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Multisystem adverse reactions have been reported, and some may be serious enough to warrant hospital admission. In general, they may be divided into 2 categories: those which involve abnormal bleeding and other effects which do not. Hemorrhage and/or necrosis are among the hazards of treatment with any anticoagulant and are the main serious complications of therapy. For additional discussion of possible hemorrhagic complications following oral anticoagulant therapy see WARNINGS. Although most of the adverse reactions for oral anticoagulant drugs have been reported for warfarin, dicumarol, and phenindione, all the drugs within this class have similar pharmacologic and clinical properties, and require the same degree of caution in monitoring adverse reactions regardless of the drug administered.
Some indanediones (phenindione)have been associated with undesirable reactions which have not been reported with the coumarins and are not counterbalanced by advantages, thus perhaps favoring the use of the coumarin-type anticoagulants. Changing from one chemical type of oral anticoagulant to the other may eliminate an adverse reaction, such as rash or diarrhea. Dermatitis is the only untoward reaction consistently associated with anisindione therapy.
Adverse reactions reported following therapy with either coumarin or indanedione anticoagulants include:nausea, diarrhea, pyrexia, dermatitis or exfoliative dermatitis, urticaria, alopecia, and sore mouth or mouth ulcers.
Side effects which have additionally been reported for coumarin derivatives include:vomit-ing, abdominal cramps, anorexia, priapism, ery-thema and necrosis of the skin and other tissues, manifesting as purple toes and cutaneous gangrene. There is no reason to expect that some or all of these adverse reactions might not occur in patients receiving anisindione.
Additional side effects attributed to the indane-dione anticoagulants include: headache, sore throat, blurred vision, paralysis of accommodation, steatorrhea, hepatitis, jaundice, liver damage, renal tubular necrosis, albuminuria, anuria, myeloid immaturity, agranulocytosis, leukocyte agglutinins, red cell aplasia, atypical mononuclear cells, leukopenia, leukocytosis, anemia, thrombo-cytopenia, and eosinophilia.
Read the Miradon (anisindione) Side Effects Center for a complete guide to possible side effects
Addition or deletion of any drug from the therapeutic regimen of patients receiving oral anticoagulants may affect patient response to the anticoagulant. Frequent determination of prothrombin time and close monitoring of the patient is essential to ascertain when adjustment of dosage of anticoagulant may be needed.
Because of the variability of individual patient response, multiple interacting mechanisms with some drugs, the dependency of the extent of the interaction on the dosage and duration of therapy, and the possible administration of several interacting drugs simultaneously, it is difficult to predict the direction and degree of the ultimate effect of concomitant medications on anticoagulant response. For example, since cholestyramine may reduce the gastrointestinal absorption of both the oral anticoagulants and vitamin K, the net effects are unpredictable. Chloral hydrate may cause an increased prothrombin response by displacing the anticoagulant from protein binding sites or a diminished prothrombin response through increased metabolism of the unbound drug by hepatic enzyme induction, thus leading to inter-patient variation in ultimate prothrombin effect. An interacting drug which leads to a decrease in prothrombin time necessitating an increased dose of oral anticoagulant to maintain an adequate degree of anticoagulation may, if abruptly discontinued, increase the risk of subsequent bleeding.
Drugs that have been reported to diminish oral anticoagulant response, ie, decreased prothrom-bin time response, in man significantly include: adrenocortical steroids; alcohol*; antacids; antihistamines; barbiturates; carbamazepine; chloral hydrate*; chlordiazepoxide; cholestyramine; diet high in vitamin K; diuretics*; ethchlorvynol; glu-tethimide; griseofulvin; haloperidol; meprobamate; oral contraceptives; paraldehyde; primidone; ranitidine*; rifampin; unreliable prothrombin time determinations; vitamin C; warfarin sodium under-dosage.
Drugs that reportedly may increase oral anticoagulant response, ie, increased prothrombin response, in man include:alcohol*; allopurinol; aminosalicylic acid; amiodarone; anabolic steroids; antibiotics; bromelains; chloral hydrate*; chlorpro-pamide; chymotrypsin; cimetidine; cinchophen; clofibrate; dextran; dextrothyroxine; diazoxide; die-tarydeficiencies; diflunisal; diuretics*; disulfiram; drugs affecting blood elements; ethacrynic acid; fenoprofen; glucagon; hepatotoxic drugs; ibuprofen; indomethacin; influenza virus vaccine; inhalation anesthetics; mefenamic acid; methyldopa; methylphenidate; metronidazole; miconazole; monoamine oxidase inhibitors; nalidixic acid; naproxen; oxolinic acid; oxyphenbutazone; pent-oxifylline; phenylbutazone; phenyramidol; pheny-toin; prolonged hot weather; prolonged narcotics; pyrazolones; quinidine; quinine; ranitidine*; sali-cylates;sulfinpyrazone; sulfonamides, long acting; sulindac; thyroid drugs; tolbutamide; triclofos sodium; trimethoprim/sulfamethoxazole; unreliable prothrombin time determinations; warfarin sodium overdosage.
Oral anticoagulants may potentiate the hypoglycemic action of hypoglycemic agents, eg, tolbut-amide and chlorpropamide, by inhibiting their metabolism in the liver. Because oral anticoagulants may interfere with the hepatic metabolism of phenytoin, toxic levels of the anticonvulsant may occur when an oral anticoagulant and pheny-toin are administered concurrently.
Drugs that reduce the number of blood platelets by causing bone marrow depression (such as antineoplastic agents) or drugs which inhibit platelet function (eg, aspirin and other non-steroidal anti-inflammatory drugs, dipyridamole, hydrochloroquine, clofibrate, dextran) may increase the bleeding tendency produced by anticoagulants without altering prothrombin time determinations. The beneficial effects on arterial thrombus formation from combined therapy with antiplatelet and anticoagulant medication must be weighed against an increased risk of inducing hemorrhage.
*Increased and decreased prothrombin time responses have been reported.
Drug/Laboratory Test Interferences: Dicu-marol and indanedione anticoagulants, including anisindione, or their metabolites may color alkaline urine red-orange, which may interfere with spectrophotometrically determined urinary laboratory tests. The color reverses when the test sample is acidified in vitro to a pH below 4.
Last reviewed on RxList: 12/8/2004
This monograph has been modified to include the generic and brand name in many instances.
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