Warfarin is the most widely used oral anticoagulant (blood thinner) medication. It acts on the liver to reduce the formation of certain clotting factors (proteins that normally allow the blood to clot).
Warfarin is available under the trade names Coumadin, Jantoven, Waran, Marevan, Lawarin and Warfant.
According to the US Food and Drug Administration, Warfarin is used for prevention of thrombosis (formation of blood clots) in people who are at high risk for thrombus (blood clot) formation or in patients who have already formed thrombus for prevention of further episodes.
Warfarin is commonly indicated in the following conditions:
Patients with artificial heart valves
Atrial fibrillation (heart disorder characterized by extremely fast and irregular contraction of the atria, or the upper chambers of the heart)
Myocardial infarction (heart disorder characterized by death of a part of the heart muscle due to blockage of the blood flow to heart)
Pulmonary embolism (obstruction of a blood vessel in the lung by a blood clot)
Deep vein thrombosis (DVT, formation of a blood clot in a deep vein in the thigh or leg)
Antiphospholipid antibody syndrome (APAS, disorder of immunity in which antibodies are formed against certain proteins in the blood)
The dose of Warfarin must be individualized for each patient according to certain criteria, such as international normalized ratio (INR), duration of therapy, population of patients and risk of bleeding.
For prevention of thrombosis in adult patients, Warfarin is usually started in a dose of 2 to 5 mg/day orally for 2 to 4 days.
Safety and effectiveness of Warfarin in children and adolescents below the age of 18 have not been established yet.
The most commonly reported Warfarin side effects are bleeding, easy bruising, nausea, vomiting, abdominal pain, diarrhea, headache, dizziness, itching, hair loss, fever and fatigue.
In 1948, Warfarin was initially introduced as a pesticide against mice and rats in residential, agricultural and industrial areas.
In the 1950s, Warfarin was found to be effective for prevention of thrombosis in many disorders.
The name Warfarin consists of 2 parts warf and arin. Warf is an acronym for Wisconsin Alumni Research Foundation, which is the organization that funded the researches to develop the drug. The ending –arin indicates its relation to Coumarin (chemical compound that occurs naturally in plants and has anticoagulant properties).
Black Box Warnings:
Warfarin may lead to fatal bleeding especially if taken for a long duration and. Patients who have any of the following disorders are at high risk of severe bleeding if they take Warfarin:
Severe heart diseases
Severe kidney diseases
Hypertension (elevated blood pressure)
Previous history of gastrointestinal tract (GIT)
Cerebral vascular diseases (diseases of blood vessels of the brain)
In cases of severe bleeding due to Warfarin, the effects of the drug can be reversed by administration of vitamin K or fresh frozen plasma.
Common Warfarin Side Effects:
Gastrointestinal Tract (GIT):
Central Nervous System (CNS):
Paresthesia (bothersome sensations of needles and pins in the extremities)
Skin and hair:
Dermatitis (inflammation of the skin)
Edema (swelling due to accumulation of fluids)
Urticaria (severe skin allergic reaction characterized by skin rash and itching)
Alopecia (partial or total loss of scalp hair)
Other Common Warfarin Side Effects:
Asthenia (body weakness)
Hypotension (drop of blood pressure)
Serious Warfarin Side Effects:
Severe bleeding which may be life-threatening
Vasculitis (inflammation of blood vessels)
Cholesterol embolism (obstruction of blood vessels by accumulation of cholesterol particles)
Anemia (reduction in hemoglobin count. Symptoms include easy fatigability, shortness of breath and skin pallor)
Gastrointestinal Tract (GIT):
Hepatitis (inflammation of the liver)
Elevated liver enzymes
Cholestatic jaundice (yellowing of skin, mucous membranes and whites of the eyes due to accumulation of certain pigments in the blood)
Allergic reactions, such as anaphylaxis (serious allergic reaction characterized by itching, drop of blood pressure, difficulty breathing and may lead to death if untreated).
Other Serious Warfarin Side Effects:
Syncope (transient loss of consciousness)
Purple toe syndrome (disorder characterized by bluish discoloration of the toes)
Soft tissue necrosis (death of soft tissues)
Gangrene (death of an organ or tissue due to insufficient blood supply)
Osteoporosis (bone disorder characterized by thinning and may lead to fractures if untreated)
Tracheobronchial calcification (deposition of calcium in the air passages of the respiratory tract)
Warfarin Contraindications, Cautions, and Drug Interactions:
Warfarin should not be given to people who have any of the following disorders:
Hypersensitivity to Warfarin
Risk for bleeding
Blood dyscrasias (blood disorders characterized by presence of abnormal cells for a long time)
Threatened abortion (pregnancy disorder characterized by pain and vaginal bleeding any it may lead to miscarriage if untreated)
Recent trauma to the eye or nervous system
Eclampsia and pre-eclampsia (pregnancy disorders characterized by hypertension and leakage of proteins into the urine)
Caution should be taken when Warfarin is administrated to people who have any of the following disorders:
Sever kidney diseases
Severe liver diseases
Altered intestinal flora (microorganisms that normally live in the intestinal tract)
Chronic debilitating diseases, such as malignant tumors
Diabetes mellitus (DM)
Polycythemia (blood disorder characterized by high count of red blood cells “RBCs”)
Deficiency of protein C or S (certain types of proteins that present in the blood and prevent formation of clots)
Congestive heart failure (CHF)
Warfarin should not be used at the same time with any of the following medications:
Antiplatelet drugs, such as aspirin
The aforementioned contraindications, cautions, and interactions of Warfarin are examples of the most important ones. For specific concerns consult your physician or pharmacist and for a complete list see the manufacturer’s prescriber guidelines.
Warfarin acts on the liver to reduce the formation of vitamin K-dependant clotting factors, such as, factor 2, 7, 9 and 10, as well as protein C, S and Z.
Warfarin is metabolized by the liver cytochrome P-450 enzymes (CYP P-450), such as 1A2, 2C8, 2C18, 2C9, 2C19 and 3A4. Its plasma half-life is highly variable but often ranges from 20 to 60 hours.
Warfarin is excreted in the urine and bile (yellow-green fluid that is secreted by the liver and stored in the gallbladder).
Pregnancy and Lactation:
According to the FDA, Warfarin is classified as a drug X medication, meaning that it is contraindicated for pregnant women to take Warfarin.
When Warfarin is given during the first 3 months of pregnancy, a group of birth defects known as fetal Warfarin syndrome (FWS) can occur. FWS is characterized by low birth weight, developmental disturbances, narrowed nasal bridge, scoliosis (abnormal lateral “side-to-side” curvature of the spine) and deposition of calcium in the spinal column, femur (bone of the thigh) and heel bone.
Other fetal and neonatal side effects of Warfarin during pregnancy include abortion (miscarriage), stillbirth (death of a fetus inside the uterus), neonatal death and premature labor (birth that occurs before 37 weeks of pregnancy), eye defects, convulsions, .
For pregnant women who have artificial heart valve, Warfarin is classified as category D medication, meaning that the drug may be given but with caution.
Warfarin does not pass into the breast milk, however, caution should be exercised when giving this drug to a nursing mother.
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