EASY INR

MANAGEMENT
IS THAT AN OXYMORON?

Andrea Rushfeldt
B.Sc. Pharmacy
FIRST STEP WHAT IS AN INR?
INR = International Normalized Ratio
PT = Prothrombin time (time it takes to cause a
thrombus/clot)
The INR standardizes the PT so it can be
compared using different lots of lab reagents and
from person to person
Target INR for most patient is 2.0 to 3.0
Target INR for patients with mechanical heart
valves is 2.5 to 3.5 as greater risk of clotting
If INR is too low = blood is too thick (too quick to
clot)
If INR is too high = blood is too thin (takes too
long to clot)
NEXT STEP WHAT IS WARFARIN?
Warfarin (Coumadin )
Blood thinner is a misnomer an anticoagulant
(decrease chance of forming a clot
inappropriately)
Inhibits production of the vitamin-K dependent
clotting factors (factors II, VII, IX and X)
Half-life of clotting factors ranges from 4-72
hours therefore maximal effect not reached until
2-5 days (anticoagulation effects begin within 24
hours).
Highly protein bound (~99%) so only 1% of active
drug is free to act in the body = many drug
interactions
Ie. Consider change to 98% protein bound = double
active drug levels!
WARFARIN THERAPEUTICS
Metabolized in the liver by the CYP450 system =
many drug interactions
Patients > 60 years have a greater response to effects
Liver dysfunction potentiates effects of warfarin
(reduced synthesis of clotting factors, serum protein
and reduced metabolism)
Side-effects hemorrhage and rarely
gangrene/necrosis (tell patient to watch for blood in
stool, urine, nose, vomit, sputum)
Indications: to prevent DVT (deep vein thrombosis)
and PE (pulmonary embolism) stroke, MI, CHF,
AFib (other arrythmias), valve disorders, cancer, post-
surgical (low mobility), other coagulopathies
 WARFARIN DRUG
INTERACTIONS

How much time do I have?

Mechanisms to keep in mind:

metabolism, protein binding,
effects on vitamin K and
clotting factors
WARFARIN INTERACTIONS
Disease-state Food interactions
interactions sources of vitamin K

Diarrhea Green leafy vegetables

Fever & (kale, collard, spinach)
hyperthyroidism Broccoli, brussels
(increased break down sprouts, onions
of clotting factors) Lettuce (all types),
Liver function cabbage
Vigorous exercise Okra, cucumber, peas
(variable effect) Bread crumbs, spinach
noodles, plums
Protein status
Pistachio nuts
Alcoholism (variable)
WARFARIN DRUG INTERACTIONS
Antibiotics Other drug interactions

Almost all antibiotics Increased effect:

kill the GI flora, fibrates, statins,
bacteria which cimetidine, quinidine,
produce vitamin K so amiodarone, vitamin E
increase INR (>800 IU), topical
salicylates, NSAIDs,
Some CYP450 Dilantin, Plavix, Ticlid,
interactions also acetaminophen in
Cipro, erythromycin, higher doses
Biaxin, sulfas, flagyl, Decrease effect:
azole antifungals Tegretol, rifampin,
barbiturates, HRT (pro-
embolic), Questran
WARFARIN HERBAL INTERACTIONS
Known increase in effect Known decrease in effect

Bromelain St. Johns Wort

Dong quai (enzyme inducer)
Garlic Coenzyme Q10
Ginko biloba Probiotics?
Ginseng (the Gs)
Many, many, many
consult the Natural
Medicines Drug
Database or the CPS
NO WONDER ITS SO HARD TO
KEEP PEOPLE ON TARGET!!!

Remember that none of the

medications , foods, herbals are off
limits with warfarin intake and
lifestyle must be consistent and the
dose can be adjusted accordingly
MONITORING INR
Do not monitor INR more frequently than every
2-3 days (remember half-life of clotting factors)
Monitor every 2-3 days initially, when not at
target, while adjusting dose or when making
changes to medication regimen or lifestyle
If stable, prolong monitoring to weekly or
biweekly and eventually to monthly if
appropriately
Watch for trends versus blips!
ANALYZING THE INR RESULTS
ASSESSMENT!!!
Trends = look at all of the patients INR over
time, if gradually increasing or decreasing, adjust
dose before they fall out of range
Blips = ask patient what has changed (meds,
lifestyle, diet, OTCs, herbs, compliance)
Note an INR is a measurement of clotting time
at that exact moment and reflects changes over
the last 1-5 days (versus HgA1C average of last
3 mths) so very important to differentiate blips
versus trends
Compliance and understanding very important
ADJUSTING WARFARIN DOSE
General rule of thumb = 5-10% up or down (average
weekly dose)
Other factors to consider:
o Greater personal risk if the patient bleeds or clots?
o How far below/above target are they?
o Previous reactions to dose changes (ie. sensitivity)
o Trends and blips
Some patients require very creative dosing:
5mg alternating with 4.5mg
5mg 4 times per week & 4.5mg 3 times per week
5mg 5 times per week & 4.5mg twice weekly
Yes some patients are THAT sensitive!
Some debate on exactness of splitting tablets
(consider half-life, taking the other jagged piece the
next day probably ok)
Availabilities: 1mg, 2mg, 2.5mg, 3mg, 4mg, 5mg, 6mg,
7mg, 10mg tabs (make sure the patient has the right
tools to make the dose you are suggesting and that
they understand)
NOW COMES THE EASY PART

INR Action
< 1.5 Reload x 0-2 doses, increase weekly dose by 5-
10%
1.5 1.9 Reload x 0-1 doses, increase weekly dose by 0-
10%
2.0 3.0 No change (unless you are watching for trends)
3.1 3.5 Hold 0-1 doses, decrease weekly dose by 0-10%
3.6 4.9 Hold 0-2 doses, decrease weekly dose by 5-15%,
5.0 9.0 Hold warfarin until therapeutic, Vitamin K
only if bleeding, then reinitiate at 10-20%
reduced dose
>9 Vitamin K 3-5mg PO if any bleeding x 0-2
doses

Reload = giving up to twice the current daily dose

This chart applies for target INR 2.0 3.0
VITAMIN K DOSING
See chart provided
Clinical setting: is the patient currently bleeding,
any other risk factors for bleeding, urgency of
INR normalization desired?
Therapeutic options hold warfarin if no serious
risks or administer vitamin K p.o.
Vitamin K 2-5 mg
Oral vitamin K is preferred in patients who have
additional risk factors for bleeding
IV clotting factors if ER situation
AN EXERCISE IN OBVIOUSNESS:

Over-reacting (or under-reacting) just makes

your job harder as it will be more difficult and
take longer to get the patient to target.

Do not hold doses longer than 2 days as you will

be starting from scratch!
CASE STUDY
Case: Mr. Dupont is a 73 year old with a history of Afib
and hypertension. He is currently using metoprolol
100mg BID and Altace 10mg. Current warfarin dose
is 3.5mg QD.
1) His INR comes back at 1.6, what do you do?
i. Assessment no significant changes in diet, other meds,
lifestyle, etc.
ii. Adjust warfarin dose:
3.5mg QD x 7 days per week = 24.5mg per week x 1.1 (10%
increase) = 26.95mg / 7 days = 3.85mg per day!
Approximate to 4mg alternating with 3.5mg +/- reload dose of
7mg today

2) What if the INR was 1.8?

i. Maybe increase by 5% only to 3.5mg 5 times per week
and 4mg two times a week, no reload
CASE STUDY CONT.
3) What if the INR was 3.6?
i. Assessment I had a headache early this week
and popped a few Advil
ii. Advise A better choice for your headaches might
be Tylenol
iii. Decrease daily dose by 5-10%

4) What if the INR was 3.6 and Mr. Dupont has

had a past history of a GI bleed due to
NSAID use?
i. Assessment higher risk of bleeding (GI
bleed and age)
ii. Adjustment Hold 1 dose and decrease daily
dose by 5-10%
REFERENCES
o e-CPS
o Pharmalearn Anticoagulation