Healthy Living

What Is the Difference Between Warfarin and Plavix?

What Is the Difference Between Warfarin and Plavix?

Differences in Description

Warfarin is an anticoagulant or blood thinner under the brand names Coumadin and Jantoven. It is used to prevent the formation and migration of blood clots. Originally, it was marketed as a pesticide. Since then, it has become one of the most frequently prescribed oral medications in North America. However, it can cross the placental barrier during pregnancy, which can result in spontaneous abortion, fetal bleeding, neonatal death, preterm birth, or stillbirth. It can also cause adverse effects such as purple toes syndrome, valve and artery calcification, osteoporosis, and drug interactions.

Warfarin along with several regulatory factors inhibits the synthesis of biologically active forms of various clotting factors, which are vitamin K-dependent. Warfarin also reduces the risk of stroke or heart attack, and is used to prevent the formation of new blood clots. This anticoagulant works by decreasing blood clotting proteins and allows a smooth blood flow in the body. The FDA approved warfarin in 1954. It is available in the form of injections and tablets.

Expert Answers

Is plavix( clopidogrel ) a blood thinner?

Have a question aboutWarfarin?Ask a doctor now

Plavix is a structurally an antiplatelet agent and is pharmacologically similar to ticlopidine. It helps inhibit blood clots in a variety of conditions. It is used in conditions such as coronary artery disease, peripheral vascular disease, and cerebrovascular disease. The generic version of Plavix is clopidogrel, which is sold by Sanofi and Bristol-Myers Squibb. P2Y12 adenosine diphosphate receptors are found on the platelet membrane and Plavix is an irreversible inhibitor of this receptor.

It is also associated with several serious side effects such as various forms of hemorrhage, severe neutropenia, and cardiovascular edema. The generic name of Plavix is clopidogrel bisulfate. Plavix is generally prescribed following a heart attack or stroke. It is also prescribed for peripheral artery disease or unstable angina. To prevent another heart attack, Plavix is usually combined with aspirin. The drug was approved by the US FDA in 1997.

Indications

Warfarin is used for the treatment of the following conditions:

Plavix is used to reduce atherosclerotic events such as stroke, myocardial infarction, and vascular death in patients who had a recent stroke, established peripheral arterial disease, or myocardial infarction.

Pharmacodynamics

Warfarin is a racemic mixture of two active isomers. It is a coumarin anticoagulant, which is used in the prevention and treatment of thromboembolic diseases such as thromboembolism, pulmonary embolism, and venous thromboembolism. It is also used to prevent ischemic stroke in patients with atrial fibrillation.

Plavix is metabolized by cytochrome p450 (CYP450) since it is a prodrug. It inhibits platelet aggregation by producing active metabolites. These active metabolites inhibit the selective binding of adenosine diphosphate (ADP) to the platelet receptor P2Y12 and the ADP-mediated activation of glycoprotein GPIIb/IIIa complex. 

Mechanism of Action

Warfarin depletes the reduced form of vitamin K by inhibiting vitamin K reductase. Vitamin K is a cofactor for the carboxylation of glutamate residues on the N-terminal regions of vitamin K-dependent proteins. Hence, it limits the gamma-carboxylation and the subsequent vitamin K-dependent coagulant protein activation. Thus, the synthesis of coagulant factors II, VII, IX, and X, which are vitamin K dependent proteins, and the synthesis of anticoagulant proteins C and S are inhibited.

The prothrombin levels are also decreased due to the depression of 3 out of 4 vitamin K-dependent coagulation factors. Moreover, the amount of thrombin generated and fibrin-bound thrombin are also decreased. Thus, the thrombogenicity of clots is reduced.

The binding of adenosine diphosphate (ADP) to the platelet receptors is inhibited by the active metabolite of Plavix. Thus, the ADP-mediated activation of the glycoprotein GPIIb/IIIa complex is inhibited. According to some proposed theories, a defect in the storage sites of the platelet granules to the outer membrane is involved in the inhibition. The P2Y12 subtype of ADP receptors is important in platelet aggregation, which is specifically and irreversibly inhibited. Moreover, the cross-linking of protein fibers is inhibited. There is also no direct interference that occurs with the GPIIb/IIIa. For fibrinogen, this glycoprotein is a major receptor, but fibrinogen is prevented from binding to platelets because of its impaired activation. Thus, platelet aggregation is inhibited. The active metabolite of clopidogrel inhibits platelet aggregation induced by agonists through blocking the amplification of platelet activation.

Side Effects

The common side effects of warfarin include:

It may also cause bleeding, which can be serious and may even be fatal. Skin necrosis or gangrene may also happen after using warfarin. Seek immediate medical attention if you experience the following symptoms:

  • Pain in any part of the body
  • A change in body temperature
  • Painful toes
  • Discoloration of toes 
  • Swelling
  • Unusual bleeding
  • Headache
  • Dizziness
  • Weakness

Serious side effects include:

  • Vomiting
  • Coughing up blood
  • Unusual bruising
  • Nose or gum bleeding
  • Heavy vaginal bleeding
  • Wound that won't stop bleeding
  • Black-colored or bloody stool
  • Dark-colored or red urine
  • Swelling of the lips, face, tongue, and throat
  • Hives
  • Difficulty breathing

Common side effects caused by Plavix include:

Other side effects that may be experienced:

  • Chest pain that spreads to the shoulder, arm, or jaw
  • Sudden weakness or numbness
  • Confusion
  • Balance problems
  • Vision or speech problems
  • Fever
  • Purple or red pinpoint spots under the skin
  • Yellowing of the skin, eyes, or mouth
  • Unusual vaginal or rectal bleeding

Risks

People above 65 years old have an increased risk of bleeding, especially those who have a history of stroke, stomach or intestinal bleeding, and high blood pressure. Moreover, people with heart disease, cancer, kidney problems, low blood count as well as people who have undergone surgery are more prone to bleeding. 

Taking other medications that contain heparin and nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of bleeding. In the case of warfarin, life-threatening bleeding may occur if a person has a history of stomach bleeding, kidney or liver problems, high blood pressure, or drug interactions.

The risk of bleeding may also increase due to lifestyle changes, genetic factors, diet, and alcohol use. Individuals with a bleeding disorder should not use warfarin. This drug must also be avoided if you had a recent surgery, need a spinal tap or epidural, or when anticipating surgery.

Plavix does not let the platelets clump together, which prevents blood from clotting. Thus, even a minor injury will increase the risk of bleeding. Plavix should not be used in the case of stomach ulcer, head injury, or bleeding in the brain.

The doctor must also be informed if you are planning on becoming pregnant. Plavix may also become less effective if taken along with Nexium or Prilosec. Life-threatening bleeding may occur if Plavix is taken along with other blood thinners. Unexplained bruising or purple spots on the skin may also occur.

Advantages

Warfarin

  • More affordable than the branded version since the drug is in the generic form.
  • If bleeding happens, there is another drug prescribed by the doctor to reverse the effect of warfarin.
  • Warfarin is available in various strengths.
  • It is widely available and is the most commonly used blood thinner.

Plavix

  • It can lower the risk of stroke or heart attack.
  • It needs to be taken only once a day.
  • A genetic test is available to determine whether Plavix is an effective treatment option for you.

Disadvantages

Warfarin

  • There is an increased risk of bleeding and bruising.
  • Regular blood work is required to ensure whether the medicine is working properly or not.
  • If your diet, exercise pattern, or alcohol consumption changes, then the daily dose of warfarin also changes.
  • Many drugs and supplements interact with warfarin.

Plavix

  • It increases the risk of bleeding and bruising, which can be potentially life-threatening.
  • It is not safe to take along with other supplements and medications.
  • A plasma transfusion is required to stop bleeding.

Absorption

Following oral administration, warfarin is rapidly absorbed with considerable interindividual variations. It is also percutaneously absorbed. Clopidogrel-related metabolites are excreted in the urine. 

Metabolism

Predominantly, warfarin is metabolized by cytochrome P450, which yields 6- and 7-hydroxylated metabolites. These hydroxylated metabolites are conjugated before being excreted in the bile and urine. Warfarin UGT1A1 is responsible for the production of 6-O glucuronide. UGT1A10 may also possibly contribute. In the formation of 7-O glucuronide warfarin, UGT1As may be responsible. Compared to R-warfarin, S-warfarin has a higher potency. There can also be a dramatic decrease in clearance and higher toxicity of the medication due to genetic polymorphisms.

The metabolism of Plavix is rapid, hepatic, and extensive by hydrolysis to the main circulating metabolite. Of all the circulating drug-related compounds, carboxylic acid derivatives account for nearly 85 percent. In the plasma and urine, a glucuronic acid derivative of the carboxylic acid derivative has been found. The platelet inhibiting effect is not present in the parent compound nor is the carboxylic acid derivative found. 

Route of Elimination

Warfarin is almost entirely eliminated through metabolism. Very little goes in the urine as unchanged warfarin. Generally, the metabolites are excreted in the urine and excreted to a lesser extent in the bile.

In the case of Plavix, almost 50 percent total radioactivity is excreted in the urine and over 46 percent excreted in the stool after 5 days of dosing.

Pregnancy, Breastfeeding, and Children

Warfarin has been associated with birth defects, miscarriage, and other abnormalities. Do not take this medication unless your doctor specifically says otherwise. No studies have shown the presence of warfarin in breast milk. However, breastfeeding mothers should be careful when taking this medication. In children, the use of warfarin requires close monitoring. The data regarding the effects of Plavix on nursing infants is insufficient.

Drug Interactions

Warfarin may interact with the following drugs:

  • Erythromycin
  • Ciprofloxacin
  • Clarithromycin
  • Sulfamethoxazole
  • Metronidazole
  • Fluconazole
  • Carbamazepine
  • Phenytoin
  • Amiodarone
  • Phenobarbital

It may also interact with over-the-counter medications such as:

  • Ibuprofen
  • Aspirin
  • Acetaminophen
  • Naproxen
  • Cimetidine
  • Omeprazole

Plavix may interact with some drugs and cause unusual or increased bleeding. They include:

  • Ibuprofen
  • Etodolac
  • Diclofenac
  • Meloxicam
  • Celecoxib
  • Naproxen
  • Indomethacin
  • Other NSAIDs

There are reports of Plavix interaction with some acid-reducing drugs such as omeprazole or esomeprazole. These drugs can reduce the effectiveness of Plavix. The following are some medications that also inhibit enzymes:

  • Fluoxetine
  • Cimetidine
  • Fluvoxamine
  • Fluconazole
  • Voriconazole
  • Ticlopidine
  • Ketoconazole
  • Etravirine
  • Felbamate

Related Clinical Trials