Transcript Pharmacokinetics Warfarin

Pharmacokinetics:
Warfarin
Allie Punke ([email protected])
The Basics
• Most of the anticoagulant activity of warfarin is due to which
isomer? S
• What clotting factors does warfarin inhibit? 7, 9, 10, 2
• Protein C +S
• Which factor is reflected in the measurement of PT/INR? 7
• Which factor is responsible for the antithrombotic effect? 2
and 10
The Basics
• When do we recommend loading doses of warfarin? And what
is the dose? Healthy, young patients: 10 mg X 2 doses (2 days)
• How is the interaction with tube feedings avoided?
• Hold tube feedings 1 hour before and 1 hour after warfarin is
given
• Which enzymes metabolize warfarin?
• R: 1A2, 2C19, 3A4
• S: 2C9 and 3A4
True OR False
• A patient taking Cefdinir may experience a lowering of her INR
due to the gut flora being altered. False (INR would be
increased)
• The interaction of aspirin and warfarin is due to warfarin being
displaced from protein binding sites causing an increased INR.
False (It doesn’t displace binding sites)
• Low Extraction Drug: Css,u= D/Clint
• A chronic alcoholic can be expected to have consistently
decreased INR. True
• Patients who smoke may require less warfarin, since they are
more “sensitive” to it. False
Application
• Warfarin, a highly protein bound drug, is added on to a
patient’s medication regimen along with a drug that displaces
warfarin from albumin. How should we handle this?
• A. Because warfarin is a High E drug, the dose should be reduced
to prevent excess free warfarin.
• B. Because warfarin is a Low E drug, the dose should be increased
to ensure therapeutic INR.
• C. Because warfarin is a Low E drug, the dose should be reduced
to prevent excess free warfarin.
• D. Because warfarin is a Low E drug, no change needs to be made.
Application
• A patient is being managed on warfarin for atrial fibrillation.
Additionally, her physician wants to start her on amiodarone.
The physician asks you how to manage the interaction.
• A. The interaction usually occurs after being on amiodarone for 3
months and the dose of warfarin does not depend on the dose of
amiodarone.
• B. The interaction usually occurs after being on amiodarone for
about 2 weeks and the dose of amiodarone can be used to guide
the dosing of warfarin.
• C. The interaction time is variable, but the dose of amiodarone
can be used to guide the dosing of warfarin.
• D. The interaction time is variable and the dose of warfarin does
not depend on the dose of amiodarone.
Application
• The patient is started on 200 mg of amiodarone. How should
the dose of warfarin be adjusted if she takes 5 mg of warfarin
daily?
Application
• A patient needs to be started on a bile acid sequestrant.
Which would be best to recommend to avoid a documented
interaction with warfarin? Welchol
• How can we tell the patient to take cholestyramine or
colestipol with warfarin? Take 1 hour before or 4-6 hours after
Application—To Load or Not to Load
• MB, 24 YO woman, was diagnosed with a DVT and needs to be
initiated on warfarin. Should we give her a LD or not? Yes
• JP, 75 YO, needs to be started on warfarin. Actual Body
Weight= 58 kg. PMH=history of liver disease. Home
medications= lisinopril and hydrochlorthiazide, amiodarone.
Should we give him a LD or not? No (elderly, liver disease,
weight)
Application-Drug Interactions
• Match each drug with Increased or Decreased INR
• Garlic Increased
• Amiodarone Increased
• Barbiturates Decrease
• Rifampin Decreased
• Ginseng Procoagulant
• Septra Increase
• Metronidazole Increase
• Black cohosh Antiplatelet
• St. John’s Wort Decreased
• Carbamazepine Decreased
• Fab 5: Increase INR:
• - Flagyl, FQ, fluconazole, aminodarone, bactr
• Fluoroquinolones Increased
Application-Drug Interactions
• How do we manage these drug interactions?
• Rifampin:
• Onset of interaction: 5-10 days
• Dosage change: Increase warfarin by 100-200%
• Offset of interaction: Decrease warfarin by 50% 1-2 weeks after
rifampin is D/C
Application
• BA, a 85 year old patient, is taking warfarin correctly, but she
has been taking double of her levothyroxine dose chronically
for the past 1.5 months. How (if at all) does this affect INR?
• A. Her INR will be elevated due to the levothyroxine inhibiting the
metabolism of warfarin
• B. Her INR will be decreased due to impaired metabolism of
clotting factors
• C. Her INR will be elevated due to rapid metabolism of clotting
factors
• D. Her INR will be decreased due to the excess levothyroxine
stimulating metabolism of warfarin
Summary
• Always check for drug interactions if a patient is taking
warfarin.
• Know when a LD is appropriate.
• Know how certain disease states and medications can affect
the dose of warfarin.
• Always counsel on the effects of Vitamin K foods and
recommend to maintain a consistent diet of these.
Questions?