Acenocoumarol, Fenprocoumon (Adverse effects)

Certain variants in the VKORC1 gene are relevant for the dosing of some drugs and may also contribute to the predisposition to manifest some adverse reactions. This is the case, for example, of c.-1639C>T which influences the risk of bleeding with acenocoumarol and phenprocoumon treatment.

Both acenocoumarol and phenprocoumon are two vitamin K antagonist oral anticoagulant drugs and coumarin derivatives. Acenocoumarol (Sintrom®) is one of the most widely used oral anticoagulants, acting at the hepatic level by preventing the formation of active coagulation factors, acting as a vitamin K antagonist.

Compared to Warfarin, its effect is slightly less long lasting so it 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 hemorrhagic blood dyscrasia, recent or foreseen surgical interventions on the central nervous system, ophthalmological operations and traumatic interventions that expose large tissue surfaces.

Contraindications in peptic ulcer or bleeding in gastrointestinal, urogenital or respiratory tract, cerebrovascular bleeding, acute pericarditis, pericardial effusions, severe arterial hypertension, severe hepatic or renal insufficiency. Contraindicated drugs 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 hepatic and/or mild or moderate renal insufficiency, or to patients with severe cardiac insufficiency.

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

The medical professional should be cautious when prescribing acenocoumarol or fenprocoumon to patients with known or suspected protein C or S deficiency, thyrotoxicosis.

Extreme precautions should be taken in patients with tumors, renal diseases, infections, inflammations, absorption disorders.

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

In high-risk patients, discontinue treatment gradually.

SIDE EFFECTS

Hemorrhages 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, clofibric acid and analogues, disulfiram, disulfiram, fluoroquinolones, clofibric acid and analogues. clofibric acid and analogues, disulfiram, ethacrynic acid, cimetic acid and analogues, disulfiram, ethacrynic acid, cimetic acid and analogues. etacrynic acid, cimetidine, glucagon, paracetamol, paracetamol, cimetidine and analogues.cimetidine, paracetamol, citalopram, fluoxetine, sertraline, fluvastatin, atorvastatin, simvastatin, metronidazole, miconazole (including locally applied), sulfonamides (including co-trimoxazole), tolbutamide, chlorpropamide, thyroid hormones, tamoxifen, tramadol, noscapine, prokinetic agents, prokinetic pump inhibitors, tamoxifen, tramadol, noscapine, protic 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), platelet aggregation inhibitors (clopidogrel, ticlopidine, ASA and derivatives), phenylbutazone or pyrazole derivatives.nics, other NSAIDs (non-steroidal anti-inflammatory drugs), cyclo-oxygenase-2 inhibitors, high doses of IV methylprednisolone, urokinase, streptokinase, alteplase, thrombin inhibitors, vitamin E.

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

Acenocoumarol/phenprocoumon can increase the serum concentration of hydantoin.

They increase the hypoglycemic effect of sulfonylurea derivatives.

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

TRADE NAME

Sintrom ® (Acenocoumarol)

Genes analyzed

VKORC1

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