Phenindione

222.24

222.24

201-454-4

5M7Y6274ZE

757269|41693

DTXSID5023453

LEAFLETS FROM ALCOHOL|CREAMY WHITE TO PALE YELLOW CRYSTALS OR CRYSTALLINE POWDER

B - Blood and blood forming organs

2914399090

34.1

2.9

Solid

1.343g/cm3

149-151 °C

243.3 °C (0.3 mmHg)

208 °C

1.703

2.30e-02 g/L

2-8°C

ALMOST ODORLESS

4.5 IN SATURATED SOLN @ 25 °C

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

SOLN IN ALKALIES ARE RED, IN CONCN H2SO4 BLUE

III

6.1(b)

UN 2811 6.1/PG 3

3

25-43

36/37/39-45

NK6125000

T

P280-P301 + P310

H301-H317

|Danger|H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]|P261, P264, P270, P272, P280, P301+P310, P302+P352, P321, P330, P333+P313, P363, P405, and P501|Aggregated GHS information provided by 40 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Oral, mouse: LD50 = 175 mg/kg; Oral, rat: LD50 = 163 mg/kg.

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.

88%

For the treatment of pulmonary embolism, cardiomyopathy, atrial fibrillation and flutter, cerebral embolism, mural thrombosis, and thrombophili. Also used for anticoagulant prophylaxis.

Anticoagulants|...ORAL ANTICOAGULANTS ARE USEFUL IN PREVENTION & TREATMENT OF VARIETY OF THROMBOEMBOLIC DISORDERS. /ORAL ANTICOAGULANTS/|...INDICATIONS FOR ANTICOAGULANTS...1) MYOCARDIAL INFARCTION, 2) RHEUMATIC HEART DISEASE, 3) CEREBROVASCULAR DISEASE, 4) VENOUS THROMBOSIS & PULMONARY EMBOLISM, & 5) DISSEMINATED INTRAVASCULAR COAGULATION. /ANTICOAGULANTS/

IT IS INADVISABLE TO CARRY OUT LONG-TERM THERAPY IN CHRONIC ALCOHOLIC, IN INDIVIDUAL WHO MAY REQUIRE INTENSIVE SALICYLATE THERAPY, OR IN CASES OF MALIGNANT HYPERTENSION & ACTIVE TUBERCULOSIS. ORAL ANTICOAGULANT THERAPY DURING PREGNANCY CARRIES SIGNIFICANT HEMORRHAGIC RISK FOR FETUS. /ORAL ANTICOAGULANTS/|...CONTRAINDICATED IN HEMORRHAGIC TENDENCIES, BLOOD DYSCRASIAS, ULCERATIVE LESIONS OF GI TRACT, DIVERTICULITIS, COLITIS, SUBACUTE BACTERIAL ENDOCARDITIS, THREATENED ABORTION, RECENT OPERATIONS ON BRAIN OR SPINAL CORD. REGIONAL & LUMBAR-BLOCK ANESTHESIA, VITAMIN K DEFICIENCY...HEPATIC OR RENAL DISEASE. /ORAL ANTICOAGULANTS/|CHANGES IN AVAIL OF VITAMIN K ALTER THERAPEUTIC RESPONSE TO ORAL ANTICOAGULANTS. ... NEWBORN ARE PARTICULARLY SENSITIVE TO ORAL ANTICOAGULANTS. ... RENAL INSUFFICIENCY, FEVER, & SCURVY ENHANCE OR PROLONG ORAL ANTICOAGULANT RESPONSE. /ORAL ANTICOAGULANTS/|IT CANNOT BE EMPHASIZED TOO STRONGLY THAT TREATMENT OF EACH PT IS HIGHLY INDIVIDUALIZED MATTER. PT ON ANTICOAGULANT THERAPY MUST BE FOLLOWED BY MEANS OF PROTHROMBIN TIME TESTS & OBSERVED CAREFULLY FOR ANY DEVELOPMENT OF BLEEDING TENDENCY. /ANTICOAGULANTS/|For more Drug Warnings (Complete) data for PHENINDIONE (15 total), please visit the HSDB record page.

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.

Agents that prevent BLOOD CLOTTING. (See all compounds classified as Anticoagulants.)

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/

Hepatic.

5-10 hours

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/

...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.

2 Phenyl 1,3 indandione

...IS AVAIL FOR ORAL USE IN 20- & 50-MG TABLETS.

HPLC METHOD FOR DETN OF 2-PHENYL-1,3-INDANDIONE: RANGE 25 NG TO 3 MUG.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals