Drugs List
- warfarin 1mg tablets
- warfarin 1mg/ml oral suspension sugar-free
- warfarin 3mg tablets
- warfarin 500microgram tablets
- warfarin 5mg tablets
Therapeutic Indications
Uses
Anticoagulant for:
prophylaxis and treatment of pulmonary embolism
prophylaxis of systemic embolism in rheumatic heart disease
prophylaxis of systemic embolism in atrial fibrillation
prophylaxis and treatment of venous thrombosis
prophylaxis after insertion of prosthetic heart valves
transient ischaemic attack
Dosage
Initial dose: 10mg daily, for 2 days. Dose should be adjusted according to individual patient requirements.
Maintenance dose: 3mg to 9mg daily, to be taken at the same time each day. The exact maintenance dose depends on prothrombin time usually reported as International Normalised Ratio (INR), or other appropriate coagulation tests.
Dosage for children has not been established.
The following unlicensed doses may be suitable:
Initial dose: 200 micrograms/kg as a single dose, for 1 day. Maximum dose should not exceed 10mg.
Maintenance dose: 100 micrograms/kg once a day for 3 days, maximum of 5mg per dose. Adjust dose based on individual patient response and INR levels. Doses of 50 micrograms/kg to 300 micrograms/kg once a day, up to 400 micrograms/kg once a day may be required.
The following unlicensed doses may be suitable:
Initial dose: 200 micrograms/kg as a single dose, for 1 day.
Maintenance dose: 100 micrograms/kg once a day for 3 days. Adjust dose based on individual patient response and INR levels. Doses of 50 micrograms/kg to 300 micrograms/kg once a day, up to 400 micrograms/kg once a day may be required.
Use with caution in renal impairment.
There is an increased risk of over coagulation in patients with renal disease.
Avoid in severe renal impairment.
The Renal Drug Handbook states that the dose is as given to patients with normal renal function.
Administration
For oral administration, usually once daily.
It is recommended that the doses are taken at the same time each day.
If the oral formation is replaced by or replaces another warfarin product then patients should be closely monitored in the period following the change.
Contraindications
Pregnancy - (see Pregnancy)
Within 48 hours postpartum
Within 72 hours of surgery where there is a severe risk of bleeding
Haemorrhagic stroke
Clinically significant bleeding
Severe renal impairment
Severe hepatic impairment
Precautions and Warnings
Not all formulations are licensed for all indications.
The MHRA has advised that most adverse events reported with warfarin are due to over anticoagulation so the need for continued therapy should be reviewed regularly and discontinued when no longer required.
Patients should be given a patient-held information booklet (warfarin card) and informed of the need for regular blood tests and of symptoms for which they should seek medical attention. Patients should be advised to carry the alert card at all times.
Monitor prothrombin times regularly.
The INR should be monitored more frequently in patients at an increased risk of over coagulation (e.g. patients with severe hypertension, hepatic or renal disease) and in patients for whom adherence to the dosage regimen may be difficult. Changes to patient's clinical condition may necessitate more frequent measurement of INR and dose adjustment. Such changes include:
Changes in weight
Acute illness (including diarrhoea or vomiting)
Cardiac failure
Alteration or introduction of concurrent medication.
Tobacco smoke induces the cytochrome P450 isoenzyme CYP1A2, by which warfarin is partially metabolised. This may result in reduced plasma level of warfarin. Dosage adjustment may be required if smoking started or stopped during treatment with warfarin.
Alcohol and NSAIDs may potentiate the effect of warfarin. Patients should be advised to avoid these unless under the guidance of a clinician.
Limited evidence suggests that grapefruit juice may cause a modest rise in some patients taking warfarin.
Patients should be advised to avoid simvastatin unless under the guidance
Pregnancy and Lactation
Pregnancy
The use of warfarin is contraindicated throughout pregnancy. Women of child-bearing age should use effective contraception.
Based on human experience, warfarin causes congenital malformations and foetal death when administered during pregnancy. Use in the first trimester carries a significant risk to the foetus. A characteristic pattern of abnormalities called Foetal Warfarin syndrome has been seen in infants exposed during the sensitive period believed to be in the 6th to 9th week of gestation (Briggs, 2011) (Schaefer (2007) clarifies this as week 8 after last menstrual period (LMP) or week 6 post conception). Features of foetal warfarin syndrome include low birth weight, eye defects, hypoplasia of extremities, developmental retardation, seizures, scoliosis, hearing loss and congenital heart disease. Other risks to the foetus noted include central nervous system defects (possibly linked to haemorrhage and subsequent scarring), spontaneous abortion, mid-face and lung hypoplasia, still birth, prematurity and neonatal death (Briggs, 2011). In addition, use near term carries the risk of foetal/neonatal haemorrhage (Briggs, 2011).
Women on warfarin who are planning a pregnancy should be transferred to heparin or low molecular weight heparin pre-conception or at the very latest before the sixth week post conception (information from Clinical Knowledge Summaries states week 7 after conception). Schaefer (2007) states that elective termination of pregnancy is not recommended if unplanned exposure occurs in early pregnancy. Close follow up is recommended for all exposures. High risk patients will present prescribing dilemmas and may require overruling of the contraindication during some periods of the pregnancy, despite the known risks. Information published on the Clinical Knowledge Summaries suggests that all women with venous thromboembolism taking warfarin and who are planning a pregnancy are referred to a specialist. If the woman continues to take warfarin in the pre-conception period, adequate pregnancy planning must be undertaken so that warfarin can be stopped prior to the seventh week after conception.
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Lactation
Use with caution. There is a consensus that maternal therapy with warfarin carries little risk for the normal, full-term breast fed infant.
Warfarin is highly protein bound and therefore very little warfarin would be expected to appear in the milk. In the small number of cases followed, insignificant amounts of warfarin have been detected in breast milk. Some authorities take the cautious approach of advising observation of the infant for signs of bleeding e.g. bruising, petechiae, and the use of oral vitamin K supplements in the infant. Consideration may be given to determining the coagulation status of the infant, especially if born pre-term (Schaefer, 2007)
Side Effects
Haemorrhage
Alopecia
Rash
Diarrhoea
Hypersensitivity reactions
Jaundice
Hepatic impairment
Skin necrosis
"Purple toes" syndrome
Nausea
Vomiting
Pancreatitis
Purpura
Fever
Epistaxis
Haemothorax
Decrease in haematocrit
Cerebral haemorrhage
Rectal haemorrhage
Gastro-intestinal haemorrhage
Haematemesis
Melaena
Haematuria
Decrease in haemoglobin
Ecchymosis
Erythematous rash
Haematoma
Anaemia
Skin reactions
Calciphylaxis