AJ, Wiener KK, Sarris J. Herbal medicine use behaviour in Australian adults who experience anxiety: a descriptive study. BMC Complement Altern Med. 2016;16(1):1–12.

    Article  Google Scholar 

  22. Hughes GD, Aboyade OM, Beauclair R, Mbamalu ON, Puoane TR. Characterizing herbal medicine use for noncommunicable diseases in urban South Africa. Evid based Complement Alternat Med. 2015;2015:736074.

    Article  Google Scholar 

  23. Routledge PA, Bracchi R. Adverse drug reactions to herbal medicines. Adverse Drug Reaction Bulletin. 2021;331(1):1283–6.

    Article  Google Scholar 

  24. Welz AN, Emberger-Klein A, Menrad K. Why people use herbal medicine: insights from a focus-group study in Germany. BMC Complement Altern Med. 2018;18(1):1–9.

    Article  Google Scholar 

  25. Fasinu PS, Bouic PJ, Rosenkranz B. An overview of the evidence and mechanisms of herb–drug interactions. Front Pharmacol. 2012;3:69.

    Article  Google Scholar 

  26. Parvez MK, Rishi V. Herb-drug interactions and hepatotoxicity. Curr Drug Metab. 2019;20(4):275–82.

    Article  CAS  Google Scholar 

  27. Mahmoud D. The Prevalence of Clinically Relevant Herb-Drug Interactions between Herbal Products and Anti-Cancer Therapy in Older Adults with Cancer. 2021.

    Google Scholar 

  28. Van Leeuwen R, Brundel D, Neef C, van Gelder T, Mathijssen R, Burger D, et al. Prevalence of potential drug–drug interactions in cancer patients treated with oral anticancer drugs. Br J Cancer. 2013;108(5):1071–8.

    Article  Google Scholar 

  29. Engdal S, Klepp O, Nilsen OG. Identification and exploration of herb-drug combinations used by cancer patients. Integr Cancer Ther. 2009;8(1):29–36.

    Article  Google Scholar 

  30. Ganzera M, Schneider P, Stuppner H. Inhibitory effects of the essential oil of chamomile (Matricaria recutita L.) and its major constituents on human cytochrome P450 enzymes. Life Sci. 2006;78(8):856–61.

    Article  CAS  Google Scholar 

  31. Fahim SM, Mishuk AU, Cheng N, Hansen R, Calderón AI, Qian J. Adverse event reporting patterns of concomitant botanical dietary supplements with CYP3A4 interactive & CYP3A4 non-interactive anticancer drugs in the US Food and Drug Administration Adverse Event Reporting System (FAERS). Expert Opin Drug Saf. 2019;18(2):145–52.

    Article  CAS  Google Scholar 

  32. Engdal S, Nilsen OG. In vitro inhibition of CYP3A4 by herbal remedies frequently used by cancer patients. Phytother Res. 2009;23(7):906–12.

    Article  Google Scholar 

  33. Levy I, Attias S, Ben-Arye E, Goldstein L, Schiff E. Potential drug interactions with dietary and herbal supplements during hospitalization. Intern Emerg Med. 2017;12(3):301–10.

    Article  Google Scholar 

  34. Chi D, Ding D, Zhao Q, Liang X, Wu W, Luo J, et al. Potential herb–drug interactions in community-dwelling older adults in China: the Shanghai Aging Study. Aging Clin Exp Res. 2020;32(12):2677–85.

    Article  Google Scholar 

  35. Tan M, Win MT, Khan SA. The use of complementary and alternative medicine in chronic pain patients in Singapore: a single-centre study. Ann Acad Med Singapore. 2013;42(3):133–7.

    Article  Google Scholar 

  36. Mi T, Li X, Zhou G, Qiao S, Shen Z, Zhou YJA, et al. HIV disclosure to family members and medication adherence: role of social support and self-efficacy. AIDS Behav. 2020;24(1):45–54.

    Article  Google Scholar 

  37. Zargaran A, Borhani-Haghighi A, Salehi-Marzijarani M, Faridi P, Daneshamouz S, Azadi A, et al. Evaluation of the effect of topical chamomile (Matricaria chamomilla L.) oleogel as pain relief in migraine without aura: a randomized, double-blind, placebo-controlled, crossover study. Neurol Sci. 2018;39(8):1345–53.

    Article  Google Scholar 

  38. Mahboubi M. Mentha spicata as natural analgesia for treatment of pain in osteoarthritis patients. Complement Ther Clin Pract. 2017;26:1–4.

    Article  Google Scholar 

  39. Agbabiaka TB, Spencer NH, Khanom S, Goodman C. Prevalence of drug–herb and drug–supplement interactions in older adults: a cross-sectional survey. Br J Gen Pract. 2018;68(675):e711–7.

    Article  Google Scholar 

  40. Kargozar R, Azizi H, Salari R. A review of effective herbal medicines in controlling menopausal symptoms. Electron Physician. 2017;9(11):5826.

    Article  Google Scholar 

  41. Pietrzyński Ł, Pysz-Waberski D, Pietrzyńska T, Kliber M, Gisterek I. Prevalence of complementary and alternative therapy use by patients with advanced and metastatic cancer. Palliative Medicine in Practice. 2022;16(2):108–16.

    Article  Google Scholar 

Download references

Acknowledgements

We thank cancer patients and their families for their participation in this study and also, and we are particularly grateful to the staff of oncology clinics for helping us with data collection. We greatly appreciate Professor Mir Tajadini, Sharifi Far, and Rameshk for all the helpful advice in identifying medicinal plant species used as herbal medicines.

Funding

The research deputy of the Kerman University of Medical Sciences funded this study. (Grant number, 95000567).

Author information

Authors and Affiliations

Authors

Contributions

All authors contributed to the conceptualization of the study and its methodology. H.S., A.B., S.A., B.K.K. and H.T. was responsible for data curation. Formal analysis and validation were conducted M.S.B, S.M. and A.P. also validated the study. H.S. was the project administrator and wrote the original draft. S.A., S.G.P. and S.H supervised the project. All authors reviews and edited the final version. The author(s) read and approved the final manuscript.

Corresponding authors

Correspondence to Abbas Pardakhty or Hamid Sharifi.

Ethics declarations

Ethics approval and consent to participate

The ethics committee of Kerman University of Medical Sciences provided ethical approval for the study. Oral informed consent was obtained from the participants. The approval for verbal informed consent was given by the ethics committee of Kerman University of Medical Sciences (ethics no: IR.KMU.REC.1396.1278) because of the retrospective nature of the study. The researchers confirm that all methods were performed in accordance with the relevant guidelines and regulations at the local and international levels.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bazrafshani, M.S., Pardakhty, A., Kalantari Khandani, B. et al. The prevalence and predictors of herb-drug interactions among Iranian cancer patients during chemotherapy courses. BMC Complement Med Ther 23, 41 (2023). https://doi.org/10.1186/s12906-023-03869-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12906-023-03869-1

Keywords