D4. TECHNICIANS NUTRITION S IMPACT ON MEDICATIONS 3:15-4:15PM

D4. TECHNICIANS NUTRITION S IMPACT ON MEDICATIONS 3:15-4:15PM ACPE UAN: 107-000-14-034-L01-T Activity Type: Knowledge-Based 0.1 CEU/1.0 hr Learning Objectives for Technicians: Upon completion of this CPE activity participants should be able to: 1. Describe at least one way nutrition can affect drug absorption and metabolism 2. Give three examples of a drug-food interaction 3. Identify foods that commonly decrease warfarin s effectiveness 4. Give two examples of medications that need to be taken on an empty stomach 5. Explain why certain medications can not be taken with antacids, aluminum, calcium, iron, magnesium, and zinc Speaker: Elizabeth Amelon, PharmD, is currently a PGY2 Pediatric Pharmacy Resident at the University of Iowa Hospitals and Clinics and an Adjunct Instructor with the University of Iowa College of Pharmacy. She graduated from the University of Iowa College of Pharmacy in 2012 and completed an ASHP-accredited PGY1 Pharmacy Practice Residency at the University of Iowa Hospitals and Clinics in 2013. Her interests include oncology, cardiology, and critical care. Speaker Disclosure: Elizabeth Amelon reports no actual or potential confl icts of interest in relation to this CPE activity. Off-label use of medications will not be discussed during this presentation. FEBRUARY 7-9, 2014 THE MEADOWS EVENTS & CONFERENCE CENTER ALTOONA, IOWA

Nutrition s Impact on Medications ELIZABETH AMELON, PHARMD, BCPS PGY2 PEDIATRIC PHARMACY RESIDENT UNIVERSITY OF IOWA HOSPITALS AND CLINICS Faculty Disclosure Elizabeth Amelon reports she does not have actual or potential conflicts of interest associated with this presentation Elizabeth Amelon has indicated that off-label use of medication will not be discussed during this presentation 1

Learning Objectives Upon completion of this activity, pharmacy technicians should be able to: 1. Describe at least one way nutrition can affect drug absorption and metabolism 2. Give three examples of a drug-food interaction 3. Identify foods that commonly decrease warfarin s effectiveness 4. Give two examples of medications that need to be taken on an empty stomach 5. Explain why certain medications cannot be taken with antacids, aluminum, calcium, iron, magnesium, and zinc Audience Background Information How many technicians work in a hospital? How many technicians work in a retail pharmacy? Other? 2

Pre-Assessment Questions 1. What is one way that food can affect drug absorption? 2. Which pair is NOT a common drug-food interaction? 3. Which food would most likely decrease the effectiveness of warfarin? 4. Which medication(s) is/are best absorbed when taken on an empty stomach? 5. Why shouldn t quinolone antibiotics be taken with calcium containing products? Why Is This Topic Important? 1 3

Why Is This Topic Important? Drug-food interactions can lead to: Drug toxicity Side effects Loss of therapeutic efficacy/ therapy failure Increased drug efficacy Diminished drug side effects Background 2,3 Definition of a drug-food interaction: the effect produced when some drugs and certain foods or beverages are taken at the same time Drug-food interactions can cause: Reduced drug absorption Increased drug absorption Delayed drug absorption Accelerated drug absorption No effect on drug absorption Food can affect the bioavailability (degree and rate at which a drug is absorbed into systemic circulation), metabolism, and excretion of medications 4

Basic Pharmacokinetics 1 Absorption Movement of the medication into the bloodstream (systemic circulation) Drug dissolution must occur prior to absorption Distribution Process by where medications move away from the site of absorption into other areas of the body Metabolism Process by which the body breaks down the medication Excretion Process by which the medication is eliminated from the body Oral Absorption 1,4 Oral medications pass through the esophagus into the stomach Once in the stomach, the drug dissolves Drugs can be absorbed in the stomach or in the small intestine depending on the ph of the medication 5

Oral Absorption 1,4 Gastric residence time may vary from a few minutes to 2-3 hours depending on the presence of food Pyloric sphincter allows food to pass from the stomach into the small intestine Small intestine has a large surface area Most drug absorption occurs in the small intestine Food s Effect on Drug Absorption 5 Gastric emptying time can play a role in the rate of drug absorption Solid foods tend to delay gastric emptying Delayed gastric emptying will slow absorption of drugs that are absorbed in the small intestine but not of those that are absorbed from the stomach Foods/beverages can change the gastric ph and can alter drug absorption Beverages can alter drug dissolution 6

Food s Effect on Drug Absorption 1 Food can affect the rate at which a medication is absorbed Food can affect the amount of medication that gets absorbed (increased or decreased absorption) Food s Effect on Metabolism 6 Enzymes Food can inhibit or induce enzymes Cytochrome p450 enzymes Distribution of the CYP isoform enzymes in the liver 7

Food s Effect on Elimination 1,7 Food can alter renal excretion of some medications Food can alter urinary ph Food can compete with drugs for renal tubular reabsorption Drug-Food Interaction Examples 8

Warfarin (Coumadin) 1,8 Anticoagulant ( blood thinner ) Indication: prophylaxis and treatment of thromboembolic disorders Mechanism of action: inhibits the production of vitamin K dependent clotting factors (factors II, VII, IX, X, and protein C and S) Food s Effect on warfarin (Coumadin) 1,9 Foods rich in vitamin K can decrease the effectiveness of warfarin Common foods rich in vitamin K include: Green leafy vegetables Kale Spinach Brussels sprouts Collard greens Broccoli Consistent diet is important 9

Grapefruit Juice 1,10 Grapefruit juice can increase the bioavailability of several different drugs Common drug interactions: Dihydropyridine calcium channel blockers (amlodipine, felodipine, nifedipine) Increased levels can lead to hypotension and peripheral edema Statins (simvastatin, atorvastatin, lovastatin) Increased levels can lead to rhabdomyolysis (muscle breakdown) Grapefruit Juice 11 Common drug- grapefruit interactions: amiodarone astemizole alprazolam atorvastatin benzodiazepines buspirone carbamazepine carvedilol cerivastatin cilostazol clarithromycin Clomipramine codeine cyclosporine dapsone dextromethorphan diazepam diltiazem estrogens erythromycin felodipine fentanyl finasteride haloperidol indinavir lercanidipine lidocaine lovastatin midazolam methadone nelfinavir nifedipine nicardipine nimodipine nisoldipine nitrendipine ondansetron paclitaxel progestins progesterone quinidine ritonavir salmeterol saquinavir simvastatin tacrolimus trazodone triazolam vincristine zaleplon zolpidem 10

Grapefruit Juice 1,10,12 Grapefruit juice contains furanocoumarins which irreversibly inhibit CYP 3A CYP3A is responsible for metabolism of over 50% of the most commonly used drugs Normal consumption of grapefruit juice only inhibits CYP3A in the cells lining the small intestine Large amounts of grapefruit juice can affect hepatic CYP3A activity Avoid drinking large amounts (> 1 quart/day) Iron 13 Mineral/ supplement Indication: prevention and treatment of low iron levels/ anemia Iron is best absorbed on an empty stomach Food decreases iron absorption Vitamin C (ascorbic acid) increases absorption Reduces ferric iron (Fe3+) to ferrous iron (Fe2+) which is better absorbed This reduction occurs in a low ph 11

Levothyroxine (Synthroid) 14,15 Levothyroxine (T 4 ) is a synthetic form of the thyroid hormone thyroxine Indications: hypothyroidism Should be taken on an empty stomach, 30 minutes before food Food decreases bioavailability and can lead to signs/symptoms of hypothyroidism Lamson MJ, et al. A standard meal significantly reduced T4 bioavailability by 40% Proton Pump Inhibitors 14,16 Examples: omeprazole (Prilosec), lansoprazole (Prevacid), rabeprazole (Aciphex), pantoprazole (Protonix), esomeprazole (Nexium) Indications: GERD Mechanism of action: inhibit gastric acid secretion by blocking the H+/K+ ATPase pump ( proton pump ) in parietal cells Best to take 30 minutes prior to morning meal The amount of H+/K+ ATPase in the parietal cells is highest after a prolonged fast 12

Bisphosphonates 14,17 Examples: alendronate (Fosamax), ibandronate (Boniva), risedronate (Actonel) Indications: prevention and treatment of osteoporosis Mechanism of action: prevent bone breakdown Take on an empty stomach at least 30-60minutes prior to food with a full glass of plain water Beverages (orange juice, coffee, mineral water) and food can reduce the absorption by ~60% Anti-infectives 14 Take on an EMPTY stomach Take with FOOD Take with or without food Ampicillin Amoxicillin/Clavulanate (Augmentin) Azithromycin Penicillin V Nitrofurantoin (Macrobid) Cephalexin (Keflex) Dicloxacillin Cefpodoxime (Vantin) Cefadroxil (Duricef) Tetracycline Cefuroxime (Ceftin) Cefprozil (Cefzil) Doxycycline Itraconazole capsules Cefixime (Suprax) Rifampin (Rifadin) Metronidazole (Flagyl) Cefdinir (Omnicef) Metronidazole ER (Flagyl ER) Ciprofloxacin (Cipro) Itraconazole solution Levofloxacin (Levaquin) Cefaclor (Ceclor) Moxifloxacin (Avelox) Voriconazole (Vfend) Erythromycin (Ery-Tab) Sulfamethoxazole- trimethoprim (Bactrim) Rifabutin (Mycobutin) 13

Metronidazole (Flagyl) 1,14,18 Antibiotic Avoid alcohol or products containing ethanol during therapy and for at least 3 days after therapy Metronidazole can block hepatic enzyme aldehyde dehydrogenase which can then cause accumulation of acetaldehyde in the blood Metronidazole (Flagyl) 14 Accumulation of acetaldehyde in the blood causes a disulfiram-like reaction: Nausea/vomiting Headache Sweating Severe flushing Increased heart rate Low blood pressure 14

Fluoroquinolone (Quinolone) Antibiotics 14,19 Examples: ciprofloxacin, levofloxacin, moxifloxacin Take either 2 hours before or 6 hours after products containing magnesium, calcium, aluminum, iron, or zinc (multivitamins, antacids, etc) Divalent or trivalent cations can interfere with the body s ability to absorb quinolone antibiotics Multivalent cations can chelate with the quinolones resulting in antibiotic inactivation Tetracycline Antibiotics 14 Examples: doxycycline, tetracycline Take on an empty stomach 1 hour before or 2 hours after meals Avoid dairy products 1 hour before or 2 hours after Absorption may be decreased if taken with dairy products 15

Itraconazole Capsules 14 Antifungal Do not give with antacids Food increases absorption Take with food Absorption is enhanced by an acidic environment Take with cola drinks Avoid grapefruit juice Itraconazole Solution 14 Antifungal Do not give with antacids Food decreases the bioavailability Take on an empty stomach Take 1 hour before or 2 hours after meals Avoid grapefruit juice 16

Posaconazole 14 Antifungal Must be given within 20 minutes following a full meal Bioavailability is increased ~3 times when given with a nonfat meal Bioavailability is increased ~4 times when given with a highfat meal May be given with an acidic carbonated beverage Voriconazole 14 Antifungal Food decreases absorption Take 1 hour before or 1 hour after a meal 17

Monoamine Oxidase Inhibitors (MAOIs) 17 Class of antidepressants Examples: phenelzine, tranylcypromine Avoid foods high in tyramine Chocolate Cheese (especially aged cheeses) Cured meats High levels of tyramine can cause a sudden, dangerous increase in blood pressure Also avoid foods high in tyramine when taking linezolid (an antibiotic) Lithium 14 Antimanic agent ( mood stabilizer ) Indication: management of bipolar disorder It is important to maintain a normal fluid and salt intake while on this medication Lithium and sodium compete for tubular reabsorption in the kidney Do not start a low salt diet while on this medication A low salt diet can result in increased reabsorption of lithium and increased drug levels 18

Lithium 1,14 Na+ Li+ Drug- Alcohol Interactions 20 Two types of drug-alcohol interactions: Pharmacokinetic interactions (alcohol interferes with medication metabolism) Example: metronidazole/alcohol interaction Pharmacodynamic interactions (alcohol enhances the effects of the medication, ie drowsiness) 19

Drug- Alcohol Interactions 20 Pharmacodynamic interactions Alcohol can intensify effects of certain medications Mixing alcohol with certain medications can cause nausea, vomiting, headaches, drowsiness, or fainting Common classes of medications in which alcohol should be avoided: Benzodiazepines Opioids Muscle relaxants Antihistamines Antidepressants Sedatives and hypnotics Antipsychotics Dietary Supplements 21 Definition: product taken by mouth that contains a dietary ingredient intended to supplement the diet Dietary ingredients may include: vitamins, herbs, botanicals, amino acids, minerals, enzymes, organ tissues, or metabolites FDA classifies dietary supplements as foods instead of drugs Dietary supplements do not need approval from FDA before they are marketed Can cause many drug interactions 20

With or Without Food 17 Food can have a significant impact on certain medications Some medications work better, worse, faster, or slower on a full or empty stomach Food can protect the stomach from irritating medications NSAIDS (aspirin, diclofenac, ibuprofen, naproxen) In general, an empty stomach means 1 hour before or 2 hours after eating Summary Foods/beverages can have a profound influence on medication therapy Foods/beverages can influence drug absorption, metabolism, and elimination Important to read auxiliary labels/ medication bottles Patients should consult with their pharmacist if they have questions on how to take their medications 21

Post-Assessment Questions 1. What is one way that food can affect drug absorption? a) Inhibition of cytochrome P450 enzymes b) Induction of cytochrome P450 enzymes c) Alteration of gastric residence time d) Both a and b Post-Assessment Questions 2. Which pair is NOT a common drug-food interaction? a) Metronidazole (Flagyl)/ Alcohol b) Warfarin (Coumadin)/ Vitamin K containing foods c) Tetracycline/ Dairy products d) Metronidazole (Flagyl)/ Dairy products 22

Post-Assessment Questions 3. Which food would most likely decrease the effectiveness of warfarin? a) Chocolate b) Pizza c) Spinach d) Ice cream Post-Assessment Questions 4. Which medication(s) is/are best absorbed when taken on an empty stomach? a. Warfarin (Coumadin) b. Iron c. Levothyroxine (Synthroid) d. Both b and c 23

Post-Assessment Questions 5. Why shouldn t quinolone antibiotics be taken with calcium containing products? a) Calcium can chelate the quinolone antibiotic resulting in antibiotic inactivation and decreased absorption b) Calcium can interfere with the elimination of the quinolone antibiotic c) It is fine to take calcium containing products directly with quinolone antibiotics d) Calcium containing products can cause severe nausea/vomiting if taken with quinolone antibiotics Questions? elizabeth-amelon@uiowa.edu 24

References 1. Google images 2. FDA Consumer Health Information. Avoiding Drug Interactions. www.fda.gov/consumer/updates/interactions112808.html 3. Medical Dictionary. http://medical-dictionary.thefreedictionary.com/drug-food+interaction 4. The Merck Manual for Health Care Professionals. Drug Absorption. http://www.merckmanuals.com/professional/clinical_pharmacology/pharmacokinetics/drug_absorption.html#v1108963 5. Welling, Peter G. "Effects of food on drug absorption." Annual review of nutrition 16.1 (1996): 383-415. 6. Sadee, Wolfgang. "The relevance of missing heritability in pharmacogenomics." Clinical Pharmacology & Therapeutics (2012). 7. Yaheya M. Drug-Food Interactions and Role of Pharmacist. Asian Journal of Pharmaceutical and Clinical Research. October-December 2009. 2(4). 8. Lexi Comp 9. MedlinePlus. Vitamin K. http://www.nlm.nih.gov/medlineplus/ency/article/002407.htm 10. Hanley, Michael J., et al. "The effect of grapefruit juice on drug disposition." Expert opinion on drug metabolism & toxicology 7.3 (2011): 267-286. 11. GlobalRPh. Drug Tables- Drug food interactions. http://www.globalrph.com/drugfoodrxn.htm 12. Hamilton, M. D., and MD Faaem Hamilton. Tarascon Pharmacopoeia 2012 Deluxe Lab Coat Edition. Jones & Bartlett Publishers, 2011. 13. Hallberg L, Brune M, Rossander L. The role of vitamin C in iron absorption. Int J Vitam Nutr Res Suppl. 1989;30:103-8. 14. UpToDate 15. Lamson, M. J., et al. "Quantitation of a substantial reduction in levothyroxine (T4) absorption by food." Thyroid 14.876 (2004): 4. 16. Mejia, Alex, and Walter K. Kraft. "Acid peptic diseases: pharmacological approach to treatment." (2009): 295-314. 17. U.S. Food and Drug Administration. Avoid Food-Drug Interactions- A Guide from the National Consumers League and U.S. Food and Drug Administration. 18. Visapaa, J. P., et al. "Lack of disulfiram-like reaction with metronidazole and ethanol." The Annals of pharmacotherapy 36.6 (2002): 971-974. 19. Lomaestro, Ben M., and George R. Bailie. "Absorption interactions with fluoroquinolones." Drug Safety 12.5 (1995): 314-333. 20. Weathermon, Ron, and David W. Crabb. "Alcohol and medication interactions." Alcohol research & health: the journal of the National Institute on Alcohol Abuse and Alcoholism 23.1 (1999): 40. 21. U.S. Food and Drug Administration (FDA). Q&A on Dietary Supplements. http://www.fda.gov/food/dietarysupplements/qadietarysupplements/default.htm#fda_role. Accessed on January 12, 2014. 25