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INTRODUCTION Dietary and herbal supplements are commonly used by patients who are also taking prescription and over-­ the ­ counter medicines, and thus the likelihood of significant interactions between biologically active constituents in supplements and medi­ cations is quite high (1–4). Although biological interactions between drugs are well documented, the importance of drug and natu­ ral supplement interactions is slowly being recognized as a pos­ si­ ble ­ factor contributing to adverse effect and clinical outcomes (4,5).This is particularly impor­ tant in vulnerable populations, such as the frail el­ derly with their reduced functional reserves, pregnant ­ women, and patients with altered nutritional status or compromised immunity. Even minor alterations in drug bioavailability due to pharmacokinetic (relationship between administered dose and concentration of the drug in systemic circulation) or pharmacodynamic (relationship between concentration of the drug in circulation and the observed response) interactions with other­ wise innocuous dietary or herbal supplements can have significant consequences to the body’s finely balanced homeostasis, predisposing to reactions that result in injury (see Box 29-1). BOX 29-1 ​ Are Supplements Necessary?­ People at risk for malnutrition (e.g., malabsorption, vegan diet, history of alcoholism, gastric bypass surgery, hemodialysis for renal failure, critical illness requiring parenteral nutrition) may need nutrient supplementation (6). However, for most of the population , a well-­ balanced diet typically provides the daily allowance of essential vitamins and minerals (7). Although healthy individuals do not benefit from (and may be harmed by) high doses of vitamins, minerals, or herbs, many have the mistaken belief that such supplementation can prevent aging and associated diseases (8). Supplements in reasonable quantities are likely safe in the young and healthy, but long-­ term use concomitant with medi­ cations could have adverse effects, especially in ­ people at risk, such as el­ derly patients with chronic conditions. It is estimated that adverse drug events are responsible for more than 770,000 injuries and deaths, with an associated estimated cost of $3.5 billion, in the United CHAPTER 29 Interactions Between Supplements and Medi­cations Sulaiman Sultan, Ahad Jahangir, Ihor B. Gussak, John B. Kostis, A. Jamil Tajik, and Arshad Jahangir Types of Drug-­ Supplement Interactions / 371 ter summarizes vari­ ous types of drug-­ supplement interactions and highlights ­ factors that increase predisposition to interactions. TYPES OF DRUG-­ SUPPLEMENT INTERACTIONS Active chemical constituents in herbal and dietary supplements can interact with medi­ cations at physical, chemical, physiological, and pathophysiological levels (19,20) ­ These interactions have been classified into four types depending on the site of interaction; see ­ Table 29-1 (4). Type I Interactions­ These physicochemical reactions usually occur outside the body, such as in the enteral feeding tube or intravenous tubing. The reactions are usually observed in patients receiving medi­ cations and parenteral nutrition through intravenous access, such as in the intensive care unit. Precipitation of calcium phosphate in parenteral nutrition formulation by an antibiotic (e.g., ceftriaxone) is an example of a type I physical interaction potentially leading to a serious adverse vascular event that can become life-­ threatening (21). Chelation of drugs such as fluoroquinolones by enteral nutrition, reducing their effectiveness, is additional example of a type I drug-­ supplement interactions (22). Type II Interactions In ­ these interactions, the supplement affects the bioavailability of the drug through metabolism (type IIA), transport (type IIB), or chelation (type IIC). The interactions result from modulation of drug-­ metabolizing enzymes within enterocytes before systemic absorption. Type IIA Interactions A good example of a type IIA interaction of high clinical relevance occurs between active constituents in grapefruit juice (naringenin, furanokumarin , bergamottin), irreversibly inhibiting the cytochrome P450 (CYP) isoenzyme 3A4 (CYP3A4) in enterocytes and increasing blood levels of several CYP3A4 substrate drugs (23). CYP3A4 enzyme is involved in oxidative metabolism of more than 50% of all prescription medi­ cations, States annually. Most of ­ these adverse drug events are due to medi­ cation errors that occur during prescribing , transcribing, dispensing, administering, adhering to, or monitoring a drug. However, the incidence and prevalence of adverse events resulting from interactions of drugs with dietary and herbal supplements is not known, but addressing­ these interactions may contribute to a reduction in adverse drug events (9). In a random sample of the noninstitutionalized U.S. population, about 81% reported using at least one prescription medi­ cation, over-­ the-­ counter medi­ cation, or dietary supplement in the preceding week. Among the population of adults 65 years and older, about 58% reported taking 5 to 9 medi­ cations over the course of the year and 18% reported 10...


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