CONTINUING EDUCATION Drug Interactions With Dietary Supplements by Chenita W. Carter, PharmD; Maegan Boyd, PharmD; and Megan Nelson, PharmD pon successful completion of this ar- this CE presentation, there Useful Websites ticle, pharmacists should be able to: will be a review of the most 1. Describe the common uses and commonly used dietary ■ www.mskcc.org/mskcc/html/44.cfm proposed mechanisms of action supplements including an Memorial Sloan-Kettering Cancer Center of 19 dietary supplements. explanation of the therapeutic Contains an entire database of dietary 2. Describe adverse effects associated with the uses as well as the potential supplement medicines. Of note on U this site is that chemotherapy drug use of dietary supplements. adverse effects of each. Also, 3. Describe the mechanisms of drug interactions each section will address interactions are included with all other involving a given dietary supplement. possible drug interactions re- drug interactions. 4. Evaluate resources for pharmacists, physi- lated to the supplement. After ■ www.altnature.com/gallery/index.html cians, and consumers for dietary supplements. completing this presentation, Alternative Nature Enterprises the reader will be adept at re- Contains information about the most Pharmacy Technician CE Objectives viewing a patient’s complete commonly used herbs. It includes pictures 1. Describe the common uses of 19 herbal supplement and medication of the natural source, as well as information therapies. list and identifying potential about its use and adverse effects. 2. Describe adverse effects associated with the drug-supplement interactions. use of dietary supplements. 3. List prescription drugs that interact with di- ANTACIDS etary supplements. Antacids are one of the most common drugs that are purchased over the counter. Most people do not consider INTRODUCTION them to be medications and therefore do not list them Patients understand that interactions between as such. This can be an issue when new medications two prescription medications, or “drug-drug are prescribed as drug-drug interactions can occur with interactions,” can be very dangerous. Pharma- antacids. There are three main types of antacids: alumi- cists can easily scan for these possible interac- num, calcium, and magnesium based. All three types can tions using drug information software available at interact with medications in different ways. most pharmacies and hospitals. With a complete Aluminum-based antacids release a free aluminum list of a patient’s medications, the pharmacist ion when they react with hydrochloride in the stomach. can prevent many drug-drug interactions from The aluminum ion is then available for intraluminal binding occurring. But what about the list of over-the- and adsorption to drugs. Aluminum-based antacids also counter products that patients are taking that decrease gastrointestinal motility, which can affect drugs they don’t consider to be medications or drugs? in several ways. Decreased motility prolongs the expo- Dietary supplements (see Table 1) and vitamins sure of acid-labile drugs to the hydrochloric acid of the have just as much potential to cause drug inter- stomach, which can lead to degradation and decreased actions as prescription medications. Throughout total absorption. Also, the delay in gastric emptying can www.americaspharmacist.net May 2012 | america’s PHARMACIST 37 affect drugs stabile in an acidic environment by leading to tration of antacids and certain antimicrobials increased serum concentrations and resulting in toxicity. should be avoided. Calcium carbonate antacids release carbonate when The last group of interactions involves they react with hydrochloride, which can alkalize the urine anti-inflammatory agents, specifically nonste- and decrease excretion. This interaction is commonly roidal anti-inflammatory drugs (NSAIDs) and seen when antacids are given concomitantly with digoxin, glucocorticoids. Changes in gastric emptying resulting in digoxin toxicity from decreased excretion. due to antacids decrease the bioavailability of Magnesium-based antacids increase gastroin- anti-inflammatory agents resulting in a decrease testinal motility, which can decrease the absorption of in absorption. Also, an increase in the gastric pH drugs from the gastrointestinal tract. This is particularly results in decreased drug dissolution, resulting true for medications that require prolonged intestinal in a decrease in bioavailability. Concomitant contact for absorption. administration of antacids and anti-inflammatory Antacids have been shown to interact with numer- agents should be avoided. ous medications. Drug interactions are a result of either increased gastric pH or presence of a cation. Common BLACK COHOSH interactions are found with thyroid replacement (cation), Black cohosh is a rhizome of Cimicifuga racemosa antibiotics (cation), iron supplementation (gastric pH), and or Actaea racemosa. It contains phytoestrogens enteric coated products (gastric pH). Changes in absorp- that mimic the effects of estrogen, and is used to tion may also be observed due to changes in gastrointes- treat the symptoms of menopause and dysmen- tinal motility. Calcium slows GI motility while aluminum and orrhea. Clinical studies are conflicting whether magnesium both speed motility. The rest of this section black cohosh possesses estrogenic activity. Cur- will give a brief overview of these specific groups. rently marketed products claim to work with the The three major cardiovascular drugs interactions body to reduce night sweats, vaginal dryness, that have been studied extensively are the quinidine and hot flashes. anti-arrhythmics, beta blockers, and angiotensin con- Adverse effects associated with the use of verting enzyme (ACE) inhibitors. Quinidine excretion is black cohosh include nausea, headache, rash, extensively decreased due to the alkalinization of urine, and dizziness. Due to case reports of autoim- resulting in toxicity and prolongation of the QT interval. mune hepatitis and liver failure associated with Beta blockers are rendered nearly ineffective due to the use of black cohosh, liver function tests decreased absorption as a result of both a change in the should be monitored frequently. Black cohosh gastric emptying and an increase in the gastric pH. ACE has been reported to stimulate uterine contrac- inhibitors also experience decreased absorption due tions, so its use should be avoided in pregnan- to changes in gastric emptying. Antacids may reduce cy. Use of black cohosh is not recommended serum levels of cardiovascular medications therefore in women with a history of breast cancer and concomitant administration of antacids and cardiovascu- other estrogen-dependent tumors or endome- lar medications should be avoided. trial cancer. Interactions between antimicrobials and antacids can Black cohosh has the potential to interact be traced as far back as the early to mid-1980s. When with medications used for the treatment of given concomitantly, fluoroquinolones, macrolides, and menopausal symptoms, and may potentiate the tetracyclines bioavailability is significantly reduced, pos- effects of hepatotoxic agents. Metabolism of sibly leading to treatment failure. It is believed that one of drugs that are eliminated through cytochrome the functional groups on these drug molecule chelates P450 (CYP) 2D6 enzyme may be inhibited with the metallic cations. The chelation leads to decreased the coadministration of black cohosh, resulting bioavailability and absorption. Interaction with antifungals, in increased levels of these medications. Cau- most notably itraconazole, occurs due to the increase in tion should be taken if patients are prescribed gastric pH, leading to decreased dissolution of the drugs agents metabolized via this pathway. (See Table and thus decreased absorption. Concomitant adminis- 2 for CYP-related information.) 38 america’s PHARMACIST | May 2012 www.americaspharmacist.net CHAMOMILE that is metabolized by these enzymes, there is an increase Chamomile may be the herb with the earliest in serum concentrations of the concomitant drug that can recorded history. Its use can be dated back to lead to toxicity. Chamomile interacts with warfarin (Couma- 90 BC when Pliny the Elder, a Roman natural- din®), leading to bleeding events. The exact mechanism of ist and philosopher, extensively wrote of its use this interaction is not fully understood. in healing. Ancient Egyptians used it cure the “ague” also known as acute fever. It is used for CO-ENZYME Q10 anything from hay fever and muscle spasms, to Co-enzyme Q10 (Co-Q10) is a substance that has been menstrual disorders and insomnia. used for a variety of disorders associated with oxidative There are several varieties of chamomile. stress. Co-Q10 is a fat-soluble molecule with a structure Roman and German are the two most com- similar to quinones and is commonly known as ubiqui- monly used and chamomile is most frequently none. Studies on beef cattle conducted in 1957 discov- consumed as a drinking tea. Chamomile is ered that Co-Q10 was found in high quantities in areas of metabolized into about 120 different metabolites high cellular turnover. Specifically the heart, kidney, liver, including 28 terpenoids and 36 flavonoids. The pancreas, and brain contained the highest quantities. terpenoids and flavonoids are thought to be re- Co-Q10 is essential for the transfer of electrons needed sponsible for chamomile’s medicinal properties. for the production of adenosine triphosphate. It has also