Travel Health Conference April 27, 2018 Jamie Falk, BScPharm, PharmD
Presenter: Jamie Falk Drug interactions in travelers with chronic conditions I have no conflicts to disclose
By attending this session the attendee will be able to: 1. Identify common drug interactions (DI) that may arise with travel medications and medications used for a variety of common chronic conditions. 2. Determine if a potential DI with a travel medication can be ignored, managed or should be completely avoided depending on the comorbidities and clinical circumstance of the patient. 3. Provide advice to patients on what to do to minimize risk of interactions in question, what to watch for, and what to do if the interaction occurs while travelling. T R A V E L T O P I C S motion sickness malaria chemoprophylaxis travelers diarrhea altitude sickness
Pharmacokinetic: Results from interference by a drug on another drug s Absorption, Distribution, Metabolism or Elimination Predictability? Pharmacodynamic: Occurs when effects of the object drug are stimulated or inhibited by the precipitant drug Predictability?
How to minimize the Uncle Bill & Uncle Harry interaction: 1. Don t invite one of them (desirable, but often impossible) 2. Stagger their arrivals (awkward, but sometimes works) 3. Have them overlap for the minimum time possible (minimize exposure) 4. Hope that they re in an agreeable mood (i.e. you were worried for nothing)
What is the onset & duration of effect? How long until effects of DI occur? How long after drug discontinuation will effects last? Is the drug interaction clinically important? Magnitude of effect Therapeutic index of the drugs involved Risk factors for individual patients How can the DI be prevented or managed?
#1 John is a 60-year old engineer who will be doing an irrigation project in Malawi. Medical history: Aortic valve replacement (2016) HTN GERD Meds: Warfarin 4mg daily (last INR = 2.3) Losartan 50mg daily Indapamide 2.5mg daily Rabeprazole 20mg daily prn What are his options for malaria prophylaxis?
rxfiles.ca: My two main sources: 1) 2)
1) 2) SUPPORTING DOCUMENTATION (Micromedex) RELIABILITY RATING (Lexicomp) The level of the documentation (Excellent, Good, Fair, Unknown) supporting the interaction is also shown for each interaction listed
Doxycycline Atovaquone/Proguanil Mefloquine
1. Hope for the best 2. INR test at a local clinic in Malawi (?) 3. Point of care testing machine to take with 4. Better yet monitor at his lab after being on med for 1-2 weeks before leaving What is the onset & duration of effect? How long until effects of DI occur? How long after d/c will effects last? Is the drug interaction clinically important? Magnitude of effect Therapeutic index of the drugs involved Risk factors for individual patients How can the DI be prevented or managed? 5. Watch closely for signs of bleeding Warfarin half-life = ~36hrs High INR bad if major bleed Narrow What are his risks for major bleed? e.g. HASBLED score?
Bismuth subsalicylate prophylaxis: the problem ongoing & high dose which may enhance anticoagulant effect likely best avoided Azithromycin Ciprofloxacin Potential for increased INR Good news: short-term (1-3 days), so DI is also short-term unlikely to pose a serious risk watch for signs of bleeding limit to 1-day course if possible
#2 Gail is a 64-year old retired teacher who is heading to Thailand to visit her daughter Medical history includes: GERD Type-2 diabetes Hypertension Depression Medications: Pantoprazole 40mg daily Metformin 850mg BID Gliclazide MR 60mg daily Ramipril 5mg daily Sertraline 100mg daily To treat moderate/severe traveler s diarrhea, should it occur, she s been given a prescription for: CHOOSE YOUR OWN ADVENTURE! azithromycin or ciprofloxacin
Oh yeah, she didn t tell you that she also takes calcium 500mg BID Minerals (Ca, Al, Mg, Fe) and fluoroquinolones (FQ) FQ forms a chelate with the cation bioavailability of FQ e.g. Calcium can bioavailability of cipro to 60% Al-Mg antacids can bioavailability of levo to 55% Solution: Ask patients about supplements, document & educate accordingly Easy solution: Stop mineral while on FQ Difficult solution: Take FQ 2 hrs before or 4-6 hrs after cation
What is the onset & duration of effect? How long until effects of DI occur? How long after d/c will effects last? Is the drug interaction clinically important? Magnitude of effect Therapeutic index of the drugs involved Risk factors for individual patients How can the DI be prevented or managed? TdP isn t cool if it happens, but it is rare Difficult without not taking the offending drug(s) Important: IMHO, one of the scariest but most over-rated drug interactions
QTc prolongation risk factors: Old age (>65) Female Congenital QT syndrome Underlying structural cardiac disease/hypertrophy HypoMg 2+ HypoK + Concurrent use of other QTc prolonging drugs Questions to address: Is there even a problem Are there modifiable risk factors Are both meds needed? https://crediblemeds.org/new-drug-list/
Keeping in mind that tx is 1-3 days How do we assess Gail?
Azithro + sertraline in a 70-year old female with history of MI on furosemide for mild CHF Ciprofloxacin + sertraline in a 60-year old male with no previous heart disease Diuretics + Diarrhea low K low Mg 4-5 QT risk factors 1 QT risk factor Likely still do it? Advice for both don t use unless you need to Advice for her have lytes checked before you go? limit to 1-day course if at all possible alternate antibiotic???
Gail forgot to tell you that she also takes simvastatin 40mg for CV risk prevention Are there any concerns? For azithro: theoretically, yes Azithro risk of simvastatin intolerance (e.g. myalgias) likely due to simvastatin concentrations But again, is this a big concern for 1-3 days? Probably not But, azithro has a long t 1/2 DI may occur for several days afterward: 1) mention myalgias to Gail 2) prescribe cipro instead? probably not
CIHI 2008
#3 Sue is a 76-year old with multiple stable comorbidities. She comes in to the pharmacy for her usual refills: Ranitidine 150mg BID Amlodipine 5mg daily Oxybutynin 5mg BID Levothyroxine 75 mcg daily Amitriptyline 50mg HS She also asks if she can get some Gravol because she and her husband are celebrating their 50 th on a cruise. What load are we talking about?
Dizziness Drowsiness Confusion Delirium Dry mouth Urinary retention Constipation Swelling (edema)
Is the potential benefit > risk/annoyance for your patient?
1) Obviously https://wwwnc.cdc.gov/travel/yellowbook/2018/the-pre-travel-consultation/motion-sickness 2) Ask if any of the classic anticholinergic symptoms are currently present 3) If she is insists on using one of these products (e.g. dimenhydrinate or scopolamine): a) Caution her on what could occur b) Start with the lowest dose (little flexibility with scopolamine patch)
#4: HIGH ON LIFE Don is planning a trip to Tanzania. He plans to check off a few items on his bucket list. His first few weeks will be spent on safari and he ll conclude with attempting to climb Mount Kilimanjaro. Medications: Doxycycline (to start pre-travel) Metformin 1000mg BID Atorvastatin 10mg daily Hydrochlorothiazide 12.5mg daily Ibuprofen prn for shoulder pain He s asking about something for prevention of altitude sickness
to avoid using 1.Acetazolamide: risk of lactic acidosis with metformin (Lexicomp ) 2.Dexamethasone: commonly blood glucose? 3.Nifedipine: metabolized by CYP3A4 concurrent use of doxycycline (CYP3A4 inhibitor) could nifedipine concentrations lower BP Advice for Don? don t be a hero stay hydrated bring your BG monitor
What is the onset & duration of effect? How long until effects of DI occur? How long after drug discontinuation will effects last? Is the drug interaction clinically important? Magnitude of effect Therapeutic index of the drugs involved Risk factors for individual patients How can the DI be prevented or managed?
jamison.falk@umanitoba.ca @JamisonFalk