Is warfarin an enzyme inducer?
Long-term phenytoin use with warfarin can decrease the INR since it is a CYP inducer. [5] Rifampin is also a CYP enzyme inducer. Due to the increase in warfarin metabolism, a higher daily dose may be necessary. Patients on warfarin should avoid or minimize alcohol consumption.
Is warfarin an inducer or inhibitor?
Examples of Common Drug-Drug Interactions Involving the Cytochrome P450 Enzyme System
| Drug(s)/product | Enzyme inhibitor or inducer | Drug(s) |
|---|---|---|
| Amiodarone (Cordarone) | CYP2C9 and CYP3A4 inhibitor | Warfarin (Coumadin) |
| Carbamazepine (Tegretol), phenobarbital, phenytoin (Dilantin) | CYP3A4 inducer | Ethinyl estradiol-containing contraceptives |
Is warfarin a CYP inhibitor?
The anticoagulant drug warfarin occurs as a pair of enantiomers that are differentially metabolized by human cytochromes P450 (CYP). R-warfarin is metabolized primarily by CYP1A2 to 6- and 8-hydroxywarfarin, by CYP3A4 to 10-hydroxywarfarin, and by carbonyl reductases to diastereoisomeric alcohols.
What kind of inhibitor is warfarin?
Warfarin is a vitamin K antagonist and inhibits synthesis of vitamin K–dependent clotting factors (II, VII, IX, X) and proteins C and S.
Is warfarin a P450 inducer?
ABSTRACT. The required dose of the oral anticoagulant warfarin varies greatly, and overdosing often leads to bleeding. Warfarin is metabolised by cytochrome P450 enzymes CYP2C9, CYP1A2 and CYP3A.
What are inducers and inhibitors?
This system can be inhibited or induced by drugs, and once altered can be clinically significant in the development of drug-drug interactions that may cause unanticipated adverse reactions or therapeutic failures. Drugs that cause CYP450 drug interactions are referred to as either inhibitors or inducers.
How do you administer warfarin?
Warfarin comes as a tablet to take by mouth. It is usually taken once a day with or without food. Take warfarin at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand.
Is warfarin a CYP inducer?
Initiation of cytochrome P-450 (CYP)-inducing anticonvulsant medications during warfarin therapy may decrease anticoagulant effect and necessitate frequent warfarin dose adjustments to maintain therapeutic response measured by the international normalized ratio (INR).
What factor does warfarin inhibit?
Warfarin is thought to interfere with clotting factor synthesis by inhibition of the C1 subunit of the vitamin K epoxide reductase (VKORC1) enzyme complex, thereby reducing the regeneration of vitamin K1 epoxide.
Is warfarin a substrate of CYP?
R-warfarin is mainly metabolised by the CYP enzymes CYP1A2 and CYP3A, with CYP3A likely to be the most important. CYP3A activity is derived from CYP3A4 and CYP3A5 that have similar substrate specificities.
How do you remember enzyme inducers and inhibitors?
Cytochrome P450 (CYP450) enzymes can be inhibited or induced by some drugs, resulting in significant drug interactions that can cause unanticipated adverse reactions or therapeutic failures. An easy way to remember the mnemonic is; CRAP GPs spend all day on SICKFACES.com.
What are the drug interactions between warfarin and other medications?
As a result, its metabolism is subjected to an extensive list of drug interactions of enzyme inducers and enzyme inhibitors. Enzyme inducers decrease the amount of active warfarin in the body and thus decrease its efficacy (decrease INR). These include alcohol, allopurinol, paracetamol, SSRIs, lipid-regulating drugs, influenza vaccine. 7
What is warfarin used for?
Warfarin is the anticoagulant of choice for the prevention of thromboembolic events in patients with mechanical heart valves and valvular atrial fibrillation, as well as in patients with end-stage renal failure. 1
Does vitamin K affect the effectiveness of warfarin?
As warfarin is an antagonist of vitamin K, consuming an excess of foods containing vitamin K may reduce warfarin’s efficacy and thus require higher doses to maintain therapeutic INR levels.
Why does warfarin induce a hypercoagulable state?
Paradoxically, warfarin induces a hypercoagulable state because the suppression of protein C occurs much quicker than that of the coagulation factors, due to protein C having a short half-life (approximately eight hours). 8