drug interactions in pharmacy related practice j. bolt

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Drug Interactions in Pharmacy Practice:

Recognition and Management of Clinically Relevant Drug-Drug Interactions

Jennifer Bolt BSc.Pharm, ACPR, PharmDResidency & Education CoordinatorRegina Qu’Appelle Health [email protected] May 2016

mailto:[email protected]

Presenter Disclosure

• I have previously received speaker honorarium from Boehringer Ingelheim

Learning Objectives

1. State the 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

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Prevalence and Prevention of Drug-Drug

Interactions

Drug Interactions

Definition: “The effects 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

Prevalence of Drug Interactions

• Over 2500 pairs of potentially interacting medications

• 2nd most common preventable adverse drug reaction in community practice

Expert Opin Drug Saf 2012;11(1):83-94Int J Clin Pract 2007;;61(1):157-61

Prevalence of Drug Interactions

• 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%


Risk Factors for DDI

Patient Specific Factors

• Advanced age

• Genetic polymorphisms

• Concomitant diseases

Drug Specific Factors

• Polypharmacy

• Narrow therapeutic range

• Dose

Expert Opin Drug Saf 2012;11(1):83-94Int J Clin Pharm 2013;35:455-62

Other Factors

• Multiple prescribing physicians

• Self-prescription

• Prolonged length of stay

General Principles for Prevention 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


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Management of Commonly Encountered and Clinically Significant Drug-Drug Interactions

Case 1

Past Medical History

• 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

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

Case 1


• Hydrochlorothiazide 12.5mg PO daily

• Irbesartan 300mg PO daily

• Amlodipine 5mg PO daily


• Metformin 500mg PO BID

• Sitagliptin 100mg PO daily


• Phenytoin 300mg PO HS

Potential Drug Interactions with the Addition of Rivaroxaban?

Pharmacokinetics of Direct Oral Anticoagulants

Europace DOI: 10.1093/europace/euv309

Europace DOI: 10.1093/europace/euv309

Effect of Direct Oral Anticoagulant AUC from Drug-Drug Interactions

Risk of Major Bleeding with ASA and Oral Anticoagulation

Arch Intern Med 2007;167:117-24

Bleeding risk of Patients with acute venous thromboembolism taking ASA

JAMA Intern Med 2014;174(6):947-53

JAMA Intern Med 2014;174(6):947-53

Bleeding risk of Patients with acute venous thromboembolism taking ASA

Anticoagulants and Antiplatelets

Can J Cardiol 2012;28:125-36

Am J Cardiol 2014;114:583-6

Bleeding risk in Patients receiving SSRI’s and OAC

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

Case 2

Past Medical History:

• HIV (+)

• HCV (+)

• COPD

• Previous IVDU abuse


• 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

Atazanavir + Omeprazole

HIV Medicine 2007;8:457-64

Case 2

He is also 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

Case 2


• 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?

Fluticasone and Ritonavir

JIAPAC 2009;8(2):113-21

DDI ConsiderationsAnti-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

Case 3

Past Medical History:

• Myocardial Infarction (2006)

• Heart failure

• Type II Diabetes Mellitus

• Chronic Pain

Medication Prior to Admission:


• Ramipril 5mg PO daily

• Metoprolol 12.5mg PO BID


• Furosemide 40mg PO daily

• Spironolactone 25mg PO daily

• Metformin 500mg PO TID

• Glyburide 5mg PO BID


• Methadone 5mg PO TID

ID: 72 year old, 52kg female with a urinary tract infection

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

QT Prolongation

• Electrolyte disturbances: 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 agePharmacotherapy 2010;30(7):684-701 Am J Health-Syst Pharm 2008;65:1029-38NEJM 2004;350:1013-22 http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm073153.pdf

http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm073153.pdf

http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm073153.pdf

Circ Cardiovasc Qual Outcomes 2013;6:479-87

Case 3

Medication Prior to Admission:


• Ramipril 5mg PO daily

• Metoprolol 12.5mg PO BID


• Furosemide 40mg PO daily

• Spironolactone 25mg PO daily

• Metformin 500mg PO TID

• Glyburide 5mg PO BID


• Methadone 5mg PO TID

The prescription is instead written for SMX/TMP DS– 1 tab PO BID. Any potential DDI’S?

TMP/SMX and Drugs Affecting the Renin-Angiotensin-Aldosterone System

BMJ 2014;349:g6196

Co-trimoxazole and sudden death in patients receiving inhibitors of renin-angiotensin system

Trimethoprim-Sulfamethoxazole and risk of sudden death among patients taking

spironolactone

CMAJ 2015;187(4):E138-E143

SMX/TMP and Sulfonylureas

Drug-Drug Interactions Among Elderly Patients Hospitalized for Drug Toxicity

JAMA 2003;289;1652-58

Hypoglycemia after Antimicrobial Drug Prescription for Older Patients Using Sulfonylureas

JAMA Intern Med 2014;174(10):1605-12

DDI ConsiderationsAntibiotics

• High risk DDI with antibiotics are rare but can be clinically relevant

• Identification of those at highest risk population is essential

Overall Considerations for Managing Potential DDI’s

• Outcome of the interaction if it were to occur• Clinical significance• Ease of treatment

• Likelihood of occurrence

• Ability to monitor for outcome

Summary

• Potential DDI are 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

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Drug Interactions in Pharmacy Practice:

Recognition and Management of Clinically Relevant Drug-Drug Interactions

Jennifer Bolt BSc.Pharm, ACPR, PharmDResidency & Education [email protected] May 2016

mailto:[email protected]

drug interactions in pharmacy related practice j. bolt

Healthcare