Rosex - General Information:

An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Rosex is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Rosex is also used as a rodenticide. [PubChem]

    Pharmacology:

    Rosex, a coumarin anticoagulant, is a racemic mixture of two active isomers. It is used in the prevention and treatment of thromboembolic disease including venous thrombosis, thromboembolism, and pulmonary embolism as well as for the prevention of ischemic stroke in patients with atrial fibrillation (AF).

    Rosex for patients

    Rosex Interactions

    Drugs may interact with COUMADIN through pharmacodynamic or pharmacokinetic mechanisms. Pharmacodynamic mechanisms for drug interactions with COUMADIN are synergism (impaired hemostasis, reduced clotting factor synthesis), competitive antagonism (vitamin K), and altered physiologic control loop for vitamin K metabolism (hereditary resistance). Pharmacokinetic mechanisms for drug interactions with COUMADIN are mainly enzyme induction, enzyme inhibition, and reduced plasma protein binding. It is important to note that some drugs may interact by more than one mechanism.

    The following factors, alone or in combination, may be responsible for INCREASED PT/INR response

    ENDOGENOUS FACTORS

    blood dyscrasias —

    diarrhea

    hyperthyroidism

    see CONTRAINDICATIONS

    elevated temperature

    poor nutritional state

    cancer

    hepatic disorders

    steatorrhea

    collagen vascular disease

    infectious hepatitis

    vitamin K deficiency

    congestive heart failure

    jaundice

     

    EXOGENOUS FACTORS

    Potential drug interactions with COUMADIN are listed below by drug class and by specific drugs.

    Classes of Drugs

    5-lipoxygenase Inhibitor

    Antiparasitic/Antimicrobials

    HMG-CoA Reductase

    Adrenergic Stimulants, Central

    Antiplatelet Drugs/Effects

    Inhibitors

    Alcohol Abuse Reduction

    Antithyroid Drugs

    Leukotriene Receptor Antagonist

    Preparations

    Beta-Adrenergic Blockers

    Monoamine Oxidase Inhibitors

    Analgesics

    Cholelitholytic Agents

    Narcotics,prolonged

    Anesthetics, Inhalation

    Diabetes Agents, Oral

    Nonsteroidal Anti-Inflammatory

    Antiandrogen

    Diuretics

    Agents

    Antiarrhythmics

    Fungal Medications, Intravaginal,

    Psychostimulants

    Antibiotics

    Systemic

    Pyrazolones

    Aminoglycosides (oral)

    Gastric Acidity and Peptic

    Salicylates

    Cephalosporins, parenteral

    Ulcer Agents

    Selective Serotonin

    Macrolides

    Gastrointestinal

    Reuptake Inhibitors

    Miscellaneous

    Prokinetic Agents

    Steroids, Adrenocortical

    Penicillins, intravenous,

    Ulcerative Colitis Agents

    Steroids, Anabolic (17-Alkyl

    high dose

    Gout Treatment Agents

    Testosterone Derivatives)

    Quinolones (fluoroquinolones)

    Hemorrheologic Agents

    Thrombolytics

    Sulfonamides, long acting

    Hepatotoxic Drugs

    Thyroid Drugs

    Tetracyclines

    Hyperglycemic Agents

    Tuberculosis Agents

    Anticoagulants

    Hypertensive Emergency Agents

    Uricosuric Agents

    Anticonvulsants

    Hypnotics

    Vaccines

    Antidepressants

    Hypolipidemics

    Vitamins

    Antimalarial Agents

    Bile Acid-Binding Resins

     

    Antineoplastics

    Fibric Acid Derivatives

     

    Specific Drugs Reported

    acetaminophen

    fluconazole

    penicillin G,intravenous

    alcohol

    fluorouracil

    pentoxifylline

    allopurinol

    fluoxetine

    phenylbutazone

    aminosalicylic acid

    flutamide

    phenytoin

    amiodarone HCl

    fluvastatin

    piperacillin

    aspirin

    fluvoxamine

    piroxicam

    atorvastatin

    gemfibrozil

    pravastatin

    azithromycin

    glucagon

    prednisone

    capecitabine

    halothane

    propafenone

    cefamandole

    heparin

    propoxyphene

    cefazolin

    ibuprofen

    propranolol

    cefoperazone

    ifosfamide

    propylthiouracil

    cefotetan

    indomethacin

    quinidine

    cefoxitin

    influenza virus vaccine

    quinine

    ceftriaxone

    itraconazole

    ranitidine

    celecoxib

    ketoprofen

    rofecoxib

    cerivastatin

    ketorolac

    sertraline

    chenodiol

    levamisole

    simvastatin

    chloramphenicol

    levofloxacin

    stanozolol

    chloral hydrate

    levothyroxine

    streptokinase

    chlorpropamide

    liothyronine

    sulfamethizole

    cholestyramine

    lovastatin

    sulfamethoxazole

    cimetidine

    mefenamic acid

    sulfinpyrazone

    ciprofloxacin

    methimazole

    sulfisoxazole

    cisapride

    methyldopa

    sulindac

    clarithromycin

    methylphenidate

    tamoxifen

    clofibrate

    methylsalicylate ointment

    tetracycline

    COUMADIN overdose

    (topical)

    thyroid

    cyclophosphamide

    metronidazole

    ticarcillin

    danazol

    miconazole

    ticlopidine

    dextran

    (intravaginal,systemic)

    tissue plasminogen

    dextrothyroxine

    moricizine hydrochloride

    activator (t-PA)

    diazoxide

    nalidixic acid

    tolbutamide

    diclofenac

    naproxen

    tramadol

    dicumarol

    neomycin

    trimethoprim/sulfamethoxazole

    diflunisal

    norfloxacin

    urokinase

    disulfiram

    ofloxacin

    valproate

    doxycycline

    olsalazine

    vitamin E

    erythromycin

    omeprazole

    zafirlukast

    ethacrynic acid

    oxaprozin

    zileuton

    fenofibrate

    oxymetholone

     

    fenoprofen

    paroxetine

     

    also: other medications affecting blood elements which may modify hemostasis dietary deficiencies prolonged hot weather unreliable PT/INR determinations

    increased and decreased PT/INR responses have been reported.

    The following factors, alone or in combination, may be responsible for DECREASED PT/INR response

    ENDOGENOUS FACTORS

    edema

    hypothyroidism

    hereditary coumarin resistance

    nephrotic syndrome

    hyperlipemia

     

    EXOGENOUS FACTORS

    Potential drug interactions with COUMADIN (Warfarin Sodium) are listed below by drug class and by specific drugs.

    Classes of Drugs

    Adrenal Cortical Steroid Inhibitors

    Antithyroid Drugs

    HMG-CoA Reductase Inhibitors

    Antacids

    Barbiturates

    Immunosuppressives

    Antianxiety Agents

    Diuretics

    Oral Contraceptives,

    Antiarrhythmics

    Enteral Nutritional Supplements

    Estrogen Containing

    Antibiotics

    Fungal Medications, Systemic

    Selective Estrogen Receptor

    Anticonvulsants

    Gastric Acidity and

    Modulators

    Antidepressants

    Peptic Ulcer Agents

    Steroids, Adrenocortical

    Antihistamines

    Hypnotics

    Tuberculosis Agents

    Antineoplastics

    Hypolipidemics

    Vitamins

    Antipsychotic Medications

    Bile Acid-Binding Resins

     

    Specific Drugs Reported

    alcohol

    COUMADIN underdosage

    phenytoin

    aminoglutethimide

    cyclophosphamide

    pravastatin

    amobarbital

    dicloxacillin

    prednisone

    atorvastatin

    ethchlorvynol

    primidone

    azathioprine

    glutethimide

    propylthiouracil

    butabarbital

    griseofulvin

    raloxifene

    butalbital

    haloperidol

    ranitidine

    carbamazepine

    meprobamate

    rifampin

    chloral hydrate

    6-mercaptopurine

    secobarbital

    chlordiazepoxide

    methimazole

    spironolactone

    chlorthalidone

    moricizine hydrochloride

    sucralfate

    cholestyramine

    nafcillin

    trazodone

    clozapine

    paraldehyde

    vitamin C (high dose)

    corticotropin

    pentobarbital

    vitamin K

    cortisone

    phenobarbital

     

    also: diet high in vitamin K unreliable PT/INR determinations

    Increased and decreased PT/INR responses have been reported.

    Because a patient may be exposed to a combination of the above factors, the net effect of COUMADIN on PT/INR response may be unpredictable. More frequent PT/INR monitoring is therefore advisable. Medications of unknown interaction with coumarins are best regarded with caution. When these medications are started or stopped, more frequent PT/INR monitoring is advisable.

    It has been reported that concomitant administration of warfarin and ticlopidine may be associated with cholestatic hepatitis.

    Botanical (Herbal) Medicines

    Caution should be exercised when botanical medicines (botanicals) are taken concomitantly with COUMADIN. Few adequate, well-controlled studies exist evaluating the potential for metabolic and/or pharmacologic interactions between botanicals and COUMADIN. Due to a lack of manufacturing standardization with botanical medicinal preparations, the amount of active ingredients may vary. This could further confound the ability to assess potential interactions and effects on anticoagulation. It is good practice to monitor the patient’s response with additional PT/INR determinations when initiating or discontinuing botanicals.

    Specific botanicals reported to affect COUMADIN therapy include the following:

    • Bromelains, danshen, dong quai (Angelica sinensis), garlic, Ginkgo biloba, and ginseng are associated most often with an INCREASE in the effects of COUMADIN.

    • Coenzyme Q10 (ubidecarenone) and St. John’s wort are associated most often with a DECREASE in the effects of COUMADIN.

    Some botanicals may cause bleeding events when taken alone (e.g., garlic and Ginkgo biloba) and may have anti-coagulant, antiplatelet, and/or fibrinolytic properties. These effects would be expected to be additive to the anticoagulant effects of COUMADIN. Conversely, other botanicals may have coagulant properties when taken alone or may decrease the effects of COUMADIN.

    Some botanicals that may affect coagulation are listed below for reference; however, this list should not be considered all-inclusive. Many botanicals have several common names and scientific names. The most widely recognized common botanical names are listed.

    Botanticals that contain coumarins with potential anticoagulant effects:

    Alfalfa

    Celery

    Parsley

    Angelica (Dong Quai)

    Chamomile

    Passion Flower

    Aniseed

    (German and Roman)

    Prickly Ash (Northern)

    Arnica

    Dandelion3

    Quassia

    Asa Foetida

    Fenugreek

    Red Clover

    Bogbean1

    Horse Chestnut

    Sweet Clover

    Boldo

    Horseradish

    Sweet Woodruff

    Buchu

    Licorice3

    Tonka Beans

    Capsicum2

    Meadowsweet1

    Wild Carrot

    Cassia3

    Nettle

    Wild Lettuce

    Miscellaneous botanticals with anticoagulant properties:

    Bladder Wrack (Fucus)

    Pau d’arco

     

    Botanicals that contain salicylate and/or have antiplatelet properties:

    Agrimony4

    Dandelion3

    Meadowsweet1

    Aloe Gel

    Feverfew

    Onion5

    Aspen

    Garlic5

    Policosanol

    Black Cohosh

    German Sarsaparilla

    Poplar

    Black Haw

    Ginger

    Senega

    Bogbean1

    Ginkgo Biloba

    Tamarind

    Cassia3

    Ginseng (Panax)5

    Willow

    Clove

    Licorice3

    Wintergreen

    Botanticals with fibrinolytic properties:

    Bromelains

    Garlic5

    Inositol Nicotinate

    Capsicum2

    Ginseng (Panax)5

    Onion5

    Botanticals with coagulant properties:

    Agrimony4 Mistletoe

    Yarrow

    Goldenseal

     

    1 Contains coumarins and salicylate.

    2 Contains coumarins and has fibrinolytic properties.

    3 Contains coumarins and has antiplatelet properties.

    4 Contains salicylate and has coagulant properties.

    5 Has antiplatelet and fibrinolytic properties.

    Effect on Other Drugs

    Coumarins may also affect the action of other drugs. Hypoglycemic agents (chlorpropamide and tolbutamide) and anticonvulsants (phenytoin and phenobarbital) may accumulate in the body as a result of interference with either their metabolism or excretion.

    Special Risk Patients

    COUMADIN (Warfarin Sodium) is a narrow therapeutic range (index) drug, and caution should be observed when warfarin sodium is administered to certain patients such as the elderly or debilitated or when administered in any situation or physical condition where added risk of hemorrhage is present.

    Intramuscular (I.M.) injections of concomitant medications should be confined to the upper extremities which permits easy access for manual compression, inspections for bleeding and use of pressure bandages.

    Caution should be observed when COUMADIN (or warfarin) is administered concomitantly with nonsteroidal antiinflammatory drugs (NSAIDs), including aspirin, to be certain that no change in anticoagulation dosage is required. In addition to specific drug interactions that might affect PT/INR, NSAIDs, including aspirin, can inhibit platelet aggregation, and can cause gastrointestinal bleeding, peptic ulceration and/or perforation.

    Acquired or inherited warfarin resistance should be suspected if large daily doses of COUMADIN are required to maintain a patient’s PT/INR within a normal therapeutic range.

    SIDE EFFECTS

    Potential adverse reactions to COUMADIN may include:

    • Fatal or nonfatal hemorrhage from any tissue or organ. This is a consequence of the anticoagulant effect. The signs, symptoms, and severity will vary according to the location and degree or extent of the bleeding. Hemorrhagic complications may present as paralysis; paresthesia; headache, chest, abdomen, joint, muscle or other pain; dizziness; shortness of breath, difficult breathing or swallowing; unexplained swelling; weakness; hypotension; or unexplained shock. Therefore, the possibility of hemorrhage should be considered in evaluating the condition of any anticoagulated patient with complaints which do not indicate an obvious diagnosis. Bleeding during anticoagulant therapy does not always correlate with PT/INR.

    • Bleeding which occurs when the PT/INR is within the therapeutic range warrants diagnostic investigation since it may unmask a previously unsuspected lesion, e.g., tumor, ulcer, etc.

    • Necrosis of skin and other tissues.

    • Adverse reactions reported infrequently include: hypersensitivity/allergic reactions, systemic cholesterol microembolization, purple toes syndrome, hepatitis, cholestatic hepatic injury, jaundice, elevated liver enzymes, vasculitis, edema, fever, rash, dermatitis, including bullous eruptions, urticaria, abdominal pain including cramping, flatulence/bloating, fatigue, lethargy, malaise, asthenia, nausea, vomiting, diarrhea, pain, headache, dizziness, taste perversion, pruritus, alopecia, cold intolerance, and paresthesia including feeling cold and chills.

    Rare events of tracheal or tracheobronchial calcification have been reported in association with long-term warfarin therapy. The clinical significance of this event is unknown.

    Priapism has been associated with anticoagulant administration, however, a causal relationship has not been established.

     

    Rosex Contraindications

    Anticoagulation is contraindicated in any localized or general physical condition or personal circumstance in which the hazard of hemorrhage might be greater than the potential clinical benefits of anticoagulation, such as:

    Pregnancy

    COUMADIN is contraindicated in women who are or may become pregnant because the drug passes through the placental barrier and may cause fatal hemorrhage to the fetus in utero. Furthermore, there have been reports of birth malformations in children born to mothers who have been treated with warfarin during pregnancy.

    Embryopathy characterized by nasal hypoplasia with or without stippled epiphyses (chondrodysplasia punctata) has been reported in pregnant women exposed to warfarin during the first trimester. Central nervous system abnormalities also have been reported, including dorsal midline dysplasia characterized by agenesis of the corpus callosum, Dandy-Walker malformation, and midline cerebellar atrophy. Ventral midline dysplasia, characterized by optic atrophy, and eye abnormalities have been observed. Mental retardation, blindness,a nd other central nervous system abnormalities have been reported in association with second and third trimester exposure. Although rare, teratogenic reports following in utero exposure to warfarin include urinary tract anomalies such as single kidney, asplenia, anencephaly, spina bifida, cranial nerve palsy, hydrocephalus, cardiac defects and congenital heart disease, polydactyly, deformities of toes, diaphragmatic hernia, corneal leukoma, cleft palate, cleft lip, schizencephaly, and microcephaly.

    Spontaneous abortion and stillbirth are known to occur and a higher risk of fetal mortality is associated with the use of warfarin. Low birth weight and growth retardation have also been reported.

    Women of childbearing potential who are candidates for anticoagulant therapy should be carefully evaluated and the indications critically reviewed with the patient. If the patient becomes pregnant while taking this drug, she should be apprised of the potential risks to the fetus, and the possibility of termination of the pregnancy should be discussed in light of those risks.

    Hemorrhagic tendencies or blood dyscrasias.

    Recent or contemplated surgery of: (1) central nervous system; (2) eye; (3) traumatic surgery resulting in large open surfaces.

    Bleeding tendencies associated with active ulceration or overt bleeding of: (1) gastrointestinal, genitourinary or respiratory tracts; (2) cerebrovascular hemorrhage; (3) aneurysms-cerebral, dissecting aorta; (4) pericarditis and pericardial effusions; (5) bacterial endocarditis.

    Threatened abortion, eclampsia and preeclampsia.

    Inadequate laboratory facilities.

    Unsupervised patients with senility, alcoholism,or psychosis or other lack of patient cooperation.

    Spinal puncture and other diagnostic or therapeutic procedures with potential for uncontrollable bleeding.

    Miscellaneous major regional, lumbar block anesthesia, malignant hypertension and known hypersensitivity to warfarin or to any other components of this product.

    Rosex more info

    Indication, Mechanism Of Action, Drug Interactions, Food Interactions, etc..