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Latka 42

Latka 42 - General Information

An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Latka 42 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. Latka 42 is also used as a rodenticide. [PubChem]

 

Pharmacology of Latka 42

Latka 42, 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).

 

Latka 42 for patients

 

Latka 42 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.

 

Latka 42 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.

 

Additional information about Latka 42

Latka 42 Indication: For the treatment of retinal vascular occlusion, pulmonary embolism, cardiomyopathy, atrial fibrillation and flutter, cerebral embolism, transient cerebral ischaemia, arterial embolism and thrombosis.
Mechanism Of Action: Latka 42 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.
Drug Interactions: Not Available
Food Interactions: Avoid drastic changes in dietary habit.
Consult your doctor before taking large amounts of Vitamin K (Green leafy vegetables).
Avoid alcohol.
Avoid St.John's Wort.
Limit garlic, ginger, gingko, and horse chestnut.
Generic Name: Warfarin
Synonyms: Warfarin sodium
Drug Category: Rodenticides; Anticoagulants; Coumarin and Indandione Derivatives
Drug Type: Small Molecule; Approved

Other Brand Names containing Warfarin: Athrombin; Athrombin-K; Athrombine-K; Brumolin; Co-Rax; Coumadin; Coumafen; Coumafene; Coumaphen; Coumaphene; Coumarins; Coumefene; D-Con; Dethmor; Dethnel; Dicusat E; Frass-Ratron; Jantoven; Kumader; Kumadu; Kumatox; Kypfarin; Latka 42; Mar-Frin; Marevan; Maveran; Panwarfin; Place-Pax; Prothromadin; RAX; Rosex; Sofarin; Solfarin; Sorexa Plus; Temus W; Tintorane; Tox-Hid; Vampirinip II; Vampirinip III; Waran; Warf 42; Warfarat; Warfarin Plus; Warfarin Q; Warfarine; Warficide; Warfilone; Zoocoumarin;
Absorption: Not Available
Toxicity (Overdose): LD50=374 (orally in mice)
Protein Binding: 99.5%
Biotransformation: Metabolized by hepatic microsomal enzymes.
Half Life: 1 week
Dosage Forms of Latka 42: Tablet Oral
Chemical IUPAC Name: 2-hydroxy-3-(3-oxo-1-phenylbutyl)chromen-4-one
Chemical Formula: C19H16O4
Warfarin on Wikipedia: https://en.wikipedia.org/wiki/Warfarin
Organisms Affected: Humans and other mammals