2-PHENYL-1,3-INDANDIONE

Phenindione is an anticoagulant and vitamin K antagonist. It inhibits the reduction of vitamin K₁ epoxide to vitamin K₁ by vitamin K₁ epoxide reductase in rat liver homogenates in a concentration-dependent manner. In vivo, phenindione (500 mg/kg) inhibits prothrombin synthesis and conversion of vitamin K₁ epoxide to vitamin K₁ in rats by 50 and 57%, respectively. Dietary administration of phenindione (4 mg/kg per day) inhibits aortic atherosclerosis or intracardial thrombosis in rat models of diet-induced atherosclerosis or intravascular thrombosis, respectively.

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Oral anticoagulant (indanedione).

Like coumarin derivatives, phenindione, a compound of the indandione class, acts by altering biosynthesis of coagulant proteins in the liver. It is used for preventing and treating thrombosis, thrombophlebitis, and thromboembolism. However, because of a number of side effects such as polyurea, polydipsia, tachycardia, and others, it is rarely used in practical medicine.

ChEBI: Phenindione is a beta-diketone and an aromatic ketone. It has a role as an anticoagulant. It derives from a hydride of an indane.

Hedulin (Sanofi Aventis).

Anticoagulant

Phenindione, 3-phenylindan-1,3-dion (24.1.16), is synthesized in two ways. The first consists of condensating benzaldehyde with phthalide in the presence of sodium ethoxide. Evidently, the resulting phenylmethylenphthalide (24.1.15) rearranges under the reaction conditions to give the desired phenindione (24.1.16). The second method consists of condensation of phenylacetic acid with phthalic anhydride, forming phenylmethylenphthalide (24.1.15), which rearranges further in the presence of sodium ethoxide to phenindione.

Potentially hazardous interactions with other drugs There are many significant interactions with coumarins. Prescribe with care with regard to the following:
Anticoagulant effect enhanced by: alcohol, amiodarone, anabolic steroids, aspirin, aztreonam, bicalutamide, cephalosporins, chloramphenicol, cimetidine, ciprofloxacin, dronedarone, fibrates, clopidogrel, cranberry juice, danazol, dipyridamole, disulfiram, fibrates, grapefruit juice, levofloxacin, macrolides, metronidazole, nalidixic acid, neomycin, norfloxacin, NSAIDs, ofloxacin, paracetamol, penicillins, ritonavir, rosuvastatin, sulphonamides, thyroid hormones, testosterone, tetracyclines, tigecycline, tramadol, trimethoprim.
Anticoagulant effect decreased by: oral contraceptives, rifamycins, vitamin K.
Anticoagulant effects enhanced/reduced by: anion exchange resins, corticosteroids, dietary changes, enteral feeds.
Analgesics: increased risk of bleeding with IV diclofenac and ketorolac - avoid.
Anticoagulants: increased risk of haemorrhage with apixaban, dabigatran, edoxaban and rivaroxaban - avoid.
Ciclosporin: there have been a few reports of altered anticoagulant effect; decreased ciclosporin levels have been seen rarely

Hepatically metabolised. Metabolites of phenindione often colour the urine pink or orange.

Crystallise the dione from EtOH (m 156o) or CHCl3 (m 148-150o). [Beilstein 7 H 808, 7 III 4100, 7 IV 2570.]