MAREVAN Tablet Ref.[116011] Active ingredients: Warfarin

For oral use.

Adults

The typical induction dose is 10 mg daily for 2 days but this should be tailored to individual requirements. The daily maintenance dose is usually 3 to 9 mg taken at the same time each day. The exact maintenance dose depends on the prothrombin time or other appropriate coagulation tests.

Control tests should be made at regular intervals and the warfarin dosage should be adjusted in accordance with the results obtained. Once the maintenance dose is established, it is rarely necessary to alter it.

In emergencies, anticoagulant therapy should be initiated with heparin and warfarin together.

Concomitant heparin therapy affects the results of control tests and should be discontinued at least 6 h before the first test is carried out.

Children

Dosage for children has not been established.

Elderly

As for adults, but dosage may need to be lowered.

Renal impairment

Caution is advised in patients with renal impairment (see section Warnings and Precautions).

Hepatic impairment

Caution is advised in patients with hepatic impairment (see section Warnings and Precautions).

Signs and Symptoms

Abnormal bleeding is the main sign of warfarin overdose and may be manifested by blood in the stools, haematuria, malaena, petechiae, excessive menstrual bleeding, excessive bruising, or persistent oozing from superficial injuries.

Treatment

If the patient presents within 1 hour of ingestion of more than 0.25 mg/kg or more than the patient's therapeutic dose, consider activated charcoal (50 g for adults; 1 g/kg for children).

In cases of life-threatening haemorrhage

Stop warfarin treatment, give prothrombin complex concentrate (factors II, VII, IX, and X) 30-50 units/kg or (if no concentrate is available) fresh frozen plasma 15 mL/kg.

Non-life-threatening haemorrhage

When anticoagulation can be suspended, give slow intravenous injection of phytomenadione (vitamin K1) 10-20 mg for adults (250 µg/kg for a child).

Where rapid re-anticoagulation is desirable (e.g. valve replacements) give prothrombin complex concentrate (factors II, VII, IX, and X) 30-50 units/kg or (if no concentrate available) fresh frozen plasma 15 mL/kg. Monitor INR to determine when to restart normal therapy.

Monitor INR for at least 48 hours post overdose.

Patients on long-term warfarin therapy without major haemorrhage

• INR >8.0, no bleeding or minor bleeding – stop warfarin, and give phytomenadione (vitamin K1) 0.5-1 mg for adults, 0.015-0.030 mg/kg (15-30 µg/kg) for children by slow intravenous injection or 5 mg by mouth (for partial reversal of anticoagulation, give smaller oral doses of phytomenadione e.g. 0.5- 2.5 mg using the intravenous preparation orally); repeat dose of phytomenadione if INR is still too high after 24 hours. Large doses of phytomenadione may completely reverse the effects of warfarin and make re-establishment of anticoagulation difficult.
• INR 6.0-8.0, not bleeding or minor bleeding – stop warfarin, restart when INR <5.0.
• INR <6.0 but more than 0.5 units above target value – reduce dose or stop warfarin, restart when INR <5.0.

Patients NOT on long-term anticoagulants without major haemorrhage

Measure the INR (prothrombin time) at presentation and sequentially every 24-48 hours after ingestion depending on the initial dose and initial INR.

• If the INR remains normal for 24-48 hours and there is no evidence of bleeding, there should be no further monitoring necessary.
• Give vitamin K1 (phytomenadione) if:
  • There is no active bleeding and the patient has ingested more than 0.25 mg/kg OR
  • The prothrombin time is already significantly prolonged (INR >4.0)

The adult dose of vitamin K1 is 10-20 mg orally (250 µg/kg body weight for a child). Delay oral vitamin K1 at least 4 hours after any activated charcoal has been given. Repeat INR at 24 hours and consider further vitamin K1.

Further management should be as clinically indicated or as recommended by the national poisons centre, where available.

The expiry date is indicated on the packaging.

Replace cap securely and protect from light.

Not all presentations are available in every country.