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Key points

  • We recommend to consult your poison centre with the use of this antidote.
  • Do not give vitamin K prophylactically if the INR is normal.
  • Risk of bleeding is higher if INR is greater than 5 and also in elderly or hypertensive patients.
  • Onset of action on INR: Warfarin, 8 to 12 hrs; "Superwarfarin" 48-72 hrs.
  • Rodenticides containing "Superwarfarin" such as brodifacoum can cause anticoagulation lasting several months.
  • Oral route is preferred when it appears there is no immediate risk of bleeding. The SC route is not recommended due to erratic absorption. IM is generally not recommended due to risk of hematoma; some prefer to avoid IV because of the risk of a severe reaction (e.g. anaphylaxis, shock, cardiac arrest) even during slow IV infusion.

+ Synonyms and other terms

  • AquaMEPHYTON®
  • Phytonadione
  • Vitamine K1

+ Indications

  • Risk of bleeding following use of vitamin K antagonist.

+ Dosage

+ Pediatric Dose

  • Active bleeding:
    • Use in combination with prothrombin complex concentrates (1st line) or fresh frozen plasma (2nd line) for rapid clotting factor replacement.
    • Vitamin K1: 1 to 5 mg slow IV over 30 minutes.
      • Check the INR every 6-8 hrs and repeat vitamin K1 as needed.
  • No active bleeding:
    • Patient not receiving anticoagulant therapy with Warfarin:
      • Vitamin K1: 1 to 5 mg PO.
      • INR equal or greater than 1.5 but less than 5: Check the INR every 24 hrs and repeat vitamin K1 as needed.
      • INR equal or greater than 5: Check INR every 8-12 hrs and repeat vitamin K1 as needed.
    • Patient receiving anticoagulant therapy with warfarin: Consult physician or hematologist.

+ Adult Dose

  • Active bleeding:
    • Use in combination with prothrombin complex concentrates (1st line) or fresh frozen plasma (2nd line) for rapid replacement of clotting factors.
    • Vitamin K1: 5 to 10 mg slow IV over 30 minutes.
      • Check the INR every 6-8 hrs and repeat vitamin K1 as needed. Some patients have received up to 125 mg/day of vitamin K1.
  • No active bleeding:
    • Patient not receiving anticoagulant therapy with Warfarin:
      • Vitamin K1: 2.5 to 10 mg PO.
      • INR equal or greater than 1.5 but less than 5: Check INR every 24 hrs and repeat vitamin K1 as needed.
      • INR equal or greater than 5: Check INR every 8-12 hrs and repeat vitamin K1 as needed.
    • Patient receiving anticoagulant therapy with warfarin:Consult physician or hematologist.

+ Renal Impairment

No data suggests that the dose should be modified for short-term use.

+ Hepatic Impairment

No data suggests that the dose should be modified for short-term use.

+ Hemodialysis Patient

No data suggests that the dose should be modified for short-term use.

+ Pregnancy

  • Safety has not been established.
  • Nonetheless, do not hesitate to use vitamin K1 during pregnancy if the expected toxic effects pose a significant risk of morbidity or mortality.
  • No information suggests modifying the dose for a short-term use

+ Obese or Overweight Patient

No data suggests that the dose should be modified for short-term use.

+ Adverse effects

  • Especially if IV injection is too rapid: cyanosis, dizziness, hypotension, bronchospasm, death.
  • Anaphylaxis after IV administration.

+ Monitoring

  • Hypersensitivity reactions
  • INR
  • Bleeding

+ End of treatment

  • When the INR is stable at desired level for 48 hours.
  • This usually occurs within days with warfarin, but sometimes only after several weeks with "Superwarfarins" (e.g., brodifacoum, difenacoum, chlorophacinone).

+ Special Notes on Administration

Enteral route (PO or NG tube)

  • PO
    • Use injectable formulation diluted in juice.
  • NG
    • Use injectable formulation diluted in SWFI.
    • Pre-rinse NG tube with 15-30 ml of SWFI.
    • Administer the antidote by NG tube.
    • Rapidly rinse NG tube with 15-30 ml of SWFI.

Intravenous Route (IV)

  • Direct IV:
    • Not recommended. Heightened risk of anaphylactoid reactions.
  • Slow IV infusion:
    • Dilute the dose in 10 ml of compatible solution.
    • Slowly infuse at a maximum rate of 1 mg/min.

Subcutaneous Route (SC)

  • This administration route is no longer recommended.
  • Erratic absorption.

Intramuscular Route (IM)

  • This administration route is no longer recommended.
  • Risk of hematoma if INR is very high.
  • Erratic absorption.

Intraosseous Route (IO)

  • No data available

Compatibility

Partial list only. Consult the pharmacist on duty at your health care facility.

  • Compatible solutes: ½NS, NS, D5W, D10E, D5W+NS, D5W+½NS, D5W+¼NS, RS.
  • Y-site compatibility:alfentanil, aminophylline, atropine, benztropine, sodium bicarbonate, bretylium, calcium (chloride or gluconate), dexamethasone, digoxin, diphenhydramine, dopamine, epinephrine, esmolol, famotidine, fentanyl, folic acid, furosemide, standard heparin, hydrocortisone, regular insulin , isoproterenol, ketorolac, labetalol, lidocaine, mannitol, meperidine, metoclopramide, metoprolol, midazolam, morphine, MVI, naloxone, nitroglycerin, sodium nitroprusside, norepinephrine, ondansetron, pentobarbital, phenobarbital, phentolamine, phenylephrine, potassium (chloride), procainamide, prochlorperazine, propranolol, protamine, pyridoxine, ranitidine succinylcholine, sufentanil, thiamin, vasopressin, verapamil.
  • Y-site incompatibility: Dantrolene, diazepam, diazoxide, magnesium (sulfate), phenytoin.

+ Available products

+ Amount required to treat a person weighting 70kg during 24 hours

  • At least 100 mg.

+ References

Bateman, D. Nicholas, and Colin B. Page. 2016. “Antidotes to Coumarins, Isoniazid, Methotrexate and Thyroxine, Toxins That Work via Metabolic Processes.” British Journal of Clinical Pharmacology 81 (3):437–45.


© Centre antipoison du Québec, CIUSSS de la Capitale-Nationale, 2017. The information contained in this site may be cited, provided the source is acknowledged. Any use for commercial or advertising purposes is strictly prohibited.

Last updated : 2022-12-12