Downloaded 74 times
More Related Content
Similar to Drug interactions in pharmacy related practice j. bolt
More from PASaskatchewan
Drug interactions in pharmacy related practice j. bolt
- 1. S Drug Interactions inPharmacy Practice: Recognition and Management of Clinically Relevant Drug-Drug Interactions Jennifer Bolt BSc.Pharm, ACPR, PharmD Residency & Education Coordinator Regina Qu’Appelle Health Region jennifer.bolt@rqhealth.ca 1 May 2016
- 2. Presenter Disclosure • Ihave previously received speaker honorarium from Boehringer Ingelheim
- 3. Learning Objectives 1. Statethe prevalence of drug interactions 2. Describe the implications of drug interactions to patient care 3. Recognize patients who are at high risk for clinically significant drug interactions 4. Identify some of the common potential drug interactions and recommend management strategies to mitigate the risk of these interactions
- 4. S Prevalence and Prevention ofDrug-Drug Interactions
- 5. Drug Interactions Definition: “Theeffects of one drug are changed by the presence of a concomitant drug” Classified as: • Pharmacokinetic: • Changes to absorption, distribution, metabolism, excretion • Pharmacodynamic: • Synergistic or antagonistic changes in physiologic response to medication Expert Opin Drug Saf 2012;11(1):83-94
- 6. Prevalence of DrugInteractions • Over 2500 pairs of potentially interacting medications • 2nd most common preventable adverse drug reaction in community practice Expert Opin Drug Saf 2012;11(1):83-94 Int J Clin Pract 2007;;61(1):157-61
- 7. Prevalence of DrugInteractions • Between 35 – 60% of elderly patients are exposed to potential drug- drug interactions (DDI) • Only 5 – 15% of potential DDI’s are clinically significant • Incidence of actual DDI in outpatient setting leading to: • Emergency visit: 0 – 0.17% • Hospital admission: 0 – 6.2% • Re-hospitalization: 0 – 7.6% • Incidence of actual DDI during hospitalization: 5.3 – 14.3% Expert Opin Drug Saf 2012;11(1):83-94
- 8. Risk Factors forDDI Patient Specific Factors • Advanced age • Genetic polymorphisms • Concomitant diseases Drug Specific Factors • Polypharmacy • Narrow therapeutic range • Dose Expert Opin Drug Saf 2012;11(1):83-94 Int J Clin Pharm 2013;35:455-62 Other Factors • Multiple prescribing physicians • Self-prescription • Prolonged length of stay
- 9. General Principles forPrevention of Drug Interactions • If possible, minimize: • Number of medications • Length of therapy • Dosage • Be aware of self-prescription, non-prescription drugs, samples • Review medication regimen for necessity and appropriateness on a regular basis Expert Opin Drug Saf 2012;11(1):83-94
- 10. S Management of Commonly Encountered andClinically Significant Drug-Drug Interactions
- 11. Case 1 Past MedicalHistory • Hypertension • Type II Diabetes Mellitus • Hyperlipidemia • Depression • Remote history of seizures Medications Prior to Admission: • ASA 81mg PO daily • Hydrochlorothiazide 12.5mg PO daily • Irbesartan 300mg PO daily • Amlodipine 5mg PO daily • Atorvastatin 10mg PO daily • Metformin 500mg PO BID • Sitagliptin 100mg PO daily • Citalopram 20mg PO daily • Phenytoin 300mg PO HS 64 year old, 100kg male seen in Emergency Department with chest pain/shortness of breath
- 12. Case 1 Laboratory Findings •WBC 6.2, HgB 129, PLT 341 • SCr 88 umol/L • CK (-), Troponin (-) Diagnostics • CT/PE: Pulmonary Embolism • ECG: within normal limits Vitals • HR 87 • BP 144/88 • RR 16 • SaO2 94% on RA Prescription written for: Rivaroxaban 15mg PO BID x 3/52 then 20mg daily
- 13. Case 1 • ASA81mg PO daily • Hydrochlorothiazide 12.5mg PO daily • Irbesartan 300mg PO daily • Amlodipine 5mg PO daily • Atorvastatin 10mg PO daily • Metformin 500mg PO BID • Sitagliptin 100mg PO daily • Citalopram 20mg PO daily • Phenytoin 300mg PO HS Potential Drug Interactions with the Addition of Rivaroxaban?
- 14. Pharmacokinetics of DirectOral Anticoagulants Europace DOI: 10.1093/europace/euv309
- 15. Europace DOI: 10.1093/europace/euv309 Effectof Direct Oral Anticoagulant AUC from Drug-Drug Interactions
- 16. Risk of MajorBleeding with ASA and Oral Anticoagulation Arch Intern Med 2007;167:117-24
- 17. Bleeding risk ofPatients with acute venous thromboembolism taking ASA JAMA Intern Med 2014;174(6):947-53
- 18. JAMA Intern Med2014;174(6):947-53 Bleeding risk of Patients with acute venous thromboembolism taking ASA
- 19. JAMA Intern Med2014;174(6):947-53 Bleeding risk of Patients with acute venous thromboembolism taking ASA
- 20. Anticoagulants and Antiplatelets CanJ Cardiol 2012;28:125-36
- 21. Am J Cardiol2014;114:583-6 Bleeding risk in Patients receiving SSRI’s and OAC
- 22. DDI Considerations: Oral Anticoagulants •Prudent to avoid co-prescription with direct oral anticoagulants and P-Glycoprotein and Cytochrome P450 inducers or inhibitors • Assure current and valid indication for ASA if used in addition to OAC • Assess bleed risk with all concomitant medications
- 23. Case 2 Past MedicalHistory: • HIV (+) • HCV (+) • COPD • Previous IVDU abuse Medications Prior to Admission: • Atazanavir 300mg PO daily • Ritonavir 100mg PO daily • Emtricitabine 200mg PO daily • Tenofovir 300 mg PO daily • SMX-TMP SS PO daily 52 year old male seen in clinic for ++ GERD symptoms Prescription Written for: Pantoprazole 40mg PO daily
- 24. Atazanavir + Omeprazole HIVMedicine 2007;8:457-64
- 25. Case 2 He isalso sent for pulmonary function tests to assess his COPD and it is found to have severe COPD: FEV1/FVC 55%, FEV1 42% As such, he is ordered: Tiotropium 18mcg inhaled once daily Fluticasone/salmeterol 500mcg/50mcg – 1 puff BID
- 26. Case 2 Medications Priorto Admission: • Atazanavir 300mg PO daily • Ritonavir 100mg PO daily • Emtricitabine 200mg PO daily • Tenofovir 300 mg PO daily • SMX-TMP SS PO daily Potential Drug Interactions with the Addition of Tiotropium, Salmeterol and Fluticasone?
- 27. Fluticasone and Ritonavir JIAPAC2009;8(2):113-21
- 28. DDI Considerations Anti-Retroviral Therapy •High potential to affect or be affected other medications • Significant clinical implications when concentration of ARV’s are affected • Medications not systemically administered still have potential for interaction
- 29. Case 3 Past MedicalHistory: • Myocardial Infarction (2006) • Heart failure • Type II Diabetes Mellitus • Chronic Pain Medication Prior to Admission: • ASA 81mg PO daily • Ramipril 5mg PO daily • Metoprolol 12.5mg PO BID • Atorvastatin 10mg PO daily • Furosemide 40mg PO daily • Spironolactone 25mg PO daily • Metformin 500mg PO TID • Glyburide 5mg PO BID • Citalopram 20mg PO daily • Methadone 5mg PO TID ID: 72 year old, 52kg female with a urinary tract infection
- 30. Case 3 Laboratory findings: •WBC 10.8 PMN 8.4 • SCr 124 umol/L, K 3.3, Mg 0.61 • U/A: Leuk estrase (+), Nitrate (+) Vital Signs: • HR 90 • BP 112/62 • RR 18 • SaO2 96% on R/A Prescription Written for: Ciprofloxacin 500mg PO BID x 7 days
- 31. QT Prolongation • Electrolytedisturbances: Hypokalemia, Hypomagnesemia, Hypocalcemia • Cardiac rhythm disturbances: Bundle branch block, long QT (≥450ms), bradycardia, recent conversion from atrial fibrillation to normal sinus rhythm • Congenital conditions: LQTS, Ion channel polymorphisms • Cardiac comorbidities: heart failure, myocardial infarction • QT prolonging medications: higher risk with rapid infusions and drug interactions • Digoxin therapy • Organ dysfunction: Liver or renal • Female sex • Older age Pharmacotherapy 2010;30(7):684-701 Am J Health-Syst Pharm 2008;65:1029-38 NEJM 2004;350:1013-22 http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guida nces/ucm073153.pdf
- 32. Circ Cardiovasc QualOutcomes 2013;6:479-87
- 33. Circ Cardiovasc QualOutcomes 2013;6:479-87
- 34. Case 3 Medication Priorto Admission: • ASA 81mg PO daily • Ramipril 5mg PO daily • Metoprolol 12.5mg PO BID • Atorvastatin 10mg PO daily • Furosemide 40mg PO daily • Spironolactone 25mg PO daily • Metformin 500mg PO TID • Glyburide 5mg PO BID • Citalopram 20mg PO daily • Methadone 5mg PO TID The prescription is instead written for SMX/TMP DS– 1 tab PO BID. Any potential DDI’S?
- 35. TMP/SMX and DrugsAffecting the Renin-Angiotensin-Aldosterone System
- 36. BMJ 2014;349:g6196 Co-trimoxazole andsudden death in patients receiving inhibitors of renin-angiotensin system
- 37. Trimethoprim-Sulfamethoxazole and riskof sudden death among patients taking spironolactone CMAJ 2015;187(4):E138-E143
- 38.
- 39. Drug-Drug Interactions AmongElderly Patients Hospitalized for Drug Toxicity JAMA 2003;289;1652-58
- 40. Hypoglycemia after AntimicrobialDrug Prescription for Older Patients Using Sulfonylureas JAMA Intern Med 2014;174(10):1605-12
- 41. DDI Considerations Antibiotics • Highrisk DDI with antibiotics are rare but can be clinically relevant • Identification of those at highest risk population is essential
- 42. Overall Considerations for ManagingPotential DDI’s • Outcome of the interaction if it were to occur • Clinical significance • Ease of treatment • Likelihood of occurrence • Ability to monitor for outcome
- 43. Summary • Potential DDIare extremely common • Incidence of clinically significant ADR secondary to DDI is low • Pharmacists must be aware of the high risk scenarios/ populations and recommend management/monitoring strategies when appropriate
- 44. S Drug Interactions inPharmacy Practice: Recognition and Management of Clinically Relevant Drug-Drug Interactions Jennifer Bolt BSc.Pharm, ACPR, PharmD Residency & Education Coordinator jennifer.bolt@rqhealth.ca 1 May 2016
Editor's Notes
- #6 Parameters: AUC, Cmax, t1/2
- #7 Hospitalization data – largest study showed 8.7% of pts subject to an actual DDI, and 91% were pharmacodynamic in nature Common DDI in this population include: hypokalemia with diuretic and corticosteroid, oversedation in ICU >15,000 articles published o DI over past 30 yrs Ducharme and Boothy – retrospective analysis of ADR’s in hospitalized patients. 1/3 were ADR’s prior to admission, and 1/3 were deemed preventable Of the preventable ADR’s, DDI were the second most common reason for ADR Commonly involved drugs included anticoagulants and anticonvulsants
- #8 Hospitalization data – largest study showed 8.7% of pts subject to an actual DDI, and 91% were pharmacodynamic in nature Common DDI in this population include: hypokalemia with diuretic and corticosteroid, oversedation in ICU
- #15 Reactions 2014;1492:15 – CBZ and riva for DVT px – developed PE Pgp inhibitors increase the serum concentration of affected drug. PGP inducers decrease the serum concentration of affected drug Majority of studies on relevance of PGP interaction are laboratory in nature, with no/little clinical context Bleeding and thrombotic events have not been analyzed based on co-medications
- #16 Reactions 2014;1492:15 – CBZ and riva for DVT px – developed PE Pgp inhibitors increase the serum concentration of affected drug. PGP inducers decrease the serum concentration of affected drug Majority of studies on relevance of PGP interaction are laboratory in nature, with no/little clinical context Bleeding and thrombotic events have not been analyzed based on co-medications
- #17 MA of trials comparing OAC to OAC + ASA Included 9 studies for efficacy (4000 pts) and 10 studies for safety (4200 pts) No difference in mortality Decreased rate of thromboembolic events in those with mechanical valve, but not difference in those with AF or CAD as indication RE-DEEM, APPRAISE and ATLAS ACS – all showed increase rates of bleed in population primarily taking DAPT
- #18 Utilized EINSTEIN DVT and EINSTEIN PE cohort to compare major bleeding and clinically relevant bleeding in pts receiving therapy alone, or therapy with NSAID or ASA
- #19 15% of 8246 pts took ASA (85% did not take ASA) Event rates for clinically relevant bleeding and major bleeding in ASA and no ASA groups However, those who received ASA were on average older and had lower creatinine clearance
- #20 Adjusted HR showed increased rates of clinically relevant bleeding in both group, with no increase in major bleeding Clinically relevant non-major bleeding: associated with medical intervention, unscheduled contact with physician, temporary cessation of study treatment, patient discomfort or effect on ADLs
- #21 No clear guidelines for what to do in VTE, but the AF guidelines provide guidance regarding when to use OAC vs. dual vs. triple therapy
- #22 SSRI affect Platelet aggregation Data from the ATRIA cohort of 13,559 pts with AF – 9100 pts received warfarin – used for this analysis – Kaiser Permanente database 19% took an SSRI Adjusted for ATRIA bleed risk and INR > 3 Incomplete data on NSAID or ASA use Finland study looking at Primary Intracerebral Hemorrhage found that use of serotonin-modulating antidepressant was independent risk factor for fatality in PICH in pts on warfarin
- #24 One study suggested that up to 40% of pts receiving ARV’s are subject to clinical relevant DIs
- #25 ATZ requires acidic environment for dissolution and absorption Involved 20 healthy volunteers, not HIV (+) patients Significant inter-patient variability – 25% of pts experienced a greater than 50% reduction in AUC and Cmin of ATZ Also looked as fosamprenavir – no significant difference. Looking at previous PK data – 4/5 studies show similar results suggesting do not co-administer Retrospective chart review at HIV clinic in 2006 showed that 25% of patients fail to achieve/maintain virologic response when using combination
- #28 Clinical relevance of systemic absorption of ICS is debatable, and often overlooked in clinical practice. However, a component of it is absorbed, and can interact with ritonavir as the systematically absorbed flutic is metabolized by 3A4 Usually a delay in onset because takes time for metabolic changes, may be confused with lipodystrophy (shortest has been 2-4 wks) Adrenal suppression Mixed population – adults and children, low dose ritonavir boost and high dose treatment ritonavir doses, mixed dose and route of flutic (inhaled or nasal) Some pts required glucocorticoid replacement PO to alleviate symptoms of adrenal suppression More recent case in 2014 of pts with Cushings disease and bilateral knee avascular necrosis Minimal data on other ICS despite the fact that they (budesonide, beclo, ciclesonide) are metabolized by 3A4 as well – different PK parameter (increased Vd with fluti, longer receptor binding half life
- #32 Torsades de pointes is an adverse drug reaction that is highly dependent on the presence of risk factors, and drug-induced TdP is an extremely rare event in patients without any risk factors. Over 90% of patients who develop TdP have ≥1 risk factors, and 71% have ≥2 risk factors.”
- #36 Co-trimoxazole is known to block sodium/potassium channels in the renal collecting duct (impair renal potassium elimination). Complimentary hyperkalemia effects of MRS and ACE/ARB which work by blocking aldosterone affects – similar to other potassium sparing diuretics such as amiloride TMP specifically decreases urinary potassium excretion up to 40% Previous data suggested that use of SMX-TMP in pts on spiro (in comparison to amoxil) increased risk of hospitalization 12 fold and SMX-TMP in pts on RAAS Blockade increase hospitalization 7 fold Both studies out of the Canadian Drug Safety and Effectivness Research Network (CDSERN) group out of Toronto
- #37 Population based nested case-controlled study in Ontario residents aged 66 and older receiving ACEI or ARB Cases – SCD within 7 days of Rx for SMX-TMP, Cipro, Norflox, NTF, amoxil. Controls received drug but didn’t die Repeated analysis at 14 days to capture delayed hyperkalemia (which authors state is possible with TMP) 1-4 controls per case ? Validation of disease risk index Population – 1.6 M. Almost 40,000 death, 1110 within 7 days of Abx. 1027 matched Median age 82, different disease severity (charleston score), more HF, more loop diuretics Didn’t significantly change when HF was included as a covariate
- #38 Population-based nested case control study performed with Ontario database. Linked data from prescription database to CIHI discharge abstract database Elderly pts (age >65). Outpt data Cases = those that died within 14 days of receiving rx for SMXTMP, cipro, norflox, NTF, amoxil 1-4 controls for each case – required to have received study med in previous 14 days Amoxil is reference Abx Disease index not validated (developed for this study), majority >85 yrs Some significant difference in populations – duration of spiro, HF, diuretic use, RAAS inhibitor, Charleston comorbid index Population = >200,000 pts, almost 12,000 experienced SCD, 350 within 14 days of Abx Exposure rate 0.74%
- #39 SMX/TMP inhibit glyburide metabolism via VYP 2C9
- #40 Nested case control study over 7 years Cases – glyburide users admitted to hospital with principal diagnosis of hypoglycemia 50 controls for each case – matched on multiple factors Exposure – any rx for SMXTMP in 1 wk prior to index hospitalization Multivariate analysis controlling for other medications that could influence outcome, including history of hospitalization for same (9covairates) Age 71 on average 10-14 drugs 909 pts admitted for hypoglycemia, LOS 4 day and 1.3% died
- #41 Texas medicare data – users of glipizide or glyburide – at least 1 day overlapping supply of antimicrobial – within past 14 days Comparators of Azithro, amoxil, cephalexin b/c no known link to hypoglycemia 65,000 episodes of overlapping rx in glyburide pts in 30,000 pts Levofloxacin – proposed mechanism – inhibitrs ATP sensitive K+ channels affecting insulin release Clarithro – PGP inhibitor – cohort studies support May be PGP inhibitor. Other cohort studies suggesting an increased hypoglycemia events in pts on SU Metronidazole – proposed mechanism – inhibitor of 2C9