Adverse Drug Reactions & Drug Interactions PDF

ADVERSE DRUG REACTIONS AND DRUG-DRUG INTERACTIONS Presented by: Alyssa Soares, PharmD PGY-2 Pharmacy Resident A LITTLE BIT ABOUT ME! 2  OBJECTIVES Define adverse drug reactions (ADRs) and adverse drug events (ADEs...

ADVERSE DRUG REACTIONS AND DRUG-DRUG INTERACTIONS Presented by: Alyssa Soares, PharmD PGY-2 Pharmacy Resident A LITTLE BIT ABOUT ME! 2  OBJECTIVES Define adverse drug reactions (ADRs) and adverse drug events (ADEs) Discuss trends in ADR/ADE data National data Highlight interdisciplinary collaboration related to ADRs/ADEs Discuss drug-drug interactions (DDIs) Review an ADR patient case Prepared by Pharmacy Services 3  DEFINITIONS Adverse Drug Reaction: any undesirable or unexpected medication related event that requires discontinuing a medication, modifying the dose, requires or prolongs hospitalization, results in disability, requires supportive treatment, is life-threatening, or results in death, results in congenital abnormalities or occurs following vaccination. Medication Error: any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the health care professional, patient, or consumer. Prepared by Pharmacy Services 4  ADVERSE DRUG EVENTS (ADE) 770,000 people are injured or die each year in hospitals from adverse drug events (ADEs) Patients who experienced adverse drug events (ADEs) were hospitalized an average of 8 to 12 days longer; hospitalization cost $16,000 to $24,000 more. $5.6 million each year per hospital depending on hospital size. National hospital expenses estimated at between $1.56 and $5.6 billion annually Agency for Healthcare Research and Quality (AHRQ) WHY ARE ADES AND ADRS IMPORTANT? 6  SORTING ALL THESE OUT! 7 Reproduced from: Gandhi TK, Seger DL, Bates DW. Identifying drug safety issues: from research to practice. Int J Qual Health Care 2000; 12(1):69-76. By permission of Oxford University Press. Copyright © 2000.  GOALS AND OBJECTIVES FOR ADVERSE DRUG REACTION REPORTING To foster an environment To trend data and that supports and communicate empowers all health care information on confirmed providers to report ADRs suspected ADRs To identify opportunities for improvement in medication use practices utilizing a collaborative, multidisciplinary approach Prepared by Pharmacy Services 8  REPORTING OF ADRS Commonly used methods for detecting ADEs and ADRs include: Voluntary reporting Chart review Computerized surveillance Direct observation The incidence of reporting varies based on type of detection ADR trigger tools may more reliably increase detection over voluntary reporting Use of antidotes (ie: methylene blue, dexrazoxane) 9 FDA MEDWATCH FDA MedWatch 10  FDA has been evaluating reports of suicidal thoughts or actions in patients treated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs). Used to treat patients with type 2 diabetes and obesity for weight loss Preliminary data does not find evidence that using these medications causes suicidal thoughts or actions Patients should not stop taking their GLP-1 RAs without consulting with a health care professional Health care professionals should monitor for and advise patients using these agents to report new or worsening depression, suicidal thoughts, or any unusual changes in mood or behavior  The incidence of counterfeit medications has risen dramatically in recent years Unregulated online marketplaces and use of social media for advertisement is driving record profits for criminal groups As many as 7 out of 10 counterfeit tablets seized by DEA contained a fatal amount of fentaNYL Other common adulterants include lead, mercury, toxins or harmful chemicals Active ingredients are also lacking leading to ineffective treatment ISMP recommends educating staff and providers about the adverse reactions associated with counterfeit medications Utilize open ended questions with patients to discuss where they obtain their medications Assess medications carefully for spelling errors, appearance, and quality issues and report any concerns  Kentucky passes law preventing practitioners from being criminally charged for medical errors Wrong drug error due to use of abbreviation The provider intended to start pre-exposure prophylaxis for HIV with APRETUDE (cabotegravir) injection and oral lead in with VOCABRIA (cabotegravir) but ordered CABENUVA (cabotegravir/rilpivirine) injection The provider routinely utilized the unsafe abbreviation “CAB” and selected the wrong product from the EHR Caught by reviewing pharmacist who noted the patient was HIV negative ISMP recommends avoiding abbreviations and checking EHR and other systems to ensure that HIV antiviral abbreviations are not automatically populated or included in drug name fields, use brand and generic names, and create order-sets to guide prescribing and educating staff about the risk of mix-ups with these drugs  MEDICAL EVENT REPORTING SYSTEM: SAFETYNET Online reporting system for reporting both medication errors and adverse drug events Confidential and Protected Medication Safety Work Database allows for aggregation and review of events for analysis 14 MEDICAL EVENT REPORTING SYSTEM: SAFETYNET 15 16  CLASSIFYING ADES Can be broken down to timing of occurrence: 1. Prior to hospitalization Outpatient setting or emergency department (ED) intervention 2. During hospitalization 3. Following discharge Home Facility ADEs reported in the outpatient setting contribute to ED visits and hospital admissions 17  HIGH-RISK CONDITIONS FOR ADES ADEs can occur in any area of the hospital Most common settings include ICUs and off hours Children, older adults and patients with multiple comorbidities Some medications are more commonly associated Anticoagulants, anti-hyperglycemic drugs, sedatives, narcotics, antibiotics, antipsychotics, chemotherapy 18  NARANJO SCALE Adverse Drug Reaction Probability Scale Method to assess whether there is a causal relationship between an identified clinical event and a drug utilizing a questionnaire 19  ADVERSE REACTION REPORTING PROGRAM BASED IMPROVEMENTS New and Improved: Guidelines and order sets developed for safe use of high-risk medications Contraindications, use criteria and warnings built in Alerts for members of the health care team to guide use Safety review of medications for Formulary Removal from Formulary due to ADR concerns (ex: IV iron products) Assessment prior to approval for Formulary Accreditation requirement to have an established ADR reporting program Prepared by Pharmacy Services 20 MID-POINT BREAK QUESTIONS? 21 DRUG-DRUG INTERACTIONS 22  DRUG-DRUG INTERACTIONS The risk of ADEs increases as the number of prescribed interacting medications increases Most drug interactions involve commonly used medications Well established in the primary literature Included in tertiary references for easy checking Healthcare systems utilize electronic tools to help detect drug-drug interactions 23  WHERE DO DRUG INTERACTIONS COME FROM? Cytochrome P450 Enzyme System Superfamily heme containing proteins exist in many different isoforms (isoenzymes) primarily associated with the liver Responsible for metabolism of drugs Source of many drug-drug interactions! Cytochrome enzyme inhibitors and inducers are most implicated Call your friendly pharmacist! As many drugs will require dosage adjustments or alternatives based on the interaction DDI Table  CYTOCHROME P450 MEDIATED INTERACTIONS Effects of cytochrome interactions lead to increases or decreases of levels of medications Elevations in drug levels may result in significant toxicity Reductions in drug levels may result in under or non-treatment CYP450 interactions are expressed as a gradient Some interactions are contraindicated and should never be co- prescribed Others are less-severe and can be managed with dose changes 26  WHERE DO DRUG INTERACTIONS COME FROM? Direct drug binding Drug is chemically bound to another drug or substance that decreases the amount of available drug Resulting in inadequate drug levels and undertreatment of disease state Ex: tetracycline antibiotics experience significantly reduced levels when taken with divalent cations (Ca2+ Mg2+ Fe2+), iron, or dairy products 27  WHERE DO DRUG INTERACTIONS COME FROM? Additive properties due to therapeutic effects Ex: Use of several antiplatelet/anticoagulant agents in combination increases risk of bleeding Triple therapy for a post-myocardial infarction patient with atrial fibrillation Aspirin plus clopidogrel plus apixaban All medications are indicated; however, risks need to be weighed carefully Especially with other medications that the patient takes 28  RESOURCES FOR DRUG INTERACTIONS Drug-drug interaction checking software is available on multiple platforms and apps Some are more disease specific than others leading to more nuanced approach for therapy modifications Recommend discussion with your pharmacist colleagues for additional considerations 29  RESOURCES FOR DRUG INTERACTIONS Disease specific resources 30  TRY THIS! Search Up-To-Date for these combinations of medications Warfarin and amiodarone Digoxin and clarithromycin Rifampin and colchicine Search The University of Liverpool COVID-19 Drug Interaction Checking Tool for these combinations of medications Paxlovid and atorvastatin Paxlovid and verapamil Paxlovid and tacrolimus 31 32  QUESTIONS FOR THOUGHT How and to whom would you report any adverse effects associated with a drug therapy? What do you do when you encounter a drug-drug interaction? What resources would you utilize? What types of considerations would be important? Are there any drug-drug interactions you would ignore? 33 QUESTIONS? 34 LIFESPAN ADR REPORTING CASE REPORT  CONFLICT OF INTEREST DISCLOSURE STATEMENT Nothing to disclose regarding any of the medications and/or manufacturers mentioned in this presentation  ADR C ASE 60-year-old male with worsening SOB and DOE c/w NYHA class III symptoms of CHF presenting to outpatient provider PMH: HTN, HLD, T2DM, Afib; hx of DVT/CVA, CAD, CHF, and obesity Medications: aspirin, atorvastatin, empagliflozin, furosemide, glipizide, lisinopril, and metformin Found to have abnormal EKG followed by stress test demonstrating significant baseline ICM with an EF ~ 40 - 45%; worsened with stress, reduced to ~ 25%  ADR C ASE Pt underwent cardiac workup including catheterization with evidence of a large infarct in the RCA territory, reversible ischemia in the CFX territory and some of the LAD Cardiac catheterization: Chronically occluded RCA 95% LAD 80% OM Subsequently referred for surgical revascularization with surgery appointment scheduled upon bed availability and acuity of condition  ADR C ASE PROGRESSION CABG X 4: LIMA to LAD POD #2 SVG to OM1 PS x 6 hours with good oxygenation SVG to OM2 and ventilation SVG to Diag Bicarb slightly decreased, but pH WNL POD #0 POD #3 Arrived on unit with vasopressor Remained with high AG metabolic support acidosis Intubated overnight due to high O2 Evaluation for RTA requirement/ inability to wean off vent POD #1 POD #4 Stable Persistent AGMA with normal lactic Nitroglycerin for HTN acid Extubated but reintubated as Renal team consulted inadequate oxygenation Concern for mild DKA d/t pre op treatment with empagliflozin  ADR C ASE POD #2 POD #3 POD #4 Plasma glucose 96 – 177 mg/dL 163, 164 mg/dL 187 – 282 mg/dL pH 7.40 7.28 7.24 pCO2 40 mmHg 38 mmHg 39 mmHg pO2 166 mmHg 170 mmHg 325 mmHg HCO3 25 mEq/L 18 mEq/L 17 mEq/L TCO2 26 mEq/L 19 mEq/L 18 mEq/L Ketones -- Positive Positive Anion gap 8 mEq/L 19 mEq/L 19 mEq/L O2 saturation 96% 96% 97% EMPAGLIFLOZIN (JARDIANCE ®) Empagliflozin is a sodium glucose co- transporter 2 (SGLT2) inhibitor Utilized for treatment of diabetes and heart failure Reduces renal reabsorption of filtered glucose Lowers renal threshold for glucose Increases urinary glucose excretion Euglycemic Diabetic Ketoacidosis (EDKA) presents with serum glucose