Drug information of Phenindione

Phenindione


An indandione that has been used as an anticoagulant. Phenindione has actions similar to warfarin, but it is now rarely employed because of its higher incidence of severe adverse effects.

Mechanism of effect

Phenindione inhibits vitamin K reductase, resulting in depletion of the reduced form of vitamin K (vitamin KH2). As vitamin K is a cofactor for the carboxylation of glutamate residues on the N-terminal regions of vitamin K-dependent proteins, this limits the gamma-carboxylation and subsequent activation of the vitamin K-dependent coagulant proteins.

The synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins C and S is inhibited. Depression of three of the four vitamin K-dependent coagulation factors (factors II, VII, and X) results in decreased prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.

Pharmacodynamic

Phenindione thins the blood by antagonizing vitamin K which is required for the production of clotting factors in the liver. Anticoagulants such as Phenindione have no direct effect on an established thrombus, nor do they reverse ischemic tissue damage (damage caused by an inadequate blood supply to an organ or part of the body).

However, once a thrombus has occurred, the goal of anticoagulant treatment is to prevent further extension of the formed clot and prevent secondary thromboembolic complications which may result in serious and possibly fatal sequelae.

Pharmacokinetics

  • Absorption: Absorbed slowly from the gastrointestinal tract.
  • Protein binding: 88%
  • Metabolism: Hepatic.
  • Half life: 5-10 hours

Dosage

Adults:

  • Usual starting dose of 200mg on the first day
  • After the first day, the dose is usually reduced to 100mg a day.

From the third day of treatment, the doctor will adjust your dose up or down depending on the results of the blood test which will be performed at the start and at regular intervals during your treatment.

Alerts

On rare occasions Dindevan Tablets can cause serious skin conditions,including one called calciphylaxis that can start with a painful skin rash but can lead to serious complications.This adverse reaction occurs more frequently in patients with chronic kidney disease.

Points of recommendation

  • You will have regular blood tests to see how long it takes for your blood to clot. These blood tests are very important to make sure you are taking the right dose. Blood tests will be more frequent if you have had your dose of phenindione changed, if you have started or stopped taking other medicines or have liver or kidney problems.
  • Do not drink large amounts of alcohol
  • Avoid drinking Cranberry juice
  • Some foods like liver, broccoli, brussels sprouts and green leafy vegetables may interfere with the action of Phenindione
  • Avoid taking any food supplements when taking Phenindione.
  • If you think you may have become pregnant, contact your doctor as soon as possible.
  • Phenindione Tablets contain lactose which is a form of sugar. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

Pregnancy level

D


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