Traveling with Chronic Medical

Conditions:

Anticoagulation, Diabetes, and

Sleep Apnea

Mary-Louise Scully, United States

Fons Van Gompel , Belgium

Financial Disclosures

Mary-Louise Scully M.D.

None myself -

Husband - is medical director and holds some equity in

Setpoint Medical, a medical device company for rheumatoid

arthritis and Crohn’s disease treatment

Traveling on Anticoagulation

Asia Pacific (APTHS) Meeting 2014

Ho Chi Minh City

Case 1

70 year old female

•travelling to rural Uganda to participate in opening ceremonies for a girls school – she was a major donor to the project.

•has a h/o atrial fibrillation and is now maintained on rivaroxaban (Xarelto) 20 mg /day after switching from Coumadin 5 years ago.

•comes for pre-travel preparation to get vaccines and discuss specifics of her anti-coagulation in the context of her plans for travel to a remote area.

71 year old on Rivaroxaban for travel to Uganda

Topics to discuss :

• Vaccination of the anti-coagulated patient

• Dosage and timing adjustments with time zone changes

• Drug interactions with New Oral Anticoagulants (NOACs)

• Use of portable devices with Vitamin K Antagonists (VKAs)

• Emergency reversal if severe bleeding

Traveling on Anticoagulation Agents

New Oral Anticoagulants (NOACs)

•Rivaroxaban (Xarelto)

•Apixaban (Eliquis)

•Dabigatran (Pradaxa)

•Edoxaban ( Savaysa) – newest

Vitamin K Antagonists (VKA)

Warfarin/Coum

adin

Decreased

synthesis of

Vitamin K-

dependent

coagulation

factors II, VII,

IX, and X

(inhibition of

gamma

carboxylation )

Dabigatran - Direct Thrombin ( Factor IIa) inhibitor

Rivaroxaban, Apixapan, Enoxaban -Factor Xa inhibitors

Anticoagulation

* Susan Lambe M.D. UCSF Reversing the New Anticoagulants

*

NOAC versus VKAVKA NOAC

Half Life Long 3-6 days Short 5-17 h

Food Influence YES NO

Drug Interactions HIGH LOW

Need for Lab work YES NO

Reversal if bleeding YES NO

NOAC - Lack of need for monitoring and no effect from change

in diet with travel might make NOAC appealing

VKA - Availability of reversal agents, like FFP globally, longer

half life, food influence, need for monitoring

Travel Medicine and Infectious Disease (2014) 12, 7-19

J Travel Med 2009; 16: 276–283

Vaccines in Anticoagulated Patients

70 yo female for Travel to Uganda on Rivaroxaban

Will likely need :

Yellow Fever (SQ)

Hepatitis A (or A+ B) (IM)

Typhoid (IM or Oral)

Tdap (IM)

Subcutaneous – not a problem

Intramuscular – Concern about risk of hematoma

Group I SQ ( YF, JE, MMR all ok) Group II – SQ or IM,

Group III – IM but if SQ now impaired response

When IM vaccines needed

•Fine needle ≤23 gauge, firm pressure 2 min

•INR should be < 4.5

Actual occurrence of hematomas seem rare/low

J Trav Med

2009;16:276-83

Reingold et al. SQ versus IM of the licensed vaccines

U.S/Germany

IM Vaccination on NOAC’s? Maybe 24 hours after last dose of NOAC’s

•Rivaroxaban recommended with evening meal, vaccinate late afternoon?

•Dabigatran and Apixaban dosed twice/day, could omit one dose

•Renal impaired need longer interval

None of which have I been doing ! so far no problems,

What are people doing in their clinics?

Ringwald, J et al. Trav Med Infect Dis

2014;12:7-19.

So now our 70 y.o. for travel to Uganda

on Rivaroxaban is all properly

vaccinated but then asks you

“Doctor want do I do about time changes

with travel and my medication?

When to medicate – Where am I ?

Traveling East

• shortening of the day

Traveling West

• prolongation of the day

Crossing the International Dateline

• total confusion !

Time TravelPatient at home

takes her Xarelto

6pm

California

Paris

Leaves CA at 6pm

Takes her Xarelto

Flight time 12 hrs

9 Time Zones

9 hours ahead

Local time 3 pm

Only 6 am (her body)

If at 6pm Paris time

she take s her dose,

it’s only really 14 hrs

since her last dose

***Company has no

guidance. Left to the

discretion of the

prescribing doctor !

What to do?

Set alarm for 3 a.m.?

?Move back the dose

1-2 hours per day

until back to 6 pm

? Adjust dose by 25-

50%

•coumadin –ok likely

•NOACs no data

Coumadin –

•Longer half life, no adjustment unless > 6 time zones,

•lots of experience in adjusting dose, not the case with NOACs

For AF and

DVT/PE

prevention

Dose is 20 mg

/ day

Triangular pill

!

NOAC’s Dosing in Travel –

Ask an Heme Expert ?

Hematologist #1

•Early dose -less concerned as dosed higher in DVT treatment

•Delayed dose – although half life shorter, physiologic effect longer

Hematologist # 2

•Early dose – less concerned NOAC ‘s not affecting whole pro-coagulant

system, like coumadin where early dosing might increase bleeding

Hematologist # 3

•Think about reason on NOAC in first place, is risk of bleeding in remote

place without access to medical care > that risk of stroke off meds for 2

weeks ?

•ie A Fib think about left atrial size, ejection fraction, previous stroke/clot

71 y.o. female to Uganda on Rivaroxaban

Should she consider a drug holiday?

D-Dimer – can predict stroke risk

•If + on anticoagulation should not be stopped

•If – could consider

* Consultation with patient’s cardiologist and/or heme a must !

71 year old on Rivaroxaban for travel to Uganda

What about malaria prophylaxis and maybe an antibiotic for travelers diarrhea ?

What are potential drug interactions with her rivaroxaban?

Apixapan / rivaroxaban –substrates CYP 450 isoform CYP3A4 and P-glycoprotein

Dabigitran – only P - glycoprotein

Anticoagulation and Travel Meds

Coumadin

•Chloroquine – none

•Mefloquine - ? INR(Only 2 case reports )

•Malarone – ? INR atovaquone 1500mg/day 1 report

proguanil (1 case / in package insert)

•Doxy – INR

•Cipro – INR

•Azithro - INR

NOACs

•Chloroquine – none

•Mefloquine – INR

•Malarone – none

•Doxy – none

•Cipro – none

•Azithro - INR

Our pt could use either Malarone or Doxy for malaria

prophylaxis and cipro for TD

Drug Interactions: NOAC

Also mefloquine, azithomycin

* Dose reduction needed with renal insufficiency and contraindicated if CrCl

of 30 (dabigitran) or 15 (rivaroxaban, apixiban)

Monitoring of INR During Travel

Portable INR Machines

Battery operated

Protime Advantage did have

rechargeable batteries but no longer on

market since Jan 2015.

Remaining 2 in US rechargeable

batteries “not recommended” by

company

(device

discontinu

ed)

INR Devices at the “Extremes”Meter

•alert comes on if “too hot” or “too cold” – High > 95 ° F

– Low < 50 ° F

•Meter “fried” if > 158° F, “frozen” if -4 ° F

time for an new machine!

Test strips –– Best kept at room temp, and definitely < 90 degrees

– If kept in refridgerator, allow to come to room temp before using

Advice for managing elevated INR while traveling

General guidelines

Now with Internet / Skype- can likely contact physician for advice as well.

Reversal with bleeding problems

Coumadin

Vitamen K

Fresh Frozen Plasma

Prothrombin complex

Concentrates

NOACs

? in development

Activated charcoal

Prothrombin complex

concentrates

Dialysis - only

dabigatran

Assumes medications and

high level medical care

available

Less likely to be available

in resource poor areas

��

UNC Healthcare ED Anticoagulation

Reversal Guidelines

Susan Lambe M.D. UCSF Reversing

the New Anticoagulants

Protocols for Bleeding -

NOACs

Sleep Apnea and Travel

Case

41 year old male

• Sailing at sea alone for 45 days from California to Hawaii and on to Vancouver, Canada on a sailboat he has specially outfitted for one man operation.

• Although planning to have a satellite phone and GPS he comes in for help with prescription medications for emergency use if needed

• Also has a h/o sleep apnea for which he nightly uses his CPAP machine and wants to discuss aspects of his remote travels and use of this device.

Sleep-Related Breathing Disorders

Abnormal respiration during sleep. Affected persons have repetitive

pauses during sleep but breathe normally when awake.

Obstructive Sleep Apnea (OSA) - collapse of the throat or airway

Risk factors

– older age, obesity, male gender

– Smoking, nasal congestion, menopause, Family Hx

Central Sleep Apnea - repetitive cessation or decrease of both

airflow and ventilatory effort during sleep

– Congestive heart failure, Traumatic Brain Injury

– High altitude periodic breathing

Sleep Apnea

Obstructive Sleep Apnea

a

Sleep ApneaSymptoms – nocturnal choking or gasping, un-refreshing sleep,

excessive daytime sleepiness, poor concentration

Apnea/Hypopnea Index - > 5 episodes / hour + 1 symptom of

disturbed sleep, or >15 episodes / hour

Decreased O2 Saturation, cardiac arrhythmias, increased arterial

pressure

Other

•Traffic Accidents (NEJM. 1999;340:)(11):847-851

•Cardiovascular Disease (Lancet. 2005; 365(9464):1046-1053

•Exercise tolerance

Sleep Apnea and CPAP

CPAP – Continuous Positive Airway Pressure delivered nocturnally

is the most effective therapy for sleep apnea

First case – Patient with severe sleep apnea,

considering tracheostomy, willing to be first subject

Sleep Apnea and CPAP

CPAP – Continuous Positive Airway Pressure delivered nocturnally

is the most effective therapy for sleep apnea

CPAP Equipment

Getting better and smaller all the time !

Courtesy Prof. Verbraecken UA-Antwerp

CPAP Equipment

Quieter machines

Humidity added

Variety of face masks

Nasal pillows popular

Sleep Apnea and Travel

Smaller portable

machines

Battery packs

Solar rechargers

Auto Adjusting for

changes in altitude

Many online resources

www.cpap.com

www.sleepmedicine.com

Courtesy Prof. Verbraecken UA-Antwerp

Dental Devices for Sleep Apnea

Device is made and fitted by a dentist

Usually one- time expense

Might be a good option for travel

Dental Devices for Sleep Apnea

Device is made and fitted by a dentist

Usually one- time expense

Might be a good option for travel

Sleep Apnea / Altitude / Diamox

51 patients (48 male), Zurich Switzerland, July- Nov 2009

Randomized, DB, Placebo to either CPAP or CPAP + Diamox

Studied at 490 m, 1630 m (5348 ft), and 2590 m (8497 ft)

Diamox dose was 250mg am and 500mg pm

Sleep Apnea / Altitude / DiamoxConclusions :

• Combined CPAP + Diamox had improved nocturnal

oxygenation saturation, better control of sleep apnea at

altitude, reduced insomnia compared to CPAP alone.

• Confirmed CPAP alone is effective at altitude, Diamox to

enhance treatment.

• Did not improve exercise performance, no difference in

subjective sleepiness, or psychomotor testing.

CPAPCertainly not a substitute for “urgent descent” but

…..

48 yo anesthesiologist, Annapurna circuit, HAPE at 4450 m, unable

to evacuate, used Diamox and CPAP overnight

• machine data showed at increasing altitude - increased in

auto-adjusted CPAP and decreased apnea hypopnea index

(AHI).

• ? Possible use in HAPE treatment in remote areas

http://www.alaskasleep.com

CPAP Travel Tips

1. Plan Ahead

2. Letter from physician for equipment

3. Have Proper adaptor and plugs

4. Consider purchasing / renting back up battery pack for

power outages

5. Bring Extra Supplies (esp mask cushions)

6. When packing machine empty water from humidifier

7. If planning on using CPAP during flight check that

seating has power outlets

8. Keep a copy of your prescription in case equipment

fails/breaks

• Name and Brand of Mask

• Machine type and manufacturer

• Pressure settings

Cleaning

Mask –

daily

Tubing –

Weekly

Soap and

“clean”

water

? Camping

challenge

Have CPAP will travel …