2-Phenyl-1H-inden-1,3(2H)-dion

LEAFLETS FROM ALCOHOL

CREAMY WHITE TO PALE YELLOW CRYSTALS OR CRYSTALLINE POWDER

PRACTICALLY INSOL IN COLD WATER; SOL IN CHLOROFORM; SLIGHTLY SOL IN WARM WATER; READILY SOL IN ALKALINE SOLN; SOL IN METHANOL, ETHANOL, ETHER, ACETONE, BENZENE

2.30e-02 g/L

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Pharmaceuticals

149-151 °C

148 - 151 °C

160.15 Ų [M+K]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

145.9 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Danger

H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]

P261, P264, P270, P272, P280, P301+P316, P302+P352, P321, P330, P333+P317, P362+P364, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 43 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

The primary antidote to phenindione poisoning is immediate administration of vitamin K1 (initially slow intravenous injections of 10-25 mg repeated all 3-6 hours until normalisation of the prothrombin time; then 10 mg orally four times daily as a "maintenance dose"). It is an extremely effective antidote, provided the poisoning is caught before too much damage has been done to the victim's circulatory system. At high doses phenindione can affect the body for many months, and the antidote must be administered regularly for a long period of time. (L1257)

HALOPERIDOL WAS FOUND TO REDUCE PROTHROMBIN TIME NORMALLY PRODUCED BY PHENINDIONE.

ACTIVITY OF...INDANDIONE ANTICOAGULANT PHENINDIONE HAVE ALSO BEEN ENHANCED BY C-17-ALKYLATED ANDROGENS.

CORTICOTROPIN & ADRENOCORTICOSTEROIDS HAVE BEEN REPORTED TO CAUSE SEVERE HEMORRHAGE WHEN GIVEN WITH ORAL ANTICOAGULANTS... /ANTICOAGULANTS/

ANTIPYRINE (IN VIVO) & SULFINPYRAZONE (IN VITRO) HAVE BEEN REPORTED TO INTERACT WITH WARFARIN & SHOULD BE USED CAUTIOUSLY IN PT RECEIVING ANTICOAGULANTS. /ANTICOAGULANTS/

For more Interactions (Complete) data for PHENINDIONE (12 total), please visit the HSDB record page.

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 decresed prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots. (A308)

...COLORS URINE RED-ORANGE. ...REPORTS OF SENSITIVITY REACTIONS... MOST COMMON OF THESE ARE RASH, PYREXIA, & LEUKOPENIA; OCCASIONALLY LEUKOCYTOSIS OCCURS. THESE...ARE ACCOMPANIED BY FEVER, MALAISE, & HEADACHE. RASH IS...ERYTHEMATOUS & MACULAR...OCCASIONALLY PAPULAR &...WITH SCALING & ITCHING.

RARELY...EXFOLIATIVE DERMATITIS. SERIOUS RENAL DAMAGE WITH EXTENSIVE TUBULAR NECROSIS HAS BEEN REPORTED. ALBUMINURIA & MASSIVE EDEMA HAVE ALSO BEEN OBSERVED. OTHER...TOXIC EFFECTS INCL DIARRHEA, PARALYSIS OF ACCOMMODATION, & BLURRED VISION. ...REPORTS OF HEPATITIS & AGRANULOCYTOSIS. ...DEATHS HAVE OCCURRED...

UNTOWARD EFFECTS...INCL JAUNDICE...NEPHROPATHY... URINARY DISCOLORATION MAY MASK IMPORTANT SIGN... FOR THIS REASON, MORE SERIOUS HEMORRHAGIC EPISODES OCCUR WITH THIS DRUG THAN WITH ANY OTHER PROTHROMBOPENIC DRUG.

...HAS ANTITHYROID ACTION &...IMPAIR URATE REABSORPTION BY RENAL TUBULES & THUS INCR AMT OF URIC ACID IN URINE.

B - Blood and blood forming organs

QB - Blood and blood forming organs

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. Phenindione has actions similar to warfarin, but it is now rarely employed because of its higer incidence of severe adverse effects.

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.

.../ANTICOAGULANTS/ BLOCK HEPATIC FORMATION OF FACTORS II, VII, IX, & X BY COMPETITIVELY INHIBITING ACTION OF VITAMIN K. ... COUMARIN ANTICOAGULANTS MAY ALSO AFFECT TRANSPORT OF VITAMIN K TO ITS SITE OF ACTION. /ANTICOAGULANTS/

ORAL ANTICOAGULANTS HAVE ONLY ONE MAJOR PHARMACOLOGICAL EFFECT--INHIBITION OF BLOOD-CLOTTING MECHANISMS BY INTERFERING WITH HEPATIC SYNTH OF VITAMIN K-DEPENDENT CLOTTING FACTORS. ...EXERT THEIR INITIAL EFFECT IN VIVO ONLY AFTER LATENT PERIOD... /ORAL ANTICOAGULANTS/

Hepatic.

Hepatic. Half Life: 5-10 hours

Absorbed slowly from the gastrointestinal tract.

DURATION OF RESPONSE IS DIRECTLY PROPORTIONAL TO T/2 OF DRUG IN PLASMA. LARGER INITIAL DOSE (LOADING DOSE) OF DRUG, SOONER DESIRED THERAPEUTIC RESPONSE IS ATTAINED... /ORAL ANTICOAGULANTS/

BOTH ITS ONSET & DURATION OF ACTION ARE SHORTER THAN THOSE OF DICUMAROL & WARFARIN. THERAPEUTICALLY EFFECTIVE PROTHROMBIN TIME IS ATTAINED IN 24 TO 48 HR. AFTER DISCONTINUATION OF MAINTENANCE THERAPY, PROTHROMBIN TIME RETURNS TO NORMAL IN 1 TO 4 DAYS.

WELL ABSORBED FROM GI TRACT...PEAK PROLONGATION OF PROTHROMBIN TIME 18-48 HR, DURATION 1-4 DAYS...CIRCULATING /DRUG/ ALMOST COMPLETELY BOUND TO PLASMA PROTEINS. UPTAKE...BY ERYTHROCYTES IS VARIABLE...DISTRIBUTED TO LIVER, LUNGS, SPLEEN...KIDNEYS /HUMAN, ORAL/

MEDICATION

Phenindione is an anticoagulant drug derived from coumarin. (L1262) For the treatment of pulmonary embolism, cardiomyopathy, atrial fibrillation and flutter, cerebral embolism, mural thrombosis, and thrombophili. Also used for anticoagulant prophylaxis.