Herbal medicine consumption has dramatically increased globally. ¹ This is due to widespread self-medication among populations, as these products are safe with minimum adverse effects, are inexpensive, and have better compatibility and cultural acceptability. ^{2 , 3} Additionally, marketing strategies by manufacturers through different methods, such as media, have increased consumers’ awareness about herbal products. ⁴ Nevertheless, the use of herbal medicines, either alone or in combination with other conventional medicines, without informing physicians or pharmacy practitioners may lead to detrimental clinical outcomes.

Herbal product use is common in Arab countries, including Jordan. ⁵ They are available at community pharmacies as registered prepackaged products. Notably, patients use conventional medications concurrently with herbal products for the treatment of various conditions, ⁶ as they are easily purchased without a prescription. However, this has gained significant attention due to the potential risk of drug-herb interactions, as some herbs may mimic, increase, or decrease the action of conventional medications, which is important to consider with drugs that have a narrow therapeutic index, such as warfarin or digoxin. ⁷ Consequently, investigating the safe use of herbal products is considered a major priority.

Herbal product-drug interactions are based on either pharmacokinetic or pharmacodynamic mechanisms. ⁸ Herbal products may alter drug absorption (e.g., pectin reduces lovastatin absorption), ⁹ drug metabolism (e.g., St. John’s wort might increase warfarin metabolism, thus decrease its efficacy), ¹⁰ or drug renal excretion (e.g., digoxin renal excretion is increased by St. John’s wort). ¹¹ Furthermore, such interactions may have an additive or synergistic effect. For example, aspirin’s antiplatelet effect is enhanced by ginkgo biloba. ¹² On the other hand, some herbal products may antagonize the action of some medications. For example, green tea can antagonize the anticoagulant effect of warfarin as green tea contains small amounts of vitamin K, which may alter warfarin’s action. ¹³

The prevalence of cardiovascular diseases has increased worldwide. ¹⁴ Most patients have been prescribed anticoagulants, antiplatelets, digoxin, antihypertensives, and antihyperlipidemic agents, which may have a synergistic or antagonistic interaction with herbal products, consequently raising patients’ morbidity and mortality risks. ^{10 , 15} Therefore, the use of herbal products should not be initiated without careful consideration of possible drug-herb interactions.

Since pharmacists are the connection between the patient and drug utilization, they are the main attainable health care practitioners ¹⁶ and they receive more queries about medications. ¹⁷ Therefore, they play a pivotal role in advising patients and creating awareness of the safe, proper, and rational use of herbal products. ¹⁸ Nevertheless, to advise patients properly, pharmacists must have noticeable knowledge about herbal products’ therapeutic indications, doses, side effects, and potential interactions with conventional medicines. Inadequate knowledge about herbal products may result in potentially severe adverse events.

Therefore, the present study was conducted to assess the attitude, knowledge, awareness, and dispensing practices among pharmacy practitioners regarding the safe use of herbal drugs and their potential interactions with cardiovascular medications.

Herbal product use has increased tremendously globally and in Arab countries, ^{37 , 38} including Jordan. ^{5 , 39 , 40} It has been reported that 80.2% of the laypeople population use herbal products in Jordan ⁴¹ ; herbal remedies are favored by individuals, as evidenced by previous studies, because they are natural and, consequently, safe. Meanwhile, herbal products have good efficacy and low cost. ^{42 , 43}

Knowledge and awareness of drug-herb interactions are substantial for delivering safe and effective drug therapy. Although herbal products are natural and, therefore, safe, ⁴⁴ some herbal products can affect P-glycoprotein drug transporters, cytochrome P450 enzymes, and other metabolic enzymes ⁴⁵ ; this may result in potential drug interactions, particularly with narrow window medications, if they are taken simultaneously, ⁴⁶ which can result in life-threatening consequences and increase health care costs. Recent studies have demonstrated serious interactions between herbal remedies and medications used in cardiovascular diseases. ^{11 , 47 , 48} Therefore, this study was the first one conducted in Jordan to assess the knowledge and awareness of pharmacy practitioners concerning the interaction of herbal products and cardiovascular medications.

This study revealed that more than half of respondents dispensed herbal remedies without a prescription, ⁴⁹ specifically for the treatment and control of different illnesses, mainly gastrointestinal problems, ^{50 , 51} obesity, ⁵² and diabetes. ⁵⁰ Notably, respondents had medium knowledge about herbal products, which was mainly gained from university during their years of study, where they were exposed to herb-related academic courses in the pharmacy curriculum. ⁵³ Other participants chose websites, product leaflets and other colleagues or medical representatives as sources of information about herbal products. ⁵⁴ A large proportion of respondents also relied on the internet to gain knowledge about herbal products; however, media and internet information are not often supervised by a medical or pharmaceutical institution to ensure the accuracy of the information. It has been reported that Missouri’s pharmacists’ knowledge reference towards herbal products was determined by the familiarity of the pharmacists with resource accessibility rather than resource quality. ⁵⁵ Thereby, providing access to authenticated resources, in addition to offering educational programs for pharmacy practitioners about herbal products, is strongly needed.

Despite pharmacy practitioners’ knowledge about herbal products, they usually informed patients about herbal medicine indications, interactions with conventional medications, and conditions that make herbal products unsafe. ⁴⁵ Nevertheless, not caring about herbal products available in community pharmacies impedes pharmacy practitioners from discussing the use of herbal medicines with consumers when purchasing or asking about them, ⁵⁶ this suggests that pharmacy practitioners should be aware about their role in guiding the safe and effective use of herbal products by better communication with patients. ⁵⁷ Additionally, other barriers that could impede pharmacy practitioners and have a considerable influence from discussing herbal remedies are a lack of knowledge or lack of authoritative resources about herbal products. ^{58 , 59} To facilitate patients’ acquisition of adequate herbal product counselling, pharmacy practitioners’ education programs and training should be implemented to ascertain the awareness of herbal product counselling and consolidate the provided professional pharmaceutical care services. ^{60 , 61} Because the prevalence of cardiovascular diseases has increased dramatically in Jordan, ⁶² this may expand the number of patients’ taking multiple cardiovascular medications in addition to herbal remedies. Some herbal products may have adverse cardiovascular effects, whilst others may interact with cardiovascular medications, such as ginseng, gingko biloba, St. John’s wort, garlic, and induce serious consequences. For example, patients taking anticoagulants, such as warfarin, should avoid the use of ginseng and ginkgo biloba, as they can increase warfarin’s anticoagulant effect, thereby increasing the risk of bleeding. ⁶³ Green tea may antagonize warfarin’s anticoagulant effect, ⁶⁴ therefore reducing warfarin’s effectiveness.

St. John’s wort may induce the activity of cytochrome P450 isoenzymes CYP1A2, CYP3A4, and CYP2C9 ⁶⁵ ; thus, it may reduce the plasma concentration of co-medications like digoxin, ³² simvastatin, ⁶⁶ and warfarin, ⁶⁷ which may reduce their therapeutic efficacies. It has been reported that a patient who had used aspirin for five years experienced eye bleeding after the addition of gingko biloba self-medication for one week. ⁶⁸ Therefore, pharmacy practitioners should be vigilant regarding patient counselling on herbal-drug interactions if they are used concurrently with cardiovascular medications to achieve the intended therapeutic outcomes and minimize health complications.

This study revealed that pharmacy practitioners’ overall knowledge score about herbal product interactions with cardiovascular drugs is significantly different based on their age, education level, and years of experience. It was expected that older pharmacy practitioners with more years of work experience and a higher educational level attained, would demonstrate a higher overall knowledge score. Unexpectedly, participants with less than one year of work experience had a significantly higher knowledge score compared to participants who had 6 to 10 years’ experience. The possible explanation is they are newly graduated and have taken courses related to herbal products recently in their studies, as shown in Figure 2, that 68.1% of the respondents relied on their university study courses to gain information about herbal products.

As well, postgraduate education is correlated with more educational courses being studied, which might be relevant to herbal products. However, previous studies have not specifically demonstrated the impact of demographic factors on pharmacy practitioners‘knowledge about herbal product interactions with traditional medications, but they have established that age, education level, and experience (year) influence their general knowledge related to herbal products. ⁶¹ Regarding the findings of pharmacy practitioners’ practice on the use and dispensing of herbal products, 38.4% agreed that herbal products are effective to improve patient’s health, ⁶⁹ 32.3% agreed they are safe and have limited drug interactions, ⁴⁵ whilst 43.1% strongly agreed they need more knowledge about herbal medicine, which could be achieved by providing courses to workers on the use of herbal products, their side effects, and medicine interactions. Therefore, educational courses on herbal medicine are mandatory. ⁷⁰ However, their attitudes about stopping conventional medication while using herbal products were positive if there were any drug interactions (36.6%), while others said patients should not stop using conventional medicine (25%). ⁷¹ Patients with chronic diseases who use herbal remedies without informing their physicians, or even physicians who do not guide patients about using these products, may increase potential drug-herb interactions, particularly cardiovascular drugs, which induce detrimental health complications. ⁷² Therefore, a lack of counselling that warns patients about the risk of inappropriate consumption of herbal products will aggravate the condition; pharmacy practitioners play a pivotal role in ensuring patients adhere to the safe use of herbal remedies.

In summary, pharmacy practitioners’ having good knowledge is compulsory for good practice. ⁷³ It is essential for pharmacy practitioners to broaden their knowledge pertaining to the adverse effects of herbal products and drug-herb interactions to provide the desired pharmaceutical care to patients, which can be achieved by identifying reliable information resources about herbal products, attending mandatory educational courses on herbal product dispensing in community pharmacies, and advising patients when they are seeking herbal products. All of these recommendations will equip them for good practice, thus, implementing pharmaceutical care services to ascertain the rational and appropriate use of medications.

The interaction between cardiovascular medications and herbal products is potentially significant, particularly with narrow therapeutic index medications. Because herbal products are more dispensed as over-the-counter medications, and pharmacy practitioners in this study had shown medium knowledge about herb-drug interactions, it is crucial to increase their awareness and knowledge regarding herbal products by educational programs focused on herb indications, drug interactions, and adverse effects. Additionally, it is important for Jordan pharmacists’ association to provide reliable resources. The association plays an important role in collaboration with pharmacy colleges at all Jordanian universities, as pharmacy practitioners in community pharmacies are the main accessible health care providers.

Participants provided written informed consent.