Anisindione

252.26

252.26

204-186-6

S747T1ERAJ

759629

DTXSID3022611

C47398

Pale yellow crystals from acetic acid or ethanol|FINE WHITE TO CREAM-WHITE CRYSTALLINE POWDER

2914509090

43.37000

2.85800

Solid

1.1824 (rough estimate)

156-157 °C

355.44°C (rough estimate)

199.8ºC

1.5600 (estimate)

1.28e-02 g/L

Anisindione tablets should be stored in tight containers at a temperature of less than 40 deg celsius, preferably between 15 to 30 deg celsius.

4.45E-08mmHg at 25°C

ODORLESS OR HAS SLIGHTLY SWEET ODOR

III

6.1(b)

2811

STABLE IN LIGHT & AIR

P264, P270, P301+P312, P330, P501

H302

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl anisindione, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P264, P270, P301+P312, P330, and P501|The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

An overdose is likely to cause abnormal bleeding, for which the symptoms include: bleeding from gums or nose, blood in urine or stools, excessive bleeding from minor cuts, patches of discoloration or bruises on the skin.

Corticotropin and adrenocorticosteroids...reported to cause severe hemorrhage when given with oral anticoagulants...this is rather puzzling, since thrombotic episodes are stated to occur more frequently in pt on steroid therapy, and oral anticoagulants...advised in prophylaxis of such complications. /oral anticoagulants/|Large doses of salicylates have often been assoc with bleeding problems, especially in pt receiving oral anticoagulants. This may be due to direct gastric irritation, suppression of platelet function, or true hypoprothrombinemic effect. ...latter would be antagonized by vitamin K. /oral anticoagulants/|Antimicrobials and other agents that alter intestinal microflora may enhance anti-vitamin K effect of oral anticoagulants, but this is usually not seen unless there is dietary deficiency of vitamin k. /oral anticoagulants/|Thiazide diuretics and ethacrynic acid may enhance effects of oral anticoagulants. /oral anticoagulants/|For more Interactions (Complete) data for ANISINDIONE (21 total), please visit the HSDB record page.

SRP: Persons with bleeding disorders or who are taking anticoagulants should be protected from exposure.

Not Known

For the prophylaxis and treatment of venous thrombosis and its extension, the treatment of atrial fibrillation with embolization, the prophylaxis and treatment of pulmonary embolism, and as an adjunct in the treatment of coronary occlusion.

...Oral anticoagulants are useful in prevention and treatment of variety of thromboembolic disorders. /oral anticoagulants/|...Indications for anticoagulants...myocardial infarction...rheumatic heart Disease...cerebrovascular disease...venous thrombosis and pulmonary embolism, and ...disseminated intravascular coagulation. /oral anticoagulants/|Oral anticoagulants are used to prevent the progression or recurrence of acute deep vein thrombosis or pulmonary embolism following initial course of heparin. They also are effective in preventing venous thromboembolism in patients undergoing orthopedic or gynecological surgery and systemic embolization in patients with acute myocardial infarction, prosthetic heart valves, or chronic atrial fibrillation. /Oral anticoagulants/|Anticoagulants are indicated for prophylaxis and/or treatment of venous (or arterial /Not included in US product labeling/) thrombosis (and its extension) and pulmonary embolism, deep vein thrombosis (DVP) or pulmonary embolism (treatment). Oral anticoagulatns are used during and following initial heparin therapy to decrease the risk of extension, recurrence, or death. /Anticoagulants; Included in US product labeling/|For more Therapeutic Uses (Complete) data for ANISINDIONE (11 total), please visit the HSDB record page.

Serious, sometimes fatal, toxic reactions were reported occasionally in patients receiving phenindione (no longer commercially available in US), and the possibility of these reactions should be considered in patients receiving anisindione. Adverse effects reported with phenindione (no longer commercially available in US) include dermatologic reactions such as such as urticaria and rash (usually erythematous and macular), which sometimes progressed to exfoliative dermatitis; nephrotic reactions, including anuria and albuminuria with massive edema and tubular necrosis; hepatotoxicity manifested by hepatitis and jaundice; and hematologic reactions manifested by eosinophilia, agranulocytosis or leukopenia (resulting from either maturation arrest or granulocytic hypoplasia), leukocytosis, anemia, thrombecytopenia, atypical mononuclear cells, the presence of leukocyte agglutinins, agranulocytosis, aplastic anemia, and red cell aplasia. In addition, hemorrhagic infarction and necrosis of the skin, alopecia, steatorrhea, sore throat and mouth, parlysis of accommodation and blurred vision, diarrhea, nausea, fever, malaise, and headache have been reported in patients receiving the drug.|In patients with alkaline urine, the urine may be red-orange during therapy with anisindione and patients should be informed of this possibility.|The only consistently reported adverse nonhemorrhagic effect of anisindione is dermatitis. However, agranulocytosis and hepatitis also have been reported with the use of this drug.|Conversely, anisindione (plasma half-life, 3-5 days).../is/ so long-acting that.../it/ may be Hazardous if hemorrhage occurs...|For more Drug Warnings (Complete) data for ANISINDIONE (30 total), please visit the HSDB record page.

Anisindione is a synthetic anticoagulant and an indanedione derivative. It is prescribed only if you cannot take coumarin-type anticoagulants such as coumadin as anisindione is a powerful drug with serious potential side effects. Anticoagulants decrease the clotting ability of the blood and therefore help to prevent harmful clots from forming in the blood vessels. These medicines are sometimes called blood thinners, although they do not actually thin the blood. They also will not dissolve clots that already have formed, but they may prevent the clots from becoming larger and causing more serious problems.

Accumulation does not occur with repeated dosing.

Not Known|...PLASMA HALF-LIFE, 3-5 DAYS...

Like phenindione, to which it is related chemically, anisindione exercises its therapeutic action by reducing the prothrombin activity of the blood. By inhibiting the vitamin K–mediated gamma-carboxylation of precursor proteins, the formation of active procoagulation factors II, VII, IX, and X, as well as the anticoagulant proteins C and S is prevented. Anisindione has no direct thrombolytic effect and does not reverse ischemic tissue damage, although it may limit extension of existing thrombi and prevent secondary thromboembolic complications.|Oral anticoagulants have no direct effect on circulating clotting factors. Instead they block hepatic formation of factors II, VII, IX, and X by competitively inhibiting action of vitamin K. Synthesis of these factors is dependent upon sufficient supply of vitamin.|The oral anticoagulants block the regeneration of reduced vitamin K and thereby induce a state of functional vitamin K deficiency. The mechanism of the inhibition of reductase(s) by the coumarin drugs is not known. There exist reductases that are less sensitive to these drugs but that act only at relatively high concentrations of oxidized vitamin K; this property may explain the observation that administration of sufficient vitamin K can counteract even large doses of oral anticoagulants. /Oral Anticoagulants/|Both 4-hydroxycoumarin derivatives and indandiones (also known as oral anticoagulants) are antagonists of vitamin K. Their use as rodenticides is based on the inhibition of the vitamin K-dependent step in the synthesis of a number of blood coagulation factors. The vitamin K-dependent proteins ...in the coagulation cascade... are the procoagulant factors II (prothrombin), VII (proconvertin), IX (Christmas factor) and X (Stuart-Prower factor), and the coagulation-inhibiting proteins C and S. All these proteins are synthesized in the liver. Before they are released into the circulation the various precursor proteins undergo substantial (intracellular) post-translational modification. Vitamin K functions as a co-enzyme in one of these modifications, namely the carboxylation at well-defined positions of 10-12 glutamate residues into gamma-carboxyglutamate (Gla). The presence of these Gla residues is essential for the procoagulant activity of the various coagulations factors. Vitamin K hydroquinone (KH2) is the active co-enzyme, and its oxidation to vitamin K 2,3-epoxide (KO) provides the energy required for the carboxylation reaction. The epoxide is than recycled in two reduction steps mediated by the enzyme KO reductase... . The latter enzyme is the target enzyme for coumarin anticoagulants. Their blocking of the KO reductase leads to a rapid exhaustion of the supply of KH2, and thus to an effective prevention of the formation of Gla residues. This leads to an accumulation of non-carboxylated coagulation factor precursors in the liver. In some cases these precursors are processed further without being carboxylated, and (depending on the species) may appear in the circulation. At that stage the under-carboxylated proteins are designated as descarboxy coagulation factors. Normal coagulation factors circulate in the form of zymogens, which can only participate in the coagulation cascade after being activated by limited proteolytic degradation. Descarboxy coagulation factors have no procoagulant activity (i.e. they cannot be activated) and neither they can be converted into the active zymogens by vitamin K action. Whereas in anticoagulated humans high levels of circulating descarboxy coagulation factors are detectable, these levels are negligible in warfarin-treated rats and mice. /Anticoagulant rodenticides/

Vitamin K1 is a specific antidote for anticoagulants, such as anisindione, which reduce prothrombin activity in the blood. Vitamin K1 may be administered orally or by injection, if the patient is not bleeding or if bleeding is slight. A few hours after the administration of vitamin K1 preparations, such as phytonadione, prothrombin activity increases and clotting time decreases. In the presents of more active hemorrhage, however, transfusions of whole blood or plamsa are required until the desired level of prothrombin activity is achieved. Treatment with vitamin K1 is the only adjunctive in such cases.

/HUMAN EXPOSURE STUDIES/ Untoward effects incl hemorrhagic diathesis resulting from overdose and Dermatitis.|/HUMAN EXPOSURE STUDIES/ Bleeding is the major toxicity of oral anticoagulant drugs. ... Especially serious episodes involve sites where irreversible damage may result from compression of vital structures (e.g., intracranial, pericardial, nerve sheath, or spinal cord) or from massive internal blood loss that may not be diagnosed rapidly (e.g., gastrointestinal, intraperitoneal, retroperitoneal). /ORAL ANTICOAGULANTS/

2-(4-methoxyphenyl)-1H-indene-1,3(2H)-dione

ANISINDIONE IS AVAILABLE FOR ORAL USE IN 50-MG TABLETS.

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