Acenocoumarol, Phenprocoumon (Dosage)

Both acenocoumarol and phenprocoumon are two vitamin K antagonist oral anticoagulant drugs and coumarin derivatives.

Acenocoumarol (Sintrom ® brand name) is one of the most widely used oral anticoagulants. It prevents the formation in the liver of the active coagulation factors II, VII, IX and X and protein C, by inhibiting the gamma carboxylation of precursor proteins mediated by vitamin K, so that acenocoumarol and phenprocoumon are antagonists of vitamin K.

They have a slightly shorter duration of effect than warfarin, which could be an advantage in case of bleeding due to overdose.

CONTRAINDICATIONS

Hypersensitivity to coumarin derivatives.

Contraindicated in pregnancy, lack of cooperation of the patient, hemorrhagic diathesis or haemorrhagic blood dyscrasia, recent or planned surgical interventions in the central nervous system, ophthalmological operations and and traumatic interventions that expose large areas of tissue.

Contraindicated in peptic ulcer or bleeding in the gastrointestinal, urogenital or respiratory tract, cerebrovascular bleeding, acute pericarditis, pericardial effusions, severe arterial hypertension, severe hepatic or kidney failure. Drugs contraindicated in patients with hereditary, acquired coagulopathies and thrombocytopenias with platelet counts less than 50x109/L and in situations with increased fibrinolytic activity.

PRECAUTIONS

Precautions should be taken when these drugs are intended to be prescribed to patients with mild to moderate hepatic and/or renal impairment, or to patients with severe heart failure.

Precautions in the case of the elderly and children (more frequent monitoring of the coagulation parameters should be performed in these cases).

Medical professional should be cautious when prescribing acenocoumarol or phenprocoumon to patients with known or suspected protein C or S deficiency, cautions in patients with thyrotoxicosis.

Extreme precautions in patients with tumors, kidney diseases, infections, inflammations and absorption disorders.

Intramuscular injections should be avoided during treatment (risk of bruising). Caution in surgical and diagnostic interventions.

In high-risk patients stop treatment gradually.

SIDE EFFECTS

Bleeding in any organ. Calciphylaxis.

PHARMACOLOGICAL INTERACTIONS

The effect of coumarin derivatives is potentiated by: allopurinol, anabolic steroids, androgens, amiodarone, quinidine, erythromycin, tetracyclines, clindamycin, neomycin, chloramphenicol, amoxicillin, cephalosporins (2nd and 3rd generation), fluoroquinolones, ac. clofibric and analogous, disulfiram, ac. ethacrynic, cimetidine, glucagon, paracetamol, citalopram, fluoxetine, sertraline, fluvastatin, atorvastatin, simvastatin, metronidazole, miconazole (even applied locally), sulfonamides (including cotrimoxazole), tolbutamide, chlorpropamide, thyroid hormones, tamoxifen, tramadol, noscapine, prokinetic agents , proton pump inhibitors, antacids, viloxacin and corticosteroids (methylprednisolone, prednisone).

Do not use with substances that modify hemostasis (danger of gastrointestinal bleeding): heparin (except those situations where rapid anticoagulation is required), inhibitors of platelet aggregation (clopidogrel, ticlopidine, AAS and derivatives), phenylbutazone or pyrazolone derivatives, other NSAIDs (non-steroidal anti-inflammatory drugs), inhibitors of cyclo-oxygenase 2, high doses of methylprednisolone IV, urokinase, streptokinase, alteplase, thrombin inhibitors, vitamin E.

The antithrombotic effect may be diminished by aminoglutethimide, barbiturates, carbamazepine, cholestyramine, griseofulvin, oral contraceptives, rifampicin, thiazide diuretics, azathioprine, 6-mercaptopurine, ritonavir, nelfinavir, H. perforatum.

Acenocoumarol/phenprocoumon can raise the serum concentration of hydantoin..

Both drugs can increase the hypoglycaemic effect of sulfonylurea derivatives.

Avoid taking these drugs together with alcohol, currant juice, foods high in vitamin K (spinach, cauliflower, cabbage).

BRAND NAME

  • Sintrom ® (Acenocumarol)

Gene or region studied

  • CYP2C9
  • CYP4F2
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