COMMON DRUG INTERACTIONS: A PRACTICAL REVIEW FOR PHARMACY TECHNICIANS

Transcription

1 COMMON DRUG INTERACTIONS: A PRACTICAL REVIEW FOR PHARMACY TECHNICIANS SATURDAY/4:30-5:30PM ACPE UAN: L01-T 0.1 CEU/1.0 hr Activity Type: Knowledge-Based Learning Objectives for Pharmacy Technicians: Upon completion of this CPE activity participants should be able to: 1. Identify medications that commonly interact with other agents 2. Recall medications that may adversely affect certain conditions or disease states. 3. Determine when a drug interaction requires intervention from a pharmacist. Speaker: Shannon Rudolph, PharmD, MS, PhD, BCGP Shannon E. Rudolph is a graduate of the University of Buffalo. She completed a community pharmacy residency with University of North Carolina at Chapel Hill and Moose Pharmacy in Concord, NC. She currently serves as the Executive Fellow for the Iowa Pharmacy Association. Speaker Disclosure: Shannon Rudolph reports no actual or potential conflicts of interest in relation to this CPE activity. Off-label use of medications will not be discussed during this presentation.

2 Common Drug Interactions: A Practical Review For Pharmacy Technicians Shannon E. Rudolph, PharmD Disclosure Dr. Shannon Rudolph reports no actual or potential conflicts of interest associated with this presentation 1

3 Learning Objectives Upon successful completion of this activity, participants should be able to: 1. Identify medications that commonly interact with each other. 2. Recall medications that may adversely affect certain conditions or disease states. 3. Determine when a drug interaction requires intervention from a pharmacist. Why are Drug Interactions Important? 82% of Americans take routine medication - 29% take > 5 medications Adverse drug events (ADEs) cause 1 million emergency department visits each year and cost approximately $3.5 billion annually - More than 40% of these ADEs are thought to be preventable CDC Medication Safety Program. Accessed 21 December

4 Chicago Tribune. Pharmacies miss half of dangerous drug combinations. 15 December Range in severity Drug Interactions Most drug interactions happen after the medication is taken, but some are physical or chemical reactions when drugs come in contact with each other - ex. Phenytoin and dextrose Not all drug interactions result in adverse drug events - Some drug interactions are actually intentional (have positive health effects) 3

5 Types of Drug Interactions Pharmacodynamic Pharmacokinetic Antagonistic Additive Synergistic Absorption Distribution Metabolism Excretion Opioids and naloxone Multiple diabetes medications SMX/TMP Ciprofloxacin and milk Phenytoin and divalproex CYP3A4 interactions NSAIDS and kidney disease Are All Drug Interactions Bad? Naloxone and opioids - Naloxone blocks the effects of opioids, which can be life-saving in an overdose situation Anti-infectives - Some medications actually boost each other to have stronger effects than each would have alone = 3 - Example: SMX/TMP Lidocaine and epinephrine - Epinephrine constricts blood vessels, keeping the lidocaine anesthetic mostly local instead of spreading throughout the body 4

6 Types of Drug Interactions Drug- Disease State Drug- Rx Drug- OTC Drug- Food Drug- Beverage Drug- Lab Tests Common Drug Interactions 1. Warfarin 2. Selective Serotonin Reuptake Inhibitors 3. Fluconazole 4. Antiarrhythmics 5. Opioids 6. Acetaminophen 7. NSAIDs 8. Minerals & Supplements 9. Proton Pump Inhibitors 10.Nitrates 5

7 WARFARIN Warfarin Type of Interaction: Interaction With: Adverse Drug Reaction: Drug-Drug Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) Increased bleeding risk Stomach ulcers, increased bruising, etc. Recommendation: Facts and Comparisons. Warfarin Sodium. Accessed 6 February Avoid use of NSAIDs with warfarin Use a different, more appropriate analgesic (ex. Acetaminophen < grams/day) or heat/cold packs 6

8 Warfarin Type of Interaction: Interaction With: Adverse Drug Reaction: Recommendation: Drug-Food Foods high in vitamin K Green leafy vegetables (ex. spinach, kale) Vitamin K decreases the effects of warfarin Avoid abrupt changes in dietary vitamin K Maintain a consistent diet Facts and Comparisons. Warfarin Sodium. Accessed 6 February Food Micrograms of Vitamin K per Serving Collards, cooked or frozen, ½ cup 530 Turnip Greens, cooked or frozen, ½ cup 426 Spinach, raw, 1 cup 145 Kale, raw, 1 cup 113 Broccoli, chopped and cooked, ½ cup 110 Soybeans, roasted, ½ cup 43 Carrot juice, ¾ cup 28 Pumpkin, canned, ½ cup 20 Pomegranate juice, ¾ cup 19 Salad Dressing, Caesar, 1 tablespoon 15 Pine nuts, dried, 1 ounce 15 Blueberries, raw, ½ cup 14 Iceberg Lettuce, raw, 1 cup 14 National Institute for Health. 7

9 SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIs) SSRIs Type of Interaction: Interaction With: Adverse Drug Reaction: Recommendation: Drug-Drug Multiple serotonergic medications used together Antidepressants, triptans, fentanyl, tramadol, etc. Serotonin syndrome Fast heart rate, tremor, rigidity, GI symptoms, seizures, confusion, and/or hallucinations Limit use of serotonin medications together If necessary, start low and go slow and educate patient on potential side effects 8

10 St. John s Wort May be effective in treating Major Depressive Disorder Thought to increase amounts of serotonin, norepinephrine, and dopamine in the brain Duplicate therapy with SSRIs (do NOT use together) Many, many drug interactions Linde K, Berner M, Egger M, Mulrow C. St. John's wort for depression: meta-analysis of randomised controlled trials. Br J Psychiatry. 2005;186: Facts and Comparisons. St Johns Wort. Accessed 6 February Patient Case #1 Brian is a 37 year-old patient with a history of depression and hypercholesterolemia. You are working in the community pharmacy and Brian asks for refills on his two routine prescriptions and brings in a prescription for venlafaxine ER 75mg daily written by Dr. Rhodes. His medication list includes the following: Simvastatin 20mg daily (x 3 years) (Dr. Campbell) Escitalopram 10mg daily (x 1 year) (Dr. Campbell) What do you do? 9

11 Patient Case #1 A. Fill both prescriptions as is. Ask pharmacist to counsel on potential side effects. B. Refuse to fill the new prescription for venlafaxine because he is already taking escitalopram, both of which are antidepressants. Fill other two prescriptions and give to clerk to cash Brian out in a timely manner. C. Consult with prescriber regarding duplication in therapy and determine regimen that increases efficacy and decreases potential for side effects. D. Discuss drug interaction with Brian and recommend St. John s Wort instead of venlafaxine because it is safer and has been shown to have anti-depressant effects. PHQ-9 Screening American Academy of Family Physicians. PHQ-9 confirmation of depression and patient monitoring. Accessed 6 February

12 PHQ-9 Screening Monitor for efficacy of first medication before adding additional medications FLUCONAZOLE 11

13 Fluconazole Type of Interaction: Interaction With: Adverse Drug Reaction: Recommendation: Drug-Drug LOTS of medications Slows the breakdown of CYP 3A4 medications which causes them to increase in the body Potentially increased side effects of the drug being inhibited Determine severity of potential interaction.. Common Medications Metabolized by CYP 3A4 Alprazolam Amiodarone Amlodipine Atorvastatin Clarithromycin Colchicine Cyclosporine Diltiazem Lovastatin Nifedipine Simvastatin Verapamil 12

14 Alert Fatigue Alerts for potentially life-threatening allergy-medication combinations resulted in an override 72.8% % of the time 60% of contraindicated drug interactions were inappropriately classified Topaz M, Seger DL, Slight SPR, et al. Rising drug allergy alert overrides in electronic health records: an observational retrospective study of a decade of experience. J Am Med Inform Assoc May;23(3): doi: /jamia/ocv143. Epub 2015 Nov 17. Hatton RC, Rosenberg AF, Morris CT, et al. Evaluation of contraindicated drug-drug interaction alerts in a hospital setting. Ann Pharmacother Mar;45(3): doi: /aph.1P533. Epub 2011 Mar 8. Factors to Consider: Fluconazole and Simvastatin Patient A Never experienced side effects from simvastatin Patient B History of statin-induced myopathy Prescribed a 1-day regimen of fluconazole Prescribed a 14-day regimen of fluconazole 13

15 ANTIARRHYTHMICS Antiarrhythmics Type of Interaction: Interaction With: Adverse Drug Reaction: Recommendation: Drug-Drug LOTS of medications Heart arrhythmias QT prolongation and/or Torsades de Pointes Assess risk for QT Prolongation when using these medications 14

16 Prolonged QT Syndrome May lead to Torsades de pointes Medications that May Cause QT Prolongation Antiarrhythmics Amiodarone Dofetilide Flecainide Sotalol Others Azithromycin Chlorpromazine Ciprofloxacin Citalopram Clarithromycin Escitalopram Fluoxetine Ziprasidone 15

17 OPIOIDS Opioids Type of Interaction: Interaction With: Adverse Drug Reaction: Recommendation: Drug-Drug Benzodiazepines Examples: alprazolam, clonazepam, diazepam, lorazepam, temazepam, triazolam Additive respiratory depression May cause stopped breathing and death Avoid combined use Educate patients about the serious risks Recommend naloxone Facts and Comparisons. Opioid analgesics. Accessed 6 February FDA Drug Safety Communication August

18 FDA Drug Safety Communication (8/31/16) A U.S. Food and Drug Administration (FDA) review has found that the growing combined use of opioid medicines with benzodiazepines or other drugs that depress the central nervous system (CNS) has resulted in serious side effects, including slowed or difficult breathing and deaths. Opioids are used to treat pain and cough; benzodiazepines are used to treat anxiety, insomnia, and seizures. In an effort to decrease the use of opioids and benzodiazepines, or opioids and other CNS depressants, together, we are adding Boxed Warnings, our strongest warnings, to the drug labeling of prescription opioid pain and prescription opioid cough medicines, and benzodiazepines. FDA Drug Safety Communication August FDA Drug Safety Communication (9/20/17) Based on our additional review, the U.S. Food and Drug Administration (FDA) is advising that the opioid addiction medications buprenorphine and methadone should not be withheld from patients taking benzodiazepines or other drugs that depress the central nervous system (CNS). The combined use of these drugs increases the risk of serious side effects; however, the harm caused by untreated opioid addiction can outweigh these risks. Careful medication management by health care professionals can reduce these risks. We are requiring this information to be added to the buprenorphine and methadone drug labels along with detailed recommendations for minimizing the use of medication-assisted treatment (MAT) drugs and benzodiazepines together. FDA Drug Safety Communication September

19 Other Risk Factors for Respiratory Depression Opioids combined with: - Obstructive lung disease (COPD) - Kidney disease - Liver disease - Alcohol use - Other medications that slow central nervous system (CNS) can slow breathing Facts and Comparisons. Opioid analgesics. Accessed 6 February FDA Drug Safety Communication August Patient Case #2 Susan is a 62 year-old patient with a history of hypertension, COPD, chronic pain (car accident 8 years ago), depression, and anxiety. She is adherent to her medications and fills each every 30 days. Her medication list is as follows: Fluticasone/salmeterol 250mcg/50mcg inhaled twice daily (x 10 yrs) Tiotropium 2.5mcg inhaled daily (x 6 months) Lisinopril 20mg daily (x 20 years) Oxycodone ER 60mg BID (increasing doses x 8 yrs) Diazepam 5mg BID PRN (increasing doses x 7 yrs) Today she brings in a prescription for oxycodone ER 80mg BID and diazepam 10mg QID PRN. 18

20 Patient Case #2: Medication Reconciliation Prior Medication List New Medication List Fluticasone/salmeterol 250mcg/50mcg inhaled BID Tiotropium 2.5mcg inhaled daily Lisinopril 20mg daily Oxycodone ER 60mg BID Diazepam 5mg BID PRN Fluticasone/salmeterol 250mcg/50mcg inhaled BID Tiotropium 2.5mcg inhaled daily Lisinopril 20mg daily Oxycodone ER 80mg BID Diazepam 10mg QID PRN Patient Case #2 What risk factors does Susan have for respiratory depression and opioid overdose? A. She is not at risk of opioid overdose since she has been on these medications for years. B. Combination of opioid and benzodiazepine C. Respiratory illness D. B and C 19

21 Iowa Board of Pharmacy. Naloxone Standing Order. November ACETAMINOPHEN 20

22 Acetaminophen Type of Interaction: Interaction With: Adverse Drug Reaction: Recommendation: Drug-Disease State Liver Disease Worsening of liver disease Liver breaks down APAP into toxic metabolites Avoid use or use with extreme caution at lowest possible dose if necessary Facts and Comparisons. Acetaminophen. Accessed 6 February Acetaminophen package insert. Accessed 6 February APAP Metabolism APAP Non-toxic metabolites Excreted from body Toxic NAPQI metabolite Liver Damage 21

23 APAP APAP Metabolism Usually the predominant pathway Non-toxic metabolites Excreted from body Toxic NAPQI metabolite Liver Damage Pathway increases when system overloaded Acetaminophen and Acetaminophen? Type of Interaction: Interaction With: Adverse Drug Reaction: Recommendation: Drug-Drug Acetaminophen-containing products used in combination with other acetaminophen-containing products Liver damage and/or failure Maximum daily dosage (no more than 4g daily) Educate patients about reading OTC labels 22

24 Maximum Daily Dosages FDA official guidance= 4,000mg Package insert = usually 3,000mg (or 3,250mg) - Manufacturer specific FDA also limited prescription medications to 325mg per dosage unit FDA Drug Safety Communication. Prescription Acetaminophen Products to be Limited to 325 mg Per Dosage Unit; Boxed Warning Will Highlight Potential for Severe Liver Failure. 13 January Acetaminophen Combination Products ~80% of patients do NOT know that acetaminophen is in common prescription medications Saab S, Konyn PG, Viramontes MR, et al. Limited knowledge of acetaminophen in patients with liver disease. Clin Transl Hepatol Dec 28;4(4): doi: /JCTH Epub 2016 Dec

25 NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs) NSAIDs Type of Interaction: Interaction With: Adverse Drug Reaction: Recommendation: Drug-Disease State Gastrointestinal Ulcer Disease Bleeding risk and reactivation of GI ulcers Do not use in active ulcers Caution in patients with history of ulcers Use an NSAID with less risk (ex. celecoxib) Use with misoprostol or proton pump inhibitor (PPI) if NSAID therapy is necessary American College of Gastroenterology. Management of patients with ulcer bleeding. Am J Gasteroenterol :

26 NSAIDS AND KIDNEY DISEASE Type of Interaction: Interaction With: Adverse Drug Reaction: Recommendation: Drug-Disease State Kidney Disease Worsening of kidney disease Do not use in severe kidney disease Use different, more appropriate analgesic instead Facts and Comparisons. Nonsteroidal Anti-Inflammatory Agents. Accessed 6 February Chronic Kidney Disease. Accessed 6 February

27 X Chronic Kidney Disease. Accessed 6 February MINERALS & SUPPLEMENTS 26

28 Minerals and Supplements Type of Interaction: Interaction With: Adverse Drug Reaction: Recommendation: Drug-OTC Rx Drug: Levothyroxine, ciprofloxacin, doxycycline OTC Drug/Mineral: Calcium, magnesium, iron, etc. Some medications will bind to minerals forming a compound that cannot be absorbed easily Take the medications at separate times to minimize the potential for binding to each other in the GI tract Spacing of Medications Levothyroxine minutes before food and other medications Doxycycline - Take on empty stomach or 1-2 hours after meals Ciprofloxacin - 2 hours before food or 6 hours after food Synthroid. [Prescribing Information] Oracea [Prescribing Information) Doryx. [Prescribing Information] Cipro [Prescribing Information] 27

29 Patient Case #3 Flora is a 55 year-old female with a history of hypothyroidism. Your pharmacy performs bone density screenings and it was recommended that she take calcium supplementation to decrease risk of osteoarthritis. She comes to the counter with a bottle of Calcium 600mg + Vit D and to pick up a refill on the following medication: Levothyroxine 137mcg daily What do you do? Patient Case #3 A. Ask the pharmacist to counsel on proper spacing of levothyroxine with Calcium + Vitamin D. B. Recommend she take the medications together to increase convenience and adherence. C. Recommend she take calcium without the vitamin D. Vitamin D may decrease absorption of levothyroxine, while calcium does not affect the absorption. D. Recommend she take two tablets of levothyroxine each morning to compensate for decreased absorption. 28

30 PROTON PUMP INHIBITORS Proton Pump Inhibitors Type of Interaction: Interaction With: Adverse Drug Reaction: Recommendation: Drug-Drug Omeprazole (or esomeprazole) with clopidogrel Reduces the effectiveness of clopidogrel Potential to increase risk of heart attack Recommend to prescriber changing to alternative PPI Plavix (clopidogrel). [Prescribing Information] Bridgewater(NJ): Bristol-Myers Squibb Co.;

31 Proton Pump Inhibitors Type of Interaction: Interaction With: Adverse Drug Reaction: Recommendation: Drug-Food or Drug-Supplement Vitamins and minerals B12, magnesium May reduce absorption of some vitamins and minerals Some vitamins and minerals require an acidic environment to be absorbed in the GI tract Limit duration of use of PPIs Use lowest effective dose FDA Drug Safety Communication: Possible increased risk of fractures of the hip, wrist, and spine with the use of proton pump inhibitors. 25 May FDA Drug Safety Communication: Low magnesium levels can be associated with long-term use of Proton Pump Inhibitor drugs (PPIs). 2 March NITROGLYCERIN 30

32 Sublingual Nitroglycerin Tablets Type of Interaction: Interaction With: Adverse Drug Reaction: Recommendation: Chemical Reaction Plastic Packaging Nitroglycerin breaks down and adheres to plastic bottles Only dispense in the glass containers from the manufacturer Nitrostat (nitroglycerin sublingual tablets). [Prescribing Information]. Pfizer Clinical Decision Support Resources Pop-Up Boxes - May need to manually enter a code to override DUR Screen - May list different classifications/severity of drug interactions Tertiary resources Literature review Others? 31

33 What Should I Do? 1. Take drug interactions seriously 2. Make sure a complete medical history is obtained for each patient 3. Discuss with the pharmacist if you suspect a concern 4. Pay close attention to OTC purchases 5. Teach patients how to read Drug Facts label 32