Contents
Dosing
Average Daily Dosing
- Most patients: start therapy at 5mg daily and adjust according to INR results
- Sensitive patients: start therapy at 1 – 2.5mg daily and adjust according to INR results
Factors that increase sensitivity to warfarin:
| Age > 75 years | Clinical congestive heart failure |
| Asian race | Clinical hyperthyroidism |
| Elevated baseline INR | End stage renal failure |
| Fever | Malignancy |
| Diarrhea | Following heart valve replacement |
| Known CYP2C9 variant | Hepatic disease |
| Hypoalbuminemia | Decreased overall oral intake |
| Malnutrition | CYP-inhibition drug interactions |
Flexible Initiation Method
- This nomogram is useful in hospitalized patients in whom INR can be checked on a daily basis.
- Several studies have confirmed that 5mg initiation achieves therapeutic anticoagulation as rapidly as 10mg initiation but with a lower frequency of supra-therapeutic INRs.
- The 10mg initiation nomogram should only be used in relatively young and healthy patients who are likely to be insensitive to warfarin, or in patients taking concurrent medications known to induce warfarin metabolism.
- Please note that loading doses of warfarin are NOT RECOMMENDED.
| Day | INR | Dose (5 mg Initiation) | Dose (10 mg Initiation) |
|---|---|---|---|
| 1 | - | 5mg | 10mg |
| 2 | <1.5 | 5mg | 7.5-10mg |
| 1.5-1.9 | 2.5mg | 2.5mg | |
| 2-2.5 | 1-2.5mg | 1-2.5mg | |
| >2.5 | 0 | 0 | |
| 3 | <1.5 | 5-10mg | 5-10mg |
| 1.5-1.9 | 2.5-5mg | 2.5-5mg | |
| 2-2.5 | 0-2.5mg | 0-2.5mg | |
| 2.5-3 | 0-2.5mg | 0-2.5mg | |
| >3 | 0 | 0 | |
| 4 | <1.5 | 10mg | 10mg |
| 1.5-1.9 | 5-7.5mg | 5-7.5mg | |
| 2-3 | 0-5mg | 0-5mg | |
| >3 | 0 | 0 | |
| 5 | <1.5 | 10mg | 10mg |
| 1.5-1.9 | 7.5-10mg | 7.5-10mg | |
| 2-3 | 0-5mg | 0-5mg | |
| >3 | 0 | 0 | |
| 6 | <1.5 | 7.5-12.5mg | 7.5-12.5mg |
| 1.5-1.9 | 5-10mg | 5-10mg | |
| 2-3 | 0-7.5mg | 0-7.5mg | |
| >3 | 0 | 0 |
Maintenance Dosing Nomogram
| For Goal INR 2-3 | Dosing Adjustments | For Goal INR 2.5-3.5 |
|---|---|---|
| INR < 1.5 | Consider a booster dose of 1 ½ -2 times daily maintenance dose Consider resumption of prior maintenance dose if factor causing decreased INR is transient [e.g.: missed warfarin dose(s)] If a dosage adjustment is needed, increase maintenance dose by 10%–20% |
INR < 2.0 |
| INR 1.5-1.7 | Consider a booster dose of 1 ½ – 2 times daily maintenance dose Consider resumption of prior maintenance dose if factor causing decreased INR is considered [e.g.: missed warfarin dose(s)] If a dosage adjustment is needed, increase maintenance dose by 5-15% |
INR 2.0–2.3 |
| INR 1.8–1.9 | No dosage adjustment may be necessary if the last two INRs were in range, if there is no clear explanation for the INR to be out of range, and if in the judgment of the clinician, the INR does not represent an increased risk of thromboembolism for the patient Consider a booster dose of 1 ½ – 2 times daily maintenance dose Consider resumption of prior maintenance dose if factor causing decreased INR is transient [e.g.: missed warfarin dose(s)] If a dosage adjustment is needed, increase maintenance dose by 5%–10% |
INR 2.3–2.4 |
| 2.0-3.0 | Desired Range | 2.5-3.5 |
| 3.1-3.2 | No dosage adjustment may be necessary if the last two INRs were in range, if there is no clear explanation for the INR to be out of range, and if in the judgment of the clinician, the INR does not represent an increased risk of hemorrhage for the patient Consider continuation of prior maintenance dose if factor causing elevated INR is transient [e.g.: acute alcohol ingestion] If a dosage adjustment is needed, decrease maintenance dose by 5%–10% |
3.6-3.7 |
| 3.3-3.4 | Consider holding ½ to 1 dose Consider resumption of prior maintenance dose if factor causing elevated INR is transient [e.g.: acute alcohol ingestion] If a dosage adjustment is needed, decrease maintenance dose by 5%–10% |
3.8-3.9 |
| 3.5-3.9 | Consider holding 1 dose Consider resumption of prior maintenance dose if factor causing elevated INR is transient [e.g.: acute alcohol ingestion] If a dosage adjustment is needed, decrease maintenance dose by 5%–15% |
4.0-4.4 |
| > 4.0 | Hold until INR < upper limit of therapeutic range Consider use of mini-dose oral vitamin K Consider resumption of prior maintenance dose if factor causing elevated INR is transient [e.g.: acute alcohol ingestion] If a dosage adjustment is needed, decrease maintenance dose by 5%–15% |
> 4.5 |
Simplified Nomogram for Warfarin Maintenance Dosing
| Goal INR 2-3 | Recommendation | Goal INR 2.5-3.5 |
|---|---|---|
| <2 | Reload x 0-1 Increase by 5-15% |
<2.5 |
| 2-3 | No change | 2.5-3.5 |
| 3.1-3.5 | Decrease by 0-15% | 3.6-4 |
| 3.6-4 | Hold 0-1 dose Decrease by 5-15% |
4-4.5 |
| >4 | Hold until therapeutic +/- mini-dose vitamin K Decrease by 10-20% |
>4.5 |
Adapted from Crowther MA, Harrison L, Hirsch L. Ann Intern Med 1997; 127:332-3
Frequency of Monitoring
Warfarin Maintenance Therapy Monitoring Schedule
| Dose held today in patient with significant over anticoagulation | In 1 – 2 days |
| Dosage change today | Within 1 – 2 weeks |
| Dosage change < 2 weeks ago | Within 2 – 4 weeks |
| Routine follow-up of medically stable & reliable patients | Every 4 – 8 weeks |
| Routine follow-up of medically unstable or unreliable patients | Every 1 – 2 weeks |
After Hospital Discharge Warfarin Monitoring
| If patient or therapy is unstable | In 1-3 days |
| If patient of therapy is stable | In 3-7 days |
Chromogenic Factor X (CHRF10)
Used instead of INR to monitor warfarin in patients bridged with direct thrombin inhibitors that might interfere with INR.
Learn about Chromogenic Factor X (CHRF10)
Drug Interactions
Listed Drug Interactions (Hint: Use the Search Box or Sort by Column)
| Drug/Drug Class | Effect on INR | Proposed Mechanism | Significance (A) | Management (B) |
|---|---|---|---|---|
| acarbose | increased | Unexplained Mechanisms | 4 - Major or Moderate | 0 - Not Listed |
| acetaminophen | increased | Inhibition of Warfarin Metabolism | 2 - Moderate | 3 - Minimize Risk |
| alcohol (acute use) | increased | Inhibition of Warfarin Metabolism | 4 - Major or Moderate | 3 - Minimize Risk |
| alcohol (chronic use) | decreased | Induction of Warfarin Metabolism | 4 - Major or Moderate | 3 - Minimize Risk |
| allopurinol | increased | Inhibition of Warfarin Metabolism | 4 - Major or Moderate | 3 - Minimize Risk |
| aminoglutethamide | decreased | Induction of Warfarin Metabolism | 2 - Moderate | 3 - Minimize Risk |
| amiodarone | increased | Inhibition of Warfarin Metabolism | 1 - Major | 3 - Minimize Risk |
| amitriptyline | increased | Inhibition of Warfarin Metabolism | 0 - Not Listed | 4 - No Action Needed |
| Androgens | increased | Unexplained Mechanisms | 1 - Major | 2 - Usually Avoid Combination |
| aprepitant | decreased | Induction of Warfarin Metabolism | 4 - Major or Moderate | 3 - Minimize Risk |
| ascorbic acid | decreased | Unexplained Mechanisms | 5 - Minor | 3 - Minimize Risk |
| aspirin/salicylates | no effect | Increased Bleeding Risk | 1 - Major | 2 - Usually Avoid Combination |
| azathioprine | decreased | Unexplained Mechanisms | 2 - Moderate | 3 - Minimize Risk |
| azithromycin | increased | Inhibition of Warfarin Metabolism | 1 - Major | 5 - No Interaction |
| Azole Antifungals | increased | Inhibition of Warfarin Metabolism | 1 - Major | 3 - Minimize Risk |
| Barbiturates | decreased | Induction of Warfarin Metabolism | 1 - Major | 2 - Usually Avoid Combination |
| bosentan | decreased | Induction of Warfarin Metabolism | 2 - Moderate | 3 - Minimize Risk |
| capecitabine | increased | Inhibition of Warfarin Metabolism | 1 - Major | 3 - Minimize Risk |
| carbamazepine | decreased | Induction of Warfarin Metabolism | 2 - Moderate | 3 - Minimize Risk |
| carboplatin | increased | Unexplained Mechanisms | 1 - Major | 0 - Not Listed |
| celecoxib | increased | Inhibition of Warfarin Metabolism | 1 - Major | 4 - No Action Needed |
| Cephalosporins | increased | Decreased Synthesis of Clotting Factors | 2 - Moderate | 2 - Usually Avoid Combination |
| chloral hydrate | increased | Protein Binding Displacement | 3 - Minimal | 3 - Minimize Risk |
| chloramphenicol | increased | Inhibition of Warfarin Metabolism | 2 - Moderate | 0 - Not Listed |
| cholestyramine | decreased | Reduced Absorption of Warfarin | 2 - Moderate | 3 - Minimize Risk |
| cimetidine | increased | Inhibition of Warfarin Metabolism | 1 - Major | 2 - Usually Avoid Combination |
| ciprofloxacin | increased | Inhibition of Warfarin Metabolism | 1 - Major | 3 - Minimize Risk |
| clarithromycin | increased | Inhibition of Warfarin Metabolism | 1 - Major | 3 - Minimize Risk |
| clofibrate | increased | Unexplained Mechanisms | 1 - Major | 2 - Usually Avoid Combination |
| clopidogrel/ticlopidine | no effect | Increased Bleeding Risk | 0 - Not Listed | 4 - No Action Needed |
| colestipol | decreased | Reduced Absorption of Warfarin | 2 - Moderate | 3 - Minimize Risk |
| Contraceptives, Oral | decreased | Increased Clotting Factor Synthesis/Activity | 0 - Not Listed | 2 - Usually Avoid Combination |
| Corticosteroids | either | Unexplained Mechanisms | 2 - Moderate | 4 - No Action Needed |
| cyclophosphamide | increased | Unexplained Mechanisms | 1 - Major | 3 - Minimize Risk |
| cyclosporin | decreased | Unexplained Mechanisms | 4 - Major or Moderate | 4 - No Action Needed |
| delavirdine | increased | Inhibition of Warfarin Metabolism | 4 - Major or Moderate | 0 - Not Listed |
| diazoxide | increased | Protein Binding Displacement | 0 - Not Listed | 4 - No Action Needed |
| dicloxacillin | decreased | Induction of Warfarin Metabolism | 2 - Moderate | 4 - No Action Needed |
| diltiazem | increased | Unexplained Mechanisms | 0 - Not Listed | 4 - No Action Needed |
| Direct Thrombin Inh. | increased | Additive Anticoagulant Response | 2 - Moderate | 0 - Not Listed |
| disopyramide | increased | Unexplained Mechanisms | 5 - Minor | 4 - No Action Needed |
| disulfiram | increased | Inhibition of Warfarin Metabolism | 2 - Moderate | 2 - Usually Avoid Combination |
| efavirenz | increased | Inhibition of Warfarin Metabolism | 4 - Major or Moderate | 0 - Not Listed |
| erythromycin | increased | Inhibition of Warfarin Metabolism | 1 - Major | 3 - Minimize Risk |
| ethacrynic acid | increased | Protein Binding Displacement | 4 - Major or Moderate | 4 - No Action Needed |
| ethcholvynol | decreased | Induction of Warfarin Metabolism | 2 - Moderate | 3 - Minimize Risk |
| etoposide | increased | Unexplained Mechanisms | 1 - Major | 0 - Not Listed |
| felbamate | increased | Unexplained Mechanisms | 4 - Major or Moderate | 4 - No Action Needed |
| fenofibrate | increased | Unexplained Mechanisms | 1 - Major | 3 - Minimize Risk |
| fluorouracil | increased | Inhibition of Warfarin Metabolism | 1 - Major | 3 - Minimize Risk |
| fosphenytoina | either | Induction or Inhibition of Warfarin Metabolism | 2 - Moderate | 3 - Minimize Risk |
| gefitinib | increased | Unexplained Mechanisms | 2 - Moderate | 0 - Not Listed |
| gemcitabine | increased | Unexplained Mechanisms | 1 - Major | 3 - Minimize Risk |
| gemfibrozil | increased | Unexplained Mechanisms | 1 - Major | 2 - Usually Avoid Combination |
| glutethamide | decreased | Induction of Warfarin Metabolism | 2 - Moderate | 2 - Usually Avoid Combination |
| glyburide | increased | Unexplained Mechanisms | 0 - Not Listed | 3 - Minimize Risk |
| griseofulvin | decreased | Induction of Warfarin Metabolism | 2 - Moderate | 3 - Minimize Risk |
| heparin/LMWHs | increased | Additive Anticoagulant Response | 0 - Not Listed | 3 - Minimize Risk |
| ifosfamide | increased | Inhibition of Warfarin Metabolism | 4 - Major or Moderate | 0 - Not Listed |
| influenza vaccine | increased | Unexplained Mechanisms | 4 - Major or Moderate | 4 - No Action Needed |
| isoniazide | increased | Inhibition of Warfarin Metabolism | 4 - Major or Moderate | 3 - Minimize Risk |
| isotretinoin | increased | Unexplained Mechanisms | 4 - Major or Moderate | 4 - No Action Needed |
| leflunamide | increased | Inhibition of Warfarin Metabolism | 4 - Major or Moderate | 0 - Not Listed |
| levofloxacin | increased | Inhibition of Warfarin Metabolism | 1 - Major | 4 - No Action Needed |
| lovastatin | increased | Inhibition of Warfarin Metabolism | 1 - Major | 3 - Minimize Risk |
| mefloquine | increased | Unexplained Mechanisms | 4 - Major or Moderate | 3 - Minimize Risk |
| menthol | decreased | Unexplained Mechanisms | 4 - Major or Moderate | 4 - No Action Needed |
| mercaptopurine | decreased | Unexplained Mechanisms | 2 - Moderate | 3 - Minimize Risk |
| mesalamine | increased | Unexplained Mechanisms | 4 - Major or Moderate | 3 - Minimize Risk |
| methimazole | decreased | Reduced Catabolism of Clotting Factors | 1 - Major | 3 - Minimize Risk |
| metronidazole | increased | Inhibition of Warfarin Metabolism | 1 - Major | 2 - Usually Avoid Combination |
| mineral oil | increased | Unexplained Mechanisms | 5 - Minor | 4 - No Action Needed |
| mitotane | decreased | Induction of Warfarin Metabolism | 4 - Major or Moderate | 3 - Minimize Risk |
| moxifloxacin | increased | Inhibition of Warfarin Metabolism | 1 - Major | 0 - Not Listed |
| nafcillin | decreased | Induction of Warfarin Metabolism | 2 - Moderate | 3 - Minimize Risk |
| nalidixic acid | increased | Inhibition of Warfarin Metabolism | 2 - Moderate | 3 - Minimize Risk |
| neomycin | increased | Impaired Vitamin K Production by Gut Flora | 5 - Minor | 3 - Minimize Risk |
| norfloxacin | increased | Inhibition of Warfarin Metabolism | 1 - Major | 3 - Minimize Risk |
| NSAIDs | no effect | Increased Bleeding Risk | 1 - Major | 2 - Usually Avoid Combination |
| ofloxacin | increased | Inhibition of Warfarin Metabolism | 1 - Major | 3 - Minimize Risk |
| omeprazole | increased | Inhibition of Warfarin Metabolism | 4 - Major or Moderate | 4 - No Action Needed |
| orlistat | increased | Inhibition of Warfarin Metabolism | 4 - Major or Moderate | 4 - No Action Needed |
| paclitaxel | increased | Unexplained Mechanisms | 1 - Major | 0 - Not Listed |
| phenytoina | decreased | Induction or Inhibition of Warfarin Metabolism | 2 - Moderate | 3 - Minimize Risk |
| prasugrel | no effect | Increased Bleeding Risk | 0 - Not Listed | 0 - Not Listed |
| primidone | decreased | Induction of Warfarin Metabolism | 1 - Major | 2 - Usually Avoid Combination |
| progestins | increased | Unexplained Mechanisms | 4 - Major or Moderate | 4 - No Action Needed |
| propafenone | increased | Inhibition of Warfarin Metabolism | 4 - Major or Moderate | 3 - Minimize Risk |
| propoxyphene | increased | Unexplained Mechanisms | 4 - Major or Moderate | 3 - Minimize Risk |
| propranolol | increased | Unexplained Mechanisms | 4 - Major or Moderate | 4 - No Action Needed |
| propylthiouracil | decreased | Reduced Catabolism of Clotting Factors | 1 - Major | 3 - Minimize Risk |
| Protease Inhibitors | decreased | Unexplained Mechanisms | 4 - Major or Moderate | 3 - Minimize Risk |
| quinidine | increased | Inhibition of Warfarin Metabolism | 1 - Major | 3 - Minimize Risk |
| quinine | increased | Inhibition of Warfarin Metabolism | 1 - Major | 0 - Not Listed |
| reserpine | increased | Unexplained Mechanisms | 0 - Not Listed | 4 - No Action Needed |
| ribavirin | decreased | Unexplained Mechanisms | 4 - Major or Moderate | 3 - Minimize Risk |
| Rifamycins | decreased | Induction of Warfarin Metabolism | 2 - Moderate | 2 - Usually Avoid Combination |
| rofecoxib | increased | Inhibition of Warfarin Metabolism | 1 - Major | 4 - No Action Needed |
| simethicone | decreased | Reduced Absorption of Warfarin | 0 - Not Listed | 4 - No Action Needed |
| simvastatin | increased | Inhibition of Warfarin Metabolism | 1 - Major | 4 - No Action Needed |
| spironolactone | decreased | Hemoconcentration of Clotting Factors | 5 - Minor | 4 - No Action Needed |
| SSRIs | increased | Inhibition of Warfarin Metabolism | 4 - Major or Moderate | 3 - Minimize Risk |
| sucralfate | decreased | Reduced Absorption of Warfarin | 5 - Minor | 3 - Minimize Risk |
| Sulfa Antibiotics | increased | Inhibition of Warfarin Metabolism | 1 - Major | 3 - Minimize Risk |
| Sulfinpyrazone | increased | Inhibition of Warfarin Metabolism | 1 - Major | 2 - Usually Avoid Combination |
| tamoxifen | increased | Unexplained Mechanisms | 4 - Major or Moderate | 0 - Not Listed |
| telithromycin | increased | Inhibition of Warfarin Metabolism | 1 - Major | 4 - No Action Needed |
| temafloxacin | increased | Inhibition of Warfarin Metabolism | 1 - Major | 4 - No Action Needed |
| terbinafine | decreased | Induction of Warfarin Metabolism | 4 - Major or Moderate | 0 - Not Listed |
| testosterone | increased | Unexplained Mechanisms | 4 - Major or Moderate | 0 - Not Listed |
| Tetracyclines | increased | Impaired Vitamin K Production by Gut Flora | 1 - Major | 3 - Minimize Risk |
| Thiazide Diuretics | decreased | Hemoconcentration of Clotting Factors | 5 - Minor | 4 - No Action Needed |
| Thrombolytics | increased | Additive Anticoagulant Response | 1 - Major | 0 - Not Listed |
| Thyroid Hormones | increased | Increased Catabolism of Clotting Factors | 1 - Major | 3 - Minimize Risk |
| tolterodine | increased | Unexplained Mechanisms | 4 - Major or Moderate | 4 - No Action Needed |
| tramadol | increased | Unexplained Mechanisms | 2 - Moderate | 0 - Not Listed |
| trazodone | decreased | Unexplained Mechanisms | 2 - Moderate | 4 - No Action Needed |
| trastuzumab | increased | Unexplained Mechanisms | 4 - Major or Moderate | 0 - Not Listed |
| vitamin E | increased | Decreased Synthesis of Clotting Factors | 1 - Major | 3 - Minimize Risk |
| vitamin K | decreased | Increased Clotting Factor Synthesis/Activity | 2 - Moderate | 3 - Minimize Risk |
| zafirlukast | increased | Inhibition of Warfarin Metabolism | 0 - Not Listed | 3 - Minimize Risk |
Drug Interaction Scale
| Significance Rating (A) | Criteria | Management Rating (B) | Criteria |
|---|---|---|---|
| 0 | Not listed | 0 | Not listed |
| 1 | Severity - Major: The effects are potentially life-threatening or capable of causing permanent damage. Documentation: interaction is suspected, probable or established |
1 | Avoid combination |
| 2 | Severity - Moderate: The effects may cause deterioration in a patient's clinical status. Additional treatment, hospitalization, or an extended hospital stay may be necessary. Documentation: interaction is suspected, probable or established |
2 | Usually avoid combination |
| 3 | Severity - Minimal: The effects are usually mild; consequences may be bothersome or unnoticeable but should not significantly affect the therapeutic outcome. Additional treatment is usually not required. Documentation: interaction is suspected, probable or established |
3 | Minimize risk |
| 4 | Severity – Major or Moderate Documentation: Interaction is possible |
4 | No action needed |
| 5 | Severity: Minor Documentation: possible OR Severity: Major, Moderate or Minor Documentation: interaction is unlikely |
5 | No interaction |
A. Tatro DS (ed). Drug Interaction Facts. St Louis MO: Wolters Kluwer, 2010
B. Hansten P,Horn J. Drug Interactions Analysis and Management. St Louis MO: Wolters Kluwer 2010.
Warfarin Reversal
Guidelines for Reversal of Anticoagulation
Patient Assessment Nomogram
Patient Education
Warfarin Tablet Identification
